Osseointegration of dental implants

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Information about Osseointegration of dental implants

Published on March 7, 2014

Author: indiandentalacademy



INTRODUCTION Osseointegration in clinical dentistry depends on an understanding of the healing & reparative capacities of hard and soft tissues. Its objective is a predictable tissue response to the placement of tooth root analogues. Such a response must be a highly differentiated one, and one that becomes organized according to functional demands. The word osseointegration consists of “OS” the Latin word for bone and “Integration” derived from the Latin words meaning the state of being combine into a complete whole. In 1952, Dr. Per – Ingvar Branemark, M.D., Ph.D. had studied the concept of tissue integrated prostheses at the Laboratory of Vital Microscopy at the University of Lund, and subsequently at the Laboratory for Experimental Biology at the University of Goteborg.15 The basic aim has been to define limits for clinical implantation procedures that will allow bone and marrow tissues to heal fully and remain as such, rather than heal as a low differentiated scar tissue with unpredictable sequelae. The studies involved analyses on tissue injury and repair in diverse sites in different animals, with particular reference to micro vascular structure and function. Special emphasis was placed on analyzing the disturbances caused in the intravascular rheology of blood by means of series of different methodological approaches. 1

The notion of permanently anchoring a prosthesis in bone through the skin or mucosa has fascinated clinical researchers over the years. The anticipated (and encountered) biomechanical difficulties have been formidable ones, since the clinical remit is to almost simultaneously control atleast four factors.63 1. The selection of an acceptable biocompatible material and a correct implant design. 2. The preparation of a host bone site, which ensures a predictably favorable healing response, one that can cope with subsequent stress loading. 3. The design and fabrication of a prosthesis that does not undermine that integrity of the acquired bony attachment. 4. The provision of a sealing mechanism at the implant skin or implant – mucosal junction. 2


REVIEW OF LITERATURE Reishick MH, Benson D72 reported a study to evaluate the response of monkey tissue to coatings of porous alumina that were applied to chromecobalt subperiosteal denture implants. Initial results showed evidence to indicate that a direct attachment occurs to the alumina surface i.e. the tissue surrounding the removed alumina implant was tenaciously attached. Reisbick MH, Benson D and Furstman LL72 reported that permanent fixation of subperiosteal implants occurs by dense, collagenase fibrous tissue encapsulation around the frame work. An epithelial cuff may form around the implants, similar to that occurs around the natural tooth. Porosity in ceramic materials has been found to allow in growth of soft tissues. The impervious ceramics implanted in soft tissues were found to be encased by the tissues. The pilot study did by the authors investigated the effect of aluminacoated subperiosteal implants indicates a direct attachment occurs to the alumina surface, while a chrome-cobalt implant was retrieved readily with no tissue adherence. The histologic findings indicate that bond formed at the junction of the tissue attachment to the implant is the prevention of downward growth of oral epithelium. 4

Richards LW, Gourley IM, cordy DR73 conducted a pilot study to obtain basic data regarding tissue response to the implants, and to study the problems of mobility and possible infection. The results of the study showed that Ti endosteal implants, were passively accepted. There was no inflammatory response to the implants and osteoclastic activity about the blades was normal. There is no abnormal epithelial migration about the struts. Epithelium was different to the metal near the neck of the implants. A dense connective tissue generally surrounded the implants, especially thick near the gingival surface. Shpiro P, Binderman I81 reported that increased distribution of stresses on bone is obtained with the blade-type endosteal implants in comparison with the root form implants and it was demonstrated on the basis of mathematical evaluation. Pressure is defined as force acting per unit area. Greater the surface area of contact with the bone, the pressure directed by implant on bone is less. The amount of resulting pressure differs from shape of implants and bone-to-implant contact area. A mathematical evaluation of the shape of implants indicates that with the force (F) of the distance from the centre of rotation to point of force application (L) being equal and with equal surface areas (S). The resulting pressure will be less in an implant with a larger mean distance of the support 5

from the centre of rotation. So, blade type implants results in less pressure on bone as compared to the root resembling forms. Kydd WL, Oaly CH47 reported the nature of shear bond strength that develops between alveolar bone and Ti hollow implants. The implants were placed in edentulous region of the mandibles of dogs. They were conical in shape with circumferential grooves, 5 months later implants were rotated. The nature of response to torque Vs rotation indicates no actual adhesion between the bones of the Ti surface, other than frictional interaction. The contact pressure at the interface was produced by the action of the bone growing into the grooves. The stresses developed by the growing bone on contact pressure affect the pattern of bone laid resulting in cessation of growth. Roy L, Raymond J, Grenable DE14 reported a patient who had died with a 12 year subperiosteal implant denture, was studied and results of the examination of the mandible after the death revealed absence of significant damage to the approximating and adjacent tissues histologically. Thus well made subperiosteal implants CD may offer selected patients many year of denture efficiency of comfort unobtainable by other methods. Albrektsson T4,6,7 reported that the insertion of any given foreign material in a bone site is a multifacet problem that involves the implant, 6

adjacent tissue of the interface between implant and tissue. The interfacial behavior between implant and tissue is determined not only by the nature of implants (its chemical composition, surface conditions and mechanical properties) and the state of the tissue per se, but also by the technique of loading the implant. A connective tissue anchorage of dental implants is an indication of failure. The achievement of a solid bone anchorage for a dental implant can lead to predictable long-term clinical results. This appears to depend on the control of the surgical trauma, the condition of tissue bed, implant loading conditions of the biocompatibility of the material used. In this manner a meticulous clinical approach can ensure a lasting and successful bone integration of an extracorporeal substitute. Kasemo B40 reported the most important boundary conditions, which relates to the future success or failure of implant procedures provided by the surface properties of the implant. The implants are prepared first by careful, controlled mechanical shaping of pure titanium raw material. The air exposure forms an oxide layer of 100A with in a millisecond and 50-1000A within a minute. Then additional growth of oxide layer is formed by cleaning and autoclaving. The chemical properties of the interface chemistry are determined by the oxide layer and not by the metal itself. Ti implants are regarded as oxide ceramics. 7

Two types of chemical bonds may be established between biomolecules and implant surface, these are weak, long-range Vander Waals bonding and strong, short-range covalent and ionic bonds. The contributing factors to successful results which prove titanium as implant material may be combination of the chemical inertness (of its oxide), and the high dielectric constant of the oxide. Eriksson AR, Albrektsson T32 reported a study using a thermal chamber to investigate and analyze hard tissue changes after heating in the range of 470 to 500C. The results of this study showed that bone tissue is sensitive to heating at the level of 470C, and even greater injury after heating to 53 0c for 1 min. Heating to temperature of 600 or more resulted in a permanent cessation of blood flow and a bone tissue necrosis which showed no signs of repair over periods of 100 days or more. Rams T, Keyes P71 reported a study to investigate the sub gingival microbiologic flora associated with gingival tissue protruding implants using a direct phase contrast microscopy. The results showed a significantly higher levels of spirochetes and accumulated crevicular PMN‟s found in sub gingival plaque of the failed implants due to >10mm pocket formation on implants with 3-5mm pockets 8

showed higher proportions of nonmotile coccoid cells and lower levels of spirochetes of crevicular leukocyte. McKinney RV, Koth DL61 reported that endosseous dental implants function in 2 separate environments, internal environment of bone and soft tissue of the external environment of oral cavity. Based on word origin and definition, the terms permucosa, perimucosal and transmucosal can all be correctly used. A study of definitions suggests that the most descriptive term is per-perimucosal seal, where permucosal designates the vertical orientation of the implant penetration through the oral mucosa and perimucosa designates the horizontal or circumferential seal of the mucosa to the biomaterial. Gould TRL, Westbury L36 reported a study to determine the behavior of epithelium in vitro is similar to its attachment behavior in vivo by the use of small sections of Ti –coated implants inserted in human gingiva. On examination of thin sections showed epithelial cells attached to Ti in a manner similar to that observed in vitro and similar to the way in vivo, with the formation of hemidesmosomes of basal lamina. The ability of the oral epithelium to form such an attachment with the implant is the crucial factor in the determination of clinical success or failure. 9

Doundoulakis JH29 reported a study by measuring and comparing the effects of 5 sterilization methods on the Ti surface of the implant. The 5 sterilization methods are (1) endodontic glass bead sterilizer (2) autoclave conventional (3) Dry heat (4) UV radiation (5) Radio-frequency glow discharge treatment. Results showed that sterilization of low surface energy materials by radio frequency glow discharge treatment of may be recommended for obtaining a high surface energy character that correlates with induced cell adhesion of implant fixation. Kay JF, Golec TS, Riley RL43 reported that subperiosteal dental implant designs from inception share a basic design feature. The distribution of forces over a large foundation region by connected struts. The simplified strut designs used presently are modifications of former elaborate lattice designs. The design of prosthesis must allow load transfer from the denture to the post and to the strut structure without stress concentration or to cause metal failure by static / cyclic fatigue mechanism. 10

HA coatings applied to the struts of subperiosteal implants can positively affect the implant, by creating a faster and stronger attachment to the bone. And make metallic subperiosteal implant more biocompatible. Lundgren D. Bergendal T53 reported a study to investigate the pattern of occlusal forces in dentitions restored with osseointegrated implant supporting FPD‟s in the lower jaw and CD in upper jaws. The occlusal force pattern during chewing and biting showed chewing pattern was comparable to that reported for subjects which complete healthy dentitions or with tooth supported cross-arch FPD. The posterior cantilever segment in the present FPD cantilever prosthesis occluding which CD exhibited greater local forces when compared to occluding with natural teeth. Lindquist LW, Carlsson GE50 reported a study by analyzing bone resorption around fixtures in association with treatment of the edentulous mandible with fixed prosthesis of tissue-integrated implants, measured by means of stereoscopic intra oral radiography. The results of the study showed 0.5mm bone loss during first year and thereafter 0.06-0.08mm annually for an observation period of 6 years. More bone was lost around the most posterior ones. 11

Nikai H, Tsuru H78 reported a study to compare the structural differences of bone-implant interface after nontapped and tapped insertions for submerged endosseous implants using Tio2 coated and non-coated screw type Ti-alloy. Results showed that all implants by tapping insertion were healed with direct bone apposition whereas implants by nontapping insertion revealed some degrees of fibrous connective tissue intervention between bone and implant. No difference was found between Tio2 coated and non-coated materials. Koth DL, Steflick DE, Davis QB46 reported 5-year clinical results of a single crystal aluminum oxide endosteal dental implant and evaluated the clinical index parameters developed. Statistical analyses were performed on the quantifiable clinical parameters. On the basis of clinical observation and statistical analysis, the single crystal sapphire endosteal dental implant met the clinical standards and considered clinically acceptable. Statistically 77.7% of all implants placed and 95.5% of implants used as prostheses abutment were providing satisfactory service 5 years after insertion. Mentag PJ, Kosinski TF62 reported fabrication of a maxillary obturator prosthesis using the intra mobile cylinder (IMZ) dental implant system. 12

The obturator prosthesis establishes oro-nasal separation and restores missing teeth to increase chewing efficiency and an esthetic appearance and further speech articulation of resonance. The dental implant placement and the resultant increased stability of retention on the prosthesis enhanced the overall function of psycho social satisfaction of the patient. Lum LB, Beirne OR, Curtis TA51 reported a study by directly comparing the implant-bone interface of loaded and unloaded core-vent of Biotes implants placed in the same group of non-human primate. The results of this study showed that both core-vents of biotes implants adhered according to the requirements described by Branemark to achieve osseointegration when compared to the response of bone to the unloaded and occlusally loaded on non human perimeter model at light microscopic level after 5 months of occlusal loading. Campagni WV, McGlumphy EA, Peterson LJ19 reported a study to compare the difference in the stress patterns generated in photo elastic plastic by an IMZ implant with a resilient or a rigid internal element. Under a standardized cantilever load, the stress patterns were photographed in the filed of a circular polariscope. 13

The static load conditions of the model demonstrated no statistical difference between the area of stress pattern generated by an IMZ implant with or without a resilient internal element. Rieger MR, Kinzel GL, Brose MO76 reported a study to compare the use of bioactive coatings on 3 endosseous implants by using finite element analysis to determine whether bone-bonding or bone adaptation was biomechanically more beneficial. Results showed that although a bonded interface between an implant of its host tissues may be biochemically beneficial bone bonding, may not be biomechanically beneficial to the implant or the surrounding bone. Tuminelli FJ88 reported a clinical report of a technique using free vascularized bone grafts with the placement of Ti implants. The successful application of micro vascular surgery, coupled with grafting techniques of the osseointegrated Ti implants enables the author to achieve improved reconstructive results for his patient who has experienced reaction of the mandible due to cancer. The reports showed superior rehabilitation results, enables reconstructive team to restore functional esthetic levels, previously not possible after radical surgery. 14

Richter EJ74 reported that common goal for all the implant systems are to achieve a stable anchorage of implant body to bone tissue by contact osteogenesis. The implants with definite resilience integrated in the implant design can diminish to vertical, horizontal electric stresses on bone to avoid bending of the implant resulting form the elasticity of bone and to achieve a mobility that is almost equal to that of the natural teeth. Denissen HW, Kalk W, Hoof AVD27 reported an 11 year clinical research study with both unloaded bulk HA implants and loaded HA – coated Ti implants. The results indicate that the design of bulk HA and time of implantation should be changed because former causes degeneration and subsequent permucosal exposure of implant occurred while latter causes difficulty in closing the extraction wounds. Further cement fractures occasionally occurred resulted in plasma spray coatings of HA on Ti cores. Hence, this long-term research indicates that cylindrical HA implants are reliable device as natural tooth substitutes that bond directly to bone instead being simply osseointegrated. 15

Rieger MR, Brose MO, Adams WK75 reported a study to evaluate 3 endosseous post-type implant geometries: a serrated solid with 2 0 taper of a rectangular cross section, a cylindrical screw type solid of a finned solid with a 109‟ taper circular cross section. Examination of contour plots showed that increasing the material stiffness transmitted more occlusal load to apical bone for all geometry. There plots further suggests that an implanted material can be too stiff as the punching stress increases at the apex and the implants elastic behavior is not the only governing factor but the implants geometry seems to be the determining factor in properly distributing stresses from implant to the bone. Schewiger JW79 reported a study to determine whether Ti implants can be safely placed and osseointegration achieved in irradiated bone of beagle dogs. The beagle dogs were irradiated previously allowed healing and Ti implants place after 9 months and allowed to heal an additional 51/2 months for osseointegration. The obtained block specimens showed that about half of the specimens achieved osseointegration. McCartney JW58 reported ear prosthesis retained with magnets by attaching it to an implant – retained magnetic alloy. 16

The implants were placed in temporal bone to retain attachments for ear prosthesis. A screw retained magnetic allow casting was used to retain an acrylic resin magnet keeper to which silicone ear prosthesis was attached. The keeper provided vertical support for the prostheses and facilitated orientation for prosthesis insertion stability and retention was provided without the use of adhesives. Colley DR, Dellen AFV, Windeler AS et al24 reported that calcium phosphate of hydroxyl apatite is example of CPC materials that bond directly or chemically to bone. The ability to bond chemically to bone without a mechanical inter lock is an important distinction between CPC and titanium implants. The author used a method by applying hydroxyl apatite to implant surfaces and noted the thickness and physical properties of such coating affecting the surface of implants. Histological analysis of bone implant interface showed that coated implants had greater direct bone contact compared with noncoated implants. The implant sputter coated from a hydroxyapatite target will accentuate the healing of bone at the implant interface by forming an amorphous layer of CPC coating. This coating resulted in higher osseointegration rates and greater pull-out strengths. 17

Chavez H, Ortman LF22 reported that most of the implant literature suggests that successful dental implants which are immobile of any detected mobility indicate implant failure. Clinically successful implants are not immobile, but have a range mobility that is attributed primarily to the damping like character of the bon/implant interface. The range of mobility with a PTV of -6 to +2. In addition implants that support over dentures were significantly less mobile than implants that support fixed prostheses. Sagara M, Akagawa Y77 reported that the initial stages of bone healing with Ti alloy implants were compared clinically and histologically of beagle dogs for 3 groups namely Group 1 - Unloaded one-stage Group 2 - loaded one-stage Group 3 - unloaded two stage. Significant crestal bone loss in group 2 showed poor bone apposition to the bottom of the threads in the upper portion of the implant, but new bone growth was seen in group 1 to group 3. These differences could be attributed to the effect of early occlusal loading on the implant during initial bone healing. 18

Akagawa Y, Tsuru H2 reported that the clinical and histological evaluations of partially stabilized zirconia endosseous implants under unloaded and early loaded conditions in 4 beagle dogs showed loss of crestal bone height around loaded implants. The loaded new zirconia implants were not encapsulated by fibrous connective tissue as shown by the approximately 70% of the bone contact ratio, and the implants were not mobile. Lill W, Thornton B48 reported that long-term success of osseointegrated implants can be measured if the results of recover examinations are systemically documented. The optimal method is the life table analysis, which is a statistical method designed by Kaplan – mear and cutler - ederer in 1958. The author conducted the study to calculate the success potential of 683 implants (IMZ and Branemark). The results showed that loss of Branemark implants during the healing period was greater than for IMZ implants. IMZ implants were the most successful in partially edentulous mandibular Branemark system was most successful in totally edentulous. Artzi Z Tal H, Moses O, et al10 reported that success/ failure of implant depend partially on the ability of the mucosa to form a seal around the implant and the nature of the mucosa surrounding it. 19

Masticatory mucosa with stand stresses imposed on them much better than the vestibular mucosa. Further it helps to maintain adequate oral hygiene; the author discusses various mucogingival surgical techniques that can be employed during surgical phase, during prosthetic phase and after prosthetic phase. Lack of masticatory mucosa and presence of alveolar mucosa are often associated with plaque, resulting in inflammation and subsequent peri-implant destruction. Yan J, Xiang W, Baolin L et al90 reported a study to establish a method for combining bovine BMP with Ti and evaluated the early bone formation induced by the bBMP/ Ti complex in edentulous dogs. Result showed newly formed bone within the interface in two weeks and complete osseointegration occurs in four weeks. Bone formed with the apical opening of the implant within one month. So this study indicates that osseointegration can be enhanced by bBMP bone induction. The apical opening may provide a site in which osteogenesis can occur with protection from implant stress before and after loading. Charkaur HG, El waked MT21 reported a study on stress analysis comparing the ISIS implant with a stress-eliminating space of a rigid stress vent implant that are connected to the same abutment and also evaluated the new TPS implant modification, which contained a resilient material on top of the implant, with and without resilient material, with the same method. 20

The results showed that the resilient implant ISIS system showed less stress than a rigid screw-vent implant when connected to a natural abutment. The modified resilient implant head reduced stresses transferred to the implant and its head distributed load between the implant and the abutment. Nelson SK, Schuster GS66 conducted a study to evaluate the influence of Ti Surface oxide composition and surface roughness on P. gingivalis and E. Coli LPS affinity for CP1 and Grade -5 specimens. The results of this study showed that different LPS molecular structures did not influence LPS affinity for Cp 1 and Grade 5 Ti did not result in different LPS affinity and surface roughness did not influence LPS affinity. Bryant RS, Zarb GA18 conducted a study which aimed to test the hypothesis that there is no difference between older and younger adults in osseointegration. Osseointegration involves an osseous healing response that may me compromised by aging. The results of this study answers three points that First, the age alone should not be used to exclude patients from being given oral implants. Second osseointegrated implants can be maintained as patient‟s age, even in older patients as they become increasingly debilitated. 21

Finally, it lends itself diversity of prosthodontic application well in both age groups. Cooper LF26 reported that Osseointegration involves both the formation and the maintenance of bone at implant surfaces, and to identify cellular and molecular determinants of bone formation that may be used in clinical attempts to enhance or expand the application of endosseous implants for dental and craniofacial prosthetics. Osseointegration depends on the activity of osteoblastic cells to form bone and the lifelong maintenance of this bony support. Although changes in implant design, surgical technique, and restorative method may be improved with regard to osseous responses, the fundamental aspects of bone cell biology and osseous physiology must be considered as a source for additional clues of improving implant success. The cellular basis for bone formation and maintenance of bone mass should be considered in any future synergistic combination of tissue engineering principles and biointegration of alloplastic materials. The regulation of cellular activity should be the guide to the development of novel strategies for improving tissue integration of dental prostheses. Eckert SE, Wollan PC31 reported a retrospective study describing the results for implant survival, implant fracture rate, prosthetic complications, and design changes that may impact these results. 22

Implant survival in this study was independent of anatomic location of implants. Virtually all clinical performance factors were improved by design changes in implant restorative components that were brought to market in early 1991. Taylor TD86 reported that comparing any surgical or prosthodontic procedure, osseointegration has offered the greatest improvements are quality of life for patients who suffer with the effects of an edentulous condition. Results have been dramatic both functionally and from the aspect of patient satisfaction. Author critically analyzes the existing literature relative to prosthodontic problems and complications frequency of complication versus the perceived potential for complications, including implant failure, prosthesis misfit, component fracture, and screw loosening. Masuda T, Yliheikkila PK, Felton DA, et al57 reported that the clinical success of endosseous implants is associated with the formation and maintenance of bone at implant surfaces. Histologic analyses have indicated that bone formation at a variety of implant surfaces is a continuous process that supports long-term functional integration. Based on in vivo observations several generalizations have been derived regarding the nature of the interface. Experimental descriptions indicate that the implant-bone interface may be characterized in spatial and temporal terms as discontinuous. Biomechanical tests of the bone associations with implants demonstrate that the chemical composition and the surface topography of the implant influence 23

the rate and extent of bone formation at implant surfaces. The precise character and functional attributes of this interface are the focus of this investigation. Many technical difficulties are associated with its structural and chemical characterization in vivo. Despite the technically difficult nature of this type of analysis and the limitations of current histologic examinations and biomechanical tests, in vivo models of osseointegration are necessary experimental tools for the continued empirical development of clinical implant application. Kawahara H, Kawahara D, Takashima Y, et al41 reported the clinical measurements on gingival indices and morphologic observations were performed to study and verify the defending mechanism of gingival soft tissue against foreign invasions from the perspective of epithelial adhesion/attachment to implant surfaces in the monkey mandible. The following zones were observed using scanning electron microscope (1) plaque zone, suggesting susceptibility of the gingival tissue to bacterial invasion.( 2) nude zone, demonstrating indirect adhesion of epithelial cells to the implant surface through the mucous epithelial cells at the cell-implant interface as compared to cell-cell bonding within the epithelial cell layer. This study suggested that epithelial cell attachment/adhesion may play a dominant role in retaining the successful condition of a dental implant. Cooper LF, Masuada T, Yliheikkila P et al25 reviewed that the appropriate use of cell culture to evaluate substrate effects on osteoblast 24

behavior during the process of osseointegration has been considered in the context of existing reports. The interactions of osteoblasts with different substrates can be measured in terms of cytotoxicity, attachment, proliferation, and differentiation. The osteoblast culture systems that produce an osteoblast matrix opposing implant material substrates provide one model for evaluating the implant-bone interface. Alternations in osteoblast behavior at different culture substrates may reflect clinical determinants of bone formation and there substrates in vivo; however, cell responses in vitro have not been compared or correlated with in vivo outcomes. Legitimate interpretations of in vitro experiments are discussed in terms of practical, technical, and biologic limitations presented by the cell culture approach. Cell culture provides access to molecular and cellular information that fosters Nano structural engineering approaches to implant design and significant hypotheses to be tested in vivo. In this way, cell culture offers unique insights into the process and phenomenon of osseointegration. Fujimoto T, Ueda M84 reported a study to clarify the effects of steroid administration on the osseointegration of Ti implants. The results of the study revealed that osseointegration of Ti implants in the mandible as measured by torque force is not affected as strongly by steroid administration as is osseointegration in the skeletal bone. 25

Kawahara H, Takashima Y, Ong JL42 reported a study to investigate the effect of plaque extracts on the in vitro response of epithelial-like cells and the fibroblastic cells to Ti surface. The result of growth rate assay, cell morphology assay, and adhesive strength of cells shows that plaque extracts observed to have. Huja SS, Katona TR39 reported a study using finite element methods to isolate the effects of callus formation of bonding on the mechanical environment in implant-supporting bone. Healing response subsequent to implant placement is characterized by formation of calluses, rapid remodeling of bone adjacent to the implant, and an increase in interfacial bond strength. The results show the importance of the stabilizing roles provided by the callus and development of bond during the etiological phases of bone healing. Devlin H, Horner H, Ledgerton D28 the success rate of implant osseointegration is dependent on many factors such as bone mineral density, volume and vascularity of bone, implant design, ridge shape, and patient selection criteria. The authors conducted the study to examine whether a technique to measure differences in bone mineral density in the maxilla and 26

mandible might be useful to predict the likelihood of successful osseointegration. Bone densitometry of the jaws was performed with a densitometer, and bone mineral density was calculated at three regions of the maxilla and one site in the mandibular body. The results shows significant differences were found between the mean bone mineral densities of each site when compared with the three other locations. The mean bone mineral density for the mandible was twice that of the anterior maxilla. Both were significantly greater than the bone mineral density of the posterior maxilla including the hared palate. The bone mineral densities at the three maxillary sites were all highly correlated. It is concluded that the posterior maxilla had the lowest bone mineral density and in certain circumstances before implant insertion, bone augmentation, or guided tissue regeneration may be advisable to improve the rate of osseointegration. Because the radiation dose is low, dual energy x-ray absorptiometry may be a useful noninvasive technique for determining the bone mineral density before implant insertion. Almog DM, Sanchez R8 reported that the success of dental implant treatment relies on a well-developed treatment plan approach. Historically, implant placement was guided mainly by residual bone height and width, at times compromising prosthetic needs. 27

Author analyzed the amount of deviation between planned prosthetic trajectory and residual bone trajectory in and residual bone trajectory in different areas of the maxillary and mandibular dental arches, by using a tomographic survey in conjunction with imaging/surgical guides. Discrepancies between the planned prosthetic and the residual bone trajectories were greater in the mandibular molar area. This site was statistically different from other site groups. Statistically, all other site groups were not significantly different. Chang YL, Stanford CM, Keller JC, et al20 reported that when Hydroxyapatite (HA) used a coating for implants can exhibit varying levels of interaction with the biologic environment. The crystallinity of the HA-based coating has been shown to control the rate of dissolution and appears to play a role initial cellular interaction with the implant surfaces. An osteoblastic cell attachment assay was employed to examine the cell attachment to untreated and pretreated (pH5.21, 24 hours) titanium and HA coatings of less (50%) medium (75%) and high (90%) crystallinity. A slightly higher percentage of cell attachment (%CA) was found on untreated and pretreated HA surface as compared to the titanium surface. No significant difference could be found in the %CA between the 3 levels of crystallinity. However, higher levels of % CA were observed on pretreated HA surfaces than untreated HA surfaces. Elevated calcium and phosphate levels in culture medium did not have any effect on cell attachment. Scanning electron microscopic examinations 28

revealed surface degradation of the HA coating following pretreatment in the simulated inflammatory media. The results suggest that the altered surface topography may influence the initial cell attachment to HA surfaces. Orsini G, Assenza B, Scarano A, et al67 reported that the implant surface analyses were performed on 10 machined implants and on 10 sandblasted and acid-etched implants. Subsequently, sandblasted and acidetched implant cytotoxicity, morphologic differences between cells adhering to the machined implant surfaces, and cell anchorage between cells adhering to the machined implant surfaces, and cell anchorage to sandblasted and acidetched implant surfaces were evaluated. Results indicated that acid etching with 1% hydrofluoric acid / 30% nitric acid after sandblasting eliminated residual alumina particles. The average roughness of sandblasted and acid etched surfaces was about 2.15µm. Cytotoxicity tests showed that sandblasted and acid-etched implants had non-cytotoxic cellular effects and appeared to be biocompatible. Scanning electron microscopic examination showed that the surface roughness produced by sandblasting and acid etching could affect cell adhesion mechanisms. Osteoblast-like cells adhering to the sandblasted and acid-etched surfaces showed an irregular morphology and many pseudopodia. These morphologic irregularities could improve initial cell anchorage, providing better osseointegration for sandblasted and acidetched implants. 29

Placko HE, Mishra S, Weimer JJ, et al69 examined the effects of different treatments (polished, electropolished, and grit-blasted) on the surface morphology and chemistry of commercially pure titanium and titanium-6% aluminum-4% vanadium. The structure and composition of the surfaces were evaluated using scanning electron microscopy, atomic force microscopy, energy dispersive spectroscopy, Auger microprobe analysis, and x-ray photoelectron spectroscopy. Surface roughness values at large scales were nearly identical for grit-blasted and electropolished samples, while at smaller scales, electropolished and polished samples had nearly identical quantitative roughness values. The surface oxide compositions were found to be primarily titanium dioxide on both materials for all surface treatments. No vanadium was seen with either x-ray photoelectron spectroscopy or Auger microprobe analysis for the alloy, indicating a possible surface depletion. Calcium was present on the grit-blasted samples, and calcium and chlorine were detected on the electropolished samples. Squier RS, Agar JR, Duncan JP et al83 reported that the dental evaluation of the retentive capabilities of luting agents when used between metal components, such as cast metal restorations cemented onto machined metal implant abutments. Author compared the retentive strengths of 5 different classes of luting agents used to cement cast noble metal alloy metal alloy crowns to 8-degree machined titanium cementable implant abutments from the Straumann ITI implant System. Sixty prefabricated 5.5-mm solid titanium implant abutments and implants were used; 30 received the standard 30

surface preparation and the other 30 received an anodized surface preparation. Anodized implant components were used to reflect current implant marketing. Sixty castings were fabricated and randomly paired with an abutment and implant. A total of 12 casings were cemented on to the implant-abutment assembles for each of the 5 different luting agents (zinc phosphate, resin composite, glass ionomer, resin-reinforced glass ionomer, and zinc oxide-non-eugenol.) A statistically significant difference was found between the 5 cements. Of the cements used, resin composite demonstrated the highest mean retentive strength, Zinc phosphate and resin-reinforced glass-ionomer cements were the next most retentive, while glass-ionomer and zinc oxide-non-eugenol cements demonstrated minimal retention. In addition, retention was not altered by the use of an anodized abutment surface. Ramp LC, Jeffcoat RL70 conducted research into the formation, destruction, and adaptation of bone around implants would benefit from a sensitive, nondestructive, noninvasive, and quantitative technique to assess the bone-implant interface. They hypothesized that osseointegration can be quantified by sensing the mechanical impedance (or micromobility) of the implant when it is subjected to minute vibratory forces superimposed upon a quasi-static preload. To test this hypothesis, titanium root-form implants were placed in the mandibles of 4 Walker hounds and allowed to heal submerged for 3 months. The implants were exposed and characterized for osseointegration using clinical observations, quantitative radiography, and a custom-designed impedance instrument. Subsequently, arbitrarily selected 31

implants were ligated to induce bone loss and examined monthly over a 6month study period. Following the terminal examination and euthanasia, quantitative histologic measurements were made of bone adjacent to the implant, including estimates of both crestal bone height and the percent bone (bone fraction). Linearized dynamic parameters (effective stiffness and effective damping) correlated well with radiographic and histologic measures of bony support. The presence of nonlinear stiffness was clearly associated with a bimodal “Clinical impression” of osseointegration. These results confirm that, in this animal model, mechanical impedance can be used as a measure of implant osseointegration. Lumbikanonda N, Sammons R52 conducted a study on bone cell interactions with smooth titanium, titanium dioxide-blasted, titanium plasmasprayed, and hydroxyapatite plasma-sprayed implants, as manufactured for clinical use, were compared. Implants were exposed to neonatal rat osteoblast cells in suspension for a 20-minute period and, by means of scanning electron microscopy, attached cells were classified according to stage of attachment. Quantitative analysis showed that cells spread most quickly on the titanium plasma-sprayed implants. Fully spread cells on the smooth titanium implants were closely adherent to the surface, while on the titanium dioxide-blasted surface they showed no adaptation to surface irregularities. On the hydroxyapatite-coated implants, cells adhered closely only to smooth areas. To avoid the use of proteolytic enzymes for cell derivation, the authors developed a novel organ culture system in which the 32

implant was contained in a nylon pocket surrounded by bone fragments, permitting cells to migrate onto the implant surface. Cultures were maintained for up to 4 weeks, allowing comparison of cell migration, proliferation, and differentiation on the implant surfaces. Hermann JS, Schoolfield JD, Nummikoski PV, et al37 showed generally that endosseous implants can be, placed according to a nonsubmerged or a submerged technique and in 1-piece or 2-piece configurations. Recently, it has been shown that peri-implant crestal bone reactions differ significantly radiographically as well as histometrically under such conditions and are dependent on a rough/smooth implant border in 1piece implants and on the location of a microgap (interface) between the implant and the abutment/restoration in 2-piece configurations. The authors studied to evaluate whether standardized radiography as a noninvasive clinical diagnostic method correlates with peri-implant crestal bone levels as determined by histometric analysis. These data demonstrates that standardized periapical radiography can evaluate crestal bone levels around implants clinically accurately (within 0.2mm) in a high percentage (89%) of cases. These findings are significant because crestal bone levels can be determined using a noninvasive technique and block sectioning or sacrifice of the animal subject is not required. In addition, longitudinal evaluations can be made accurately such that bone changes over various time periods can be assessed. Such analyses may 33

prove beneficial when trying to distinguish physiologic changes from pathologic changes or when trying to determine causes and effects of bone changes around dental implants. Lim YJ, Oshida Y, Andres C, et al49 the attachment of cells to titanium surfaces is an important phenomenon in the area of clinical implant dentistry. A major consideration in designing implants has been to produce surfaces that promote desirable responses in the cells and tissues. To achieve these requirements, the titanium implant surface can be modified in various ways. Research was designed to elucidate the relationship between surface roughness and contact angle of various engineered titanium surfaces of commercially pure titanium, titanium-aluminum-vanadium alloy (TI-6AI-4V), and titanium-nickel (TiNi) alloy. It was found that: (1) There were no significant differences in contact angles among the media; (2) for commercially pure titanium, a combined treatment (hydrofluoric acid/nitric acid/water →sodium hydroxide →oxidation) showed the lowest Ө, while the surface treated with sulfuric acid showed the highest value; (3) for all commercially pure titanium samples, when Ө, is greater than 45 degrees, the contact angle increases linearly with Ra (hydrophobic nature) and the surface is covered with rutiletype oxide only, while the contact angle decreases linearly with Ra when Ө is less than 45 degrees (hydrophilic nature) and the surface is covered with a mixture of rutile and anatase oxides; and (4) a similar trend was found on Ti6AI-AV and TiNi surfaces. 34

Drake DR, Paul J, Keller JC30 conducted a study to assess the effects of modifying titanium surfaces, in terms of wettability, roughness and mode of sterilization, on the ability of the oral bacterium Streptococcus sanguis to colonize. An in vitro model system was developed. All surfaces were colonized by the bacteria, but to significantly different levels. Titanium samples that exhibited rough or hydrophobic (low wettability) surfaces, along with all autoclaved surfaces, were preferentially colonized. Titanium surfaces that had been repeatedly autoclaved were colonized with the levels of bacteria 3 to 4 orders of magnitude higher that other modes of sterilization. This may have implications relative to the commonly used method of autoclaving titanium implants, which may ultimately enhance bacterial biofilm formation on these surfaces. Zhu X, Kim K, Ong JL et al94 reported a study on the effect of phosphoric acid solution on the anodic oxide film of titanium. Commercially pure grade 2 titanium specimens were prepared and anodized in phosphoric acid solution at a constant current density (70A/m 2). Specimens were evaluated by means of scanning electron microscopy, x-ray diffraction analysis, electron probe microanalysis, energy-dispersive spectroscopy, profilometry, and atomic force microscopy. The anodic oxide film was observed to consist of a porous or non-uniform layer. X-ray diffraction showed anatase and amorphous oxide, with the incorporation of phosphorus. The degree of oxide crystallinity was observed to increase with an increase in voltage but decreased as the electrolyte concentration was increased. In 35

addition, the concentration of phosphorus also increased as the electrolyte concentration and voltage increased and concluded that Electrolyte concentration and voltage play an important role in governing the anodic oxide thickness, composition, and degree of oxide crystallinity. Ma J, Sorsa T, Kononen M et al54 Cellular fibronectin staining is decreased in adult Periodontitis, which implies elastase–mediated degradation of periodontal tissues. The authors studied to determine whether failing dental implants display similar changes. Cellular fibronectin and its integrin receptors were identified by immunohistochemistry and quantified by computerized image analysis. The results showed that cellular fibronectin was found in blood vessel walls, epithelial basement membranes, and fibroblasts. Cellular fibronectin staining was increased around failing dental implants but decreased in adult Periodontitis compared to healthy controls. The distribution of integrin receptor subunits α4, α5 and β1 of cellular fibronectin was similar in failing dental implants. The pathomechanisms in adult Periodontitis and failing dental implants seem to differ. They concluded that adult Periodontitis is characterized by proteolysis/ loss of cellular fibronectin, whereas failing dental implants are characterized by increased cellular fibronectin deposition, probably as a result of titanium-induced local synthesis and relatively modest degradation. 36

Geurs NC, Jeffcoat RL, McGlumphy EA, et al35 conducted a study on 2 design related independent variables control at 2 levels. Geometry (Threaded/ Cylindrical) and coating (TPS or HA) using periotest instrument. Micromobility by perio test appears to measure differences in implant behaviour that are undetectable by more conventional means. The author‟s hypothesis of the design of implant influences the time course of osseointegration showed that HA-coated implants consistently exhibited a more rapid early decrease I mobility than the identical geometry of TPS Implants. 37

DEVELOPMENT OF CONCEPT The initial concept of osseointegration stemmed from vital microscopic studies of the bone marrow of the rabbit fibula, which was uncovered for visual inspection in a modified intravital microscope at high resolution in accordance with a very gentle surgical preparation technique. With special instrumentation, the marrow could be studied in transillumination in vivo, and in situ, after the covering bone was ground down to a thickness of only 10 to 20 μm. Circulation was maintained in this thin layer of bone and with very few signs of microvascular damage, which is the earliest and most sensitive indication of tissue injury. These intravascular studies of bone marrow circulation also revealed the intimate circulatory connection among marrow, bone and joint tissue compartments.15 A series of in vivo studies on bone, marrow, and joint tissue were performed with particular emphasis on tissue reaction to various kinds of injury: Mechanical, Thermal, Chemical, and Rheologic. The studies were also concerned with the various therapeutic possibilities to minimize the effect of such trauma and further sought to identify additional traumatic factors such as wound disinfectants and to explore the development of procedures that promote predictable healing of differentiated tissues. Long–term in vivo microscopic studies of bone and marrow response to implanted titanium chambers of a screw shaped design were also performed. 38

These studies in the early 1960s strongly suggested the possibility of osseointegration since the optical chambers could not be removed from the adjacent bone once they had healed in. They observed that the titanium chambers were inseparably incorporated within the bone tissue, which actually grew into very thin spaces in the titanium. Interdisciplinary clinical cooperation with plastic surgeons and otolaryngologists enabled them to study the repair of mandibular defects and replacement of ossicles by means of autologous bone grafts. Desired anatomic shapes of bone grafts were preformed in rabbits and dogs and subsequently applied clinically with longterm follow- up. In an extensive series, the repair of major mandibular and tibial defects in dogs were studied the most successful being the one based on the prior integration of titanium fixtures on both sides of the defect to be created later. When the fixtures had become safely incorporated within the bone, a defect was created, titanium splints maintained the topographical relation between the cut edges, and an autologous graft of trabecular bone and marrow compensated for the tissue defect. Separate studies were performed on the healing and anchorage stability of titanium tooth root implants or fixtures of various sizes and designs. It was found that when such an implant was introduced into the marrows cavity, and followed by an adequate immobilized healing period, a shell of compact cortical bone was formed around the implant without any apparent soft tissue intervention between normal bone and the surface of the implant. 39

A direct correlation was observed among microtopography of the titanium surface, the absence of contamination, the preparatory handling of the bone site, and the histologic pattern elicited in the adjacent bone. In a separate study fixtures were installed in the tail vertebrae of dogs with successful integration even when abutments were allowed to pierce through the skin. On the basis of the findings in these experimental studies, they decided to perform a series of experiments that would enable them to develop clinical reconstructive procedures for the treatment of major mandibular defects, including advanced edentulous states. It was felt that both osseointegration and autologous bone graft would be useful in these clinical defect situations. Teeth were extracted in dogs and replaced by osseointegrated screwshaped titanium implants. Fixed prostheses were connected after an initial healing time of 3 to 4 months without loading; the fixtures were allowed to heal under a mucoperiosteal flap, which was then pierced for abutment connection and subsequent prosthetic treatment.5 Different types of prosthetic designs were used. Radiologic and histologic analyses of the anchoring tissues showed that integration could be maintained for 10 years in dogs with healthy bone tissue and with out progressive inflammatory reactions. 40

At the time the animals were killed, the titanium fixtures could not be removed from the host bone unless cut away. The anchorage capacity of the separate implants was determined as 100kg in the lower jaw and 30 to 50 Kg in the upper jaw. Efforts to extract the implants led to fractures in the jaw bone per se, not at the actual interface. Microradiographic analyses revealed load– related remodeling of the jaw bone around the implant, even in those cases where the implants were in very close proximity to the nasal and sinus mucoperiosteum at installation.40 These long-term experimental studies suggested the possibility of achieving and maintaining bone anchorage under unlimited loading of dental prostheses in the dog attached to osseointegrated fixtures. Soft tissue penetration of titanium abutments could be used without untoward reactions in edentulous jaws, and also for the attachment of titanium chambers for vital microscopy in rabbit and dog tibiae.68 Later vital microscopic studies were carried out on human microcirculation and intravascular behavior of blood cells at high resolution by means of an implanted optical titanium chamber in a twin – pedicled skin tube on the inside of the left upper arm of healthy volunteers. The tissues reaction as revealed by intravascular rheologic phenomenon was studied in long-term experiments in these chambers with out indications of inflammatory processes.82 It therefore, seemed reasonable to assume that bone anchorage 41

according to the principle of osseointegration might also work in humans, and they treated their first- edentulous patients in 1965. Definition of osseointegration: Previous definitions of Osseointegration have stated that the interface between the metal implant and the host should consist entirely of bone without any intervening connective tissue. Usually, when used in this context, the word “bone is interpreted as meaning calcified osseous matrix. Such an interpretation or definition is difficult to accept because bone tissue simply does not react to any implant or foreign body or to any surgical repairing situation by laying down a wall composed entirely of calcified matrix without any accompanying soft tissue.63 42

In addition, the alveolar host bone-to-metal implant interface, if it follows the traditional response to orthopedic metal devices, will be a dynamic one, subject to many changes in character, i.e., viable bone having partially cellular marrow-vascular spaces and partially inert non-viable matrix could contribute to the bone-to-metal interface.34 Some investigators believe that the definition of “osseointegration” is to refer to the osseous tissue lying next to the metal implant as containing all aspects of bone i.e., marrow-vascular spaces, hemopoietic tissue, fatty tissue, and connective tissue type I, or, to state it more simply, “calcified bone and all its accompanying soft tissue elements”. If this is the intent of the definition, we are dealing with something that we can accept and that we can use as a basis for research investigation.40 But to say that solid, calcified bone without any intervening marrow-vascular space, connective tissue space, or fatty or hemopoietic tissue is going to be juxtaposed onto the intrabony implants is to propose a situation that is difficult to achieve and unrealistic in terms of previous orthopedic and bone research. To expect the randomly arranged, fine cancellous bone pattern existing in edentulous ridges to respond with the formation of 100% dense bone to satisfy the old definition of osseointegration in not reasonable from the standpoint of osseous dynamics.68, 82. 43

Instead, one would expect a healthy bone response to be a laying down of calcified and non – calcified osseous matrix on the surface of the implant. This matrix would in turn be subject to remodeling, modification, and resorption, depending on the demands of function that later would be placed on the marrow vascular spaces, connective tissue, Vascular tissue, and soft as well as hard tissue areas. This type of osseous tissue is responsive in the long- term demands of function that may be placed colossally on the appliance and tends to lead to a healthy clinical situation.82 Osseointegration is based on the idea of a stable bone anchorage of an oral implant in contrast to a soft – tissue anchorage of the same that so known to function poorly over long terms of follow- up . This may seem peculiar as the tooth itself is anchored in soft tissue. However, a tooth is attached with a highly differentiated periodontal ligament, in sharp contrast to the poorly organized soft –tissue attachment of an oral implant. In fact, softtissue of a scar – like type is what develops around foreign materials such as metals inserted in the oral cavity, attempts to define osseointegration based on histologic criteria have failed and today the only acceptable definition seems to be based on confirmed and maintained implant stability as suggested by zarb & Alberktsson, 1991. “Osseointegration is process where by clinically asymptomatic rigid fixation of alloplastic materials is achieved, and maintained, in bone during functional loading”. 44

Definition of Branemark5 “Osseointegration is a direct structural and functional connection between ordered, living bone and the surface of a load-carrying implant”. This definition however does not survive the scrutiny of time. In the future, it seems as a structurally based definition must identify the minimal contact zone between bone and implant and if a functional connection exists it has to be demonstrated with more sensible instruments than that of a proved longterm function .In fact, in 1983 skalak pointed out that a mere bony in growth into the irregularities of the implant without any true functional connection (for example, via physical and chemical bonds) would be sufficient to carry the loads put on the oral implant devices . There have been various attempts to separate a structural and functional bone connection although different terminologies have been used by. Osborne & Newesly referred to materials as being bioinert (for example, titanium and carbon) and bioactive (glass ceramics and various types of calcium phosphates) where the former materials would be structurally connected to bone and the latter physicochemically bound.40 Meffert et al. differentiated between what was referred to as “adaptive osseointegration” and “biointegration” the latter type of connection being typical for calcium phosphates (such as hydroxyapatite) and representing a true chemical bond.68 45

OSSEOINTEGRATION Concept of Bony Anohorage Branemark (1969) FIBROINTEGRATION Concept of soft tissue anchorage Linkow (1970), James (1975), Weiss (1986) 46

CONCEPT OF OSSEOINTEGRATION Dr. Per-Ingvar Branemark Orthopaedic Surgeon Professor University of Goteborg, Sweden. 47

Historical Background The basic science and clinical research work of Branemark and his colleagues appears to have reconciled these four components into a clinically successful equation. This was first described in a 1977 monograph that was also published as supplement number 16 to the Scandinavian journal of Plastic and Reconstructive Surgery. The Branemark data were presented in 1982 to the North American Oral Surgeons and Prosthodontists representing academic institutions at the seminal Toronto Conference on Osseointegration in Clinical Dentistry. The quality of the Branemark research combined with the documented long-term efficacy of his treatment results, articulated a very strong case for the osseointegration method. In 1979, a University of Toronto faculty of Dentistry Osseointegration Research Project was undertaken, supported by funds from the Ontario Ministry of Health. 1. In a landmark paper published in 1969, Branemark et al described the phenomenon for submerged titanium implants from a clinical point of view and with decalcified histologic sections. 2. Seven years later, Schroeder et al provided the first true histologic evidence of direct bone-to-implant contact for nonsubmerged titanium implants using nondecalcified histologic sections with the titanium 48

implants still presents in the specimens. Later, these authors created the terms osseointegration and functional ankylosis. 3. Adell et al first reported the long-term documentation of osseointegrated implants in a retrospective clinical study treating fully edentulous patients with Branemark implants. The authors reported estimated implant survival rates of 86% in the mandible and 78% in the maxilla at 15 years. 4. Similar results of retrospective studies have also been reported for nonsubmerged ITI implants placed in fully edentulous patients by Babbush et al, Bruggenkate et al and Krekeler et al. 5. Zarb and Schmitt applied strict criteria for success, the examination up to 5 years demonstrated success rates above 95%. Mean success rates above 90% have also been reported for Branemark implants. 6. Roberts et al suggested that most cortical grafts are never fully resorbed but remain admixtures of dead bone despite developing net bone strengths equal to adjacent nongrafted areas. Devitalized bone could possibly lead to loss of osseointegration. 7. Carter et al have shown that compressive micro damage results from oblique fractures that run through cellular lacunae and canaliculi, 49

stimulating an extensive cellular response to repair. Repair capability is impaired in devitalized bone or alloplast combined grafts. This mechanism may help to explain findings reported by Roberts et al that early loading of dental implants led to remodelling of devitalized bone, undermining the periosteal margin integrity of titanium implants. 8. Carlsson et al showed that osseointegration does not occur unless the osseous gap between titanium and the bony surface is less than about 0.2 mm. Except through the cortical portion of the graft, this close proximity is doubtful in bone graft cases. Cellular Background to Osseointegration: The conditions for a proper bone response to occur include the presence of adequate cells, an adequate nutrition to these cells and an adequate stimulus for bone repair. The adequate cells are differentiated bone cells (osteoblast, osteoclast and osteocyte) on the one hand and undifferentiated cells that may be stimulated in the direction of an osteogenic induction on the other. In reality bone healing is dependent not only on the recruitment of new bone tissue, but also on an appropriate amount of newly formed soft-tissue, including capillaries, to take but one example. The inevitable trauma to bone at every surgical procedure involving that tissue will trigger not only the formation of new bone, but also the formation of various soft tissues. 50

The balance between the different tissue elements involved in bone repair is influenced by mediators elicited from the cells. There are antocrine as well as paracrine control mechanisms. This delicate balance may be easily Soft tissue interface Cortical bone Spongy bone 51

disturbed by external influences, for instance movements that will turn the balance in favor of new soft tissue formation instead of bone. Other known circumstances that affect bone healing are PH or 0 2 saturation. That the adequate stimulus for bone repair is „injury‟ should not lead to the false conclusion that more injury will result in a greater healing response. Too much injury will result in permanent damage to the repair tissues and healing will not start. Stages of Osseointegration: Direct bone healing, as it occurs in defects, primary fracture healing and in Osseointegration is activated by any lesion of the pre-existing bone matrix. When the matrix is exposed to extracellular fluid, noncollagenous proteins and growth factors are set free and activate bone repair. Once activated, osseointegration follows a common, biologically determined program that is subdivided in to 3 stages: 1. Incorporation by woven bone formation. 2. Adaptation of bone mass to load (lamellar and parallel-fibered bone deposition); and 3. Adaptation of bone structure to load (bone remodeling). 52

INCORPORATION BY WOVEN BONE FORMATION: The first bone tissue formed is woven bone. It is primitive type of bone tissue and characterized by a random, felt – like orientation of its collagen, fibrils, and numerous irregularly shaped osteocytes and, at the beginning, a relatively low mineral density. It grows by forming a scaffold of rods a

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