Implant Stability Change and Osseointegration Speed of ... · Osseointegration Speed of Immediately...

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Implant Stability Change and Osseointegration Speed of Immediately Loaded Photofunctionalized Implants Senichi Suzuki, DDS, PhD,* Hiroyuki Kobayashi, MD, PhD,and Takahiro Ogawa, DDS, PhDP hotofunctionalization of titanium implants, the comprehensive physicochemical and biological effects of ultraviolet (UV)-light treat- ment, has earned considerable interest and attention in the elds of titanium science, biomaterials research, and implant therapy. 16 Photofunctionaliza- tion of titanium implants increased the bone-implant contact from 55% to 98.2%, approximating an ideal level of 100%, in an animal model. 5 Conse- quently, the strength of bone-implant integration increases more than 3 times at the early stage of healing. 5 Subsequent in vivo animal studies further revealed the advantage of photofunctionalization to overcome challenging conditions. One of the studies showed that, when the implant was 40% shorter, the strength of bone-implant integration decreased by 50%. 7 More importantly, when 40% shorter implants were photo- functionalized, the strength of bone- implant integration was even greater than that of standard-length implants. Another study examined the effect of a periimplant gap in the cortical bone. 8 The presence of a periimplant gap, equivalent to half the implant diameter, resulted in signicant reduction of the strength of bone-implant integration by 70% compared with the implants with cortical support. When photofunctional- ized implants were placed in the same gap healing, the strength of bone- implant integration increased to the same level of the implants with cortical sup- port. Detailed microcomputed tomogra- phy analysis revealed that the effect can be explained by an enhanced osteomor- phogenesis around photofunctionalized implants. 8 There was robust osteogene- sis around photofunctionalized implants, which initiated at the implant interface and rapidly spread to and connected with the surrounding bone, whereas os- teogenesis around untreated implants initiated at the surface of the remote cor- tical bone and slowly approached the implant interface. The mechanism underlying the biological effects of photofunctionali- zation includes 3 property changes on *Director, Lion Implant Center, Kanagawa, Japan. Professor, Department of Hospital Administration, Juntendo University School of Medicine, Tokyo, Japan. Professor, The Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, University of California, Los Angeles, School of Dentistry, Los Angeles, CA. Reprint requests and correspondence to: Takahiro Ogawa, DDS, PhD, Laboratory for Bone and Implant Sciences (LBIS), The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, University of California, Los Angeles, School of Dentistry, 10833 Le Conte Avenue (B3-081 CHS), Box 951668, Los Angeles, CA 90095-1668, Phone: (310) 825-0727, Fax: (310) 825-6345, E-mail: togawa@ dentistry.ucla.edu. ISSN 1056-6163/13/02205-481 Implant Dentistry Volume 22 Number 5 Copyright © 2013 by Lippincott Williams & Wilkins DOI: 10.1097/ID.0b013e31829deb62 Objectives: This study evaluated the degree and rate of implant stability development for photofunc- tionalized dental implants in hu- mans. Materials and Methods: Thirty- three implants (7 patients) placed in the maxilla and immediate loaded were evaluated. Photofunctionaliza- tion was performed by treating im- plants with ultraviolet for 15 minutes immediately before placement. Implant stability was assessed by measuring the implant stability quo- tient (ISQ) weekly starting from implant placement up to 3 months. Osseointegration speed index (OSI), dened as ISQ increase per month, was also evaluated. Results: The average ISQ for photofunctionalized implants at week 6 was 78.0, which was considerably higher than the average ISQ of 66.1, reported in literature for various as- received implants after a longer healing time of 2 to 6 months. No stability dip was observed for photo- functionalized implants regardless of the initial ISQ values. The OSI for photofunctionalized implants was 6.3 and 3.1 when their initial ISQ was 65 to 70 and 71 to 75, respec- tively, whereas the OSI values for as- received implants calculated from literature ranged from -3.0 to 1.17 with an average of -0.10. Conclusions: Photofunctionali- zation accelerated and enhanced osseointegration of dental implants, providing novel and practical ave- nues for further advancement in implant therapy. (Implant Dent 2013;22:481490) Key Words: ultraviolet, titanium, superhydrophilic, hydrocarbon, super osseointegration IMPLANT DENTISTRY /VOLUME 22, NUMBER 5 2013 481

Transcript of Implant Stability Change and Osseointegration Speed of ... · Osseointegration Speed of Immediately...

Page 1: Implant Stability Change and Osseointegration Speed of ... · Osseointegration Speed of Immediately Loaded Photofunctionalized Implants Senichi Suzuki, DDS, PhD,* Hiroyuki Kobayashi,

Implant Stability Change andOsseointegration Speed of ImmediatelyLoaded Photofunctionalized ImplantsSenichi Suzuki, DDS, PhD,* Hiroyuki Kobayashi, MD, PhD,† and Takahiro Ogawa, DDS, PhD‡

Photofunctionalization of titaniumimplants, the comprehensivephysicochemical and biological

effects of ultraviolet (UV)-light treat-ment, has earned considerable interestand attention in the fields of titaniumscience, biomaterials research, andimplant therapy.1–6 Photofunctionaliza-tion of titanium implants increased thebone-implant contact from 55% to98.2%, approximating an ideal level of100%, in an animal model.5 Conse-quently, the strength of bone-implantintegration increases more than 3 timesat the early stage of healing.5 Subsequentin vivo animal studies further revealedthe advantage of photofunctionalizationto overcome challenging conditions.One of the studies showed that, whenthe implant was 40% shorter, thestrength of bone-implant integrationdecreased by 50%.7 More importantly,when 40% shorter implants were photo-functionalized, the strength of bone-implant integration was even greaterthan that of standard-length implants.

Another study examined the effect ofa periimplant gap in the cortical bone.8

The presence of a periimplant gap,equivalent to half the implant diameter,resulted in significant reduction of thestrength of bone-implant integration by70% compared with the implants withcortical support. When photofunctional-ized implants were placed in the samegap healing, the strength of bone-implant integration increased to the samelevel of the implants with cortical sup-port. Detailed microcomputed tomogra-phy analysis revealed that the effect can

be explained by an enhanced osteomor-phogenesis around photofunctionalizedimplants.8 There was robust osteogene-sis around photofunctionalized implants,which initiated at the implant interfaceand rapidly spread to and connectedwith the surrounding bone, whereas os-teogenesis around untreated implantsinitiated at the surface of the remote cor-tical bone and slowly approached theimplant interface.

The mechanism underlying thebiological effects of photofunctionali-zation includes 3 property changes on

*Director, Lion Implant Center, Kanagawa, Japan.†Professor, Department of Hospital Administration, JuntendoUniversity School of Medicine, Tokyo, Japan.‡Professor, The Weintraub Center for ReconstructiveBiotechnology, Division of Advanced Prosthodontics, Universityof California, Los Angeles, School of Dentistry, Los Angeles, CA.

Reprint requests and correspondence to: TakahiroOgawa, DDS, PhD, Laboratory for Bone and ImplantSciences (LBIS), The Jane and Jerry Weintraub Centerfor Reconstructive Biotechnology, Division of AdvancedProsthodontics, Biomaterials and Hospital Dentistry,University of California, Los Angeles, School ofDentistry, 10833 Le Conte Avenue (B3-081 CHS), Box951668, Los Angeles, CA 90095-1668, Phone: (310)825-0727, Fax: (310) 825-6345, E-mail: [email protected].

ISSN 1056-6163/13/02205-481Implant DentistryVolume 22 � Number 5Copyright © 2013 by Lippincott Williams & Wilkins

DOI: 10.1097/ID.0b013e31829deb62

Objectives: This study evaluatedthe degree and rate of implantstability development for photofunc-tionalized dental implants in hu-mans.

Materials and Methods: Thirty-three implants (7 patients) placed inthe maxilla and immediate loadedwere evaluated. Photofunctionaliza-tion was performed by treating im-plants with ultraviolet for 15 minutesimmediately before placement.Implant stability was assessed bymeasuring the implant stability quo-tient (ISQ) weekly starting fromimplant placement up to 3 months.Osseointegration speed index (OSI),defined as ISQ increase per month,was also evaluated.

Results: The average ISQ forphotofunctionalized implants at week6 was 78.0, which was considerablyhigher than the average ISQ of 66.1,

reported in literature for various as-received implants after a longerhealing time of 2 to 6 months. Nostability dip was observed for photo-functionalized implants regardless ofthe initial ISQ values. The OSI forphotofunctionalized implants was6.3 and 3.1 when their initial ISQwas 65 to 70 and 71 to 75, respec-tively, whereas the OSI values for as-received implants calculated fromliterature ranged from −3.0 to 1.17with an average of −0.10.

Conclusions: Photofunctionali-zation accelerated and enhancedosseointegration of dental implants,providing novel and practical ave-nues for further advancement inimplant therapy. (Implant Dent2013;22:481–490)Key Words: ultraviolet, titanium,superhydrophilic, hydrocarbon,super osseointegration

IMPLANT DENTISTRY / VOLUME 22, NUMBER 5 2013 481

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titanium surfaces. Photofunctionaliza-tion converts titanium surfaces fromhydrophobic to superhydrophilic andfrom electronegative to electroposi-tive.2,3,5,9–13 In addition, titanium surfa-ces, which are unavoidably covered bya significant amount of hydrocarbondur-ing aging, can be cleaned by photofunc-tionalization.2,3,5,14 Because of thesesurface changes, the recruitment, attach-ment, retention, spread, proliferation, andthe expression of functional phenotypesof osteogenic cells are remarkablyincreased.1,5,8,11,12,15,16 Among cellularbehavior and function, this study paidattention to the potential benefits obtainedby the enhanced attachment and retentionof the cells. Mechanical stimulation, suchas vibration of the titanium substrate, isknown to detach a large number of cellsfrom titanium surfaces even after the cellsare adhered.6,10,11,15,17 When an immedi-ate loading protocol is applied to dentalimplants, there is a reasonable concernthat only a limited number of remnantcells could play a subsequent role in os-seointegration. If photofunctionalizationis proven to increase cellular attachmentand retention, it may, in particular, helpimprove the process of osseointegrationin immediately loaded dental implants.

Measuring implant stability at place-ment and its subsequent change duringhealing provides useful information formonitoring the process of osseointegra-tion, planning a loading protocol, andevaluating various conditions of osseoin-tegration on implant and host sides.18–24

The use of implant stability quotient(ISQ) values based on the resonance fre-quency analysis has been extensivelyreported for its reasonable reliability andvalidity.20,25–30 Periimplant osteogenesisconsists of postsurgical reaction andremodeling of the bone and the initiationand progression of de novo bone forma-tion, which are represented as a reductionin primary stability and development ofsecondary stability, respectively.31–33 Therate of losing primary stability is knownto be faster than the development of sec-ondary stability and, thereby, causesa merging gap between the 2 processesto maintain overall implant stability,resulting in the occurrence of a stabilitydip32,33 (Fig. 1). The stability dip, includ-ing the progressive reduction of overallstability when the initial stability is high,

is considered difficult to eliminate withcurrent implants, and in fact, ISQ valuesare adequately sensitive to detect the sta-bility dip between weeks 1 and 8 afterimplant placement.19,21,26,34–37 Becauseof the stability dip, there is a principle inclinical protocol that implants should bekept unloaded until after the dip haspassed, which limits the application ofimmediate and early loading.

Thus, an important question iswhether photofunctionalization iseffective in obtaining similar results inhumans compared with animal studiesand, thereby, providing clinical advan-tages or therapeutic significance. Inparticular, we hypothesized that photo-functionalization may affect the com-monly understood time course ofa change in implant stability becauseof its capability to expedite and enhanceosseointegration as demonstrated inanimal studies. This is a perspectivecohort study to evaluate the change instability of photofunctionalized dentalimplants placed in the edentulous max-illa and immediately loaded during theirearly healing time up to 3 months.

MATERIALS AND METHODS

PatientsAmong the patients who visited

Lion Implant Center during November2011 and March 2012 for implanttherapy and who provided consent for

documentation and public presentationof their cases, 7 male patients wereselected consecutively for this study.Patients were included if they were atleast 20 years old, if they complied withoral health care instructions and neces-sary visits, and if they showed indica-tions for immediate loading in theedentulous maxilla. Patients with sys-temic or behavioral conditions thatcould potentially affect bone and softtissue healing, such as osteoporosis,diabetes, radiation treatment, bruxism,or smoking, were excluded. In total, 33implants were placed in the 7 patients.The patient and implant information isprovided in Table 1.

Surgical Procedure andPhotofunctionalization ofDental Implants

Standardized consultation and diag-nostic procedures were provided to allpatients, and a treatment plan was pre-sented and approved by the patients.Following the routine procedures oflocal anesthesia and full-thickness flapreflection, implants were placed follow-ing the standard surgical procedurerecommended by the manufacturer anddescribed in-depth elsewhere.38,39 Fourto 6 implantswere placed per edentulousmaxilla. The implant neck was posi-tioned at bone level. Multiunit straightabutments or 17-degree or 30-degreeangulated abutments were used asappropriate to correct the fixture inclina-tion. The soft tissues were readapted andsutured.

Implants used in this study hada tapered root form and identical surfacemicroscale morphology by oxidation(TiUnite,NobelReplaceTaperedGroovyRP; Nobel Biocare, Yorba Linda, CA).The dimensions of the implants arepresented in Table 1. All implants werephotofunctionalized by treating with UVlight for 15 minutes using a photo device(TeraBeam Affiny; Ushio, Inc., Tokyo,Japan) at the chair side immediatelybefore implantation (Fig. 2, A). The pho-tofunctionalization-induced change insurface property from hydrophobic tosuperhydrophilic (defined as a contactangle of water less than 5 degrees) wasconfirmed before patient visits by exam-ining several implants for their wettabil-ity to double-distilled water (Fig. 2, B).

Fig. 1. A suggested mechanism of theoccurrence of stability dip in dental implants.The total stability, as determined by theaddition of primary stability and secondarystability, normally shows a merging gap,which is called the stability dip. The stabilitydip is considered unavoidable in currentdental implants because the rate of losingprimary stability is faster than the develop-ment of secondary stability.

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These tested implants were from a sepa-rate group of the same type of implantsand not used for the patients. Further-more, photofunctionalized surfaces wereconfirmed by watching the patient’sblood spiral up the implant immediatelyafter it was in contactwith the drilled site,as typically seen in Figure 2, C. Bonequality was categorized as type 1, 2, 3,or 4 during the surgery following the cri-teria proposed by Lekholm and Zarb.40

Immediate Provisional RestorationFull-arch acrylic resin temporary

prostheses were placed on the sameday. The prostheses were fabricatedfollowing the manufacturer’s instruc-tions and as described elsewhere38,39

using autopolymerizing resin (UnifastII; GC, Tokyo, Japan) and temporaryabutments (Nobel Biocare) in thein-house laboratory. Anterior occlusalcontacts and canine guidance duringlateral movements were preferablyestablished on the provisional prosthe-ses. No cantilevers contact was givenon the provisional prostheses.

Fig. 2. Photofunctionalization of dental implants and its visualized effects on implant surfaceproperty. A, A photo device (TeraBeam; Affiny, Ushio, Inc.) used for photofunctionalization.Dental implants were treated for 15 minutes immediately before implantation. B, Implants,which were hydrophobic as received, were converted to superhydrophilic after photo-functionalization. Photographic images of 3 mL of ddH2O droplets placed on implant surfacesare shown. Two droplets (6 mL) were sufficient to entirely cover a photofunctionalized implant.C, Clinical images of untreated (as-received) and photofunctionalized dental implants whenthey were in contact with an implant site. A hemophilic conversion of the implant surfaces isevidently seen after photofunctionalization. The generated hemophilicity was robust enough tosoak up blood along the implant thread.

TABLE

1.Patient

andIm

plan

tData.

All33

Pho

tofunc

tiona

lized

Implan

tswerePlace

dintheMaxilla

andIm

med

iatelyLo

aded

.The

Distributionof

Implan

tLe

ngth

andBon

eTy

peisSho

wn

Patients

Implan

ts

Num

ber

Age

Age

Ran

geTo

talN

umbe

rDiameter

Leng

thBon

eTy

pe

759

.06

5.8

53–66

334.3mm

10mm

11.5

mm

13mm

16mm

Type

1Ty

pe2

Type

333

(100

%)

2(6.1%)

5(15.2%

)23

(69.7%

)3(9.1%)

8(24.2%

)19

(57.6%

)6(18.2%

)

Fig. 3. The ISQ values at implant placementand week 6 of healing plotted for photo-functionalized implants. Note that all implantswith an initial ISQ that was 75 or lowershowed an increase at week 6, and conse-quently, the ISQ values at week 6 were all 75or higher.

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Implant Stability Measurement andOsseointegration Speed Index

Implant stability was evaluated bymeasuring the ISQ at implant

placement (ISQi) and during the heal-ing period with a 1-week interval upto 11 weeks using Osstell ISQ(Osstell AB, Gothenburg, Sweden).

Furthermore, the rate of establishingimplant stability was evaluated by theosseointegration speed index (OSI)defined as an ISQ increase per month,that is, ([ISQ at week 6] − [ISQi])/1.5.

Statistical AnalysisThe effect of healing time on ISQ

values was evaluated by ANOVA; P,0.05 indicated statistical significance.When the effect was significant, furtherpost hoc analysis of Bonferroni wasperformed to compare the ISQi withthe ISQ at each of the subsequent timepoints. The ISQ values were comparedamong implants with different lengthsusing ANOVA. Furthermore, the effectof different bone types where implantswere placed was evaluated.

RESULTS

Implant Dimensions and Bone TypeThe diameter of all implants used in

this study was 4.3 mm, whereas theirlength varied; 13 mm implants wereusedmost often (Table 1). Amajority ofimplants (57.6%) were placed in thetype 2 bone, whereas 24.2% and18.2% implants were placed in the type1 and type 3 bones, respectively. Therewas no type 4 bone because the casesincluded in the study were selected forimmediate loading.

Change in Implant StabilityTo visualize the overall trend of

change in implant stability, ISQi valuesand the ISQ values at week 6 wereindividually plotted (Fig. 3). The ISQivaried widely from 65 to 85, whereasthe ISQ values at week 6 were con-verged to the higher level. There wasa variation in ISQ fluctuation betweenthe time of implant placement andweek6, an increase, no change, or a decrease,for implants with ISQi that were 77 orhigher. In contrast, all implants with IS-Qi 75 or lower showed an increase atweek 6. There was a clear trend thatlower the ISQi, the greater the subse-quent ISQ increase. As a result, theISQ values at week 6 were all 75 orhigher.

Next, the implants were dividedinto 3 groups depending on the range oftheir ISQi (ISQi 65–70, ISQi 71–75,and ISQi $ 76), and the ISQ values

Fig. 4. Change in implant stability for photofunctionalized implants, evaluated by ISQ values atimplant placement and subsequent healing time. Line graphs are drawn in 3 different groupsdepending on the initial ISQ values at implant placement (ISQi). A, ISQi 65 -70; B, ISQi 71 –75;and C, ISQi $ 76. *P , 0.05, **P , 0.01, statistically significant difference from the ISQi.

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starting from the implant placement up to11thweekwere plotted in a line graph foreach group (Fig. 4). When the ISQi val-ues was 65 to 70, the ISQ line graphshowed a rapid and continuous increaseup to week 6, followed by the plateau atthe increased level (Fig. 4, A). ANOVAshowed a statistically significant effect ofhealing time on the ISQ values (P ,0.05). The post hoc analysis showed thatthe ISQvalues atweek 3 and afterweek 3were significantly higher than the ISQi,supporting the rapid increase and subse-quentmaintenance of ISQ.No significantISQ decrease was found compared withthe ISQi in the entire assessment period(P. 0.05). There also was no significantISQ dip (a significantly lower ISQ valuecompared with neighbor time points)throughout the healingperiod (P. 0.05).

Similar to the ISQi 65 to 70 group,when the ISQi was 71 to 75, thesubsequent ISQ showed an increasingcourse of change (Fig. 4, B). Althoughthe rate of ISQ increase appeared lessthan that in ISQi 65 to 70 group becauseof the higher baseline, the ISQ values inthe later time points appeared to be sim-ilar between the ISQi 71 to 75 and ISQi

65 to 70 groups. A significant ISQincrease comparedwith ISQiwas foundstarting at week 2 and continued untilweek 11, except at week 3. Comparedwith ISQi, subsequent ISQ values didnot show a significant decrease or a sig-nificant dip throughout the healingperiod. In contrast with these 2 results,there was no time-dependent ISQincrease, decrease, or dipwhen the ISQiwas 76 or higher (Fig. 4, C). The meanISQ values remained higher than 76throughout the healing period withoutsignificant fluctuation in this group.

Osseointegration Speed IndexFor each of the ISQi 65 to 70, ISQi

71 to 75, and ISQi$ 76 groups, changein implant stability between the implantplacement and week 6 was tallied inTable 2. A statistically significant ISQincrease was seen in ISQi 65 to 70 andISQi 71 to 75 groups but not in ISQi$76 group. For the significant ISQchanges found, the osseointegrationspeed index (OSI) defined as the ISQincrease per month was calculated(Table 2). The OSI in ISQi 65 to 70group was 6.36 0.9 and approximately

2 times higher than that in ISQi 71 to 75group. The OSI for ISQi 71 to 75 groupwas 3.16 1.2.

Effect of Bone Type and Implant LengthTofindpotential specificity or exclu-

sivity of the effect of photofunctionaliza-tion, ISQ values were analyzed indifferent bone types. At implant place-ment, ISQi significantly variedwith bonetype (Table 3). The ISQ values were sig-nificantly lower for the type 2 and 3groups than for the type 1 group at place-ment. The interbone type differencebecame insignificant at week 6, indicat-ing that photofunctionalization waseffective in increasing the stability of im-plants with lower initial ISQ in the type 2and 3 groups.Next, ISQvalueswere ana-lyzed depending on the implant length(Table 4). The ISQi was not differentbetween “#11.5-mm” and “$13-mm”

groups. Although ISQ increased in bothgroups at week 6, therewas no differencebetween the 2 groups, indicating the eveneffect of photofunctionalization regard-less of the implant length.

DISCUSSION

By using ISQ values, this studyquantitatively evaluated the level,change, and rate of osseointegration ofphotofunctionalized dental implantsunder the immediate loading condition.One of the hypotheses we tested waswhether clinical effects of photofunc-tionalization similar to those found inanimal studies can be obtained inhumans. As mentioned in Introduction,a series of animal studies demonstratedthe accelerated and enhanced capabilityof osseointegration by photofunction-alization. To compare the osseointegra-tion capability of photofunctionalizeddental implants with that of the as-received untreated implants, we definedand calculated the OSI. The proposedOSI value represents a rate of develop-ing implant stability standardized byhealing time, providing more preciseand reasonable information rather thanthe use of an ISQ per se at a certain timepoint or an ISQ increase during unde-fined period of time and, more impor-tantly, allowing for a comparisonamongdifferent sources of data. Table 5lists ISQ values from 2 time points

Table 2. ISQ Change and OSI in Photofunctionalized Implants

Primary Stability Range(ISQi)

ISQ

OSIAt

Placement At Week 6 Change

65–70 68.4 6 1.5 77.5 6 1.4 9.5 6 1.3* 6.3 6 0.971–75 73.0 6 1.5 78.1 6 2.3 4.6 6 1.8* 3.1 6 1.2$76 78.5 6 1.6 78.1 6 2.1 −0.3 6 2.1† NA

Implants were divided into 3 groups depending on the initial ISQ value at implant placement. This table shows mean ISQ values atimplant placement and week 6 postimplantation as well as the ISQ change between the 2 time points for each group. Furthermore,the ISQ change divided by healing time of 1.5 months (6 weeks) is shown as the OSI value. The ISQ change was significant andpositive when the initial ISQ was 75 and lower.*P , 0.01; statistically significant change between 2 time points.†Not significant.NA, not applicable; ISQi, initial ISQ at implant placement; OSI, osseointegration speed index ¼ ISQ increase per month.

Table 3. ISQ in Different Bone Types

BoneType

ISQ

AtPlacement*

At Week6†

Type 1 78.6 6 2.0 77.0 6 0.0Type 2 74.1 6 4.5 78.2 6 1.6Type 3 74.0 6 2.5 78.2 6 3.2

Implants were divided into 3 groups depending on the bonetype in which implants were placed. This table shows mean ISQvalues at implant placement and week 6 postimplantation foreach group. The ISQ values in type 2 and 3 groups increasedbetween the placement and week 6, and there were nosignificant difference among the 3 groups at week 6.*P , 0.05; statistically significant difference among the three 3groups.†Not significant.

Table 4. ISQ in Groups of DifferentImplant Length

ImplantLength,mm

ISQ

AtPlacement* At Week 6*

#11.5 73.6 6 3.6 77.5 6 3.8$13 75.6 6 4.2 78.1 6 1.6

Implants were divided into 2 groups depending on the implantlength. This table shows mean ISQ values at implant placementand week 6 postimplantation for each group. Both groupsshowed a significant increase between the placement and week6 of healing. Therefore, there was no significant differencebetween the 2 groups at week 6, indicating that photofunction-alization was effective in increasing ISQ values regardless of theimplant length.*Not significant between the 2 groups.

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along with the calculated OSI in the lit-erature.18,19,26,34–37,41–46 The OSI valuesfrom this study are also listed at the bot-tom of the table. Because the initial ISQvalues were all higher than 65 in thisstudy, we focused on the publicationsdealing with initial ISQ values higherthan around 60 and at the same time,with data availability at least 2 timepoints. The following were the 3 majorfindings (Table 5): (1) a greater increasebetween the initial and secondary ISQvalues in photofunctionalized implantsthan in literature; (2) the majority ofOSI in literature was lower than 1.0and the OSI of photofunctionalized im-plants was notably higher than those inliterature; and (3) the ISQ values at

secondary time points obtained in thisstudy between 77.5 and 78.1 were high-er than any values in literature, evenwithin a shorter healing time of 1.5months.

The ISQ values are known toincrease when the initial ISQ is lowerthan 60, whereas ISQ values mostly stayunchanged or decrease when the initialISQ is higher than 60.19,21,26,35,47 Thiscommon understanding can be reaf-firmed from the data in literature listedin Table 5, showing OSI of lower than1.0 or even in the negative range below0. In this regard, the OSI of 6.3 when theinitial ISQ was 65 to 70 and the OSI of3.1 even when the initial ISQ was 71 to75 obtained in this study should be

considered remarkable. In fact, thecalculated OSI for all as-received con-ventional implants in Table 5 rangedfrom −3.0 to 1.17, with an average of−0.10. If only data with their initialISQbeing in a similar range to this study(65–75) are selected, the OSI rangedfrom −1.8 to 1.17 with an average of0.21. In both cases, the OSI values inliterature were substantially low.

Although any interpretation shouldbe carefully made because of the differ-ences in macroscopic design and sur-face morphology among implants,considerably high ISQ values obtainedin this study at week 6 may imply theadvantage of photofunctionalization tonot only expedite the process but also

Table 5. ISQ Change and Calculated OSI in the Literature and This Study

Implant Surface Conditions

ISQ

HealingTime (mo)

OSI (ISQincrease/mo)

Initial (atPlacement) Secondary*

TiUnite41 (oxidized) Immediate/early loadingmaxilla

60.1 6 3.6 62.8 6 1.6 4 0.68

TiUnite42 Immediate/early loadingmaxilla

63.3 6 6.1 64.3 6 5.3 3 0.33

TiUnite19† Includes GBR andextraction socket

68.0 63.0 3 −1.67

TiUnite43 Anterior maxilla 58.5 6 4.7 60.9 6 4.3 6 0.4Grafted anterior maxilla 61.5 6 9.0 60.2 6 6.9 6 −0.2

TiUnite44 Grafted anterior maxilla 61.9 6 6.6 63.5 6 5.7 6 0.26SLA26 (sandblasted, acid-etched)‡ ISQi 65–69 3 −1.8

ISQi $ 70 3 −3.0SLA45 Anterior maxilla 69.4 6 9.3 73.4 6 6.6 3.4 1.17

Posterior maxilla 69.9 6 8.5 74.4 6 6.9 4 1.12SLA18 Type 1 bone 62.8 6 7.2 60.7 6 3.6 3 −0.7SLA34† Mandible 60.0 62.7 2.5 1.1SLA36 Mandible 65.5 6 5.5 62.8 6 5.4 1.5 −1.8SLActive36 (sandblasted, acid-etched,

chemically modified)Mandible 64.2 6 5.0 64.1 6 3.5 1.5 −0.06

Impladent37 (sandblasted, acid andalkali treated)

ISQi 68–72 70.2 6 1.5 71.5 6 1.3 2.5 0.52

ISQi $ 72 76.7 6 3.1 74.8 6 1.3 2.5 −0.76SPI35 (sandblasted, acid etched) Type 3 bone 73.6 6 5.8 74.8 6 5.4 2 0.6

Type 4 bone 68.9 6 4.3 69.9 6 4.3 2 0.51TiOblast46 (sandblasted) Maxilla 62.3 6 5.1 63.9 6 5.5 6 0.27

Grafted maxilla 60.7 6 6.1 61.4 6 5.2 6 0.12Photofunctionalized surface

(TiUnite, oxidized)Immediate loading,

maxillaISQi, 65–70 68.4 6 1.5 77.5 6 1.4 1.5 6.3ISQi, 71–75 73.0 6 1.5 78.1 6 2.3 1.5 3.1

The ISQ change during healing and calculated OSI are compared between untreated implants in literature and photofunctionalized implants. Note that the OSI values for photofunctionalized implants areconsiderably higher than those from literature. In addition, the ISQ values achievable at week 6 of healing (1.5-month healing) in photofunctionalized implants are higher than those in any untreated implantseven after longer healing time.*Some data were obtained at loading, whereas some at prescheduled follow-up time points.†Values were read from the graph.‡Data were provided only for ISQ difference between the implant placement and 3-month follow-up.ISQi, initial ISQ at implant placement; OSI, osseointegration speed index ¼ ISQ increase per month.

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achieve a higher level of osseointegra-tion. The results were particularly sur-prising because of the following 2reasons: initial ISQ values of 65 orhigher are not expected to increasefurther, as reported in literature, andhigh ISQ values were obtained aftera healing time as short as 6 weeks.Future studies are needed to follow-upon the subsequent change of the ISQvalues of photofunctionalized implants.The higher level of osseointegrationmay lead to better success rates andlong-term predictability of implanttherapy,whichwill be a very interestingresearch topic in the future. Thus, thecurrent ISQ data and its comparisonwith literature were indeed consistentwith the results obtained from animal

studies that showed highly increasedimplant fixation in the early and latestage of healing, accelerated rate ofperiimplant bone formation, and theestablishment of bone-implant contactnearing 100%,5 supporting the hypoth-esis that photofunctionalized implantsin humans are as effective as in animalexperiments.

Discussing cases of immediateloading and with a similar type ofimplants would be of another particularinterest. A study examined the stabilitychange of implants loaded 1 to 9 daysafter implant placement to supporta full-arch fixed bridge in the maxilla.41

A total of 61 oxidized implants (6 or 8implants per maxilla) were examined.The mean ISQ, which was 60.1 6 3.6

at placement, increased to 62.8 6 1.6after 4 months, giving an OSI of 0.68.Another study evaluated implantsplaced in the partially edentulous max-illa and loaded 0 to 16 days after place-ment.42 A total of 53 oxidized implants(16 for single tooth replacement and 37for partial fixed bridges) were exam-ined. The initial ISQ of 63.3 6 6.1slightly increased to 64.3 6 5.3 after 3months, giving an OSI of 0.33. Again,there is a general understanding regard-ing ISQ values that the lower the initialvalue themore increase is expected dur-ing the subsequent healing. Despite theinitial ISQ being higher than these stud-ies, OSI values obtained at week 6 inthis study were remarkably greater.Knowing that these studies were carriedout under a similar clinical protocol andhost conditions to this study and withthe implant texture being identical to anoxidized surface used in this study, thecurrent results may genuinely demon-strate the effect of photofunctionaliza-tion in enabling a faster and morecomplete process of osseointegration.As mentioned in Introduction, the clin-ical benefit of photofunctionalizationwas particularly anticipated in suchearly/immediate loading cases becauseof the increased attachment and reten-tion of osteogenic cells, which indeedhas been proven by the quantitativeassessment of implant stability.

Another important result of thisstudy was the elimination of the stabil-ity dip or significant decrease of totalstability throughout the healing periodfor photofunctionalized implants. Highinitial ISQ values of approximately 70to 80 are bound to show a typical dipduring the subsequent healing periodor, if not a typical dip, a decrease andremain at the decreased level.19,21,26,35,47

In this study, as shown in Table 2 andFigure 4, C, implants with very highinitial ISQs (higher than 78) did notexperience a stability dip or significantdecrease during the healing period, pro-viding the compelling evidence to sup-port immediate loading. Together withthe rapid ISQ increase observed in theimplants with lower initial ISQ, the cur-rent results will help explore a newstrategy for early or immediate loadingprotocols. On the basis of the currentresults on ISQdynamics combinedwith

Fig. 5. Proposed mechanisms of appearance and disappearance of stability dip in schematicdescription. The stability dip is anticipated for as-received untreated implants as commonlyunderstood whether the primary stability is high (A) or low (C). In contrast, the stability dip iseliminated by the use of photofunctionalization, regardless of the degree of primary stability (B,D), because of faster (when the primary stability is high) and even faster (when the primarystability is low) development of secondary stability. Note that photofunctionalization did notonly expedite the rate of establishing the total stability but also increased the degree of thetotal stability. Refer to the main text for detailed explanation.

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the common understanding on how thestability dip appears, we proposea mechanism underlying the disappear-ance of the stability dip by the use ofphotofunctionalized implants (Fig. 5).There are 2 scenarios to explain the phe-nomenon of stability dip, depending onthe level of primary stability. The no-tions applied to construct the mecha-nism were as follows: (1) OSI forphotofunctionalized implants was con-siderably higher than untreated im-plants reported in literature, which ledto a rapid and steep secondary stabilitycurve slope during the early healingperiod; (2) regardless of the use of pho-tofunctionalization, implants withlower initial ISQ values tend to showhigher OSI as understood commonly;(3) in this study, an OSI with an initialISQ of 65 to 70 was, in fact, 2 timesgreater than an OSI with an initial ISQof 71 to 75; (4) not only the rate ofimplant stability but also the final levelwas increased by photofunctionaliza-tion, which indicates that the level ofsecondary stability could be higherwithphotofunctionalized implants than con-ventional implants; and (5) the rate oflosing primary stability is assumed to bethe same with or without photofunc-tionalization. In Figure 5, A and C,high-level and low-level stability dipsunavoidably take place in untreatedconventional implants because of thequicker loss of primary stability thanthe development of secondary stability.The rate of secondary stability estab-lishment, which is faster in Figure 5, Cthan in Figure 5, A, as indicated by “a’. a,” is unlikely to help eliminate thestability dip. In contrast, because of theearly shift of the secondary stabilitycurve, as indicated by “b. a,” the sta-bility dip is effectively eliminated inphotofunctionalized implants (Fig. 5,B). The increased level of total stabilityby the increased degree of secondarystability should not be overlooked. Inaddition, because of further increasedrate in the secondary stability, as indi-cated by “y¼ 2bx,” the stability dip canbe avoided even when the primary sta-bility was low (Fig. 5, D). We believethat the proposed schemes will helpunderstand how the overall anchorageof photofunctionalized implants isuniquely established and provide

a novel platform to build a new strategyfor future clinical protocols and thedevelopment of implant surfaces.

Although the interpretation shouldbe limited to the results obtained duringthe initial period of osseointegration ofup to 3 months, the quantitative analysisof implant stability by the consecutivemeasurement of ISQ values in a cohortdesign may have provided an invaluabledata set todemonstrate the expeditedandenhanced process of osseointegration inphotofunctionalized dental implants andwarrants further clinical studies to estab-lish photofunctionalization as an effec-tive measure to improve the currentimplant dentistry in multiple aspects.Photofunctionalization is a simple, prac-tical, chair-side treatment of dental im-plants that requires only 15 minutes andhas proven effective on all surface top-ographies of titanium-based materialstested, implying the versatile applicabil-ity in a wide range of dental andorthopedic implants.9,48–50 If future sur-face technologies are anticipated toexpand the indications of implant ther-apy, shorten the healing time, increasethe success rate for compromised boneconditions, and explore minimally inva-sive approaches, photofunctionalizationas presented here may provide a novelinsight and a practical avenue to pursuethose goals. Finally, the application ofphotofunctionalization should not berestricted to use in dental implants.Orthopedic implants face many, long-unsolved challenges. Photofunctionali-zation can be applied regardless of theshape and size of implants. Variousorthopedic implants, including but notlimited to spine screws, femoral stem,knee joint implants, plates, and pins,can potentially be enhanced for theirosteoconduction.

CONCLUSIONS

This study reports a quantitativeevaluation of the effect of photofunction-alization on clinical performance, specif-ically osseointegration capability, ofdental implants. Photofunctionalizationwas conducted by treating implants withUV light for 15 minutes. The generationof superhydrophilicity and hemophilicitywas confirmed after photofunctionaliza-tion. The osseointegration capability of

photofunctionalized implants placed inthe maxilla and immediately loaded wasassessed by consecutive measurementsof ISQ during the early stage of healingup to 3months alongwith the rate of ISQincrease per month, defined as the OSI.Implants with their initial ISQ at place-ment between 65 and 70 showed a rapidand robust ISQ increase during the sub-sequent healing period. Implants withtheir initial ISQ between 71 and 75 alsoshowed a rapid and significant increase.Implants with their initial ISQ of 76 orgreater maintained a high level of ISQthroughout the healing period withoutshowing any drop or progressivedecrease in ISQ. Regardless of the initialISQ, ISQ valueswere 75 or greater for allimplants by week 6. The ISQ at week 6for photofunctionalized implants rangedfrom77.5 to78.1with an averageof 78.0,whereas ISQvalues after a longer healingperiod (mostly 2–6 months) observed inliterature ranged between 60.2 and 74.8with an average of 66.1. The OSI wasconsiderably high for photofunctional-ized implants (6.3 for implants with aninitial ISQ of 65–70 and 3.1 for implantswith an initial ISQ of 71–75) thanfor untreated conventional implants inliterature ranging from −3.0 to 1.17 withan average of −0.10. In conclusion,photofunctionalization resulted in theacceleration and enhancement ofosseointegration in commercial dentalimplants.As a result, the rate of establish-ing implant stability was substantiallyincreased when initial stability was rela-tively low. When the initial stability wasrelatively high, the ISQ was maintainedat a high value, eliminating the com-monly accepted phenomenon of the sta-bility dip. In both instances, the level ofstability that implants may experiencewas considerably increased. These re-sults imply that photofunctionalizationmay provide a novel and practical possi-bility to further advance implant therapyfor its expanded indications, shortenedhealing time, improved predictability inchallenging cases, and the explorationof minimally invasive approaches duringthe treatment.

DISCLOSURE

The authors claim to have nofinancial interest, either directly or

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indirectly, in the products or informa-tion listed in the article.

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