The influence of recombinant human BMP-2 on bone-implant osseointegration: biomechanical testing and histomorphometric analysis

The healing period for bone-implant osseointegration lasts 3-6 months or even longer. The aim of this study was to investigate whether osseointegration can be enhanced by the use of bone morphogenetic protein-2 (BMP-2). In the femurs of 8 Japanese white rabbits, 16 implants were applied with 1.0 mg recombinant human BMP-2 (rhBMP-2) as group A, and the other 16 implants without rhBMP-2 as group B. Calcein green 20 mg/kg and alizarin red 20 mg/kg were injected 4 and 8 weeks after implantation, respectively. At 12 weeks, the animals were killed. In 16 implant-bone blocks, binding strength was measured by pull-out test, and the extracted implants were observed under a scanning electronic microscope. The other blocks were analysed for percentage of marked bone adjacent to the implant surface by confocal laser scanning microscope. The pull-out strengths of group A were greater than that of group B (P<0.05). Scanning electronic microscopy (SEM) showed more calcified substances on the surface of the implants of group A than B. There was more marked bone around group A than B implants at 4 weeks (P<0.05) and 8 weeks (P<0.05). rhBMP-2 improves the quantity and quality of implant-bone osseointegration. Biomechanical testing and histomorphometric analysis are reliable methods to use in researching the implant-bone interface.     

Effects of implant thread geometry on percentage of osseointegration and resistance to reverse torque in the tibia of rabbits

BACKGROUND: Dental implant thread geometry has been proposed as a potential factor affecting implant stability and the percentage of osseointegration. Therefore, the aim of this prospective, randomized, parallel arm study was to evaluate the effects of dental implant thread design on the quality and percent of osseointegration and resistance to reverse torque in the tibia of rabbits. METHODS: Seventy-two custom-made, screw-shaped, commercially pure titanium implants (3.25 mm diameter x 7 mm length) were placed in the tibiae of 12 white New Zealand rabbits. Each tibia received three implants of varying thread shapes: one with a V-shaped, one with a reverse buttress, and one with a square thread design. The rabbits were sacrificed following an uneventful healing period of 12 weeks. Implants in the right tibiae underwent histologic and histomorphometric assessments of the bone-to-implant contact (BIC) and the radiographic density of surrounding bone, while implants in the left tibiae were used for reverse-torque testing. Differences between the three thread designs were examined using analysis of variance (ANOVA). RESULTS: Data showed that the square thread design implants had significantly more BIC and greater reverse-torque measurements compared to the V-shaped and reverse buttress thread designs, while no differences were found in radiographic bone density assessments. CONCLUSION: These results indicate that the square thread design may be more effective for use in endosseous dental implant systems.     

雌激素对骨质疏松时种植体骨愈合的影响:Ⅱ骨计量学和电镜观察

目的 :研究雌激素替代治疗对骨质疏松时种植体骨愈合的影响。方法 :选用32周龄雌性SD大鼠36只 ,并随机分为假手术组、卵巢切除组及雌激素组。卵巢切除12周后于大鼠胫骨近中干骺端植入纯钛螺纹状种植体 ,雌激素组同时肌注苯甲酸雌二醇。种植术后4周及12周分两批处死大鼠 ,摘取胫骨 ;标本分别进行扫描电镜观察和骨计量学测量。结果 :在种植后4周及12周时 ,雌激素组除12周时皮质骨结合率与卵巢切除组无显著差异外 ,其它各项骨计量学参数均显著高于卵巢切除组 (P<0.05或P<0.01) ;而与假手术组比较 ,除骨矿化速度及4周时单位骨量外 ,其他各项指标均无显著差异 (P>0.05)。电镜观察种植体—骨界面愈合雌激素组和假手术组均优于卵巢切除组。结论 :雌激素替代治疗可促进实验性骨质疏松大鼠种植体骨愈合 ;该方法有助于增加临床绝经性骨质疏松患者牙种植体骨整合率     

Histomorphometric assessment of implant coated with mixture of nano-alumina and fluorapatite in rabbits

BackgroundThe application of nanoscale surface modification was found to be useful in the improvement of osseointegration of endosseous dental implants. The fluorapatite (FA)/alumina (Al₂O₃) mixture is recognized for its outstanding bioinertia and can significantly increase the biocompatibility and bioactivity of biomaterials.ObjectiveThe aim of the present work was to evaluate the bone response to nano-alumina- and fluorapatite-coated dental implants using rabbit tibiae.Material and MethodsThe coating was performed using the dip-coating method. Commercially pure titanium screw-type implants were used as a control group. The coated implants were the experimental group. Each group consisted of 12 screws that were surgically implanted in 6 healthy New Zealand rabbits. Histological and histomorphometric evaluations were performed at the bone to implant contact (BIC) interface, bone fraction area occupancy (BAFO) and fibrous tissue at 2 and 6 weeks of healing.ResultsThis analysis showed that the coated implants had more rapid osseointegration than the control group, with a significant difference after 2 and 6 weeks of healing for both groups. The histomorphometric evaluation demonstrated higher values for BIC% and BAFO% and lower values of fibrous tissue in the mixture-coated Ti implants than in the control group.ConclusionThe current study suggested that the nano-alumina and fluorapatite mixture coating is a favourable candidate for rapid osseointegration over uncoated implants.     

Peri-Implant bone response around porous-surface dental implants: A preclinical meta-analysis

IntroductionThis meta-analysis of relevant animal studies was conducted to assess whether the use of porous-surface implants improves osseointegration compared to the use of non-porous-surface implants.Material and methodsAn electronic search of PubMed (MEDLINE) resulted in the selection of ten animal studies (out of 865 publications) for characterization and quality assessment. Risk of bias assessment indicated poor reporting for the majority of studies. The results for bone-implant contact (BIC%) and peri-implant bone formation (BF%) were extracted from the eligible studies and used for the meta-analysis. Data for porous-surface implants were compared to those for non-porous-surface implants, which were considered as the controls.ResultsThe random-effects meta-analysis showed that the use of porous-surface implants did not significantly increase overall BIC% (mean difference or MD: 3.63%; 95% confidence interval or 95% CI: −1.66 to 8.91; p = 0.18), whereas it significantly increased overall BF% (MD: 5.43%; CI: 2.20 to 8.67; p = 0.001), as compared to the controls.ConclusionPorous-surface implants promote osseointegration with increase in BF%. However, their use shows no significant effect on BIC%. Further preclinical and clinical investigations are required to find conclusive evidence on the effect of porous-surface implants.     

愈合期微型种植体-骨界面的组织形态学研究

目的研究微型种植体-骨界面在不同愈合时间下的组织形态学变化。方法应用种植钉30枚,新西兰大白兔10只。采用HE染色方法,骨磨片方法对种植体-骨界面的横纵断面进行观察。结果种植体-骨界面在愈合1、2周时界面机化,以胶原纤维包绕为主;界面在4周时表现为复合骨;愈合8周时层状骨为主,出现二次改建。结论在家兔胫骨内纯钛微种植体骨钉骨整合可在8周内完成。     

国产多孔钽铌合金材料骨结合性能评价

目的: 评价国产多孔钽铌合金材料的骨结合性能。方法: 选取成年新西兰大白兔36只,将多孔钽铌合金植体植入家兔股骨髁部,术后4、8、12周分批处死家兔并取材,通过X线片、硬组织切片、扫描电镜、X线能谱分析、推出试验评价其骨结合性能。采用SPSS19.0软件包对数据进行统计学分析。结果: X线检查未见植体松脱及明显骨吸收影像,随着愈合时间延长,材料周围骨密度增高;硬组织切片甲苯胺蓝染色观察显示,骨组织与多孔钽铌材料呈凹凸嵌合状,随着愈合时间延长,大量骨组织长入材料孔隙内部,4周组材料周围及内部多为类骨质,12周组材料周围及内部骨组织成熟度明显提高;扫描电镜与X线能谱分析显示,随着时间延长,骨组织与材料接触趋于致密,孔隙内骨组织钙磷元素百分含量逐渐增高,Ca/P比值8周组与12周组显著高于4周组（P<0.05）,8周组与12周组之间无明显差异（P>0.05）;推出试验示,4周时平均剪切强度为(8.26±0.75）MPa,12周时增加至(21.04±1.46)MPa,组间比较具有统计学差异（P<0.05）。结论: 国产多孔钽铌合金材料在动物骨内具有优良的骨结合性能,是一种极具潜力的骨组织工程材料。     

低强度脉冲超声促进钛种植体骨结合的实验研究

目的 建立种植体植入动物模型,研究低强度脉冲超声(low intensity pulsed ultrasound,LIPUS)对种植体骨结合的促进作用.方法 选用雌性SD大鼠24只,每只大鼠双侧胫骨干骺端内侧植入螺纹状钛种植体.植入术后第2天对右侧胫骨种植体周围进行LIPUS刺激作为实验侧,每日20 min,左侧胫骨种植体植入部位不刺激作为自身对照侧.超声刺激后第4、8、12 周分批处死动物,每批8只,获取双侧胫骨标本.采用X线片、显微CT、组织切片等观察LIPUS对种植体骨结合的作用.结果 3个时间点种植体与骨组织之间均形成了不同程度的骨结合.显微CT组织形态计量学分析结果显示,种植体周骨结合率在实验侧第4、8、12周分别为(45.708±3.316)%、(46.231±1.954)%、(46.807±1.451)%,在对照侧分别为(43.021±3.558)%、(44.272±3.023)%、(44.894±4.215)%,第4周时差异具有统计学意义(P<0.05).种植体周骨体积分数在第4、8周,种植体周骨小梁厚度及第8周、第12周各向异性程度,实验侧均高于自身对照侧,差异有统计学意义(P<0.05).组织学切片可见实验侧种植体周新生骨组织厚度明显大于自身对照侧,骨结合量更多.结论 LIPUS可以促进种植体周围骨组织的愈合,加快种植体骨结合,并能促进骨小梁早期呈一定方向改建.

Abstract：

Objective To establish an animal model of titanium implant and to investigate the effects of low intensity pulsed ultrasound(LIPUS)on the implant osseointegration. Methods Twenty-four female Sprague Dawley(SD)rats were used. Titanium implants were inserted into tibia metaphysis bilaterally in each SD rat. Since the second day following implant surgery, LIPUS stimulation were carried out around the implant on the right side for 20 minutes per day, and implants on the left side remain untouched as self-control. Eight rats were sacrificed and tibiae specimens were harvested on the end of the 4th, 8th, and 12th week respectively. X-ray picture,micro-CT analysis and histological sections were performed to evaluate the effects of LIPUS on the implant osseointegration. Results Osseointegration at the interface between the implant and bone tissue was observed bilaterally. In the micro-CT histomorphometry analysis, the percentage of osseointegration(%OI)of experiment side were (45.708±3.316)%, (46.231±1.954)%, and (46.807±1.451)% on the end of the 4th, 8th, and 12th week. Meanwhile, the %OI of control side were (43.021±3.558)%, (44.272±3.023)%, and (44.894±4.215)% respectively. The %OI on the 4th weekend, bone volume ratio(BV/TV)on the 4th and 8th weekend,trabecular thickness(Tb. Th)and degree of anisotropy(DA)on the 8th and 12th weekend of the experiment side tibia were significantly greater than those on the control side(P<0.05). The histological examination showed that the thickness of new bone around the implant and the bone-implant contact area was obviously greater in the LIPUS treated side compared to the control side.Conclusions The LIPUS therapy may accelerate the bone healing and osseointegration at the interface between titanium implant and bone, and promote remodeling of bone trabecula on the early stage.     

Biological reactions of alveolar bone to orthodontic loading of oral implants

Enosseous oral implants have been suggested as anchorage for orthodontic appliances in cases where the existing dentition cannot provide sufficient stability. Long-term studies of oral implants have suggested that excessive loading may contribute as an etiologic factor in the pathogenesis of failing implants. The purpose of the present study was to perform a histomorphometric analysis of tissue reactions around implants subjected to a well-defined force system. The analysis was performed on undecalcified sections cut perpendicularly to the long axis of the implant. The degree of osseointegration, bone density at varying distances from the implant as well as the relative extent of resorption and formation of alveolar bone adjacent to the implant-bone interface were evaluated. The results were correlated with the local strain of the tissue estimated by the means of a finite element analysis. It was found that loading significantly influenced both the turnover and the density of the alveolar bone in the proximity of the implants. However, even unloaded implants tended to maintain the bone characteristics of the alveolar process. On the other hand, the degree of osseointegration appeared to be independent of the loading of the implant.     

Effects of a cell adhesion molecule coating on the blasted surface of titanium implants on bone healing in the rabbit femur

PURPOSE: One strategy to improve implant osseointegration is to control the quality of the bone reaction at the implant-bone tissue interface using an implant coated with biologically active substances. The purpose of this study was to investigate the effect of a tetra-cell adhesion molecule (T-CAM) coating composed of 4 cell-adhesion molecules-an arginine-glycine-aspartic acid (RGD) sequence, a proline-histidine-serine-arginine-asparagine (PHSRN) sequence, a tyrosine-histidine sequence (YH), and a glutamic acid-proline-aspartic acid-isoleucine-methionine (EPDIM)-on the rough-surfaced titanium implant on peri-implant bone formation in the rabbit femur with poor local bone conditions and minimal primary stability. MATERIALS AND METHODS: Seven T-CAM-coated (blasted/T-CAM) and uncoated (blasted) implants with a rough surface (hydroxyapatite-blasted; Ra = 1.8 microm) were placed in slightly oversized beds of the metaphyses of the right and left femurs of 7 New Zealand White rabbits with light tactile pressure, and minimal primary stability was obtained. To evaluate the effects of T-CAM coating on the peri-implant bone healing response, histomorphometric analysis was performed 8 weeks after surgery. The 2 groups were compared using the Student t test, with a significance level of P < .05. RESULTS: Compared to uncoated blasted implants at 8 weeks of healing, the blasted/T-CAM implants showed a significantly greater amount of bone-implant contact (BIC; P < .01) and new bone formation in the zones 0 to 100 microm and 0 to 500 microm lateral to the implant surface (P < .05) in the medullary space. CONCLUSION: The T-CAM coating on the rough-surfaced titanium implants significantly enhanced peri-implant bone formation in rabbit femurs with poor local bone condition.     

Bone tissue response to plasma-nitrided titanium implant surfaces

A current goal of dental implant research is the development of titanium (Ti) surfaces to improve osseointegration. Plasma nitriding treatments generate surfaces that favor osteoblast differentiation, a key event to the process of osteogenesis. Based on this, it is possible to hypothesize that plasma-nitrided Ti implants may positively impact osseointegration.

Objective

The aim of this study was to evaluate the in vivo bone response to Ti surfaces modified by plasma-nitriding treatments.

Material and Methods

Surface treatments consisted of 20% N₂ and 80% H₂, 450°C and 1.5 mbar during 1 h for planar and 3 h for hollow cathode. Untreated surface was used as control. Ten implants of each surface were placed into rabbit tibiae and 6 weeks post-implantation they were harvested for histological and histomorphometric analyses.

Results

Bone formation was observed in contact with all implants without statistically significant differences among the evaluated surfaces in terms of bone-to-implant contact, bone area between threads, and bone area within the mirror area.

Conclusion

Our results indicate that plasma nitriding treatments generate Ti implants that induce similar bone response to the untreated ones. Thus, as these treatments improve the physico-chemical properties of Ti without affecting its biocompatibility, they could be combined with modifications that favor bone formation in order to develop new implant surfaces.     

Evaluation of bone ingrowth into porous titanium implant: histomorphometric analysis in rabbits

A porous material for bone ingrowth with adequate pore structure and appropriate mechanical properties has long been sought as the ideal bone-implant interface. This study aimed to assess in vivo the influence of three types of porous titanium implant on the new bone ingrowth. The implants were produced by means of a powder metallurgy technique with different porosities and pore sizes: Group 1 = 30 % and 180 μm; Group 2 = 30% and 300 μm; and Group 3 = 40% and 180 μm;. Six rabbits received one implant of each type in the right and left tibiae and were sacrificed 8 weeks after surgery for histological and histomorphometric analyses. Histological analysis confirmed new bone in contact with the implant, formed in direction of pores. Histomorphometric evaluation demonstrated that the new bone formation was statistically significantly lower in the group G1 than in group G3, (P = 0.023). Based on these results, increased porosity and pore size were concluded to have a positive effect on the amount of bone ingrowth.     

增龄变化对钛种植体骨结合影响的实验研究

目的探讨增龄变化对钛种植体骨结合的影响，为临床判断种植预后提供理论依据。方法选择雄性SD大鼠36只，随机分成青年群、成年群和老年群，在双侧胫骨内侧窝距关节0．5cm处分别植入钛种植体2颗。三组大鼠分别在术后14天、28天、56天随机各处死4只，摘取胫骨，制作带种植体的非脱钙硬组织切片，观察组织学变化，计算骨结合率。结果青年群的成骨能力最强，种植体与骨的结合连续、紧密，成年群次之，老年群最差。老年群成骨量及骨接触率均低于青年群和成年群。以上情况对松质骨影响大，对皮质骨影响小。结论增龄变化可影响钛种植体与骨组织的结合，种植体周围新骨形成量及骨结合率随年龄增长而降低。     

The influence of systemically administered oxytocin on the implant-bone interface area: an experimental study in the rabbit

PURPOSE

The purpose of this study was to assess the effect of systemically administered oxytocin (OT) on the implant-bone interface by using histomorphometric analysis and the removal torque test.

MATERIALS AND METHODS

A total of 10 adult, New Zealand white, female rabbits were used in this experiment. We placed 2 implants (CSM; CSM Implant, Daegu, South Korea) in each distal femoral metaphysis on both the right and left sides; the implants on both sides were placed 10 mm apart. In each rabbit, 1 implant was prepared for histomorphometric analysis and the other 3 were prepared for the removal torque test (RT). The animals received intramuscular injections of either saline (control group; 0.15 M NaCl) or OT (experimental group; 200 µg/rabbit). The injections were initiated on Day 3 following the implant surgery and were continued for 4 subsequent weeks; the injections were administered twice per day (at a 12-h interval), for 2 days per week.

RESULTS

While no statistically significant difference was observed between the two groups (P=.787), the control group had stronger removal torque values. The serum OT concentration (ELISA value) was higher in the OT-treated group, although no statistically significant difference was found. Further, the histomorphometric parameter (bone-toimplant contact [BIC], inter-thread bone, and peri-implant bone) values were higher in the experimental group, but the differences were not significant.

CONCLUSION

We postulate that OT supplementation via intramuscular injection weakly contributes to the bone response at the implant-bone interface in rabbits. Therefore, higher concentrations or more frequent administration of OT may be required for a greater bone response to the implant. Further studies analyzing these aspects are needed.     

非埋植型与埋植型牙种植体骨界面改建的骨组织形态计量学研究

目的观察非埋植型与埋植型两种不同种植方式之间种植体—骨界面结合动态变化的异同。方法选用成年杂种犬8只，在其下颌分别植入埋植型与非埋植型种植体，分不同程期处死动物，采用骨组织形态计量学方法对非埋植型与埋植型种植体—骨界面愈合过程进行动态观察，比较了两者骨界面改建的异同，从定量的角度分析其变化的异同。结果非埋植型种植体骨结合率均略低于埋植型种植体，但它们之间无统计学差异。尽管非埋植型种植体植入后基桩在整个后基桩在整个愈合过程中承受了一定的咬合力，但它能与埋植型种植体一样获得良好的骨结合。结论埋植型与非埋植型种植体其新骨形成的速度与骨性结合的程度两者之间无明显差异。采用骨组织形态计量学方法定量、动态地研究种植体—骨界面结合动态变化有一定的应用价值。     

实验性骨质疏松对种植体周自体骨移植愈合影响的研究

目的研究实验性骨质疏松（OP）对兔种植体周自体骨移植愈合的影响。方法将20只雌性日本大耳白兔随机分成对照组和实验组,实验组行双侧卵巢切除术,对照组接受假手术。术后12周测量股骨骨密度（BMD）,证实OP状态。同时在2组家兔左侧胫骨近中干骺端制备骨缺损,行自体髂骨移植和同期种植体植入手术。植骨术后第8、12周分2批处死动物,切取标本制作不脱钙硬组织切片,进行组织形态学观察和骨计量学检测。结果实验组BMD显著低于对照组（P<0.001）,证实OP造模成功。植骨术后第8、12周,种植体在2组植骨区均达到了骨结合。然而,实验组植骨区内骨皮质厚度（TCB）、松质骨区骨量（BVC）、种植体骨结合率（IBCR）均显著低于对照组（P<0.01）,且新生骨量也明显少于对照组。结论实验性OP虽然不会延迟自体骨移植内种植体骨结合,但可促进植骨吸收,减少BVC,降低IBCR。因而,对于行自体骨移植同期牙种植的患者,OP是一个重要的危险因素。     

Investigation of anodized titanium implants coated with triterpenoids extracted from black cohosh: an animal study

PURPOSE

The purpose of this study was to evaluate bone response to anodized titanium implants coated with the extract of black cohosh, Asarum Sieboldii, and pharbitis semen.

MATERIALS AND METHODS

Forty anodized titanium implants were prepared as follows: group 1 was for control; group 2 were implants soaked in a solution containing triterpenoids extracted from black cohosh for 24 hours; group 3 were implants soaked in a solution containing extracts of black cohosh and Asarum Sieboldii for 24 hours; group 4 were implants soaked in a solution containing extracts of pharbitis semen for 24 hours. The implants from these groups were randomly and surgically implanted into the tibiae of ten rabbits. After 1, 2, and 4 weeks of healing, the nondecalcified ground sections were subjected to histological observation, and the percentage of bone-to-implant contact (BIC%) was calculated.

RESULTS

All groups exhibited good bone healing with the bone tissue in direct contact with the surface of the implant. Group 2 (52.44 ± 10.98, 25.54 ± 5.56) showed a significantly greater BIC% compared to that of group 3 (45.34 ± 5.00, 22.24 ± 2.20) with respect to the four consecutive threads and total length, respectively. The BIC% of group 1 (25.22 ± 6.00) was significantly greater than that of group 3 (22.24 ± 2.20) only for total length.

CONCLUSION

This study did not show any remarkable effects of the extract of black coshosh and the other natural products on osseointegration of anodized titanium implants as coating agents. Further studies about the application method of the natural products on to the surface of implants are required.     

Oral implants placed in bone defects treated with Bio‐Oss®, Ostim®‐Paste or PerioGlas: an experimental study in the rabbit tibiae

Objectives: To compare the histological features of bone filled with Bio‐Oss^®, Ostim‐Paste^® or PerioGlas placed in defects in the rabbit tibiae by evaluating bone tissue composition and the integration of titanium implants placed in the grafted bone. Material and methods: Two cylindrical bone defects, about 4 mm in diameter and 6 mm in depth, were created in the tibiae of 10 rabbits. The defects were filled with either Bio‐Oss^®, PerioGlas, Ostim^®‐Paste or left untreated, and covered with a collagen membrane. Six weeks later, one titanium sandblasted and acid‐etched (SLA) implant was inserted at the centre of each previously created defect. The animals were sacrificed after 6 weeks of healing. Results: Implants placed in bone previously grafted with Bio‐Oss^®, PerioGlas or Ostim^®‐Paste obtained a larger extent of osseointegration, although not statistically significant, than implants placed in non‐grafted bone. The three grafting materials seemed to perform in a similar way concerning their contribution towards implant osseointegration. All grafting materials appeared to be osteoconductive, thus leading to the formation of bridges of mineralized bone extending from the cortical plate towards the implants surface through the graft scaffold. Conclusions: Grafting with the above‐mentioned biomaterials did not add any advantage to the osseointegration of titanium SLA implants in a self‐contained defect.     

阿仑膦酸钠对骨质疏松种植体骨结合影响的力学研究

目的 通过力学评估研究全身应用骨吸收抑制剂阿仑膦酸钠对骨质疏松模型种植体周围骨整合的影响.方法 27只5月龄日本大耳白兔随机分成3组,每组9只:单纯卵巢切除组(OVX组),伪手术组(S组),卵巢切除加阿仑膦酸钠组CALN组).卵巢摘除后12周,双侧股骨远心端、胫骨近心端植入4枚种植钉,ALN组腹腔给予阿仑膦酸钠,OVX...     

Chronodynamic evaluation of the stages of osseointegration in zirconium laminar implants

Osteogenesis occurs throughout all stages in life, due to both bone turnover and reparative processes. Thus, osseointegration (OI) can be described as the final step in a cascade of processes involved in bone healing in relation to implants. Ten groups of 5 Wistar rats each (mean = 90 g b.w.) were used. Under ether anesthesia a zirconium laminar implant was placed in the tibia following the method previously described by our laboratory (Cabrini et al Imp Dent 2:264-7, 1993). The animals were killed at Ohs, and 1, 2, 3, 6, 7, 10, 12, 14, and 60 days post-implantation. Tibiae were resected, radiographed and processed for their embedding in methyl methacrylate. Three sections, perpendicular to the major axis of the tibia, were obtained per implant and histologic and histomorphometric studies were carried out. Volume occupied by blood clot, woven bone, percentage of OI and OI bone tissue thickness, were determined. Histologic and histomorphometric studies as function of time revealed: a) at 6 days the presence of non-osseointegrated woven bone around the device is evident increasing in volume from 7 to 10 days post-implantation, and disappearing from day 12 to 14., b) at 14 days after implantation lamellar bone formation on the surface of the zirconium implants (OI) is noticeable. Additional bone growth is observed after 60 days. This study enables quantification of peri-implant reparative process response in an unloaded, necrotic trabeculae free model showing, in the different phases of the osseointegration process, the role of the blood clot and of the appearance and disappearance of woven bone and the final stages of osseointegration. Further investigation will allow comparison of results obtained under the effect of local and/or systemic factors that might affect osseointegration.