The Journal of Implant & Advanced Clinical Dentistry ... · 38 Full Mouth Rehabilitation of...

The Journal of Implant & Advanced Clinical Dentistry

Volume 9, No. 2 February 2017

Updated Primer on Amnion-Chorion Allografts

Computer Guided Full Arch Immediately Loaded

Dental Implants

The Journal of Implant and Advanced Clinical Dentistry has been providing high quality, peer reviewed dental journals since 2007. We take pride in knowing that tens of thousands of readers around the world continue to read and contribute articles to JIACD. As you can imagine, there is a lot of expense involved in managing a top quality dental journal and we sincerely appreciate our advertisers purchasing ad space in both the journal and on the website which allows our monthly journals to continue to be free to all of our readers. In an e�ort to streamline our business practice and continue to provide no-fee, open access journals, JIACD is now sponsored exclusively by Osseofuse International Inc., a cutting edge dental implant company that provides exceptional implants and prosthetics and believes in the free distribution of information towards clinical advancements to dentists in the U.S. and around the world.

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The Journal of Implant & Advanced Clinical DentistryVolume 9, No. 2 • February 2017

Table of Contents

6 Computer Guided Full Arch Treatment Modality for the Edentulous Patient: A Case Report Dr. Dhaval P. Pandya, Dr. Ashwini Bhalerao, Dr. Kanir H. Bhatia

16 An Updated Primer on the Utilization of Amnion-Chorion Allografts in Dental Procedures Dan Holtzclaw, Robert Tofe

2 • Vol. 9, No. 2 • February 2017

The Journal of Implant & Advanced Clinical Dentistry • 3


Table of Contents

38 Full Mouth Rehabilitation of Completely Edentulous Patient with Full Arch Screw-Retained Prosthesis: A Case Report with 4 Year Follow Up Algabri RS, Alqutaibi AY, Keshk AM, Elkhadem AH, Fahmmy A, Aboalrejal HO

46 A Review of Photofunctionalization of Dental Implants Dr. Suraj Khalap, Dr. Ajay Mootha, Dr. Ramandeep Dugal


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4 • Vol. 9, No. 2 • February 2017


Tara Aghaloo, DDS, MDFaizan Alawi, DDSMichael Apa, DDSAlan M. Atlas, DMDCharles Babbush, DMD, MSThomas Balshi, DDSBarry Bartee, DDS, MDLorin Berland, DDSPeter Bertrand, DDSMichael Block, DMDChris Bonacci, DDS, MDHugo Bonilla, DDS, MSGary F. Bouloux, MD, DDSRonald Brown, DDS, MSBobby Butler, DDSNicholas Caplanis, DMD, MSDaniele Cardaropoli, DDSGiuseppe Cardaropoli DDS, PhDJohn Cavallaro, DDSJennifer Cha, DMD, MSLeon Chen, DMD, MSStepehn Chu, DMD, MSD David Clark, DDSCharles Cobb, DDS, PhDSpyridon Condos, DDSSally Cram, DDSTomell DeBose, DDSMassimo Del Fabbro, PhDDouglas Deporter, DDS, PhDAlex Ehrlich, DDS, MSNicolas Elian, DDSPaul Fugazzotto, DDSDavid Garber, DMDArun K. Garg, DMDRonald Goldstein, DDSDavid Guichet, DDSKenneth Hamlett, DDSIstvan Hargitai, DDS, MS

Michael Herndon, DDSRobert Horowitz, DDSMichael Huber, DDSRichard Hughes, DDSMiguel Angel Iglesia, DDSMian Iqbal, DMD, MSJames Jacobs, DMDZiad N. Jalbout, DDSJohn Johnson, DDS, MSSascha Jovanovic, DDS, MSJohn Kois, DMD, MSDJack T Krauser, DMDGregori Kurtzman, DDSBurton Langer, DMDAldo Leopardi, DDS, MSEdward Lowe, DMDMiles Madison, DDSLanka Mahesh, BDSCarlo Maiorana, MD, DDSJay Malmquist, DMDLouis Mandel, DDSMichael Martin, DDS, PhDZiv Mazor, DMDDale Miles, DDS, MSRobert Miller, DDSJohn Minichetti, DMDUwe Mohr, MDTDwight Moss, DMD, MSPeter K. Moy, DMDMel Mupparapu, DMDRoss Nash, DDSGregory Naylor, DDSMarcel Noujeim, DDS, MSSammy Noumbissi, DDS, MSCharles Orth, DDSAdriano Piattelli, MD, DDSMichael Pikos, DDSGeorge Priest, DMDGiulio Rasperini, DDS

Michele Ravenel, DMD, MSTerry Rees, DDSLaurence Rifkin, DDSGeorgios E. Romanos, DDS, PhDPaul Rosen, DMD, MSJoel Rosenlicht, DMDLarry Rosenthal, DDSSteven Roser, DMD, MDSalvatore Ruggiero, DMD, MDHenry Salama, DMDMaurice Salama, DMDAnthony Sclar, DMDFrank Setzer, DDSMaurizio Silvestri, DDS, MDDennis Smiler, DDS, MScDDong-Seok Sohn, DDS, PhDMuna Soltan, DDSMichael Sonick, DMDAhmad Soolari, DMDNeil L. Starr, DDSEric Stoopler, DMDScott Synnott, DMDHaim Tal, DMD, PhDGregory Tarantola, DDSDennis Tarnow, DDSGeza Terezhalmy, DDS, MATiziano Testori, MD, DDSMichael Tischler, DDSTolga Tozum, DDS, PhDLeonardo Trombelli, DDS, PhDIlser Turkyilmaz, DDS, PhDDean Vafiadis, DDSEmil Verban, DDSHom-Lay Wang, DDS, PhDBenjamin O. Watkins, III, DDSAlan Winter, DDSGlenn Wolfinger, DDSRichard K. Yoon, DDS

Founder, Co-Editor in ChiefDan Holtzclaw, DDS, MS

Co-Editor in ChiefLeon Chen, DMD, MS, DICOI, DADIA


Pandya et al

Background: Successful outcomes in the field of implantology often involve an amalgama-tion of good planning, execution of surgery and finally, accurate prosthetic rehabilitation. In the planning phase, it is possible for the surgeon to interact dynamically with a 3D reconstruction of the actual case scenario. The exact angula-tions and on the placement of implants can be pre-determined virtually. The virtual plan is then transferred to the clinical setting through the fab-rication of a surgical guide. Advances in the pros-thetic framework designs especially for a full arch implant reconstruction have led to superior final outcomes for both the patient and the clinician.

Methods: The case report involves the rehabili-tation of an edentulous mandible of a 53 year old Asian woman with a combination of mini-mally invasive flapless implant surgery and resto-ration with a screw retained framework over the implants and cementable segmented bridges.

Conclusions: Dental implant rehabilitation of a fully edentulous jaw utilizing a three step pro-tocol has a significant benefit not only to the patient in terms of reduced trauma and lessened chair side time, but also to the clinician in terms of predictability and successful outcomes.

Computer Guided Full Arch Treatment Modality for the Edentulous Patient:

A Case Report

Dr. Dhaval P. Pandya1 • Dr. Ashwini Bhalerao2 • Dr. Kanir H. Bhatia3

1. Private practice limited to periodontics and implantology; Mumbai, India

2. Private practice limited to oral and maxillofacial surgery and implantology; Mumbai, India

3. Private practice limited to cosmetic dentistry and implantology; Mumbai, India

Abstract

KEY WORDS: Dental implants, guided surgery, edentulism, case report

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Pandya et al


INTRODUCTIONAdvanced imaging and CAD/CAM technologies and their applications in enhancing treatment outcomes in implant dentistry have gained wide-spread interest. Guided implant surgery utiliz-ing these advanced technologies has significant applications in implant dentistry.1-9 The plan-ning and execution of a treatment plan in implant dentistry typically involves a team approach, with the placement of implants determined by a definitive restorative goal. Radiographic imag-ing plays a critical role in this process. More recently, cone beam computerized tomography

(CBCT) has gained popularity and is routinely used in the planning process.10 With the intro-duction and advances of 3-dimensional (3D) imaging and computer aided design and com-puter aided manufacturing (CAD/CAM) technol-ogy, implant placement can be planned virtually. This planned information is then transferred via stereolithographic (STL) rapid prototyp-ing (RP).11 With the advent of newer retriev-able metal ceramic acrylic implant- supported fixed prosthesis with titanium framework and individual crowns and bridges, the advantages are both to the patient as well as the clinician.

Figure 1: Pre-op clinical view. Figure 2: Radiographic index with markings.

Figure 3: Panoramic virtual view with index markings. Figure 4: Virtual planning 1.

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CASE REPORTA healthy 53 year old Asian female presented with a completely edentulous mandible with a desire to have implant supported fixed teeth replacement (Figure 1). Considering her back-ground from the media industry and her pro-fession involving a lot of voice make- over dubbing work, she desired fixed replacement option over the implants. Dental records were taken for the treatment planning which included pre op dental models with bite registration.

Based on the above record, a complete den-ture was fabricated. Five to six gutta percha mark-ings were done in the buccal and lingual area of the denture to make it a radiographic marker (Fig-ure 2). This was to explore the possibility of uti-lizing a flapless implant surgery approach which could be minimally invasive and may reduce the treatment and the chair side time and discomfort to the patient as well as better prosthetic out-comes compared to the conventional surgery. Investigation involved a Computerised Tomog-

Figure 5: Virtual planning 2. Figure 6: Surgical guide.

Figure 8: Healing abutments on the implants clinical view. Figure 9: Post –op panoramic X-ray.

Pandya et al


Figure 10: PMMA framework on the dental model. Figure 11: PMMA framework try- in the mouth.

Figure 12: Final framework on the dental model. Figure 13: Final framework try in the mouth.

Figure 14: Individual segmental bridges on the framework.

Figure 15: Final Post- op.

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Figure 16: Cross section virtual plan Implant 1. Figure 17: Cross section virtual plan Implant 2.


Pandya et al



raphy (CT) of the mandible with a dual scan protocol. The haematological investigations included tests which included blood CBC, Prothrombin time (PT), Partial Thromboplas-tin Time (PTT), Glycated Hemoglobin for blood sugar (HbA1C), Australia antigen for Hepatitis (HbSAg) and HIV tridot. The CT scan showed good bone quality and quantity both mesio dis-tal and bucco lingual. The radiographic mark-ers and the CT showed that distally from the mental foramen onwards there was a possi-bility to place 8mm implant in the lower right molar area because of the limitation of the dis-tance between the cortical bone and the supe-rior border of the mandibular canal. (Figure 16) Dicom format of the CT was then subjected to a virtual implant planning software (Nobel clini-cian from Nobel Biocare, Gotheberg, Sweden)

to plan the treatment. Virtual planning (Figures 4 and 5) and (Figures 16-21) and virtual pan-oramic view of six implants (Figure 3) was car-ried out to understand different parameters which included: A) Implant positions; B) Implant angulations; C) The anterior posterior (AP) spread; D) The occlusal positions of the future screw access holes. A surgical guide (Figure 6) was ordered. The patient was posted for the Surgery with pre-medications for the pro-cedure prescribed. The guide was sterilized according to the manufacturer’s instructions.

After local anaesthesia was administered, the surgical guide was placed over the man-dible intraorally with the anchor pins stabilizing it. Flapless surgery was carried out accord-ing to the drilling protocol. Six regular platform (RP, 4.3mm diameter) implants with differ-

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Table 1: Advantages and disadvantages of guided implant surgery

Advantages of Guided Surgery Disadvantages of Guided Surgery

Could offer improved precision (consistency in achieving the same implant position each time) and better accuracy (achieving desired implant location) when protocol is fol¬lowed precisely, with detailed attention to every step and with appropriate patient selection

Flapless surgery is possible (potential for lower morbidity)

Efficiency (reduced surgical time)

Faster initial healing time (reduced trauma to soft tissues)

Safety (avoidance of important anatomical structures)

Provisional restorations can be fabricated prior to the surgery

Could help control and maintain drill trajectory when implants are placed immediately in a fresh extraction socket

Longer initial treatment time (multiple steps and appointments for radiographic template fabrication)

Technique sensitive (precise data collection is important and each step in the fabrication process is critical for a successful outcome)

More radiation exposure to the patient from 3-D imaging (which is required for fabrication) compared to routine 2-dimensional imaging

Instrumentation can be awkward in limited i nterarch space situations (difficult in posterior region, especially in patients with limited mouth opening)

Reduced cooling efficiency during osteotomy (Due to the close approximation between the drill and the surgical guide; less irrigant reaches the surgical site)

Increased cost

Limited application when insufficient bone is present and bone graft¬ing is needed.

Increased complexity with the number of software available in the market and different guide fabrication protocols

Pandya et al


ent lengths were placed and RP healing abut-ments were placed immediately (Figure 8). A uniform torque of 35 Ncm was achieved on all the implants. Post op medications were pre-scribed and a delayed prosthetic loading pro-tocol was decided upon. A post op OPG was requested (Figure 9) Patient presented with pain and swelling around implant 1 (RP 8mm) 3 weeks after the surgery and on exami-nation the said implant was mobile on clini-cal examination. It was explanted and the site was allowed to heal for 8 weeks after which another RP 8mm implant was placed free hand.

Eight weeks after the new implant site was healed as examined clinically and by an intra oral Xray, impression was taken after a jig try in which involved using a low contraction acrylic Pattern resin (GC, CO , USA) to splint the impression copings. This was to verify the fit of the future framework. Based on this a Poly-methyl Methacrylate (PMMA) framework was fabricated by the laboratory to verify the fit and passivity of the framework and to ensure that there are no errors in the final framework fit. The PMMA fit was verified on the dental model (Figure10) and then in the mouth intra-orally (Figure 11). Intra oral Xrays were taken to verify the screw position and fit in the implants and only after a complete verification, the final framework was ordered. The final framework fit is verified on the dental model (Figure 12) and then intra orally in the mouth (Figure 13). The segmental cementable bridges are fitted on the framework and checked in occlusion (Figure 14). Occlusion is adjusted and final torque given to the abutment screws accord-ing to the manufacturer’s instructions with a prosthetic implant driver engaged in a torque

ratchet. The screw access holes are blocked with small cotton pellets and provisional cement. The segmental bridges are cemented with A provisional cement (TempBond, Ivoclar Vivadent) and occlusion verified (Figure 15). At this time final fit, function, phonetics, esthetics, and tissue contours are checked and recorded.

DISCUSSION Inherent in digital technology for full-arch guided implant surgery is the need for each of the multiple disciplines involved to participate in the collab-orative goal of an optimized reverse-engineered implant and prosthetic treatment plan. Diagnos-tic CBCT imaging, 3-D CBCT interactive implant planning software, implant surgical guides, implant systems and prosthetic abutments, and CAD/CAM laboratory manufacturing technol-ogy all are making advances that potentiate improved case results.18 General considerations for the fabrications of the radiographic guide:A) Optimal fit to the anatomy which would not

hinder the surgical guide fit later.B) To cover the buccal, lingual and

occlusal surfaces.C) Vestibular extension to accommodate the

guided anchor pins placement.D) To have an ideal set up of teeth in terms of

occlusion, position, occlusal height and lip and cheek support.

E) Marking of five to six (5-6) small holes of 1.5mm diameter approximately on the index.

F) Placing the points at different levels in relation to the occlusal plane.

G) Placing the markings buccally and lingually to the canines and distobuccally to the premolars and distally to the molars.

H) Fill the holes with gutta percha.

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14 • Vol. 9, No. 2 • February 2017

The purpose of the radiographic guide is the following:A) To stimulate the teeth, the soft tissue surface,

and the edentulous space during the CT scan procedure.

B) The correct design is a pre requisite for a successful treatment since, the final outcome is determined by it. The following parameters were checked in the

evaluation stage:A) Overall general health of the patient to undergo

an oral surgery. B) Intra oral examination to rule out any pathology,

mouth opening to accommodate the surgical tooling, gingival biotype, and bone morphology of the mandible.

CONCLUSIONFlapless surgery is a predictable procedure if the patient selection and surgical technique are-appropriate.15 The benefits of this procedure

are lessened surgical time; minimal changes in crestal bone levels, probing depth, and inflam-mation; perceived minimized bleeding, and lessened postoperative discomfort16 The com-bination of a screw retained prosthetic frame-work with individual crowns/bridges provides a good prognosis on a middle to long term basis.17

DISCLOSUREThe authors report no conflicts of inter-est with anything mentioned in this report. l

Correspondence:Dr. Dhaval P Pandya 6th floor, Shankar Ashish, R. C. Patel road, Off Sodawala lane, Borivali West, Mumbai 400092 India Phone: +91-9930998282Email: [email protected]

References1) Marchack CB. CAD/CAM – guided implant

surgery and fabrication of an immediately loaded prosthesis for a partially edentulous patient JProsthet Dent 2007;97:389-94.

2) Engelman MJ, Sarasen JA, Moy P Optimum placement of osseointegrated implants. J Prosth Dent 1988;59:467-73.

3) Hinckfuss S, Conrad HJ, Lim L, Lunos S, Seong WJ Effect of surgical guide design and surgeons experience on the accuracy of implant place-ment J Oral implantol 2012;(4) 38: 311-23.

4) Paulo Maulo, Miguel de Araujo N, Joao Barges, Ricardo Almeida A retrievable metal ceramic acrylic implant supported fixed prosthesis with titanium framework and all ceramic individual crowns. A retrospective clinical study with upto 10 years of follow up. http://online library.wiley.com/doi/10.1111/j.1532-849x.201100824.x/abstract.

5) Jemt T, Peterson A Precision of CNC milled tita-nium framework for implant treatment in the eden-tulous jaw Int J Prosthodon 1999:12:209-15.

6) Ortorp A, Jemt T, Clinical experience of CNC milled Ti frameworks aupported by implants in the edentulous jaw: 1 year prospective study. Clin Implant Dent Relat Rest 2000; 2:2.

7) Takahashi T, Gunne J Fit of implant frameworks: An in vitro comparision between two fabrication techniques: J Prosthet Dent 2003;89:256-60.

8) Parel SM: The single piece milled titanium implant bridge Dent today: 2003;22: 96-9.

9) Kattadiyal MT, Parciak E, Scherer MD CAD/CAM guided implant surgery : A brief review Alpha Omegan: 2014 Spring;107(1):26-31.

10) Benavidus E , Rios HF, Ganz SD, Resnik R, Reardon GT, Feldman SJ, Mah JK, Hatcher D, Kim MJ, Sohn DS, Palti A Perel ML, Judy KW, Misch CE, Wang HL Use of CBCT in implant dentistry: The ICOI consensus report Implant Dent 2012 Apr;21(2):78-86.

11) Sament D, Sukovic P, Clinthorne N Accu-racy of implant placement with stereolitho-graphic surgical guide Int J Oral Maxillofac Implants 2003;July-Aug 18(4):571-7.

12) Nobelguide procedures and planning (NobelBiocare) www.nobelbiocare.com.

13) Drago C, Peterson T. Implant labo-ratory procedures: A step by step guide, 1st ed, Wiley-Blackwell 2010 : 130-133, 255- 257 , 262- 283.

14) TestoriT, Galli F, Fabbro M: Immediate loading:A new era in oral implantology, Quintessence publishing 2011; 163-189, 377- 393.

15) Campello, Dominguez L, Camera, Domin-guez JR: Flapless Implant surgery: A 10 year clinical retrospective analysis Mar/Apr 2002; Vol 17 Issue 2, 271-276.

16) Becker W , Goldstein M , Becker BE , Sennerby L : Minimally invasive flapless implant surgery: a prospective multicenter study: Clinical Implant Dentistry and Related Research 2005, 7 Suppl 1:S21-7.

17) Maló P, de Araújo Nobre M, Borges J, Almeida R: Retrievable metal ceramic implant-supported fixed prostheses with milled titanium frame-works and all-ceramic crowns: retrospective clinical study with up to 10 years of follow-up. J Prosthodont. 2012 Jun;21(4):256-64.

18) Michael A. Pikos, DDS; Carl W. Magyar, DDS; and Daniel R. Llop, CDT: Guided Full-Arch Immediate-Function Treatment Modality for the Edentulous and Terminal Dentition Patient; Compendium in continuing educa-tion in dentistry ; Feb 2015 Vol 36, Issue 2.

Pandya et al

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Volume 8, No. 8 December 2016

Full Mouth Rehabilitation of Periodontitis Patient

Implant-Supported Milled Bar

Overdenture


Volume 8, No. 1 march 2016

Treatment of the Atrophic Maxilla with Autogenous Blocks

Modified Mandibular Implant Bar Overdenture


Volume 8, No. 3 may/JuNe 2016

Treatment of Mandibular Central Giant Cell Granuloma

Titanium Mesh Ridge Augmentation for Dental

Implant Placement


Volume 8, No. 4 July/August 2016

Mandibular Overdentures with Mini-Implants

Augmentation of Severe Ridge Defect with rhBMP-2

and Titanium Mesh

Holtzclaw et al

While placentally derived allografts have been utilized in medical procedures for over 100 years, their use in dental

procedures is relatively new with only 10 years of continuous history. As in medical procedures, the initial applications of placental grafts in den-tal procedures were with amnion products. More recently, however, advanced placental allografts such as laminated amnion-chorion products have displaced the use of amnion-only products. The

addition of a chorion layer to amnion allograft has produced a number of improvements over amnion alone including increased thickness of the mem-brane and a 20-fold increase in growth factor content. The goal of this paper is to provide an updated primer on the utilization of dehydrated human amnion-chorion membrane (dHACM) allografts in dental procedures. The science behind this material is reviewed along with an examination of current and future dental uses.

An Updated Primer on the Utilization of Amnion-Chorion Allografts in Dental Procedures

Dan Holtzclaw, DDS, MS1 • Robert Tofe, MBA2

1. Private practice limited to dental implants and oral reconstructive surgery. Austin, Texas, USA

2. Snoasis Medical, Inc. Denver, Colorado, USA

Abstract

KEY WORDS: Amnion, chorion, allograft, wound healing, review

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Holtzclaw et al


INTRODUCTIONPlacentally derived products have been used as wound healing adjuncts for more than a century in numerous medical applications. In the early 1900’s, placentally derived human amnion was uti-lized for skin transplantations as reported by Davis1 in a review of 550 treated cases. By the 1940’s amnion was routinely applied in a variety of oph-thalmologic surgeries with documentation of faster healing and improved outcomes.2,3 By the 1950’s and 1960’s amnion was being utilized in ENT pro-cedures such as mastoidectomy4 and myringo-plasty.5 More recently, placentally derived tissues such as amnion and amnion-chorion have been used in the treatment of diabetic ulcers,6,7 Moh’s micrographic surgery,8 free flap surgical treat-ment of venous insufficiency/lymphedema,9 vagi-nal reconstructive surgery,10,11 and as an adjunct to protect neurovascular bundles during prostate sur-gery,12 among others. With the successful and well documented medical applications of placentally derived amnion and amnion-chorion tissues, the crossover of these products into the realm of dental treatment is not surprising. In 2008, a multi-layered dehydrated human amnion membrane (dHAM) (BioCover™, Snoasis Medical, Denver, Colorado, USA) was introduced to the dental market as a potential treatment for gingival recession. By 2010, dehydrated human allograft composed of laminated amnion-chorion (dHAMC) (BioXclude™, Snoa-sis Medical, Denver, Colorado, USA) expanded the potential applications of placentally derived products to a much wider variety of dental pro-cedures. As placentally derived products are still relatively new to the field of dentistry, the purpose of this paper is to review the general characteris-tics of contemporary amnion-chorion products and their current applications for dental procedures.

Basic Placental Tissue/Amniotic Sac PrimerDuring pregnancy, membranes comprising the amniotic sac contain the developing embryo and fetus. The innermost membrane of the amniotic sac, the amnion, encloses the fetus and amniotic fluid, while the outer layer, or chorion, contains the amnion and interdigitates with the maternal decid-ual tissues to form the placenta. The amnion and chorion contain no blood vessels, have no direct blood supply, and receive nutrients by diffusion from the amniotic fluid and maternal decidua.13,14 Amnion contains several extracellular matrix (ECM) proteins, including fibronectin, laminins, proteoglycans, glycoproteins, and collagen types I, III, IV, V, and VI.14-16 The chorionic tissue can be up to 4 times thicker than the amnion17 and, similar to the amnion, is composed of fibronec-tin, laminins, and collagens I, III, IV, V, and VI.16 A particularly unique feature of the membranes com-posing the amniotic sac is their role in protecting the developing fetus from the maternal immune system. Although it is not fully understood why, the maternal immune system accepts the develop-

Figure 1: BioXclude™ dHACM (arrow) averages ~300µm in cross-sectional thickness.

Holtzclaw et al

18 • Vol. 9, No. 2 • February 2017

ing fetus in spite of its foreign nature. It has been postulated that immunoregulation may occur at the fetal-maternal interface which inhibits mater-nal T-cell,18 lymphocyte,19 and natural killer cell20 proliferation. This function has bestowed the term immunopriviledged upon tissues including the amnion and chorion meaning they elicit little to no immunological response in foreign hosts.21,22

Amnion-Chorion Allograft ProductionPlacental tissue used for the production of BioX-clude™ dental amnion-chorion allograft is obtained from consenting mothers delivering full-term babies via elective cesarean section surgery, as regulated by the Food and Drug Administration (FDA) and American Association of Tissue Banks (AATB).23 All donors are screened for infec-tious diseases, including but limited to, human immunodeficiency virus (HIV) type 1 and 2 anti-

bodies, HIV type 1 nucleic acid test, human T-lym-photropic virus (HTLV) type 1 and 2 antibodies, hepatitis B surface antigen, hepatitis B core total antibody, hepatitis C antibody, hepatitis C virus nucleic acid test, and syphilis.24,25 Upon collection of the placental tissues, they are placed in quaran-tine storage until clean serology reports are con-firmed. Upon acceptable serology confirmation, the amnion and chorion are isolated and prepared with the proprietary Purion® process (MiMedx, Marietta, Georgia, USA). The Purion® process was developed in 2006 as a method for gently cleansing and dehydrating amniotic membrane allografts while preserving the structural integ-rity and biochemical activity of the tissue. The Purion® process is used to produce dehydrated human amnion-chorion membrane (dHACM) whereby de-epithelialized placental amnion is laminated to chorion tissue that is sourced directly

Figure 2: Total growth factor content increases dramatically with the addition of chorion to amnion.

Holtzclaw et al


Table 1: Examples of Growth Factors, Cytokines, Chemokines, etc. Found in dHACM30

GCSF GM-CSF GDF-15 IFNγ IL-1α IL-1β

IL-1Ra IL-4 IL-5 Ang Ang-2 bFGF

BMP-5 BDNF EG-VEGF EGF FGF-4 KGF

FGF-7 IL-6 IL-7 IL-10 IL-12p40 IL-12p70

IL-15 IL-17 MCSF OPG BLC Eotaxin-2

I-309 IL-8 IL-16 MCP-1 MIG MIP-1α

MIP-1β MIP-1d RANTES GH HB-EGF HGF

IGF-1 IGFBP-1 IGFBP-2 IGFBP-3 IGFBP-4 IGFBP-6

B-NGF PlGF PDGF-AA PDGF-BB TGF-α TGF-β1

VEGF TIMP-1 TIMP-2 TIMP-4 6Ckine ADAMTS13

APRIL aFGF Activin-A Adiponectin Adipsin AgRP

ANG-1 ANG-4 ANGPTL3 ANGPTL4 Angiostatin ACE-2

BAFF BTC BMP- 2BMP-7 BMP-9 CRP

CXCL14 CXCL16 CA9 CEA Chemerin CNTF

Ckβ8-1 Clusterin CF XIV C5a Cripto-1 Cystatin A

Cystatin B Cystatin C Cystatin EM DAN DcR3 DLL1

DKK-1 DKK-3 DKK-4 Eotaxin Eotaxin-3 ENA-78

FABP2 Fetuin A FGF-6 FGF-9 FGF-19 FGF-21

Flt-3L FSH Follistatin FLRG Fractalkine Furin

GASP-1 GASP-2 Galectin-1 Galectin-2 Galectin-3 Galectin-7

Galectin-9 GDNF gp130 GCP-2 Granulysin Gas1

GROα GRO HCC-1 HAI-2 hCGβ Insulin

IGF-2 IGFBP-5 IP-10 I-TAC IL-1 F5 IL-1 F6

IL-1 F7 IL-1 F8 IL-1 F9 IL-1 F10 ST2 IL-2

IL-3 IL-6sR IL-8 IL-11 IL-17B IL-17C

IL-17E IL-20 IL-21 IL-23 IL-24 IL-27

IL-32α IL-33 IL-34 Kallikrein-5 Kallikrein-14 LAP(TFGb1)

Legumain Leptin LRIG3 Liocalin-2 Limphotactin MIF

MBL Marapsin Midkine MCP-2 NOV NSE

NT-3 NT-4 NAP-2 OSM Osteoactivin OPN

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from the amniotic sac. 26 Lamination of the amnion and chorion produces a graft that is significantly thicker (~300µm)27 (Figure 1) compared to lay-ered amnion alone (~<100µm).28 Processed dHACM are terminally sterilized by gamma irradia-tion prior to sterile packaging, which in addition to increasing the safety of the product, has proven not to affect the bioactivity of the allograft.29

Biologic and Immunoregulatory Properties of dHACMIn testing the effects of the Purion® process on the bioactivity of dHACM allografts, 226 regu-lators of healing and inflammation were identi-fied in the processed grafts.30 These include tissue promoting growth factors, immunomodu-latory cytokines, and immunomodulatory che-mokines (Table 1). While it is beyond the scope of this paper to specifically discuss the proper-ties of each of these growth factors, it is well established that these factors aid and promote healing in a variety of capacities which will be dis-cussed in this paper. It is important to note that the thicker graft produced by the lamination of amnion to chorion in the production of dHACM such as BioXclude® results in growth factor con-tent that is up to twenty times greater than that which is seen in amnion only allografts (Figure 2).31 The rich growth factor and immunomodula-tory content of dHACM likely plays a role in the anti-inflammatory, antibacterial, pain reduction, angiogenic, and enhanced wound healing prop-erties that have been identified with the product.

Anti-Inflammatory PropertiesAmniotic tissue has been shown to reduce inflam-mation in studies designed specifically to study inflammation. Solomon et al.32 cultured human

corneal limbal epithelial cells on either freshly fro-zen and thawed human amniotic membrane or tissue culture plastic. These cells were plated on amnion tissue and assayed for the expression of inflammatory cytokines. The cultures dem-onstrated that cryopreserved amnion directly suppressed the expression of pro-inflammatory cytokines at the protein and mRNA levels. In another study of transepithelial photorefractory keratectomies in rabbits, the application of fresh amnion showed a significant reduction in the number of leukocytes and less keratocyte death compared to controls, demonstrating the anti-inflammatory effects of amnion.33 When study-ing the effects of amniotic membrane on corneal wounds in rabbits via histopathologic, proteinase assay, and zymography, Kim and colleagues34 reported decreased polymorphonuclear leuko-cyte (PMN) infiltration, decreased macrophage chemotaxis, and inhibited proteinase activity at treated sites. In reviewing the use of amniotic grafts for ocular surface reconstruction, Tseng35

noted the anti-inflammatory effects of the graft as did Güell et al.36 in their treatment of symptom-atic bullous keratopathy. Koob and colleagues have performed multiple studies evaluating amni-otic tissues such as dHACM for anti-inflammatory modulators via enzyme linked immunosorbent assays (ELISA) with significant findings.37,38

Anti-Bacterial PropertiesA number of studies have demonstrated the anti-bacterial nature of amniotic tissue.39,40 Expres-sion of antimicrobial peptides such as β-defensins, elafin and SLPI, which are essential elements of the innate immune system, may be associ-ated with antibacterial properties of amniotic tis-sue.39,40 Tehrani and colleagues39 evaluated the

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antibacterial properties of cryopreserved and dehydrated amniotic tissue against a variety of bacterial strains including Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922. The results of this study noted that processing of the amniotic tissues did not adversely affect the anti-bacterial properties of graft. In a separate study, Kjaergaard and colleagues41 tested the antibac-terial properties of chorioamniotic membranes

Figure 3a: Extraction site treated with BioXclude™ dHACM at Day 0.

Figure 3b: Extraction site treated with BioXclude™ dHACM at 24 hours.

Figure 3c: Extraction site treated with BioXclude™ dHACM at 96 hours. Note migration of tissue from wound edges towards center.

Figure 3d: Extraction site treated with BioXclude™ dHACM at Day 21.

Figure 3e: Extraction site treated with BioXclude™ dHACM at 3 months.

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against Hemolytic streptococci group B (GBS), Hemolytic streptococcus group A, Staphylo-coccus aureus, Staphylococcus saprophyticus, Enterococcus faecalis, Escherichia coli, Pseu-domonas aeruginosa, Acinetobacter calcoace-ticus and Lactobacillus species. All bacterial strains were inhibited by the amniotic tissues.

Pain Reduction PropertiesNumerous studies have noted the pain reduc-tion properties of amniotic grafts when used for a wide variety of applications. In evaluating the treatment of venous leg ulcers, Mermet et al.42

Figure 4a: BioXclude™ dHACM (being placed into the maxillary sinus) is of similar thickness to the Schneiderian membrane.

Figure 4b: BioXclude™ dHACM self-adheres to the Schneiderian membrane in the maxillary sinus.

Figure 5: BioXclude™ dHACM may safely touch root surfaces.

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noted that all study participants experienced a significant reduction of ulcer-related pain rapidly following amniotic tissue application. In a com-parison of vestibuloplasty healing with and with-out the application of amniotic grafts, Sikkerimath et al.43 noted increased and longer lasting pain in non-treated patients. In evaluating the use of amniotic tissues as a dressing for skin grafts on burn patients, Eskandarlou and colleagues44

noted decreased pain with amniotic dressed grafts compared to standard dressings. In evalu-

Figure 6a: Mandibular molar prior to extraction. Figure 6b: Mandibular molar following extraction.

Figure 6c: Mandibular molar extraction site grafted with particulate allograft and covered with BioXclude™ dHACM.

Figure 6d: Gingival tissue healing at mandibular molar site preservation with BioXclude™ dHACM at 3 months healing.

Figure 6e: Bone healing at mandibular molar site preservation with BioXclude™ dHACM at 3 months healing.

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ating the use of amniotic tissues in combination with dental implant treatment, Velez et al.45 noted a significant reduction in pain for treated patients, especially during the first 144 hours. In the author’s personal use of dHACM in thousands of dental surgeries, he has likewise noted post-sur-gical pain reduction when the material is utilized.

Angiogenic PropertiesAngiogenic properties of chorioamniotic mem-

branes were recognized and documented in medi-cal literature as far back as the 1980’s.46,47 These findings were expanded upon over the next 30 years48-51 with findings of angiogenic factors such as endothelins, hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insu-lin-like growth factor-1 (IGF1). More recently, Koob et al.52 identified angiogenic growth fac-tors in dHACM via ELISA, examining the effects of dHACM extract on human microvascular endo-

Figure 7a: Intrabony defect at the distal of tooth #19 following hand instrumentation debridement.

Figure 7b: Intrabony defect at the distal of tooth #19 treated with GTR using particular allograft and BioXclude™ dHACM.

Figure 7c: Radiograph of intrabony defect at the distal of tooth #19 prior to GTR treatment.

Figure 7d: Radiograph of BioXclude™ dHACM GTR treated intrabony defect at the distal of tooth #19 at 48 months.

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thelial cell proliferation and production of angio-genic growth factors. The findings of this study indicated that dHACM grafts contained a multi-tude of angiogenic factors, even after processing, and that dHACM grafts promoted amplification of angiogenic stimulation via induction of endothe-lial cell proliferation/migration. Furthermore, this study also found that dHACM grafts upregulated production of endogenous angiogenic growth factors from surrounding endothelial cells and supported the formation of blood vessels in vivo.

Enhanced Wound Healing PropertiesEnhanced wound healing has been noted with amniotic grafts for more than a century on a vari-ety of different medical procedures.1-12 While these earlier studies noted improved healing of patients treated with placentally derived grafts, the exact reasons for this improved healing was a matter of speculation. The aforementioned dis-coveries of the multitude of growth and Immuno-regulatory factors30 contained in chorioamniotic membranes has provided evidence of the driving force behind the healing capacity of these grafts. The immense regenerative potential of chorioamni-otic grafts has recently been tapped for treatment of one of the most difficult healing situations in medicine, non-healing chronic diabetic foot ulcer-ations (DFU). Distal extremity ulcerations of the foot are widely considered to be one of the most significant complications of Diabetes.53 Complica-tions associated with non-healing DFU’s include pain, neuropathy, limitation of mobility, osteomyeli-tis, and even amputation.54 In fact, diabetic com-plications have been noted in up to 70% of all non-traumatic based amputations of lower limbs.55 Traditional treatment of DFU’s , referred to as the “Gold Standard” or “Standard of Care”, has

involved sharp debridement, infection manage-ment, and off-loading.53 More recently, multiple studies have utilized dHACM in the treatment of DFU and found improved healing with its appli-cation.56-58 In 2016, Zelen et al.59 compared healing of DFU’s in 100 patients over 12 weeks utilizing a variety of treatments. In this prospec-tive, randomized, controlled, parallel group, multi-center clinical trial weekly applications of collagen-alginate dressings (“Standard wound care”) were utilized for 35 patients as a control, bioengineered skin substitute graft was utilized weekly for 33 patients, and dHACM was utilized weekly for 32 patients. By 12 weeks, 51% of the standard wound care patients achieved “com-plete closure” of DFU’s compared to 73% with bioengineered skin substitute graft, and 97% with dHACM. Mean healing times for DFU’s in this study were 57.4 days for standard wound care, 47.9 days with bioengineered skin substi-tute graft , and 23.6 days with dHACM. Also in 2016, DiDomenico et al.60 published a random-ized controlled study where patients with non-healing DFU’s were treated with either traditional aforementioned “Standard of Care” treatment (SOC) or SOC in combination with chorioamni-otic graft application. Twenty patients were ran-domly assigned to each group and treated for a period of 12 weeks. Endpoint healing evaluation noted that non-healing DFU’s “healed completely” in 70% of chorioamniotic graft treated patients versus only 15% complete healing in the SOC treatment group. In 2015, Penny et al.61 noted similar healing of DFU’s in a Case Series of Dia-betic patients treated with dHACM grafts. As with the Zelen59 and DiDomenico60 studies that noted “complete healing” or “complete closure” of DFU’s by 12 weeks of dHACM treatment, Penny

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et al. noted healing of dHACM treated DFU’s by 11 weeks. These studies, and many others, dem-onstrate the ability of dHACM to stimulate heal-ing in even the most difficult of environments.

Dental Applications of dHACMWhile placentally derived grafts have been used for over a century for medical applications, their use in dentistry is relatively new. The most current

form of placentally derived allograft in dentistry is dHACM. Furthermore, the only available dHACM product for dental applications is BioXclude™ (Snoasis Medical, Denver, Colorado, USA). BioX-clude™ is a second generation placentally derived product composed of a dehydrated amnion-cho-rion laminate. Since its introduction in 2010, over 70,000 BioXclude™ dHACM grafts have been utilized for a variety of dental procedures (data

Figure 8a: Intraoral presentation of implant #20 displaying signs of peri-implantitis.

Figure 8b: Lingual view of implant #20 cleansed peri-implantitis intrabony defect.

Figure 8c: Lingual view of implant #20 grafted peri-implantitis intrabony defect.

Figure 8d: Lingual view of BioXclude™ dHACM being used for GTR treatment of implant #20 peri-implantitis intrabony defect.

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provided by Snoasis Medical, Denver, Colorado, USA). Research and documentation on the uti-lization of dHACM for dental procedures has greatly expanded over the past ten years. While the first portion of this paper focused on the his-torical medical use of this product and the science behind its effectiveness in these applications, the remainder of this paper will focus on the current and future uses of dHACM in dental procedures.

Unique Properties of dHACM in DentistryThe use of dental dHACM allografts such as BioXclude™ in lieu of traditional dental barrier membranes presents a number of new possi-bilities that are not readily available with currently available products. First and foremost, unlike tra-ditional dental barrier membranes which may be compromised when left exposed to the oral envi-ronment,62-64 BioXclude™ may be left exposed without reduced healing capacity due to bacte-rial penetration.27,65 It is likely that the multitude of growth and immunomodulatory proteins inher-ently retained in dHACM aid in the rapid epithe-lial covering of exposed surgical sites in these studies (Figures 3a-f).3,27,30,37,65 A second unique property of BioXclude™ compared to traditional dental barriers that that dHACM is extremely thin, averaging 300µm in cross sectional thickness whereas collagen barrier membranes average 700-800µm in thickness.27,66 This makes han-dling, application, and mucogingival flap adapta-tion around dHACM much easier than traditional dental membranes.27 Unlike most barrier mem-branes, dHACM is self-adhering66 and does not

Figure 8e: Intraoral presentation of implant #20 at 24 months after treatment.

Figure 8f: Pre-surgical radiograph of implant #20 with intrabony defect at mesial (arrow).

Figure 8g: Post-surgical radiograph of implant #20 at 24 months after treatment.

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Figure 9a: Ridge split of deficient posterior mandibular ridge for guided bone regeneration.

Figure 9b: Ridge splitting osteotome being utilized to expand mandibular ridge.

Figure 9c: Expanded mandibular ridge grafted with particular allograft.

Figure 9d: BioXclude™ dHACM being used for guided bone regeneration treatment of the grafted split ridge.

Figure 9e: Healing of BioXclude™ dHACM guided bone regeneration site at 3 months healing.

require sutures for fixation. This feature proves extremely beneficial in delicate situations such as the repair of perforated maxillary sinus mem-branes (Figures 4a,b).68,69 Furthermore, unlike tra-ditional dental barriers, dHACM BioXclude™ does not require precise trimming, may touch root sur-faces (Figure 5), and may fold upon itself without issue.68 Finally, dHACM is one of the only known dental membranes that inherently contains a mul-titude of growth factors30 and has demonstrated intense immunohistochemical staining for these

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Figure 10a: Buccal dehiscence defect prior to guided bone regeneration treatment with BioXclude™ dHACM.

Figure 10b: Walls of the buccal dehiscence defect support the overlying BioXclude™ dHACM.

factors compared to virtually none for traditional dental barriers.70 The wide variety of proper-ties unique to BioXclude™ avail the product for use in a number of different dental procedures.

Extraction Site PreservationOne of the most common applications for BioX-clude™ dHACM is for site preservation following the extraction of teeth (Figures 6a-e). The earli-est known study in which BioXclude™ dHACM was used for extraction site preservation was released by Holtzclaw et al. in 2011.71 In this 5 patient case series, extraction site preservation was performed with BioXclude™ dHACM. This particular study differed from most previously published extraction site preservation studies in the fact that the barrier was left fully exposed to the oral environment with intentional non-primary closure. Average healing times of 3 months were given prior to the placement of dental implants. At this time, all sites had healed with keratinized gingival tissue and had sufficient bone growth to allow the placement of dental implants. After nearly 6 years of loading, dental implant sur-

vival rate in this Case Series remains at 100%. A second site preservation study was later

released by Wallace and Cobb in 2011.72 In this study, 7 patients had extraction site preservation performed with BioXclude™ dHACM and freeze dried bone allograft. Unlike the earlier Holtzclaw study of 2011, the surgical sites in this particular study all received primary closure. After an aver-age healing period of 13 weeks, trephine core sampling and dental implant placements were performed. Histological analysis revealed no residual dHACM and 54.5% new bone formation.

In a 2014 case series study, Holtzclaw65 per-formed extraction site preservation procedures on 10 consecutive patients whereby teeth were removed and bone graft was placed and covered with a single layer of BioXclude™ dHACM. The grafted extraction sites had non-primary closure with the amnion-chorion barriers left fully exposed to the oral environment. After an average of 14.2 weeks of healing, all BioXclude™ treated extrac-tion sites had complete gingival closure. Trephine bone core samples obtained at this time revealed a mean 39.2% vital bone formation. After nearly

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Figure 11a: Combination bony defect in anterior mandible.

Figure 11b: Combination bony defect in anterior mandible (alternative view).

Figure 11c: Combination bony defect in anterior mandible grafted with particulate allograft.

Figure 11d: Grafted combination bony defect in anterior mandible covered with collagen membrane.

3 years following the publication of this paper, dental implants placed into these dHACM grafted sites have a 100% survival rate.

Another site preservation study was released in 2014 comparing BioXclude™ dHACM bar-rier to dense polytetrafluoroethylene (d-PTFE) barrier.73 This prospective, intra-patient, clini-cal evaluation involved 9 patients with 22 sites

(11 per group) where implants were placed at 12-14 weeks. Results from this study revealed that BioXclude™ treated sites had on average more bone volume and less resorption of alveo-lar ridge width compared to sites treated with d-PTFE barriers. Furthermore, sites treated with the resorbable BioXclude™ dHACM did not require follow up procedures for barrier removal

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Figure 11e: BioXclude™ dHACM placed on top of collagen membrane to achieve modified guided bone regeneration technique.

Figure 11f: Closure of modified guided bone regeneration site utilizing collagen membrane overlaid with BioXclude™ dHACM (Note non-primary closure at distal aspect with BioXclude™ dHACM exposed).

Figure 11g: Bone healing of modified GBR treated combination bony defect in anterior mandible at 3 months healing.

unlike the non-resorbable d-PTFE barriers.

Guided Tissue Regeneration of Periodontal and Peri-Implantitis DefectsThe first published utilization of amnion-cho-rion for guided tissue regeneration (GTR) treatment of a periodontal defect occurred in

early 2011.74,75 In this case report, Holtzclaw utilized BioXclude™ dHACM to treat an intrabony periodontal defect of a mandibular molar that had probing depth measurements of 9mm and 10mm of clinical attachment loss (CAL). Following full thickness mucogingival flap elevation, the intrabony defect was thor-oughly degranulated. The cleansed defect was grafted with mineralized freeze dried bone allograft and covered with a single layer of BioXclude™ dHACM. After 6 months of healing, probing depth and clinical attach-ment improved by 6mm and 5mm respec-tively. With regular periodontal maintenance therapy, these gains have been maintained for nearly 6 years as of the writing of this paper.

A 2013 study by Holtzclaw27 involved 114 patients who were treated with GTR ther-apy from March 2010 to October 2011. Of these patients, 64 were treated with BioX-clude™ dHACM combination GTR therapy and had ≥12 months of follow-up. All patients

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Figure 12a: Perforated Schneiderian membrane during maxillary sinus lift.

Figure 12b: BioXclude™ dHACM being used to repair perforated Schneiderian membrane.

were diagnosed with localized moderate-to-severe chronic periodontitis and exhibited radiographic evidence of ≥1mm vertical osse-ous defects. Treatment involved thorough degranulation of intrabony periodontal defects and placement of bone allograft covered by BioXclude™ dHACM (Figures 7a-d). Clini-cal measurements 12 months after surgery revealed an average probing depth reduc-tion of 5.06 ± 1.37 mm and clinical attach-ment level improvement of 4.61 ± 1.29 mm.

The treatment of peri-implantitis intrabony defects follows very similar principles to the treatment of periodontal intrabony defects. While some variations do exist in terms of implant surface detoxification versus natural tooth detoxification, the basic concept and treat-ment tenets remain similar. Figures 8a-g dem-onstrate how BioXclude™ dHACM is used for treatment of a peri-implantitis intrabony defect.

Guided Bone RegenerationGuided bone regeneration (GBR) entails aug-mentation of edentulous sites which are of inad-

equate dimensions for the placement of dental implants. A vast multitude of techniques exist to accomplish GBR and most call for long last-ing barrier materials including various collagens, pericardial tissues, acellular dermal matrices, titanium mesh, resorbable mesh, expanded polytetrafluoroethylene (e-PTFE), and d-PTFE.76 Traditional tenets of GBR include barriers that create space maintenance, wound stability, epi-thelial exclusion, and graft containment. When using BioXclude™ dHACM for GBR (Figures 9a-e), an alternative thought process toward these tenets must be considered. In terms of graft containment, BioXclude™ dHACM satis-factorily satisfies the tenet. In terms of wound stability, BioXclude™ dHACM performs excep-tionally well as demonstrated by Holtzclaw et al.77 in a recent modified replication of the clas-sic 1968 flap attachment study. In terms of epi-thelial exclusion, BioXclude™ dHACM seems to oppose the tenet as its high Laminin and Laminin-5content30,70 actually encourages epi-thelial cell proliferation. While this may seem like a detriment, the high Laminin and Laminin-5

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content of BioXclude™ dHACM allows epithe-lial cells to rapidly migrate across its chorio-amniotic matrix in such a fashion that the cells do not invade the underlying bone graft. This has been verified in multiple studies that show bone augmentation sites treated with BioX-clude™ dHACM have histologic core samples of similar composition to sites that are treated with other traditional techniques.65,72 Once these epithelial cells come into contact with one another, contact inhibition halts their migra-tion,78 effectively sealing the underlying bone graft material and further preventing the migra-tion of epithelial cells into the bone graft. In this sense, BioXclude™ dHACM satisfies the tenet of epithelial cell exclusion from the under-lying bone graft in spite of the fact that it actu-ally promotes the proliferation of epithelial cells. Finally, in terms of space maintenance, BioX-clude™ dHACM occasionally satisfies this tenet, but not always, due to its thin 300µm cross sectional thickness and pliability. With small 3 walled bony defects, BioXclude™ dHACM can be effectively used as the existing bony walls provide space maintenance for GBR (Figures 10a,b). With larger 3 walled defects and 1 or 2 walled defects, a modified GBR technique may be employed whereby a stiffer barrier such as collagen or titanium is utilized for space main-tenance and BioXclude™ dHACM is overlaid on top of the barrier (Figures 11a-g). Overlay-ing the stiffer barrier with BioXclude™ allows the modified GBR technique to achieve space maintenance while still retaining the multitude of wound healing benefits provided by dHACM. The modified GBR technique was demonstrated by Holtzclaw79 in a 2016 publication that uti-lized a combination of titanium mesh overlaid

with BioXclude™ dHACM for the treatment of a severe alveolar ridge defect with recombinant human bone morphogenetic protein (rh-BMP2). Maxillary Sinus Augmentation and RepairPneumatization of the maxillary sinus is a com-mon complication of edentulism in the poste-rior maxilla. To facilitate placement of dental implants in the pneumatized maxillary sinus, augmentation is often required. The process of maxillary sinus augmentation requires care-ful elevation of the Schneiderian membrane. With rates ranging from 11% to 56%, perfora-tion of the Schneiderian membrane is the most common complication associated with maxillary sinus augmentation procedures80 and has been linked to a variety of problems including the need for procedure abortion, decreased bone formation, and a possible reduction in den-tal implant survival.81,82 BioXclude™ dHACM is uniquely qualified for repair of Schneiderian membrane perforations. In addition to its afore-mentioned wound healing properties which can augment the sinus grafting process, BioX-clude™ dHACM is of similar thickness to the Schneiderian membrane and its self-adherent nature allows the barrier to readily attach to sinus membrane sans suture. Utilization of BioXclude™ dHACM for the repair of Schneide-rian membrane perforations (Figures 12a,b) was first demonstrated by Holtzclaw69 in a 2014. In this controlled split mouth case report, heal-ing outcomes were evaluated for bilateral lat-eral window sinus augmentations performed in a single patient. One sinus was augmented with the Schneiderian membrane intact while the contralateral sinus was augmented with a perforated Schneiderian membrane that was

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repaired with BioXclude™ dHACM. The non-perforated sinus augmentation healed with more bone height and a denser, more uniform fill compared to the augmentation repaired with BioXclude™ dHACM. Both sinuses, however, had adequate healing to permit placement of multiple dental implants to support an immedi-ately loaded restoration. It must be noted that with traditional treatment, the large perforation of the Schneiderian membrane in this Case Report would have resulted in abortion of the sinus augmentation. Utilization of BioXclude™ dHACM allowed the procedure to be com-pleted on the same day and produced results that allowed for success implant delivery. After nearly four years of function, implants in both sinuses have demonstrated zero complications and the prosthesis continues to function well.

A second much larger publication examin-ing the utilization of BioXclude™ dHACM for the repair of perforated Schneiderian mem-branes was published by Holtzclaw68 in 2015. In this publication, a consecutive retrospec-tive record review was performed of all maxil-lary sinus augmentations performed during a 5 year period. Eighty three cases were identi-fied with a total of 104 sinus augmentations, of which nine perforations were noted. None of the nine cases were aborted mid-procedure and all perforations were repaired with BioX-clude™ dHACM. All cases were augmented with a combination of allograft and xenograft particulate bone. A total of 23 dental implants were placed in the augmented sinuses with perforated Schneiderian membranes and a one failure was noted according to Albrektsson suc-cess criteria. A total of 158 dental implants were placed in non-perforated augmented

sinuses with a total of three failures noted.

Treatment of Gingival RecessionTreatment of gingival recession via non-autog-enous methods has long been sought as a means of reducing second site surgical mor-bidity for patients. A number of products have been used in attempts to achieve this goal with varying degrees long term results.83-85 Many studies have evaluated the use of amnion86-89

for the treatment of gingival recession includ-ing studies that examined the use of first gen-eration BioXclude™ precursor dehydrated human amnion membrane (dHAM). In 2009, Gurinsky67 performed a 5 patient case series in which dHAM was used for root coverage procedures in lieu of traditional autogenous connective tissue grafts. The average gingi-val defect size treated was 3.3mm (± 0.84). At three month there was an average increase of 3.2 mm (±1.71) of new gingival tissue rep-resenting 97% (± 0.5) root coverage. More recently in 2016, Pundir et al.90 performed a split-mouth case series in which mucogingi-val defects were treated with either amnion or chorion allografts used in conjunction with coronally advanced flaps. After 6 months of healing, 9 of the 12 treated defects showed 100% root coverage with no statistically sig-nificant difference between the two groups. While these studies and others have evalu-ated both amnion and chorion allografts sepa-rately for root coverage, no know studies have evaluated laminated dHACM for this purpose.

Future Possibilities in Dental Treatment While dHACM has now proven efficacious for a variety of dental procedures, the unique

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properties of this product are still being evalu-ated in a number of other dental applica-tions. Currently, research with dHACM is being conducted for treatment of the follow-ing: oroantral communications, temporoman-dibular disorders, nerve injury, non-healing soft tissue defects, mucogingival root coverage, increasing zone of keratinized gingiva, and non-surgical treatment of periodontal disease.

CONCLUSIONSJust as medicine continues to expand its uti-lization of chorio-amniotic products, dentistry is doing the same. In their own right, the extremely high growth factor content, antibac-terial properties, angiogenic properties, anti-inflammatory properties, and pain reduction properties make dHACM an extremely effec-tive product. For dentistry specifically, when these properties are combined with the fact that dHACM BioXclude™ can be left exposed to the oral cavity, can touch root surfaces, is self-adherent, and bioabsorbable, the product truly offers a number of unique and useful benefits. l

Correspondence:

Dr. Dan Holtzclaw

[email protected]

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36 • Vol. 9, No. 2 • February 2017

DisclosureD Holtzclaw reports a financial interest in Snoasis Medical. R Tofe reports a financial interest in Snoasis Medical.

References1. Davis J. Skin transplantation with a review of

550 cases at the Johns Hopkins Hospital. Johns Hopkins Hospital Report. 1910;15:307–310.

2. Sorsby A, Symons HM. Amniotic membrane grafts in caustic burns of the eye (burns of the second degree). Br J Ophthalmol. 1946;30:337–345.

3. Sorsby A, Haythorne J, Reed H. Further experience with amniontic membrane grafts in caustic burns of the eye. Br J Ophthalmol 1947;31(7):409-18.

4. Liu FS, CH’EN YC, LIU JH. The use of dehydrated amniotic graft after radical mastoidectomy. Chin Med J 1959;78(5):435-8.

5. Catalano GB, Conticello S. The long-term results of myringoplasty with amnion graft. Otorinolaringologie 1969;14(2):97-102.

6. Zelen CM, Serena TE, Denoziere G, Fetterolf DE. A prospective randomized comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers. Int Wound J 2013;10:502–7.

7. Zelen CM. An evaluation of dehydrated human amniotic membrane allografts in patients with DFUs. J Wound Care 2013;22 347–8,350–1

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37. Koob TJ, Rennert R, Zabek N, Massee M, Lim JJ, Temenoff JS, Li WW, Gurtner G. Biological properties of dehydrated human amnion/chorion composite graft: implications for chronic wound healing. Int Wound J 2013;10(5):493-500.

38. Koob TJ, Lim JJ, Massee M, Zabek N, Denozière G. Properties of dehydrated human amnion/chorion composite grafts: Implications for wound repair and soft tissue regeneration. J Biomed Mater Res B Appl Biomater 2014;102(6):1353-62.

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42. Mermet I, Pottier N, Sainthillier JM, Malugani C, Cairey-Remonnay S, Maddens S, Riethmuller D, Tiberghien P, Humbert P, Aubin F. Use of amniotic membrane transplantation in the treatment of venous leg ulcers. Wound Repair Regen 2007;15(4):459-64.

43. Sikkerimath BC, Dandagi S, Gudi SS, Jayapalan D. Comparison of vestibular sulcus depth in vestibuloplasty using standard Clark’s technique with and without amnion as graft material. Ann Maxillofac Surg 2012;2(1):30-5.

44. Eskandarlou M, Azimi M, Rabiee S, Seif Rabiee MA. The Healing Effect of Amniotic Membrane in Burn Patients. World J Plast Surg 2016;5(1):39-44.

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46. Burgos H. Angiogenic and growth factors in human amnio-chorion and placenta. Eur J Clin Invest 1983;13(4):289-96.

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48. Yamahara K, Harada K, Ohshima M, Ishikane S, Ohnishi S, Tsuda H, Otani K, Taguchi A, Soma T, Ogawa H, Katsuragi S, Yoshimatsu J, Harada-Shiba M, Kangawa K, Ikeda T. Comparison of angiogenic, cytoprotective, and immunosuppressive properties of human amnion- and chorion-derived mesenchymal stem cells. PLoS One 2014; 14;9(2):e88319.

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51. Marvin KW, Keelan JA, Eykholt RL, Sato TA, Mitchell MD. Expression of angiogenic and neurotrophic factors in the human amnion and choriodecidua. Am J Obstet Gynecol 2002;187(3):728-34.

52. Koob TJ, Lim JJ, Massee M, Zabek N, Rennert R, Gurtner G, Li WW. Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration. Vasc Cell 2014;1;6:10.

53. Alexiadou K, Doupis J. Management of Diabetic Foot Ulcers. Diabetes Ther 2012;3(1):4.

54. DiDomenico LA, Orgill DP, Galiano RD, Serena TE, Carter MJ, Kaufman JP, Young NJ, Zelen CM. Aseptically Processed Placental Membrane Improves Healing of Diabetic Foot Ulcerations: Prospective, Randomized Clinical Trial. Plast Reconstr Surg Glob Open 2016;4(10):e1095.

55. Moxey PW, Gogalniceanu P, Hinchliffe RJ, et al. Lower extremity amputations—a review of global variability in incidence. Diabet Med 2011;28:1144–1153.

56. Zelen CM, Serena TE, Snyder RJ. A prospective, randomised comparative study of weekly versus biweekly application of dehydrated human amnion/chorion membrane allograft in the management of diabetic foot ulcers. Int Wound J 2014;11(2):122-8.

57. Kirsner RS, Sabolinski ML, Parsons NB, Skornicki M, Marston WA. Comparative effectiveness of a bioengineered living cellular construct vs. a dehydrated human amniotic membrane allograft for the treatment of diabetic foot ulcers in a real world setting. Wound Repair Regen 2015; 23(5):737-44.

58. Zelen CM, Gould L, Serena TE, Carter MJ, Keller J, Li WW. A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers. Int Wound J 2015;12(6):724-32.

59. Zelen CM, Serena TE, Gould L, Le L, Carter MJ, Keller J, Li WW. Treatment of chronic diabetic lower extremity ulcers with advanced therapies: a prospective, randomized, controlled, multi-centre comparative study examining clinical efficacy and cost. Int Wound J 2016;13(2):272-82.

60. DiDomenico LA, Orgill DP, Galiano RD, Serena TE, Carter MJ, Kaufman JP, Young NJ, Zelen CM. Aseptically Processed Placental Membrane Improves Healing of Diabetic Foot Ulcerations: Prospective, Randomized Clinical Trial. Plast Reconstr Surg Glob Open 2016;4(10):1095.

61. Penny H, Rifkah M, Weaver A, Zaki P, Young A, Meloy G, Flores R. Dehydrated human amnion/chorion tissue in difficult-to-heal DFUs: a case series. J Wound Care 2015;24(3):104-111.

62. Selvig KA, Kersten BG, Chamberlain AD, Wikesjö UM, Nilvéus RE.Regenerative surgery of intrabony periodontal defects using ePTFE barrier membranes: scanning electron microscopic evaluation of retrieved membranes versus clinical healing. J Periodontol 1992;63(12):974-8.

63. Simion M, Trisi P, Maglione M, Piattelli A. A preliminary report on a method for studying the permeability of expanded polytetrafluoroethylene membrane to bacteria in vitro: a scanning electron microscopic and histological study. J Periodontol 1994;65(8):755-61.

64. Sela MN, Kohavi D, Krausz E, Steinberg D, Rosen G. Enzymatic degradation of collagen-guided tissue regeneration membranes by periodontal bacteria. Clin Oral Implants Res 2003;14(3):263-8.

65. Holtzclaw D, Toscano N. BioXclude Placental Allograft Tissue Membrane Used in Combination with Bone Allograft for Site Preservation: A Case Series. J Implant Adv Clin Dent 2011;3(3):35-50.

66. Rothamel D, Schwarz F, Sager M, Herten M, Sculean A, Becker J. Biodegradation of differently cross-linked collagen membranes: an experimental study in the rat. Clin Oral Implants Res 2005;16:369-378.

67. Gurinsky B. A novel dehydrated amnion allograft for use in the treatment of gingival recession: An observational case series. J Implant Adv Clin Dent 2009;1:11-6.

68. Holtzclaw D. Maxillary sinus membrane repair with amnion-chorion barriers: A retrospective case series. J Perio 2015; 86(8): 936-940.

69. Holtzclaw D. Open sinus lift healing comparison between a non-perforated Schneiderian membrane and a perforated Schneiderian membrane repaired with amnion-chorion allograft barrier: A controlled, split mouth case report. J Implant Adv Clin Dent 2014;6(8):11-21.

70. Xenoudi P and Lucas M. IADR Meeting, Abstract #146797. San Diego, CA. March 16-19 2011.

71. Holtzclaw D, Toscano N. BioXclude Placental Allograft Tissue Membrane Used in Combination with Bone Allograft for Site Preservation: A Case Series. J Implant Adv Clin Dent 2011;3(3):35-50.

72. Wallace S, Cobb C. Histologic and Computed Tomography Analysis of Amnion-Chorion Membrane in Guided Bone Regeneration Socket Augmentation. J Implant Adv Clin Dent 2011;3(6):61-72.

73. Hassan, M, Blanchard S, Prakasam, S. AAP Poster Presentation. Sept 19-22, 2014, San Francisco, CA. University of Indiana, Department of Periodontics.

74. Holtzclaw D. Use of Amnion-Chorion in Guided Tissue Regeneration. Poster Presentation. Post #1102334 American Academy of Periodontology 97th Annual Meeting 2011, Miami Beach, FL.

75. Holtzclaw D. BioXclude™ Placental Allograft Tissue Membrane Used in Combination with Bone Allograft for Guided Tissue Regeneration Treatment of Periodontal Intrabony Defect: A Case Report. White Paper 2011; Snoasis Medical, Denver, Colorado.

76. Soldatos NK, Stylianou P, Koidou VP, Angelov N, Yukna R, Romanos GE. Limitations and options using resorbable versus nonresorbable membranes for successful guided bone regeneration. Quintessence Int. 2016 Nov 10. Epub ahead of print.

77. Holtzclaw D, Hinze F, Toscano N. Gingival flap attachment healing with amnion-chorion allograft membrane: A controlled, split mouth case report replication of the classic 1968 Hiatt study. J Imp Adv Clin Dent 2012; 4(5):19-25.

78. Puliafito A, Hufnagel L, Neveu P, Streichan S, Sigal A, Fygenson DK, Shraiman BI. Collective and single cell behavior in epithelial contact inhibition. Proc Natl Acad Sci U S A 2012;17;109(3):739-44.

79. Holtzclaw D. Dehydrated Human Amnion-Chorion Barrier used to Assist Mucogingival Coverage of Titanium Mesh and rhBMP-2 Augmentation of Severe Maxillary Alveolar Ridge Defect: A Case Report. J Implant Adv Clin Dent 2016;8(4):6-16.

80. Toscano N, Holtzclaw D, Rosen P. The effect of piezoelectric use on open sinus lift perforation: A retrospective evaluation of 56 consecutively treated cases from private practices. J Periodontol 2010; 81(1):167-171.

81. Proussaefs P, Lozada J, Kim J, Rohrer M. Repair of perforated sinus membrane with resorbable collagen membrane: A human study. Int J Oral Maxillofac Implants 2004; 19(3):413-420.

82. Hernandez-Alfaro F, Torradeflot MM, Marti C. Prevalence and management of Schneiderian membrane perforations during sinus lift procedures. Clin Oral Implants Res 2008; 19:91-98.

83. Harris RJ. A comparative study of root coverage obtained with an acellular dermal matrix versus a connective tissue graft: results of 107 recession defects in 50 consecutively treated patients. Int J Periodontics Restorative Dent 2000;20(1):51-9.

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Algabri et al

In completely edentulous patient’s rehabilita-tion with screw retained full arch fixed implant supported prosthesis, the achievement pas-

sive fit of superstructure to the implants is con-sidered as major challenge to prosthodontist. This passive fit is supposed to be one of the most vital requirements for the maintenance of the osseointegration, otherwise unfavorable

complications is expected. In this case report, full mouth rehabilitation of patient with all on-4 implant prosthesis was described. The treat-ment performed includes full arch fixed implant supported prosthesis for maxilla and mandi-ble. To verify passive fit, a secondary splinting impressions technique was used. The patient followed for four years with promising result.

Full Mouth Rehabilitation of Completely Edentulous Patient with Full Arch Screw-Retained

Prosthesis: A Case Report with 4 Year Follow Up

Algabri RS, PhD1 • Alqutaibi AY, PhD2 • Keshk AM, PhD3 Elkhadem AH, PhD4 • Fahmmy A, PhD5 • Aboalrejal HO, Ms6

1. PhD Student, Department of Prosthodontics, Faculty of Oral and Dental Medicine, Cairo University, Cairo, Egypt

2. Lecturer, Department of Prosthodontics, Faculty of Oral and Dental Medicine. Ibb University, Ibb, Yemen.

3. PhD Student, Department of Prosthodontics, Faculty of Oral and Dental Medicine, Cairo University, Cairo, Egypt.

4. Associate professor, Department of Prosthodontics - Faculty of Oral and Dental Medicine. Cairo University, Cairo, Egypt.

5. Associate professor, Department of Prosthodontics - Faculty of Oral and Dental Medicine. Cairo University, Cairo, Egypt.

6. Ms student, Department of oral and maxillofacial radiology, Faculty of Oral and Dental Medicine, Cairo University, Cairo, Egypt.

Abstract

KEY WORDS: Dental implants, Full arch, Maxilla, Mandible, Prosthetics

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INTRODUCTIONTreatment of edentulous patients with implant-retained prostheses provides predictable and successful outcomes that overcome the func-tional deficiencies which are associated with conventional dentures. Patients prefer fixed over removable prostheses because they feel that a fixed prosthesis is an integral part of their body.1 The implant-supported fixed prostheses comprise screw and cement-retained superstructures. One of the considerable challenges for screw-retained multi-unit implant prosthesis is achieving passive fit of superstructure to the implants. This pas-sive fit is supposed to be one of the most vital requirements for the maintenance of the osseo-integration. Moreover, the misfit of the implant supported superstructure may lead to unfavor-able complications.2 The manifestations of these complications may range from fracture of various components in the implant system, and even loss of osseointegration. On the other hand, cement-retained implant prostheses have the potential for being passive because of the cement space

which can compensate for superstructure dis-tortions and provide more passive fit.3 The accu-racy of pouring technique affects the accuracy of the master casts which affect prosthesis fit. The implant impression techniques can be divided into splinted or non-splinted techniques.4 The splinted impression techniques can be performed either by splinting the impression transfer copings intra-orally before impression making (primary splinted technique) or splinting the implant analogues prior to pouring of the impression (secondary splinted technique).4 In this case report, full mouth rehabili-tation of patient with all on-4 implant prosthesis was described. The treatment performed includes full arch fixed implant supported prosthesis for maxilla and mandible. The secondary splinting technique was used to decrease the discrepan-cies that result during pouring of the master casts.

CLINICAL REPORT A 58-year-old, completely edentulous, medi-cally fit male patient presented to Prosth-odontics Department, Faculty of Dentistry

Figure 1a: Intraoral photo of maxilla. Figure 1b: Intraoral photo of mandible.

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– Cairo University with history of un-reten-tive conventional complete dentures that ini-tiate sever gag reflex in January 2012. The patient asked for fixed prosthesis for the upper and lower arches. Clinical and radiographic examination revealed well developed maxil-lary and mandibular arches (Figs.1a, 1b).

Preoperative PlanningAfter primary impressions taken, diagnostic max-illary and mandibular casts were mounted on an articulator. A diagnostic wax up and set up was made to represent the anatomy and ideal posi-tion of the planned implants. A duplicate of the wax up was then converted to a radiographic

Figure 2a: Maxillary surgical stent stabilized with fixation screws.

Figure 2b: Mandibular surgical stent stabilized with fixation screws.

Figure 3a: Prepared osteotomy sites in maxilla. Figure 3b: Prepared osteotomy sites in mandible.

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guide. The patient wore the radiographic guide during CBCT scan. The CBCT data was then imported into the planning software. Virtual planning of dental implants according to the patient’s anatomy was then performed. Eight implants are planned to place, 4 for maxilla and 4 for mandible. The implants were virtu-

ally placed at 12, 15, 22, 25 site for each arch to support all on 4 maxillary and mandibular fixed prosthesis. The virtual planning was sent for construction of CAD /CAM surgical stents.

Surgical ProcedureTwo hours before the surgery the patient received

Figure 4a: Maxillary impression with acrylic resin splint. Figure 4b: Mandibular impression with acrylic resin splint.

Figure 5a: Maxillary master cast. Figure 5b: Mandibular master cast.

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2gm Amoxicillin; an additional dose of 1g twice a day for 1 week after surgery, was prescribed. Surgery was performed under local anesthesia. CAD /CAM surgical stent placed in the maxil-lary arch and fixed with anchoring pins. Flapless implant site preparation was followed. The stent was stabilized using fixation anchor screws as planned pre-operatively. Similar procedures were followed for the lower arch (Figs. 2a, 2b). The sequence of drilling was carried out

according to the manufacture instruction. Irri-gation was very strictly ensured during drilling in all proposed sites. All the implants (DENTIS, Korea) were installed in the proposed pre-operative planned sites and covering screws were placed to all implants (Figs. 3a, 3b).

Postoperative instructions were given as patients were instructed to apply ice packs for the first 24 hours and follow the antibi-otic regimen for five days. 0.2% Chlorhexi-

Figure 6a: Final restoration (maxillary view). Figure 6b: Final restoration (mandibular view).

Figure 6c: Final restoration (maximum intercuspation). Figure 7: Panoramic radiograph at 4 years post-op.

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dine mouth wash solution was prescribed for the patients at least two times daily for 3 days. The patient upper and lower den-tures were relieved and a soft liner (Acros-tone, Acrostone Relining Materials) was applied to help in seating of the denture after implant installation. After implant installation, a post-operative panoramic x-ray was made.

Prosthetic ProcedureAfter 6 months of implant placement the sec-ondary splinted impression was performed. acrylic custom trays for the patient were man-ufactured for upper and lower jaws both utilizing open tray non-splinted impression technique. Master casts generated from non-splinted coping impression technique, and the lab analogues were splinted before pour-ing the impression through joining them with low shrinkage cold cure acrylic resin (Bredent. Multisil-mask. cold cure gingival mask resin. Germany). The resin was injected to surround each implant analogue using cartridge dis-penser until it was reaching a reasonable thick-ness covering a part of the implants analogues (Figs. 4a, 4b). After one hour the imperssion, secondary splinted, was poured with extra-hard type IV dental stone(Kimberlit, Type IV Dental Stone, Protechno- Spain) that was manipulated with a vacuum machine(Vacuum mixer. BEGO Motova sl.U.S.A), with a powder/water ratio of 100g/20ml mixed for 30 sec-onds. The pouring was under constant vibration (Lab vibrator. BEGO Motova sl.U.S.A) into the impression. After set, 25 minutes, the impres-sions were separated from the casts (Figs. 5a, 5b). After that a classical steps of prosthesis construction that include verification jig con-

struction, metal framework fabrication and definite prosthesis delivery were followed. The final fit, stability and occlusion were evaluated. The patient was instructed on maintenance of the health of the oral tissues. The patient returned for a 1-week, 1-month 6-months, 12 months, 2 years and 4 years post inser-tion appointments stating that he was satisfied with the esthetics and function of the maxillary and mandibular prosthesis (Figs. 6a-c and 7).

DISCUSSIONThe All-on-4 concept is a highly successful treatment option for the edentulous patient with excellent clinical outcomes. This is achieved without major grafting and its associated costs and surgical morbidity.5 To ensure ideal place-ment of the implants providing favorable force direction on the implants and the prosthetic components, the patient denture was dupli-cated to act as a radiographic templates.6 Accurate assessment of the peri-implant site is essential for the establishment of a success-ful dental implant treatment plane. The success key of any surgical implant procedure is the proper pre-operative treatment planning. In this case, the implants were inserted through the surgical guide with a flapless technique. Accu-rate surgical guides were fabricated, precise surgical instrumentation and 3D virtual plan-ning technique aid in placing implants without raising a flap and improving their clinical out-comes.7, 8 The surgical procedures were done under complete aseptic conditions to control infection during and after implant installation. Pre-surgical antibiotics and chlorhexidine were prescribed to the patients to reduce the bac-terial load and prevent infection during the ini-

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tial healing period from the surgical wound,9 and so significant decrease in implant failure occurs with the use of postoperative antibiotics.10

For secondary impression, direct opened tray impression technique was performed as recom-mended by Filho et al.11 The open tray technique allows for the impression coping to stay in the impression. This reduces the effect of implant angulation, the deformation of the impression material upon recovery from mouth, and removes the concern for replacing the coping back into its respective space in the impression.12

Addition silicon impression material was used in this study as it produce highly accu-rate impressions because they reproduce fine surface detail, and have excellent elastic recov-ery, adequate tear strengths, and exceptional dimensional stability. Also they are compat-ible with all common die materials, can be dis-infected or sterilized, and can be repoured after delayed periods. Also they are dispensed in convenient auto-mixing dual cartridges or single tubes and are available in several vis-cosities.13 The application of auto-polymerizing acrylic resin as a splinting material had been reported in several studies.4,14-20 Jørgensen and Kono21 showed that vacuum mixing increased the compressive strength of dental stone by 20% owing to reduced gypsum porosity.

The accuracy of the master cast can be verified before the metal framework is cast. A verification jig is commonly used to record the accurate 3-dimentional relationship of the implants, serve as a guide for a corrected cast procedure, transfer occlusal relations and gnathologic recordings to the articula-tor and verify the fit of the metal framework.22

The splinting of implant copings during

impression procedure using rigid material is to stabilize and prevent the rotational, hori-zontal and vertical movements of implant cop-ings during removal of the impression and due to shrinkage of the impression material as reported by Hussaini and Wong.23 Also splint-ing of implant analogues during pouring proce-dure is to stabilize and prevent the movements of them due to expansion of the stone.24, 25

In this case, a promising result appeared, the framework generated from secondary splinting impression pouring technique was passively fit in patient mouth as indicated by single screw test and radiograph. This result suggests the impor-tant role of splinting the implant analogues prior to pouring in preventing displacement of the analogues. Deformation of impression copings during removal of non-splinted impressions is usually reversible due to the high elastic recov-ery of the addition silicone. Without this tech-nique, a distortion of non-splinted analogues may result due to expansion of gypsum prod-uct during setting that is irreversible because of the fact that analogues in the set model will be permanently fixed in the distorted position.

CONCLUSION Secondary splinting of implant analogues prior to pouring was easy and reliable method to obtain accurate master casts. Non-splinted impression pouring technique should always be verified to assess accu-racy before construct the framework. l

Correspondence:Dr. Ahmed Yaseen AlqutaibiEmail: [email protected]

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DisclosureThe authors report no conflicts of interest with anything mentioned in this case report.

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[3] Nissan J, Gross M, Shifman A, Assif D. Stress levels for well-fitting implant superstructures as a function of tightening force levels, tightening sequence, and different operators. The Journal of prosthetic dentistry. 2001;86:20-3.

[4] Del’Acqua MA, Arioli-Filho JN, Compagnoni MA, Mollo Fde A, Jr. Accuracy of impression and pouring techniques for an implant-supported prosthesis. The International journal of oral & maxillofacial implants. 2008;23:226-36.

[5] Malo P, Rangert B, Nobre M. All-on-4 immediate-function concept with Branemark System implants for completely edentulous maxillae: a 1-year retrospective clinical study. Clinical implant dentistry and related research. 2005;7 Suppl 1:S88-94.

[6] Kohyama K, Mioche L, Bourdiol P. Influence of age and dental status on chewing behaviour studied by EMG recordings during consumption of various food samples. Gerodontology. 2003;20:15-23.

[7] Worthington P, Rubenstein J, Hatcher DC. The role of cone-beam computed tomography in the planning and placement of implants. Journal of the American Dental Association. 2010;141 Suppl 3:19S-24S.

[8] Lee CY, Ganz SD, Wong N, Suzuki JB. Use of cone beam computed tomography and a laser intraoral scanner in virtual dental implant surgery: part 1. Implant dentistry. 2012;21:265-71.

[9] Abu-Ta’a M, Quirynen M, Teughels W, van Steenberghe D. Asepsis during periodontal surgery involving oral implants and the usefulness of peri-operative antibiotics: a prospective, randomized, controlled clinical trial. Journal of clinical periodontology. 2008;35:58-63.

[10] Laskin DM, Dent CD, Morris HF, Ochi S, Olson JW. The influence of preoperative antibiotics on success of endosseous implants at 36 months. Annals of periodontology / the American Academy of Periodontology. 2000;5:166-74.

[11] Filho HG, Mazaro JV, Vedovatto E, Assuncao WG, dos Santos PH. Accuracy of impression techniques for implants. Part 2 - comparison of splinting techniques. Journal of prosthodontics : official journal of the American College of Prosthodontists. 2009;18:172-6.

[12] Conrad HJ, Pesun IJ, DeLong R, Hodges JS. Accuracy of two impression techniques with angulated implants. The Journal of prosthetic dentistry. 2007;97:349-56.

[13] Mandikos MN. Polyvinyl siloxane impression materials: an update on clinical use. Australian dental journal. 1998;43:428-34.

[14] Assif D, Marshak B, Schmidt A. Accuracy of implant impression techniques. The International journal of oral & maxillofacial implants. 1996;11:216-22.

[15] Assif D, Marshak B, Nissan J. A modified impression technique for implant-supported restoration. The Journal of prosthetic dentistry. 1994;71:589-91.

[16] Assuncao WG, Filho HG, Zaniquelli O. Evaluation of transfer impressions for osseointegrated implants at various angulations. Implant dentistry. 2004;13:358-66.

[17] Vigolo P, Majzoub Z, Cordioli G. Evaluation of the accuracy of three techniques used for multiple implant abutment impressions. The Journal of prosthetic dentistry. 2003;89:186-92.

[18] Vigolo P, Fonzi F, Majzoub Z, Cordioli G. An evaluation of impression techniques for multiple internal connection implant prostheses. The Journal of prosthetic dentistry. 2004;92:470-6.

[19] Herbst D, Nel JC, Driessen CH, Becker PJ. Evaluation of impression accuracy for osseointegrated implant supported superstructures. The Journal of prosthetic dentistry. 2000;83:555-61.

[20] Inturregui JA, Aquilino SA, Ryther JS, Lund PS. Evaluation of three impression techniques for osseointegrated oral implants. The Journal of prosthetic dentistry. 1993;69:503-9.

[21] Jorgensen KD, Kono A. Relationship between the porosity and compressive strength of dental stone. Acta odontologica Scandinavica. 1971;29:439-47.

[22] De La Cruz JE, Funkenbusch PD, Ercoli C, Moss ME, Graser GN, Tallents RH. Verification jig for implant-supported prostheses: A comparison of standard impressions with verification jigs made of different materials. The Journal of prosthetic dentistry. 2002;88:329-36.

[23] Hussaini S, Wong T. One clinical visit for a multiple implant restoration master cast fabrication. The Journal of prosthetic dentistry. 1997;78:550-3.

[24] Kan JY, Rungcharassaeng K, Bohsali K, Goodacre CJ, Lang BR. Clinical methods for evaluating implant framework fit. The Journal of prosthetic dentistry. 1999;81:7-13.

[25] Wee AG, Aquilino SA, Schneider RL. Strategies to achieve fit in implant prosthodontics: a review of the literature. The International journal of prosthodontics. 1999;12:167-78.

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Algabri et al

Khalap et al

UV photofunctionalization of tita-nium implants has shown promising results of the treat-

ment outcomes. Photofunctionalized implants have shown promising findings in regards to

bone implant contact, Osteoblast response & implant stability; hence opening up the ave-nue to be incorporated in daily implant prac-tice. This article summarizes the findings of all the recent in vivo & in vitro research conducted.

A Review of Photofunctionalization of Dental Implants

Dr. Suraj Khalap1 • Dr. Ajay Mootha2 • Dr. Ramandeep Dugal3

1. Post graduate student, Department of prosthodontics & implantology, M. A. Rangoonwala Dental College & Research Centre

2. Reader, Department of prosthodontics & implantology, M. A. Rangoonwala Dental College & Research Centre

3. Professor & Head, Department of prosthodontics & implantology, M. A. Rangoonwala Dental College & Research Centre

Abstract

KEY WORDS: Dental implants, photofunctionalization, ultraviolet, titanium

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Khalap et al

INTRODUCTIONImplants have become the treatment modal-ity of choice in the recent past; titanium been the material of choice. Physicochemically, it is well known that titanium constantly absorbs organic impurities such as polycarbonyls and hydrocarbons from the atmosphere, water, and cleaning solutions.1-3 The results of dif-ferent studies indicate that the bioactivity is affected by the level of surface hydrocarbons.4-6 Fresh titanium surface has a positive charge and is cell- and protein-attractive. As the sur-face ages, the negatively charged hydrocar-bons will deposit onto the surface, cover the cationic sites and convert the surface charge of titanium to negative.7 Thus, the surface will become cell-inert or even cell-repellent.8 Various techniques were tested to overcome these difficulties but the one showing prom-ise is ultraviolet (UV) photofunctionalization

AGING OF TITANIUMThe biomechanical strength of bone-implant integration was substantially impaired depend-ing upon the age of the implants. X-ray photo-electron spectroscopy revealed significantly higher levels of oxygen-containing hydrocarbons on old titanium surfaces than on newly prepared surfaces. Indeed, the atomic percentage of car-bon continued to increase, from 16% to 62%, as the titanium surfaces aged.7 Four-week-old titanium surfaces showed only 20% to 45% of the albumin adsorption of the newly prepared surfaces with different surface topographies. UV treatment of the 4-week-old titanium surfaces increased the rate of albumin adsorption to the equivalent level (for the machined surface) or an even higher level than the new surfaces (for

acid etched and sandblasted surfaces). Simi-larly, cell attachment to 4-week-old titanium sur-faces was less than half of that observed for the new surfaces, whereas more cells attached to the UV treated 4-week-old surfaces than to the new surfaces.9 Accordingly, alkaline phospha-tase activity on the UV-treated 4-week old sur-faces was higher than that on the new surface, which was two times greater than that seen on the 4-week-old surface. The push-in value for newly prepared acid-etched implants at the early stage of week 2 was 2.2 times greater than that for 4 week-old acid-etched implants.7 Notably, the push-in value for the newly pre-pared implants at week 2 of healing was even higher than that of the 4-week old implants at week 4 of healing. The bone formation at week 2 was contiguous and extensive around the new implants, but it was localized and fragmented around the 4-week-old implants, leaving a large area covered by soft tissue.

CONCEPT OF PHOTOFUNCTIONALIZATION

UV photofunctionalization is defined as an overall phenomenon of modification of tita-nium surfaces occurring after UV treatment, including the alteration of physicochemical properties and the enhancement of biologic capabilities. UV light–induced superhydrophilic-ity of titanium dioxide was discovered in 1997.10 UV light treatment of titanium surfaces has been found to remove deposited hydrocarbons11,12 and converts the titanium surface from hydro-phobic to superhydrophilic. When oxygen-con-taining hydrocarbons are removed, Ti4+ sites are again exposed, thereby enhancing surface bioactivity.8,13 UV-treated titanium surfaces also

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manifest a unique electrostatic status and act as direct cell attractants without the aid of ionic and organic bridges, which imparts a novel physicochemical functionality to titanium, which has long been understood as a bioinert material.

MATERIALS AND METHODOLOGY

This literature review was based on the PUBMED database using the key words “photofunctionalization” and “photofunc-tionalized implants.” The search was limited to articles written in English. No exclusion/inclusion criteria were used as limited data were available. Fourteen articles were found using the key words as mentioned in Table 1.

WAVELENGTHS OF UV LIGHTGao et al.14 treated micro-arc oxidation (MAO) titanium samples were pretreated with UVA light (peak wavelength of 360 nm) or UVC light (peak wavelength of 250 nm) for up to 24 hours. UVC treatment promoted the attachment, spread, pro-liferation and differentiation of MG-63 osteoblast-like cells on the titanium surface, as well as the capacity for apatite formation in simulated body fluid (SBF). These biological influences were not observed after UVA treatment. The enhanced bioactivity was substantially correlated with the amount of Ti-OH groups, which play an impor-tant role in improving the hydrophilicity, along with the removal of hydrocarbons on the titanium sur-face. Yamada et al15 concluded that regardless of topographies, the amount of bacterial attach-ment and accumulation was lower on ultraviolet-C pre-irradiated surfaces than on the non-irradiated surface through 8 hour incubation. Thus UVC has shown more promising results than UVA.

CONTACT ANGLEAtt et al.16 assessed the hydrophilic status of dif-ferent surfaces by means of contact angle mea-surements of a water droplet showed that all newly prepared titanium surfaces were super-hydrophilic (contact angle < 5 degrees). As the titanium disks aged, the surface property changed from hydrophilic to hydrophobic (con-tact angle > 50 degrees).7,27,28 Interestingly, after UV treatment, the contact angle of the 4-week-old titanium surfaces decreased to < 5 degrees, indicating that the superhydrophilic sta-tus of these aged surfaces had been restored.

OSTEOBLAST RESPONSEVariations in the chemical and topographic prop-erties of implant surfaces result in different osteo-blastic responses.29 On acid-etched titanium surfaces, degradation of the albumin adsorption rate after 4 weeks of storage was substantial, compared with the rate seen on new surfaces. The reductions were approximately 70% for a machined surface, 60% for an acid-etched sur-face and 50% for a sandblasted surface.30 Simi-larly, a significant degradation in the adsorption capacity of fibronectin was observed on aged titanium surfaces. With respect to osteoblast behavior and function, a surface age–dependent degrading property of osteoblast attachment and proliferation was also confirmed. The num-ber of attached osteoblasts and the proliferative activity during certain time periods of incubation were reduced by 50% to 75% on 4-week-old acid-etched surfaces as compared to new acid-etched surfaces.7,27 Osteogenic functional phe-notypes such as alkaline phosphatase activity and mineralization were substantially (by approxi-mately 50%) reduced on 4-week old acid-etched


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Table 1: PUBMED database articles with the key words “photofunctionalization” and “photofunctionalized implants.”

Authors Study Type

Aita et al.12 Integration of bone with In-Vitro UV functionalized titanium

Gao et al.14 Different wavelength for In-Vitro UV photofunctionalization

Yamada et al.15 Biofilm formation In-Vitro

Att et al.16 Biologic aging of implants Review & Osseointegration

Miyauchi et al.17 Osteoblast adhesion to In-Vitro photofunctionalized TiO2

Aita H et al.18 Human mesenchymal In-Vitro stem cell migration, attachment & differentiation

Pyo et al.19 Bone implant contact, Interfacial Animal Study osteogenesis, Marginal bone seal & Removal torque

Iwasa et al.20 Micro-nano-hybrid surface to In-Vitro alleviate biological aging

Ikeda et al.21 Fluoride treated In-Vitro nanofeatured titanium

Minamikawa et al.22 Bioactivity & osteoconductivity In-Vitro of titanium alloy

Ohyama et al23 Bone implant contact FEA Study

Suzuki et al24 Implant stability change & In-Vivo Osseointegration speed

Funato et al.25 Success rate, healing In-Vivo time &implant stability

Ueno et al.26 Bone titanium integration profile In-Vitro

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titanium surfaces compared with the newly pre-pared acid-etched surfaces.7,28 Moreover, the expression levels of collagen I and osteocal-cin, as evaluated by reverse-transcriptase poly-merase chain reaction, were also not significantly different among the groups of different ages.7

Miyauchi et al.17 determined adhesion of a single osteoblast is enhanced on UV-treated nano-thin TiO2 layer with virtually no surface roughness or topographical features were deter-mined. The mean critical shear force required to initiate detachment of a single osteoblast was determined to be 1280±430 nN on UV-treated TiO2 surfaces, which was 2.5-fold greater than the force required on untreated TiO2 sur-faces. The total energy required to complete the detachment was 37.0±23.2 pJ on UV-treated surfaces, 3.5-fold greater than that required on untreated surface. The level of hydrocarbon, and not hydrophilicity level, strongly correlated with rates of protein adsorption and cell attach-ment. The study demonstrated that bone–tita-nium contact can be increased up to nearly 100% by treating titanium implants with UV light.

MESENCHYMAL STEM CELLSAita H et al.18 cultured human mesenchymal stem cells (MSCs) on acid-etched microtopographical titanium surfaces with and without 48h pretreat-ment with UVA (peak wavelength of 360nm) or UVC (peak wavelength of 250 nm). The number of cells that migrated to the UVC-treated sur-face during the first 3hours of incubation was eight times higher than those that migrated to the untreated surface. After 24hours of incuba-tion, the number of cells attached to the UVC-treated surface was over three times more than those attached to the untreated surface.

BONE IMPLANT CONTACT (BIC)Aita et al.12 reported a remarkable increase of 55% to 98.2% was achieved in BIC due to UV photofuctionalization. The result was based on the histology within the bone mar-row, where bone deposited around implants was all de novo. BIC and bone area were sig-nificantly increased in the cortical bone by pho-tofunctionalization also. Cortical bone around untreated implants contained voids and gaps near the interface, probably because of micro-gaps and tissue damage that occurred during drilling and insertion, and an inflammatory reac-tion and remodeling after surgery. It was nota-ble that the cortical zone BIC, which was as low as 70% for untreated implants, increased to 95%, at its approximately highest level.

Pyo et al.19 intensively stained the bone integrated to photofunctionalized surfaces with Calcein and tetracycline. Bone tissues that were very sensitive to both types of labeling at the very interface of photofunctionalized sur-faces suggested; early-onset, more intimate, long-lasting, robust periimplant osteogenesis. Consequently, the interthread spaces were all filled with the labeled tissues exclusively around photofunctionalized surfaces, whereas the early bone formation around untreated implants, as labeled with Calcein, occurred remotely outside the thread peak line. Surprisingly, bone around photofunctionalized implants was strongly positive to tetracycline, which indicated the long-lasting osteogenesis for these surfaces.

IMPLANT TOPOGRAPHYIwasa et al.20 evaluated the behavior of biologi-cal aging of titanium with micro-nano-hybrid topography and with microtopography alone,

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following photofunctionalization. Rat bone mar-row–derived osteoblasts were cultured on fresh disks (immediately after UV treatment), 3-day-old disks (disks stored for 3 days after UV treatment), and 7-day- old disks. The rates of cell attachment, spread, proliferation and levels of alkaline phosphatase activity and cal-cium deposition were reduced by 30%–50% on micropit surfaces, depending on the age of the titanium. In contrast, 7-day-old hybrid sur-faces maintained equivalent levels of bioac-tivity compared with the fresh surfaces. Both micropit and micro-nano-hybrid surfaces were superhydrophilic immediately after UV treat-ment. However, after 7 days, the micro-nano- hybrid surfaces became hydrorepellent, while the micropit surfaces remained hydrophilic. Ikeda et al 21 also achieved similar results with fluoride treated nanofeatured implants.

PHOTOFUCTIONALIZATION VS SURFACE ROUGHENINGMinamikawa et al.22 tested two different surface morphology, a roughened surface (sandblasted and acid-etched surface) and relatively smooth surface (machined surface). The strength of bone-implant integration examined using a bio-mechanical push-in test in a rat femur model was at least 100% greater for photofunctional-ized implants than for untreated implants. These effects were seen on both surface types. The strength of bone-implant integration for photo-functionalized machined implants was greater than that for untreated roughened implants, indi-cating that the impact of photofunctionalization may be greater than that of surface roughening.

LENGTH OF IMPLANTSOhyama et al.23 demonstrated that photo-functionalized implants of 40% shorter length showed an equivalent strength of osseoin-tegration to untreated implants with a stan-dard length. A rat study addressed how much decrease in the strength of osseointegra-tion is caused by the use of short implants.31

Implants with 40% shorter length decreased the implant anchorage by 50%. More impor-tantly, when the shorter implants were photo-functionalized, the strength of osseointegration doubled and the disadvantage of the use of short implants was eliminated.31 This was rea-sonably explained by the expanded area of the load-bearing interface and bone volume around photofunctionalized implants.12,31

IMPLANT STABILITYSuzuki et al.24 evaluated the level, change and rate of osseointegration of photofunctionalized dental implants under the immediate loading condition by using the Implant Stability Quotient (ISQ) values. One of the hypotheses tested was whether clinical effects of photofunctionalization similar to those found in animal studies can be obtained in humans. The following were the 3 major findings: (1) a greater increase between the initial and secondary ISQ values in photo-functionalized implants than in literature; (2) the majority of Osseointegration speed index (OSI) in literature was lower than 1.0 and the OSI of photofunctionalized implants was notably higher than those in literature; and (3) the ISQ values at secondary time points obtained in this study between 77.5 and 78.1 were higher than any values in literature, even within a shorter heal-ing time of 1.5 months. Another important result

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was the elimination of the stability dip or signifi-cant decrease of total stability throughout the healing period for photofunctionalized implants.

STRESSOhyama et al.23 evaluated the effects of dif-ferent BIC and lengths of implants on the dis-tribution and concentration of periimplant mechanical stress. The results indicated that the stress pattern fluctuated more substan-tially responding to the degree of BIC than to the different length of implants. Under verti-cal load, 98.2% BIC eliminated the high-stress area even around 7-mm implants. Increase in the implant length from 7 to 13 mm helped to reduce the stress level by only 15% under vertical load, whereas elevating BIC from 53.0% to 98.2% reduced stress by 50%. Also, the high-stress area around the implant neck was reduced more effectively by increas-ing BIC than by increasing the implant length.

PUSH IN VALUESAita et al.12 concluded that biomechanical anchorage of acid-etched implants increased up to more than threefold at the early-stage of healing at week 2. This threefold increase of the push-in value was obtained at week 8 of healing in the same animal model.32 In other words, the push-in value obtained by the UV-treated acid-etched implants at week 2 was equivalent to that obtained by untreated acid-etched implants at week 8, indicating that the UV-treated surface accomplished bone–titanium integration 4 times faster.

Funato et al.25 proved against the com-mon understanding, that photofunctionalized implants showed a significant ISQ increase in

compromised bone, supporting the applica-tion and successful outcome of early loading within 3 months in a large number of cases.

GAP HEALINGUeno et al.26 proved that the strength of bone-titanium integration in the gap healing model was one-third of that in the contact healing model. However, UV-treated implants in the gap healing condition produced a strength of bone-titanium integration equivalent to that of untreated implants in the contact healing con-dition. Bone volume around UV-treated implants was 2 to 3 fold greater than that around the untreated implants in the gap healing model.

DISCUSSIONThe bone formation around photofunctional-ized implants was significantly improved. Cel-lular response followed by osseointegration also showed an improvement. The implant surface and topography are not a hindrance in the photofuctionalization treatment. Accord-ing to the limited number of clinical reports, photofunctionalized implants placed in fresh extraction sockets showed high survival rate. Also, none of the photofunctionalized implants showed destructive changes in peri-implant bone during the initial healing stage

CONCLUSIONThese in vivo accomplishments originated the following biological processes on UV-treated titanium surfaces: (1) increased adsorption of protein, (2) increased osteoblast migra-tion, (3) increased attachment of osteo-blasts, (4) facilitated osteoblast spread, (5) increased proliferation of osteoblasts, and (6)

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promoted osteoblastic differentiation. How-ever, these processes should not be con-sidered as independent from each otherNo surgical complications were observed in relation to photofunctionalization, and surprisingly, the percentage of surgical complications was lower with the use of photofunctionalization suggesting the prac-ticality and safety of this technology. l

Correspondence:Dr. Suraj Khalap10th floor, SOHAM Gandhi Bhuvan,Taikalwadi, off Manorama Nagarkar marg,Matunga West, Mumbai – [email protected]

DisclosureThe authors report no conflicts of interest with anything in this article.

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