Biomaterials for Dental Implants: An Overview

BIOMATERIALS IN IMPLANTSBC Muddugangadhar et al. Biomaterials for Dental Implants: An Overview. International Journal of Oral Implantology and Clinical Research, January-April 2011;2(1):13-24Biomaterials for Dental Implants: An OverviewPresented by dr.amitPg 2nd year prosthodonticsCONTENTSINTRODUCTION TERMINOLOGIESHISTORYCLASSIFICATION OF BIOMATERIALSBIOCOMPATIBILITY CORROSION RESISTANCE CYTOTOXICITY OF CORROSION PRODUCTS METAL CONTAMINATION BIOFUNCTIONABILITYINDIVIDUAL MATERIALS METALS AND ALLOYS CERAMICS AND CARBON POLYMERS AND COMPOSITE POLYMERSSURFACE MODIFICATIONSCONCLUSIONREFERENCES

INTRODUCTIONTERMINOLOGIES Biocompatibility (Dorland's illustrated medical dictionary) Being harmonious with life and not having toxic or injurious effects on biofunction.

Biomaterial Any substance other than drug that can be used for any period as a part of a system that treats, augments or replaces any tissue, organ or function of the body.

Biomaterials are those materials that are compatible with the living tissues. The physical properties of the materials, their potential to corrode in the tissue environment, their surface configuration, tissue induction and their potential for eliciting inflammation or rejection response are all important factors under this area.INTRODUCTIONThe goal of biomaterials research

to develop implant materials

induce predictable, control-guided and rapid healing of the interfacial tissues both hard and soft

INTRODUCTIONBIODYNAMIC ACTIVITYBiotolerant Material that is not necessarily rejected but are surrounded by fibrous layer in the form of a capsule.

Bio inert Material that allows close apposition of bone on their surface, leading to contact osteogenesis.

Bioactive - Materials that allow formation of new bone onto their surface, but ion exchange with host tissue leads to formation of a chemical bond along the interface (bonding osteogenesis).

Osteoconductive the materials that forms scaffolding that allows the formation of bone.

Osteoinducitive materials that have capacity to induce bone formation de novo. E.g.- recombinant human bone morphogenetic protein 2. (rhBMP-2)

HISTORY2500 BC - Ancient Egyptians - gold ligature.

500 BC - Etruscan population - gold bands incorporating pontics.

500 BC - Phoenician population - gold wire.

300 BC - Phoenician population - Carved Ivory teeth.

600 AD - Mayan population - implantation of pieces of shell.

1700 - John Hunter - transplanting the teeth.

1809 - Maggiolo - pieces of gold.

1911 - Greenfield - iridoplatinum basket soldered with 24 carat gold.

1939 - Strock - vitallium screw to provide anchorage for replacement.

1940 - Formiggini - spiral implant - stainless steel wire.

1943 - Dahl -Subperiosteal type of implant.1948 - Goldberg and Gershkoff - Extension of frame work.Early 1960s - Chercheve - Double helical Spiral implant of Cobalt Chromium.

Early 1970s - Grenoble - Vitreous Carbon implants.

Early 1980s - Tatum - Titanium root form implant

Late 1970s and Early 1980s - Tatum - custom blade implants of Titanium alloy

1970 and 1980 - Weiss and Judy - Titanium Mushroom shaped projection (IMPLANT)

After 1980s hollow basket Core vent implant Screw vent implant Screw vent implant with Hydroxyapatite coating implant with titanium plasma spray

CLASSIFICATIONBiological biocompatibilityChemical composition Metals Ceramics Polymers Biotolerant Gold PolyethyleneCobalt-chromium alloys Polyamide Stainless steel Polymethylmethacrylate Zirconium Polytetrafluoroethylene NiobiumPolyurethane Tantalum BioinertCommercially pure titanium Aluminum oxide Titanium alloy (Ti-6Al-4V)Zirconium oxide Bioactive Hydroxyapatite Tricalcium phosphate Calcium pyrophosphate Fluorapatite Carbon:vitreous, pyrolytic BioglassFACTORS AFFECTINGBIOMATERIALS

BIOCOMPATIBILITY Corrosion resistance

Cytotoxicity of corrosion products

Metal contamination Corrosion - It is defined as loss of metallic ions from the surface of the metal to the surrounding environment.

Types of corrosion : General Galvanic Pitting FrettingCrevice Stress corrosion cracking

General corrosion - When metal is immersed in electrolytic solution the positively charged ions from the metal are transferred to electrolyte and then metal transports the negatively charged electrons.

Pitting corrosion - Along with general corrosion on the surface there is enhanced corrosion in the pit. Crevice corrosion -The local environment around the screw to bone plate interface or implant device. Where in overlay or composite type surface exists on a metallic substrate. They provide opportunities for crevice corrosion.

Galvanic corrosion It occurs when two dissimilar metallic materials are in contact in a electrolyte leading to flow of current.

Fretting corrosion It occurs when there is a micro-motion and rubbing contact within the corrosive environment.

Stress corrosion cracking The combination of high mechanical stresses and simultaneous exposure to a corrosive environment results in the failure of metallic materials by cracking where neither condition alone would cause the failure.

PROTECTION AGAINST CORROSION

Passivation

Increasing the noble metal content

Polishing the surface

Avoid dissimilar metal contactCYTOTOXICITY OF CORROSION PRODUCTS

The material should undergo only minimal amount of biochemical changes during service.

The material should have minimal reaction with the surrounding bone and the soft tissue.

Ideally the corrosion products should not produce any toxicity to the local and systemic environment.

METAL CONTAMINATION

By contacting dissimilar metals or alloys. The debris from the dissimilar metals can be embedded in the implant surface and corrode to form compounds that cause foreign body reactions in the surrounding tissue.

Two different metals in the saline solutions or body fluids may result in a localized difference of electrochemical potential and cause galvanic corrosion. So the instruments that contact titanium implant during insertion procedures either be solid titanium, titanium tipped or treated to prevent metallic transfer.

During storage, sterilization and surgical set up no other type of metal should contact the implant surface.

PHYSICAL AND MECHANICAL PROPERTIESThe macroscopic distribution of mechanical stress and strain is predominantly controlled by the shape and form of the implant.

The microscopic distribution is controlled by the Basic properties of biomaterials as -Surface chemistry, Microtopography, Modulus of elasticity and Surface attachment to the adjacent tissue.

The dental implant are less affected by alternating stresses than implants of cardiovascular and locomotive systems because of lower number of loading cycles and considerable smaller size of implants.

But in cases with Para functional habits the longevity is detrimental.

The forces exerted on implant consists of compressive tensile and shear. As for the most of the materials compressive force is greater than others.

Basic problem lies due to the difference in mechanical strength and deformability of the material and the recipient bone. The metals can be modified to achieve the required properties by work hardening or alloying.

The ability of the implant to bear the stress decreases as the number of loading cycles increases. Higher the applied load higher the mechanical stress greater the possibility of exceeding the fatigue limit of the material.

Many materials are biocompatible but cannot be used as an implant because of their low ultimate strength.

MODULUS OF ELASTICITYIt represents elastic response of an implant to the mechanical stress.

The forces applied on the implant leads to stresses within the bone.

When the applied forces are equal to stresses it acquires the state of static equilibrium.When the forces increase, it leads to deformation.

The physiologic importance of modulus of elasticity of biomaterial is related to the modulus of elasticity of the bone.

The degree of relative movement at the interface determines the health or pathologic state of interface.

The modulus of elasticity of titanium is very near to bone compared to any other material used. It is almost 6 times more stiff than dense cortical bone.

The carbon implants has compatible stiffness with bone but fail to have adequate strength to withstand physiologic load leading to microcracks and finally the failure of implant. On the other hand the aluminum oxide ceramic implant has high ultimate strength but the stiffness is 33 times greater than the stiffness of the bone which results in apparent stress shielding of interfacial bone.

The modulus of elasticity in subperiosteal implants not as important a consideration. The envelopment of the implant in the outer layer of periosteum during healing provides a stable biomechanical situation.

For bilateral/total subperiosteal implant may cause excessive relative movement due to its rigidity. So cutting these at the midline or providing individual abutment can increase flexibility.

For unilateral subperiosteal implant the negative effect of relative movement of metal is minimal.

INDIVIDUAL MATERIALSMETALSAND ALLOYSINIMPLANT DENTISTRY

Most of the materials used for implants are constructed from metals and their alloys. These includes Titanium, Tantalum, Aluminum, Vanadium, Cobalt, Chromium, Nickel and Molybdenum. These are selected on the basis of their over all strength. Less frequently used are precious metals as Gold and Platinum.

The evolution of titanium (Ti) applications to medical and dental implants has dramatically increased in the past few years because of titaniums excellent biocompatibility corrosion resistance and desirable physical and mechanical properties. Titanium has become a material of great interest in prosthodontics in recent years. A growing trend involves the use of titanium as an economical and biocompatible replacement for existing alloys. CLASSIFICATION OF TITANIUM AND ITS ALLOYSThe physical and mechanical properties of pure Ti and Ti alloys can be greatly varied with the addition of small traces of other elements such as oxygen, iron, and nitrogen.

Commercially pure titanium, is available in four different grades ASTM I to 1V - based on the incorporation of small amounts of oxygen, nitrogen, hydrogen, iron, and carbon during purification procedure.

ASTM committee on materials for surgical implants recognizes four grades of commercially pure titanium and two titanium alloys.

*ASTM - american society for testing and materials

The two alloys are Ti-6Al-4V and Ti-6A1-4V extra low interstitial (ELI).

Commercially pure titanium is also referred to as unalloyed titanium. All six of these materials are commercially available as dental implants.

Ti-6A1-4VSeveral alloys of titanium are used in dentistry. Of these alloys, Ti 6Al-4V is the most widely used.At room temperature, Ti-6A1-4V is a two-phase + alloy. At approximately 975C, an allotropic phase transformation takes place, transforming the microstructure to a single phase BCC -alloy.

Thermal treatments dictate the relative amounts of the and phases and the phase morphologies and yield a variety of microstructures and a range of mechanical properties.

PRODUCTION MACHINING AND AUTOCLAVING

Mechanical PropertiesThe modulus of elasticity of CpTi - 104 Mpa Ti alloy -113 Mpa. The yield strength of CpTi - 860 MpaTi alloy 745 Mpa.

The strength of Ti alloy is 2-4 times CpTi. The modulus of elasticity is increased from 104 Mpa to 113 Mpa.

Compared to Bone - modulus of elasticity of CpTi is 5 times and Ti alloy is 5-6 times.

Compared to Co-Cr-Mo these are twice strong and the elastic modulus

Has poor shear strength and wear resistance so unsuitable for holding bone screws.

OXIDE COATINGS The Biocompatibility of the Ti and Ti alloy is attributed to the ability of formation of passive tenacious surface oxide.Minimum of 85 to 95% of pure titanium is required to maintain passivity.

The pure titanium theoretically may form several oxides as TiO, Ti O2,Ti2O3.

The oxides form spontaneously on exposure to Ti to air.

Within a millisecond 10 thick oxide layer will be formed. In a minute the layer will become 100 thick.

The repair of the oxide layer is instantaneous if any damage occurs during insertion of Implant.

Rate of dissolution is extremely low compared to any implant metals.Cobalt Chromium Molybdenum AlloyHigh modulus (stiffness) and Low ductility.

Outstanding resistance to corrosion

Excellent biocompatibility

Commonly used for fabrication of custom design (e.g. : subperiosteal frames) by casting.Composition:63% cobalt 30% Chromium for passivation5 % Molybdenum StrengthTraces of carbon , magnesium, and nickel

Precautions: Proper fabrication techniques should be usedPoor ductility so bending can be avoided so cannot be used form blade for implants.

IRON - CHROMIUM - NICKEL BASED ALLOYSSurface is passivated to increase biocorrosion resistance.

High strength and ductility.

Used in wrought and heat treated condition.

Composition (Surgical austentite steel)18% chromium - for corrosion resistance.8% nickel - to stabilize austentic structure.0.5% carbon - as hardener.Precautions

Contraindicated in patients sensitive to nickel.

Most susceptible to crevice and pitting corrosion, so care to be taken to preserve passivated surface.

Has galvanic potential, so avoid contact with dissimilar metal.

Other Metals and AlloysGold, Platinum, Iridium and alloys of these metals are being used.

Have low strength that limits the implant design.

High cost and High density.

Due to its nobility and availability gold is continued to be used as surgical Implant materials.CERAMICSCeramics and Carbon as implant MaterialsCERAMICS

These are non organic, non metallic, non polymeric materials manufactured by compacting and sintering at elevated temperatures. These are bio compatible high strength insulators.

Have low ductility and inherent brittleness are their limitations.

Classified into :Bio active -Ca3(PO4), HydroxyapatiteBio non-reactive - Oxides of Aluminum, Titanium, Zirconium

ALUMINUM, TITANIUM, ZIRCONIUM OXIDESUsed for Endosteal root form, plate form implants

Have clear white cream or light grey color so used for anterior root formMinimal biodegradationHigh modulus of elasticityLow fracture resistanceExhibit direct interface with bone

DISADVANTAGES

Exposure to steam sterilization results in measurable decrease in strength of some ceramics. So dry heat sterilization is recommended.

Scratches or notches may induce fracture initiating sites.

Although initial testing showed adequate mechanical strengths, long term clinical results clearly demonstrate a functional design and material related limitations.

BIOACTIVE AND BIODEGRADABLE CERAMICSCalcium Phosphate Ceramics

The compositions was relatively similar to bone Ca5(PO4)3OH

Color similar to bone.

Shows good bonding with bone so it can be used when structural support is required under high magnitude loading.Mixtures with collagen, active organic compounds as bone morphogenetic proteins and with drugs have increased the range of its applications.

It is used as a coating over the metallic implants.

Modulus of elasticity is very near to bone.

DISADVANTAGES

Low mechanical tensile and shear strengths under fatigue loading.

Low attachment strength on some substrates.

Variable solubility depending on the product and their clinical applications.HYDROXYAPATITEWhen the calcium and phosphorus in the ratio of 1.5 to 1.7 are sintered in water containing atmosphere at 1200C to 1300C a crystallographic end product will be obtained that is Hydroxyapatite.

This has osseoconductive effect when comes in contact with bone.Hydroxyapatite is non porous with angular or spherical shape particles that are examples of crystalline high pure Hydroxyapatite.

Their compressive strength is 500 Mpa and tensile strength is 50-70 Mpa.

PROPERTIES OF BIOACTIVE CERAMICS

Dense polycrystalline ceramics with small crystallites have higher mechanical strength.

These ceramics are widely used as coatings on metallic implant substrates.Calcium phosphate ceramics have become a routine use by plasma spray technique.

This technique increases the surface area which in turn increases the osseointegration.

Density, Conductivity and Solubility

Density of the material increases as the percentage of crystallinity increases.

As the density / crystallinity increases the solubility decreases.

The solubility also depends on the surface area.The amorphous products are more soluble because they have less organized atomic structure.

These are susceptible to enzyme or cell mediated breakdown in the same way that of living bone.

These are non conductors of heat and electricity.

The Ceramic implant surface responds to the local pH changes by releasing Na, Ca, P and Si ions in exchange for H2 ions.

Si reacts with O2 to form Silica gel. As the concentration of phosphorus and calcium increases at the surface they combine to form calcium phosphate rich layer and the collagen fibers become incorporated into it.TISSUE RESPONSEThis way the functional integration with bone occurs with the help of natural bone cementing substance so the bond formed is strong.

CARBON AND CARBON SILICON COMPOUNDSExtensive applications for cardiovascular devices.

Excellent Biocompatibility profiles and Moduli of elasticity close to that of bone.

ADVANTAGES

Tissue attachment.

Thermal and electrical insulation.

Color control.

Provides opportunities for attachment of active biomolecules.LIMITATIONS

Poor Mechanical strength.

Time dependent changes in the physical characteristics.

Biodegradation could adversely affect Stability.

Minimal resistance to scratching or scraping.

POLYMERS AND COMPOSITESThese can be designed to match tissue properties and can be fabricated at relatively low cost.

These include polytetraflouroethylene (PTFE), polyethyleneterephthalate (PET), polymethylmethacrylate (PMMA), polypropylene (PP), polysulfone (PSF), silicon rubber (SR)

PROPERTIES

Polymers have low strengths and elastic moduli and higher elongation to fracture compared with other class of biomaterials.

Relatively resistant to biodegradation compared to bone.Most uses have been for internal force distribution connectors intended to better simulate biomechanical conditions for normal tooth functions.

Some are porous where as others are constituted as solid structural forms.

DISADVANTAGES

Sensitive to sterilization and handling techniques.

Display Electrostatic surface properties. Tend to gather dust or other particulate if exposed to semi clean oral environments.

Cleaning the contaminated porous polymers is not possible without a laboratory environment.

So the talc on the gloves or contact with towel or gauze pad or any such contamination must be avoided.

IMPLANT SURFACE MODIFICATIONS TYPES OF SURFACE ROUGHNESS1) Macrosurface Roughness.SURFACE TOPOGRAPHYScrew

Hollow basket

Core vent2)Microsurface roughness.ABRADED TiO2Al203ACID ETCHEDHClH2SO4

COATINGTPSHASurface topography relates to the degree of roughness of the surface and the orientation of surface irregularities.

ADVANTAGES OF INCREASED SURFACE ROUGHNESS1) Increased surface areas of the implant adjacent to bone.

2) Improved cell attachment to the bone.

3) Increased bone present at implant surface. 4) Increased biomechanical interaction of the implant with bone.THREADS Threads are used to maximize initial contact, initial stability, increase implant surface area and also favor the dissipation of interfacial stress. 1) Thread depth 2) Thread thickness 3) Thread Pitch 4) Thread face angle 5) Thread Helix angle

Wennerberg and co-workers

Smooth - to describe abutments, Minimally rough (0.5 to 1 m), Intermediately rough (1 to 2 m), and

Rough (2 to 3 m) be used (apart from porous surfaces for implanted surfaces).

SURFACE TOPOGRAPHY Literature reports, based on the average surface roughness surfaces with 1 m are considered smooth, and those with > 1 m are described as rough.

Blasting with particles of various diameters is one of the frequently used method of surface alteration. In this approach, the implant surface is bombarded with particles of aluminum oxide (Al2O3) or titanium oxide (TiO2), and by abrasion, a rough surface is produced with irregular pits and depressions. BLASTINGRoughness depends on particle size, time of blasting, pressure, and distance from the source of particles to the implant surface. Blasting a smooth Ti surface with Al2 O3 particles of 25 m, 75 m, or 250 m produces surfaces with roughness values of 1.16 to 1.20, 1.43, and 1.94 to 2.20, respectively.

SAND BLASTED IMPLANTSAND BLASTED AND ACID ETCHED IMPLANT

LASER INDUCED SURFACE ROUGHENING Eximer laser Used to create roughnessRegularly oriented surface roughness configuration compared to TPS coating and sandblasting SEM x 300SEM x 300SEM x 70Chemical etching is another process by which surface roughness can be increased. The metallic implant is immersed into an acidic solution, which erodes its surface, creating pits of specific dimensions and shape. Concentration of the acidic solution, time, and temperature are factors determining the result of chemical attack and microstructure of the surface. CHEMICAL ETCHING IRREGULAR SURFACE MORPHOLOGIES

Sandblasted specimen

Specimen acid etched for 1 min.

Specimen acid etched for 5 mins.

Specimen acid etched for 10 mins.Recently, a new surface was introduced that was sandblasted with large grit and acid-etched (SLA, Straumann). This surface is produced by a large grit (250 to 500 m) blasting process, followed by etching with hydrochloric-sulfuric acid. The average ra for the acid-etched surface is 1.3 m, and the sandblasted and acid-etched surface, ra=2.0 m. SANDBLASTED AND ACID ETCHED (SLA)

Sand blasting Acid etchThe objective Sand blasting surface roughness (substractive method)Acid etching cleaning Wennerberg et.al. 1996: superior bone fixation and bone adaptation

SEM 1000XSEM 7000XAcid etching with NaOH, Aqueous Nitric acid, hydrofluoric acid. Decrease in contact angle by 100 - better cell attachment.Increase in osseointegration by removal of aluminium particles (cleaning).

Lima YG et al (2000), Orsini Z et al (2000). Porous sintered surfaces are produced when spherical powders of metallic or ceramic material becomes a coherent mass with the metallic core of the implant body. Lack of sharp edges is what distinguishes these from rough surfaces. Porous surfaces are characterized by pore size, pore shape, pore volume, and pore depth, which are affected by the size of spherical particles and the temperature and pressure conditions of the sintering chamber.

POROUS

POROUS SURFACE: ADVANTAGES1. A secure, 3-D interlocking interface with bone.2. Predictable and minimal crestal bone remodelling.

3. Greater surgical options with shorter implant lengths.4. Shorter initial healing times5. Porous coating implants provide the space, volume for cell migration and attachment, thus support contact osteogenesis.

SURFACE OF A POROUS TITANIUM ALLOY IMPLANT

FIBROBLASTS CULTURED FOR 24 HOURS ON THE SURFACE OF A POROUS TITANIUM ALLOY IMPLANT. TITANIUM PLASMA SPRAY

Titanium Plasma Sprayed Coating (TPS)

Steinemann(1988) Tetsch(1991)-----6-10 times increase surface area. Roughness Depth profile of about 15m

SURFACE OF A TITANIUM PLASMA-SPRAYED IMPLANT. (SEM, MAGNIFICATION 5,000 X).

HYDROXYAPATITE COATINGS

HA coated implant bioactive surface structure more rapid osseous healing comparison with smooth surface implant. Increased initial stability Can be Indicated

Type IV bone .Fresh extraction sites. Newly grafted sites. SEM 100XHydroxyapatite [Ca10(PO4)6OH]2 coating was brought to the dental profession by DeGrootADVANTAGES OF HA-COATINGS HA coating can lower the corrosion rate of the same substrate alloys. 2. HA coatings has been credited with enabling to obtain improved bone to implant attachment compared with machined surface. 3. The bone adjacent to the implant has been reported to be better organized than with other implant materials and with a higher degree of mineralization. CERAMIC AND CERAMIC COATED IMPLANTS Ceramic materials are used to coat metallic implants to produce an ionic ceramic surface, which is thermodynamically stable and hydrophilic, thereby producing a high strength attachment to bone and surrounding tissues. These ceramic can either be plasma sprayed or coated on to the metal implant to produce bio-active surface. Aluminum oxide (Al2O3) is used as the gold standard for ceramic implants because of its inertness with no evidence of ion release or immune reaction in vivo. Zirconia (ZrO2) has also demonstrated a high degree of inertness.

OTHER SURFACE MODIFICATIONSSurface modification methods include controlled chemical reactions with nitrogen or other elements or surface ion implantation procedures. The reaction of nitrogen with titanium alloys at elevated temperatures results in titanium nitride compounds being formed along the surface. Electrochemically, the titanium nitrides are similar to the oxides (TiO2), and no adverse electrochemical behavior has been noted if the nitride is lost regionally.

The titanium substrate reoxidizes when the surface layer of nitride is removed.

Doped surfaces that contain various types of bone growth factors or other bone-stimulating agents that may prove advantageous in compromised bone beds. However, at present clinical documentation of the efficacy of such surfaces is lacking.DOPED SURFACESPhysical characteristic:Physical characteristic refers to the factors such as surface energy and charge. Hypothesis : A surface with high energy high affinity for adsorption show stronger osseointegration.

Baier RE (1986) Glow discharge (plasma cleaning) results in high surface energy as well as the implant sterilization, being conductive to tissue integration. Charge affects the hydrophilic and hydrophobic characteristic of the surface.

A hydrophilic / easily wettable implant surface : Increases a initial phase of wound healing.

Increase surface energy would disappear immediately after implant placement.

REFERENCESOsseointegration in clinical dentistry Branemark, Zarb, Albrektsson Osseointegration and occlusal rehabilitation Sumiya Hobo Contemporary Implant Dentistry Carl E.Misch Endosseous implants for Maxillofacial reconstruction Block and Kent Implants in Dentistry Block and Kent Dental and Maxillofacial Implantology John. A. Hobkrik, Roger Watson Principles and practice of implant dentistry -Charles M Weiss, Adam Weiss.

Atlas of Oral implantology - A Norman Cranin.

Sciences of dental materials - Anusavice.

The BRANEMARK system of oral reconstruction - A clinical atlas.Endosseous Implant : Scientific and Clinical Aspects George Watzak

Osseointegration in craniofacial reconstruction- T. Albrektssson.

Osseointegration in dentistry : an introduction : Philip Worthington, Brein. R. Lang, W.E. Lavelle.

Dental Clinics Of North America 1986 ; 30 (1) 25-47.

Dental Clinics Of North America 1992 ; 36, 1-17.

Implant Materials, Designs.and Surface Topographies :Their effect on Osseointegration.A Literature ReviewNikitas Sykaras et.al. IJOMI 2000 (15) 675-690. Schroeder et al.,(1981).The reactions of bone, connective tissue, and epithelium to endosteal implants with titanium-sprayed surfaces. Journal of Maxillofacial Surgery 9,15-25.

Zarb & Symington (1983).Osseointegrated dental implants: preliminary report on a replication study. Journal of prosthetic dentistry 50,271-279.

Albrektsson et al.,(1986).The long-term efficacy of currently used dental implants: a review and proposed criteria for success. International journal of Oral and Maxillofacial Implants 1,11-25.

Johansson & Albrektsson. (1987) Integration of screw implants in the rabbit. A 1- year follow-up of removal of titanium implants. International journal of 0ral and Maxillofacial Implants 2,69-75. Albrektsson & Sennerby.(1991) State of the art in Oral implants. Journal of clinical periodontology 18,474-481.

Wennerberg & Albrektsson.(1993) Design and Surface Characteristics of 13 commercially available oral implant systems. International Journal of Oral and Maxillofacial Implants 8,622-23

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