Locally delivered rhTGF-beta2 enhances bone ingrowth and bone regeneration at local and remote sites of skeletal injury.

The purposes of the present study were to determine if recombinant human transforming growth factor-beta-2 (rhTGF-beta2) enhances bone ingrowth into porous-coated implants and bone regeneration in gaps between the implant and surrounding host bone. The implants were placed bilaterally for four weeks in the proximal humeri of skeletally mature, adult male dogs in the presence of a 3-mm gap. In three treatment groups of animals, the test implant was treated with hydroxyapatite/tricalcium phosphate (HA/TCP) and rhTGF-beta2 in buffer at a dose per implant of 1.2 microg (n = 6), 12 microg (n = 7), or 120 microg (n = 7) and placed in the left humerus. In these same animals, an internal control implant treated only with HA/TCP and buffer was placed in the right humerus. In a non-TGF-beta treated external control group of animals (n = 7), one implant was treated with HA/TCP while the contralateral implant was not treated with the ceramic. In vitro analyses showed that approximately 15%, of the applied dose was released within 120 h with most of the release occurring in the first 24 h. The TGF-beta treated implants had significantly more bone ingrowth than the controls with the greatest effect in the 12 microg/implant group (a 2.2-fold increase over the paired internal control (P = 0.004) and a 4-fold increase over the external control (P < 0.001)). The TGF-beta treated implants had significantly more bone formation in the gap than the controls with the greatest effect in the 12 and 120 microg groups (1.8-fold increases over the paired internal controls (P = 0.003 and P = 0.012, respectively) and 2.8-fold increases over the external controls (P < 0.001 and P = 0.001, respectively)). Compared to the external controls, the internal control implants tended to have more bone ingrowth (1.9-fold increase, P = 0.066) and had significantly more bone formation in the gap (1.7-fold increase. P = 0.008). Thus, application of rhTGF-beta2 to a porous-coated implant-stimulated local bone ingrowth and gap healing in a weakly dose-dependent manner and stimulated bone regeneration in the 3-mm gap surrounding the contralateral control implant, a site remote from the local treatment with the growth factor.     

Additive enhancement of implant fixation following combined treatment with rhTGF-beta2 and rhBMP-2 in a canine model

BACKGROUND: Gaps at the interface between implant and bone increase the risk of diminished implant fixation and eventual loosening. The purpose of the present study was to determine if combined use of recombinant human transforming growth factor-beta 2 (rhTGF-beta2) and bone morphogenetic protein 2 (rhBMP-2) led to greater implant fixation strength in the presence of interface gaps than the use of either growth factor alone. METHODS: Twenty-eight skeletally mature adult male dogs received one porous-coated titanium implant in the proximal part of each humerus, for a total of fifty-six implantation sites. Spacers were used to establish an initial 3-mm gap between the implant and the host bone at all fifty-six sites. Forty-two implants were coated with hydroxyapatite-tricalcium phosphate and were used in three growth-factor-treatment groups in which the implants placed in the left humerus were loaded with 12 microg of rhTGF-beta2 (Group 1, seven animals), 25 microg of rhBMP-2 (Group 2, seven animals), or 12 microg of rhTGF-beta2 combined with 25 microg of rhBMP-2 (Group 3, seven animals). In these animals, the twenty-one implants that were placed in the right humerus were loaded with buffer only to serve as contralateral controls. In Group 4 (seven animals), the implants were not coated with hydroxyapatite-tricalcium phosphate, the gap in the left humerus was lightly packed with autogenous bone graft, and the gap in the right humerus was left empty to serve as a contralateral control. All animals were killed at twenty-eight days. The primary end points included three mechanical variables: fixation strength, interface stiffness, and energy to failure. Secondary end points included bone ingrowth and bone volume and trabecular architecture in the gap and in a region located 2 mm medial to the implantation site. RESULTS: The hydroxyapatite-tricalcium phosphate coating had no effect on implant fixation, bone ingrowth, or bone formation in the 3-mm gap. Individual growth factor treatments led to 2.3 to 3.2-fold increases in fixation strength and stiffness as compared with the values for the contralateral controls (p < 0.05). The combined growth factor treatment led to 5.7-fold increases in fixation strength and stiffness compared with the values for the contralateral controls (p < 0.01). Autogenous bone graft treatment was associated with 4.5 to 6.4-fold increases in implant fixation strength and stiffness as compared with the values for the contralateral controls (p < 0.01). Compared with the relevant contralateral controls, energy to failure was increased 3.5-fold in association with TGF-beta2 alone (p < 0.05), 4.5-fold in association with TGF-beta2 combined with BMP-2 (p < 0.01), and 2.5-fold in association with autogenous bone-grafting. As much as 63% of the variance in the mechanical end points was associated with variance in bone volume and architecture in the 3-mm gap and in the region of interest located 2 mm medial to the implantation site (p < 0.01). CONCLUSIONS: In this animal model, the combined use of TGF-beta2 and BMP-2 led to more secure mechanical fixation of the implant than did the use of either growth factor alone and demonstrated results that were similar to those associated with the use of autogenous bone graft.     

Efficacy of autograft and freeze-dried allograft to enhance fixation of porous coated implants in the presence of interface gaps.

Autogenous cancellous bone and freeze-dried allogeneic cancellous bone were tested in a total of 41 adult male mongrel dogs. In each humerus, an implant with a commercially pure titanium fiber metal porous coating was placed in an overreamed cavity so that a uniform 3-mm gap was present between the implant and host cancellous bone. Graft material was placed in the gap of one humerus while the gap of the other humerus was left empty and served as a paired negative control. Histologically, both autograft and allograft appeared to aid repair of the defect, but quantitatively only autograft enhanced new bone formation within the defect. Treatment with autograft significantly increased the amount of bone ingrowth within the implants by nearly three-fold at 4 weeks and eight-fold at 8 weeks. The enhancing effect was recognizable as early as 2 weeks. The strength of fixation was increased by nearly seven-fold at 4 weeks and two-fold at 8 weeks in the autograft group, but this was only statistically significant at 4 weeks. Treatment with allograft did not enhance bone ingrowth at any time period, but had a small positive effect on strength of fixation at 4 weeks.     

The effect of different mineral frames on ectopic bone formation in mouse hind leg muscles induced by native reindeer bone morphogenetic protein

Introduction Bone morphogenetic proteins (BMPs) require carrier material for slow release and framing material for osteoconduction.Materials and methods The effect of a frame on early bone formation induced by partially purified native reindeer BMP in composite implants containing 3 mg of BMP, type IV collagen and tricalcium phosphate (TCP/Col/BMP) or hydroxyapatite (HA/Col/BMP) or biphasic tricalcium phosphate-hydroxyapatite (TCP/HA/Col/BMP) or biocoral (NC/Col/BMP) was evaluated using a mouse hind leg muscle pouch model. Collagen with native reindeer BMP (Col/BMP) and corresponding implants without native reindeer BMP served as controls. Evaluation was done by incorporation of ⁴⁵Ca, radiographically and histologically 3 weeks after the implantation.Results None of the implants without native reindeer BMP were able to induce new bone visible on radiographs. The area of new bone formation in the Col/BMP (p=0.026) and TCP/HA/Col/BMP (p=0.012) groups was significantly greater than in the TCP/Col/BMP group. The optical density of the new bone area was significantly greater in the TCP/HA/Col/BMP group than in the TCP/Col/BMP (p=0.036) or Col/BMP (p=0.02) groups. ⁴⁵Ca incorporation was many times greater in all the groups containing native reindeer BMP than in the corresponding groups without BMP. In the Col/BMP (p=0.046) and TCP/HA/Col/BMP (p=0.046) groups, ⁴⁵Ca incorporation was significantly greater than in the TCP/Col/BMP group. No significant differences were found in any parameters between HA/Col/BMP and NC/Col/BMP groups and the other BMP-containing groups.Conclusions Hydroxyapatite, biocoral and biphasic tricalciumphosphate-hydroxyapatite are equally good as framing material for native reindeer BMP, while tricalciumphosphate is somewhat worse. Osteoinduction of native reindeer BMP works well with collagen alone.     

重组人骨形态发生蛋白-2用于人工关节生物固定方法的研究

目的 探讨复合重组人骨形态发生蛋白-2(rhBMP2)植入体对骨-假体界面骨长入及结合强度的作用。方法将多孔金属表面植入体(PCA)与复合．rhBMP2的PCA植入体、HA涂层植入体及：PCA表面喷涂HA植入体植入犬皮质骨并综合运用X线摄片、软X线照相、不脱钙骨组织磨片、荧光显微镜检查、骨组织计量学分析及生物力学测定等方法对骨-植入体界面的骨长入及界面的结合强度进行了比较分析。结果术后软X线照相、组织学、骨组织计量学及生物力学比较分析显示复合rhBMP2的植入体在各时间组的新生骨形成率和界面剪切强度均优于其它各组;以4周时最为明显,且差异有非常显著意义。结论植入体复合rhBMP2后在促进早期骨-假体界面的骨长入和结合强度方面优于其它各种方法,有利于早期骨与假体间的结合和固定。     

Growth of new bone guided by implants in a murine calvarial model

New methods to increase vertical bone growth are needed to permit dental implant placement in patients with low alveolar ridge height after extended periods of tooth loss. While ectopic rodent models are typically used to evaluate new osteogenic implant surface coatings, a more relevant intramembraneous rodent model was needed to address the particular clinical need to grow a new layer of bone above an existing layer of bone. In this study we report on a novel murine calvaria model in which successful vertical bone growth around miniaturized dental implants was achieved when using non-glycosylated bone morphogenetic protein-2 (ng/rhBMP-2). Twenty CD-1 mice received two Ti implants each consisting of a Ti ring implant stabilized by a Ti screw into the occipital calvarial bone. Four groups were evaluated: control Ti, Ti+20 mug ng/rhBMP-2, hydroxyapatite (HA)-coated Ti, and HA+20 mug ng/rhBMP-2. The mice were sacrificed 21 days following implant placement. MicroCT analysis showed no new bone formation around the untreated Ti or the HA-coated implants, but demonstrated new bone growth in every dimension around and above the Ti+ng/rhBMP-2 and the HA+ng/rhBMP-2 treated implants. Histopathologic analysis showed that a thin fibrous capsule covered the untreated Ti implants. Limited bone-to-implant contact (BIC) was observed for the HA-coated implants, while in contrast both ng/rhBMP-2 treated groups exhibited extensive new supracalvarial woven bone that covered the implant and merged with the calvarial plate. Histomorphometrically, supracalvarial bone heights and bone widths and BIC were not statistically different from one another for the two ng/rhBMP-2 treated groups. However, the total supracalvarial bone surface area was significantly greater (p<0.05) for the Ti+ng/rhBMP-2 implants (7.2 mm(2)) than the HA+ng/rhBMP-2 (4.0 mm(2)) treated implants. The bone density within 1 mm around the implant was also significantly greater (p<0.05) for the Ti+ng/rhBMP-2 implants (9.9%) than the HA+ng/rhBMP-2 (4.0%) implants, indicating that HA coatings may not be required for sustained release when non-glycosylated BMP-2 is used. This new murine model is capable of discriminating between various bone augmentation strategies and may represent a clinically more relevant model for alveolar bone augmentation than the commonly used ectopic muscle pouch or long bone models.     

Postmortem comparative analysis of titanium and hydroxyapatite porous-coated femoral implants retrieved from the same patient: A case study

The results of bilateral postmortem analysis of titanium and plasma-sprayed hydroxyapatite (HA) porous-coated femoral components of the same Anatomic Porous Replacement design retrieved from a 35-year-old female donor are reported. Analysis was conducted using backscattered electron imaging, histology, and radiographic techniques. The appositional bone index, percent bone ingrowth, and mineral content were measured for both implants. The results showed a 177% higher appositional bone index (P=.014) for the HA porous-coated Anatomic Porous Replacement component compared to the titanium Anatomic Porous Replacement component. Backscattered electron analysis showed 50% more bone in the HA porous-coated implant (P=.028). The mineral content analysis demonstrated that the bone ingrown into the HA porous-coated device was 23% less mineralized (P=.016). The data from this case study suggested that plasma-sprayed HA porous-coated implants may assist in increasing the amount of bone ingrowth and skeletal attachment in total hip arthroplasties.     

Early biological fixation of porous implant coated with paste-retaining recombinant bone morphogenetic protein 2

The aim of this study was to evaluate the period required for stable initial bone-implant fixation with recombinant human bone morphogenetic protein 2 (rhBMP-2) in the bone marrow of a rabbit model. The porous implants being coated with β-tricalcium phosphate/polylactide-polyethylene glycol paste with 15, 30, or 60 μg of rhBMP-2 (n = 10) were implanted into animals in 3 experimental groups. In 2 control groups, the test implants were coated without rhBMP or no paste. In all groups, the implant was inserted for 3 and 6 weeks. At 3 weeks after implantation, the BMP-treated implants in the 2 lower dose groups had significantly more bone ingrowth to the implant surface than did the control groups, and the greatest effect occurred in the 30-μg rhBMP-2 group animals.     

Osteogenic protein 1 device stimulates bone healing to hydroxyapaptite-coated and titanium implants

This study evaluated the effects of osteogenic protein 1 (OP-1) placed in a gap around uncoated and hydroxyapatite (HA)-coated implants. Unloaded cylindrical titanium alloy implants were inserted in the femoral condyles of 16 skeletally mature dogs surrounded by a 3-mm gap. The gap around the implants was filled with 325 microg OP-1 in 130 mg bovine collagen type I as carrier (OP-1 device) or collagen carrier alone or left empty. All groups were tested with both HA-coated and uncoated implants, and the animals were sacrificed after 6 weeks. Implant fixation was determined by push-out test. Bone ongrowth and bone formation were evaluated by quantitative histomorphometry. OP-1 device enhanced mechanical fixation of uncoated and HA-coated implants, resulting in a higher shear strength than implants with collagen matrix and control implants. Bone ingrowth and bone formation in the gap were also stimulated 3-fold for OP-1 groups when compared with empty controls, but no difference was found between OP-1 groups and collagen matrix groups. This study suggests that the OP-1 device placed in a gap around uncoated and HA-coated implants is capable of enhancing mechanical fixation and periimplant bone formation. The collagen carrier alone also enhanced bone ongrowth and fixation significantly.     

Aging does not lessen the effectiveness of TGFbeta2-enhanced bone regeneration.

Controversy exists over the potency of bone healing in the aged skeleton, and there is concern that enhancement of bone regeneration after use of bone-stimulating growth factors may not be effective in the aged. In this study, 30 skeletally mature beagles (1-2 or 10-12 years old) had titanium implants placed bilaterally in the proximal humerus for a period of 4 weeks in a model of intramembranous bone regeneration. A bony defect made at the time of surgery created a 3-mm gap between the implant surface and the host bone. Some of the implants were treated with recombinant human TGFbeta2 (rhTGFbeta2) at various does (0.32-35 microg per implant), and some served as paired controls. The dose response was similar in young and old animals. The most effective dose, 35 microg, led to a 3-fold increase in the volume fraction of new bone within the gap in both the young (p = 0.001) and old (p = 0.002) animals. At this dose, there was a 5-fold increase in osteoblast surface. While age did not significantly affect the quantity of new bone formed as assessed by backscatter scanning electron microscopy, the older animals had thinner regenerated trabeculae that tended to be spaced more closely than the younger animals. Coupled with the finding that the increase in osteoid was greater in the old animals compared with the young animals, these qualitative differences suggest that there may have been a slight delay in the rate or a defect of mineralization in the old animals.     

A long-term study on defect filling and bone ingrowth using a canine fiber metal total hip model.

When performing primary and revision total hip arthroplasty (THA), bone defects are often encountered. At present, grafting osseous defects with autogeneic bone is a common means of treatment. In this study, defects in bone were created in the femora and acetabula of dogs being treated with cementless THA with a fiber metal implant (Group A) or a hydroxyapatite tricalcium phosphate (HA/TCP) sprayed implant (Group B). The following methods of defect filling were compared: (1) leaving defects unfilled, (2) filling with autogeneic bone graft, (3) filling with a 50:50 mixture of autograft and a biphasic ceramic composed of HA/TCP, and (4) filling with a collagen-HA/TCP-bone marrow mixture. Analysis of defect healing and the extent of ingrowth into the overlying fiber metal, at defect sites and sites distant from defects, was made at six, 12, and 24 weeks postimplantation. Defect healing was enhanced at six and 12 weeks in all grafted groups when compared with ungrafted controls. Bone ingrowth into the porous fiber metal overlying the defects was not significantly affected by grafting the defects, compared with the ungrafted defects. The extent of bone ingrowth into the fiber metal acetabular implant at sites away from the defects increased during the entire study. In contrast, the extent of bone ingrowth on the femoral side was maximal at 12 weeks. The HA/TCP coating enhanced ingrowth into the acetabular component at 12 weeks, compared with the uncoated prosthesis, but did not enhance ingrowth on the femoral side. The data from this study demonstrate that defect healing is enhanced with graft materials. However, this does not necessarily result in increased ingrowth into porous surfaces overlying osseous defects. General bone ingrowth and ingrowth at defect sites at 12 weeks postimplantation can be enhanced on the acetabular side with the use of HA/TCP-sprayed implants. However, no positive effect is seen with the use of an HA/TCP-sprayed femoral implant.     

Comparative study of human cancellous bone remodeling to titanium and hydroxyapatite-coated implants

The human cancellous bone response was compared in weight-bearing porous hydroxyapatite (HA) and titanium-coated implants placed in the distal medial femoral condyles of consenting staged bilateral knee patients. The Institutional Review Board approved study quantified the amount of bone ingrowth, the mineral apposition rate, and the bone mineral content. Results showed that the osteoconductive HA coating increased the amount of bone ingrowth by 8% (P=.018). The HA coating did not effect the mineral apposition rate of the bone but had an 8% lower bone mineral content at the implant interface (P=.042). The influence of HA coatings on human cancellous bone appears highly focal along the coating surface. Gaps of 50–500 μm filled with fibrous connective tissue were observed along the porous-coated surfaces of both implant types suggesting that HA coatings still require precision placement adjacent to human cancellous bone.     

Fixation of titanium and hydroxyapatite-coated implants in arthritic osteopenic bone.

Retrieval studies of porous-coated prostheses have demonstrated deficient bony ingrowth in high percentages. Possible reasons for this are lack of initial mechanical stability and the presence of osteopenia. The authors studied ingrowth of osteopenic bone into titanium alloy (Ti) porous-coated implants with and without hydroxyapatite (HA) coating in an experimental dog model. Unilateral osteopenia of the knee with a 20% reduced bone density as judged by computed tomography (CT) scanning (P less than .001) was induced in 12 mature dogs by weekly intraarticular injections of Carragheenin into the right knee for 12 weeks, with the left knee serving as control. Ti porous-coated cylinders were inserted in press-fit bilaterally in the lateral femoral condyles in six dogs. HA-coated titanium plugs were implanted similarly in another sex-, age-, and weight-matched group of six dogs. Bony ingrowth after 4 weeks was significantly reduced for Ti implants in osteopenic bone compared to control bone, but HA-coated implants were covered by equal amounts of bone tissue. Bone-implant shear strength of Ti implants also was reduced in osteopenic bone compared to control bone. In control bone, the anchorage of Ti implants was stronger than HA-coated implants, whereas the fixation of Ti and HA-coated implants was equal in the osteopenic bone. The results demonstrate that the bony fixation of Ti porous-coated implants is weakened by the presence of experimentally induced osteopenia. However, the fixation of HA-coated implants was not affected by the osteopenic condition in the surrounding bone. The fixation of Ti and HA-coated implants was equal in osteopenic bone, whereas the fixation of Ti porous-coated implants was superior to that of HA-coated implants in control bone.     

Effects of hydroxyapatite tricalcium phosphate coating and intracancellous placement on bone ingrowth in titanium fibermetal implants

The purpose of this study was to compare the host—bone response to hydroxyapatite/tricalcium phosphate (HA/TCP)-coated and noncoated titanium fibermetal implants placed in a load-sharing cancellous bone environment of the distal femurs of rabbits. The influence of implantation site was also investigated by comparing these intracancellous implants with intramedullary implants evaluated in a previous study. Three parameters were measured: percentage implant perimeter surface length in contact with new bone, percentage internal fibermetal surface length in contact with ingrown bone, and percentage of available pore space filled with bone. The HA/TCP coating significantly accelerated and increased bone ongrowth, new bone formation on the perimeter and internal surface of the implants. This effect was evident as early as 2 weeks after implantation. In contrast, there was no difference between HA/TCP-coated and noncoated implants in the bone ingrowth parameter, percentage of available pore space filled with bone, or pull-out strength. Scanning electron microscopy in the backscatter mode demonstrated that new bone formed directly onto the HA/TCP-coated fibers and did not usually form directly on noncoated fibers. Analysis of fluorochrome labeling revealed that bone formation in weeks 1 through 4 was primarily woven and there-after lamellar. Compared with intramedullary placement, intracancellous placement significantly accelerated the apposition of bone to the perimeter and internal surface of HA/TCP-coated implants and both accelerated and increased bone ingrowth as a percentage of available pore volume. These data show that the host response to titanium fibermetal implants is influenced both by HA/TCP coating and by the implantation site.     

三种钙磷陶瓷材料复合重组人骨形成蛋白-2体内成骨的研究

目的 探讨和比较3种钙磷陶瓷材料HA、TCP、HA／TCP复合重组入骨形成蛋白。2(rhBMP—2)体内异位成骨效果，为临床应用提供依据。方法 取35只3月龄Wistar大鼠，将复合rhBMP—2的3种钙磷陶瓷材料(1：1)植于鼠背部肌袋内，未复合rhBMP-2的上述3种单纯陶瓷材料为对照组。术后2、4和8周取材，测定植入物碱性磷酸酶(ALP)活性，通过HE染色和计算机图像分析进行组织学和组织计量学观察，比较新生骨组织的形成。结果 术后2、4周复合植入物ALP活性测定从高到低依次为HA、HA／TCP、TCP，但在相同rhBMP—2剂量下，其差异无统计学意义(P＞0．05)，与相对应单纯支架材料比较有统计学意义(P＜0．05)；组织学和组织计量学检测结果显示各复合材料组均有新骨形成，成骨量随时间推移而增加，2周时以HA/rhBMP—2成骨量较多，但3组间差异无统计学意义(P＞0．05)；8周时新骨形成以双相陶瓷HA／TCP最佳，相关参数和图像分析有统计学意义(P＜0．05)，成骨量8周较2、4周多，有统计学意义(P＜0．01)；3种单纯支架材料各观察期均无骨样组织形成。结论 双相陶瓷材料HA／TCP是携带rhBMP—2的钙磷陶瓷良好支架材料。     

骨形态发生蛋白-2壳聚糖微球复合组织工程支架修复兔股骨髁部骨缺损的实验研究

目的 探讨重组人骨形态发生蛋白-2(rhBMP-2)壳聚糖缓释微球复合聚乳酸-聚羟乙酸/磷酸三钙(PLGA/TCP)支架修复骨缺损的可行性和有效性.方法 取健康成年新西兰大白兔45只,在40只实验动物股骨髁部制备0.6 cm×1.0 cm骨缺损.实验分4组:A组:缺损组,B组:用PLGA/TCP空白支架修复骨缺损,C组:用等量rhBMP-2复合PLGA/TCP支架修复骨缺损,D组:用rhBMP-2壳聚糖微球复合PLGA/TCP支架修复骨缺损,每组10只动物.另5只动物为正常对照组(E组).应用X线、Micro-CT和组织病理学等方法检测术后4、12 周各实验组骨缺损修复效果.结果 术后4周X线片示:A组无新骨形成.B组有少量新生骨影像形成,C、D组骨缺损部位均有新骨影像形成.术后12周,Micro-CT结果显示:D组骨密度、骨体积分数、骨小梁厚度、骨小梁数目等指标均优于B组和C组,差异均有统计学意义(P<0.05),A组末检测到上述指标.术后4剧,D组可见大量骨组织形成,有部分成熟的骨小梁,PLGA/TCP支架大部分被降解.吸收.术后12周,D组支架和微球完全降解.骨缺损被成熟骨取代;B、C、D组骨长入率分别为5.78%±1.21%、37.26%±6.45%、74.25%±8.91%,3组之间比较差异均有统计学意义(P<0.05).结论 复合rhBMP-2壳聚糖微球的PLGA/TCP支架具有良好的骨缺损修复效果,临床应用前景较好.     

Gap healing enhanced by hydroxyapatite coating in dogs.

During prosthetic implantation, gaps between the implant surface and the surrounding bone may occur resulting in reduced implant stability. In these instances bone-conductive materials might augment the formation of hosting bone into the pores of the implant and insure earlier implant stabilization and fixation by bony ingrowth. Titanium-alloy cylinders with a porous-titanium-alloy plasma spray coating were implanted into the medial femoral condyles in six mature dogs. In another group of six dogs, matched in age, weight, and gender, hydroxyapatite (HA) coated implants were used. All implants were surrounded by a 1-mm gap. Unilateral osteopenia of the knee, with a 20% reduction of bone density as judged by computed tomography scanning, was induced by 12 weekly intraarticular injections of carrageenin into the right knee before surgery. Four weeks after implantation, the HA-coated implants were compared to the parent porous-titanium implants by mechanical testing and histomorphometry. A marked positive influence of HA coating on bone mineralization and the strength of the interfacial bone between the bone and implant was found. The increment in interface shear strength and shear stiffness was three- to fivefold in osteopenic bone and two-fold in control bone. Coating of an unloaded porous-titanium-coated implant with HA accelerates the rate of bone ingrowth and thereby provides relatively high, early interfacial shear strengths in the presence of an initial gap between bone and implant even in the presence of osteopenic host bone.     

Restoration of bone defect and enhancement of bone ingrowth using partially demineralized bone matrix and marrow stromal cells

PURPOSE: This study aimed to investigate the capability of combining marrow stromal cells (MSC) and partially demineralized bone matrix (PDBM) to fill bone defect and enhance bone ingrowth using a canine non-weight-bearing gap model. METHODS: Custom-made implants with 3mm gap between the porous surface and the host bone were used. The implants were inserted into the distal femurs of 25 mongrel dogs and the gaps were randomly assigned to be filled with culture-expanded autologous MSC-loaded PDBM, autograft, fresh-frozen allograft, PDBM alone, or nothing as controls. Histomorphometry using backscattered scanning electron microscopic examination, and mechanical push-out test were performed at 6 months after surgery. RESULTS: Histomorphometry showed that amounts of bone regeneration in the gap and bone ingrowth into the porous-coated surface in the MSC-loaded PDBM-treated group were comparable to those of autograft-treated group and were significantly greater than those of allograft-treated, PDBM-treated, or non-grafted groups. Mechanical test showed the same differences. CONCLUSION: The results of this study showed that combining PDBM and autologous culture-expanded MSC restored bone stock and enhanced bone ingrowth into the porous-coated area in a canine non-weight-bearing gap model. This combination may provide an option for reconstructing bone defect when we perform a cementless revision arthroplasty.     

Composite implant composed of hydroxyapatite and bone morphogenetic protein in the healing of a canine ulnar defect

BACKGROUND AND AIMS: Hydroxyapatite (HA) has been considered as a carrier material for bone morphogenetic proteins (BMP). The aim of this study was to evaluate the capacity of a composite implant of HA and native bovine BMP to heal a 2 cm segmental defect in the canine ulna. MATERIALS AND METHODS: A composite HA+BMP implant was compared with plain HA implants and cortical autografts. The fixation was accomplished with an intramedullary Kirschner wire. The bone union was evaluated by X-rays taken at operation and after 3, 6, 9, 12, 16, 25, 35 weeks and by histology and mechanical torsion tests. RESULTS: HA implants were not able to produce complete bone union even with BMP. There was some bridging between the implant and the bone in the defects treated with either plain HA or HA+BMP implant, the bridging being slightly more pronounced with HA+BMP. The autografts showed a significantly better capacity to heal the defect. The HA implant did not resorb markedly during the study. There was no significant difference in mechanical strength between the HA and HA+BMP groups. CONCLUSIONS: HA was not an adequate bone substitute material in this study model, and BMP was not able to enhance sufficiently the poor capacity of HA to heal canine ulnar defects.     

Porous cups with and without hydroxylapatite-tricalcium phosphate coating: 23 matched pairs evaluated with radiostereometry

Migration, wear, and presence of radiolucencies were studied in 23 matched pairs of patients operated with porous-coated acetabular cups with additional screw fixation. All implants had the same type of titanium fiber mesh. In each pair, one of the cups was plasma-sprayed with a coating consisting of 70% hydroxylapatite (HA) and 30% tricalcium phosphate (TCP). Radiostereometric analysis up to 2 years after the operation revealed smaller rotations around the horizontal axis in cups with HA/TCP coating. The migration of the cup center was not significantly influenced. Evaluation of femoral head penetration in 12 of the matched pairs did not reveal any significant difference. Immediately after operation, implants with HA/TCP coating had more central radiolucencies, which, despite minimal migration, disappeared during the follow-up. The clinical results did not differ between the 2 groups. The findings of less tilting and diminishing radiolucencies in the cups with HA/TCP coating suggest a more complete ingrowth of bone and a better sealing of the interface.