Native bovine bone morphogenetic protein improves the potential of biocoral to heal segmental canine ulnar defects

We studied the effect of a composite implant consisting of coral and native bovine bone morphogenetic protein (BMP) on the healing of 2 cm segmental defects in the canine ulna. Plain coral and cortical autograft bone implants were used as controls. The fixation was temporary for 9 weeks with an intramedullary Kirschner wire (6 ulnas with a composite implant of coral and BMP, 6 with plain coral and 6 with an autograft) or a plate and screws (3 ulnas with a composite implant and 3 with plain coral). X-rays were taken at 3, 6, 9, 12, 16, 26 and 36 weeks, and mechanical torsion tests were performed at the end of the study. The score for bone formation and bone union evaluated from radiographs was significantly higher in the composite implant group than in the plain coral group at 16 weeks, but the score was even higher with autografts. BMP accelerated the resorption of the coral implant. The mechanical strength of the composite implants was higher than that of the bones with a plain coral implant (P < 0.05), while the mechanical strength of the coral implants, even with BMP, was significantly lower than the strength of autografts (P < 0.01). In conclusion, BMP enhanced the capacity of a coral implant to heal a segmental ulnar defect by increasing bone formation, but the effect of this combination was not as good as that of a cortico-cancellous autograft.     

Bovine bone implant with bovine bone morphogenetic protein in healing a canine ulnar defect

Xenograft is considered an alternative material for bone transplantation, but its bone healing capacity is inferior compared to that of autografts and allografts. Here, we tested whether bone morphogenetic protein (BMP) addition enhances the suitability of demineralized xenogeneic bovine bone for bone grafting in dogs, and whether xenogeneic bone is a suitable carrier material for BMPs. The capacity of demineralized bovine bone implants, with and without native partially purified bovine BMP, to heal a 2-cm ulnar defect was determined in six dogs over a follow-up time of 20 weeks. No instances of bone union were seen, but there was slightly more bone formation in the xenografts with BMP, though the difference was not statistically significant. The ulnas treated with an implant with BMP were also mechanically stronger, but the difference was not significant. Computed tomography scans showed no differences in the implant area in bone density, bone mineral content, or bone cross-sectional area. It is concluded that native, partially purified BMP does not sufficiently improve the suitability of bovine demineralized xenografts as a bone substitute material for dog. Demineralized xenogeneic bone does not seem to be a feasible carrier material for BMP.     

Augmentation of fracture healing by hydroxyapatite/collagen paste and bone morphogenetic protein‐2 evaluated using a rat femur osteotomy model

In fracture treatment, biological bone union generally depends on the bone's natural fracture healing capacity, even in surgically treated cases. Hydroxyapatite/collagen composite (HAp/Col) has high osteoconductivity and stimulates osteogenic progenitors. Furthermore, it has the potent capacity to adsorb bone morphogenetic proteins (BMPs). In this study, we prepared an injectable HAp/Col paste and evaluated its augmentation of bone union. Furthermore, the effect of HAp/Col paste combined with BMP‐2 was also evaluated. We used a rat femur osteotomy model with a defect size of 1 mm. Male Wistar rats were assigned to one of the following four groups; a control group without any implant, a HAp/Col implant group, a group that received an absorbable collagen sponge (ACS) implant impregnated with BMP‐2 (1 μg), and a group that received a HAp/Col implant impregnated with BMP‐2 implant. Micro‐CT analysis, three‐point bending tests, and histological evaluation were performed. Bone union was achieved in two of eight cases in the HAp/Col group, five of eight cases in the ACS + BMP‐2 group, and all cases in the HAp/Col + BMP‐2 group at 8 weeks post‐surgery. The control group did not achieve bone union. In addition, in the HAp/Col + BMP‐2 group, the biomechanical strength of the fused femurs was comparable to that of the contralateral intact femur; the ratio of the mechanical load at the breaking point of the osteotomy side relative to that of the contralateral side was 1.00 ± 0.151 (SD). These results indicate that HAp/Col paste with or without BMP‐2 augments bone union. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:129–137, 2018.     

A Bioactive Coating Enhances Bone Allografts in Rat Models of Bone Formation and Critical Defect Repair

Bone allografts are inferior to autografts for the repair of critical‐sized defects. Prior studies have suggested that bone morphogenetic protein‐2 (BMP‐2) can be combined with allografts to produce superior healing. We created a bioactive coating on bone allografts using polycondensed deoxyribose isobutyrate ester (PDIB) polymer to deliver BMP‐2 ± the bisphosphonate zoledronic acid (ZA) and tested its ability to enhance the functional utility of allografts in preclinical Wistar rat models. One ex vivo and two in vivo proof‐of‐concept studies were performed. First, PDIB was shown to be able to coat bone grafts (BGs). Second, PDIB was used to coat structural allogenic corticocancellous BG with BMP‐2 ± ZA ± hydroxyapatite (HA) microparticles and compared with PDIB‐coated grafts in a rat muscle pouch model. Next, a rat critical defect model was performed with treatment groups including (i) empty defect, (ii) BG, (iii) collagen sponge + BMP‐2, (iv) BG + PDIB/BMP‐2, and (v) BG + PDIB/BMP‐2/ZA. Key outcome measures included detection of fluorescent bone labels, microcomputed tomography (CT) quantification of bone, and radiographic healing. In the muscle pouch study, BMP‐2 did not increase net bone volume measured by microCT, however, fluorescent labeling showed large amounts of new bone. Addition of ZA increased BV by sevenfold (p < 0.01). In the critical defect model, allografts were insufficient to promote reliable union, however, union was achieved in collagen/BMP‐2 and all BG/BMP‐2 groups. Statement of clinical significance: These data support the concept that PDIB is a viable delivery method for BMP‐2 and ZA delivery to enhance the bone forming potential of allografts. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2278–2286, 2019     

Composite implant of native bovine bone morphogenetic protein (BMP), collagen carrier and biocoral in the treatment of resistant ulnar nonunions: report of five preliminary cases

Introduction Bone morphogenetic protein (BMP) has been shown to induce bone formation and union in long bone defects and nonunions. There are, however, no previous reports of BMP being used for ulnar nonunions. We report on five cases of resistant ulnar nonunions treated with a composite implant consisting of a biocoral frame, collagen carrier, and bovine BMP.Materials and methods Four diaphyseal and one olecranon ulnar nonunions were treated using BMP/coral implant combined with internal fixation. Additional autografting was used in three cases. All of the cases were challenging in their own ways: Three of the patients had been operated on earlier for their nonunion without success, one had a 40 mm bone loss, and one had a 9-month-old untreated olecranon fracture. After excision of the sclerotic surfaces of the nonunion, the gap was filled with autograft and a composite implant containing BMP. Fixation was done with a compression plate in the diaphyseal nonunions and with a tension band in the olecranon nonunion.Results Solid union was achieved in all five cases. No infections or other adverse effects were encountered.Conclusion These preliminary results suggest that BMP-containing implants might be a feasible alternative or superior to autografting in the treatment of resistant ulnar nonunions.     

硅胶膜管联合BMP/HA修复大块骨缺损机制初探

目的 探讨硅胶膜（SGM）管与骨形态发生蛋白（BMP）／羟基磷灰石（HA）复合物联合修复兔长骨缺损的机制。方法 制备兔桡骨中段1.2cm缺损,实验组缺损区外围包绕SGM，其内分别填充BMP／HA，HA材料，对照组仅填充HA；空白组骨缺损区未填充。通过X线摄片，光学显微镜和扫描电镜观察骨缺损区的影像学，组织学和超微结构变化。结果 术后1个月，SGM＋BMP／HA组骨缺损区有大量的类骨质形成。术后2个月，SGM＋BMP／HA组大量骨膜来源的分化细胞沿SGM管的内，外面及HA间隙向骨缺损区内生长，植入区可见大片的膜内成骨征象。术后3个月，GM＋BMP／HA组骨缺损区愈合。此时，SGM＋HA组与对照组骨缺损区有少量新骨形成，空白组缺损区为纤维组织充填。结论 SGM管与BMP／HA联合修复骨缺损的机制为SGM的屏障作用使骨缺损区受到引导成骨和诱导成骨的双重作用，其中诱导成骨方式为膜内骨发生。     

Osteokonduktion und Hydroxylapatitkeramiken

In an animal study, the capacity of hydroxyapatite (HA) ceramics for osteoconduction was examined in cortical trephine defects in the tibial diaphysis of minipigs. The HA cylinders used had a spongy structure with interconnecting open pores and did not demonstrate any osteoconductive effect in the initial phase, resulting in a overall poor healing of the bone defects. In the late phase of defect regeneration bone was found to cover implant structures preferentially. This result can be interpreted as secondary osteoconduction, or even as an affinity of nonresorbed HA implants for bone based on the chemical and crystallographic relationship between HA and bone mineral.     

Regenerative repair of bone defects with osteoinductive hydroxyapatite fabricated to match the defect and implanted with combined use of computer-aided design, computer-aided manufacturing, and computer-assisted surgery systems: a feasibility study in a canine model

BackgroundCurrently, regenerative repair of large bone defects that result from bone tumor resection or severe trauma is a challenging issue because of the limited regenerative potential of bone and treatment modalities. The aim of this study was to achieve repair of large bone defects to the original three-dimensional (3D) anatomical state by combining computer-aided technologies and local delivery of bone morphogenetic protein (BMP) in a canine model.MethodsComputed tomography (CT) images of the pelvic bone of each dog were obtained, and an imaginary spherical malignant bone tumor of 15-mm diameter was placed in the left ilium of a canine on the 3D CT image. Resection of the whole tumor with a 10-mm margin of healthy bone was planned preoperatively by using computer-aided design (CAD) software. In addition, an image of the implant to be used to fill the resulting bone defect was constructed on the computer image. A porous hydroxyapatite (HA) implant identical to the imaged bone defect was made by shaving a tetragonal porous apatite block (40 × 20 × 10 mm) with a computer-aided manufacturing system operated by using the CT-image data of the bone defect obtained from the CAD system. To resect the iliac bone as planned preoperatively on the 3D CT image, computer-aided surgery was performed using the CT data. The defect was filled with the HA implant fabricated as described and coated with a putty carrier either with BMP-2 (BMP group, n = 6) or without BMP-2 (control group, n = 6).ResultsIn the BMP group, new bone formation was noted around each implant on CT images at 3 weeks after surgery and was remodeled to restore the original anatomy of the ilium on serial CT images. At 12 weeks, the implant was enclosed within new bone, and histological analysis revealed bone formation on and within the implant. Little bone formation was noted in the control group.ConclusionsThis new method may enable efficacious and precise regenerative repair of large bone defects without bone grafting.     

Repair of bone defects in revision hip arthroplasty by implantation of a new bone-inducing material comprised of recombinant human BMP-2, Beta-TCP powder, and a biodegradable polymer: an experimental study in dogs.

A recombinant BMP-2-retaining putty-form implant in combination with a hip prosthesis was used to reconstruct a canine hip joint with defects similar to those encountered in revision total hip arthroplasty (THA). The bone defects were made by resecting the medial half of the proximal femur and the superior acetabular bone with inner iliac wall perforation in 10 dogs. In five dogs, hip prostheses were implanted with the putty material consisting of a synthetic polymer (poly D,L-lactic acid-polyethylene glycol block copolymer), beta-tricalcium phosphate powder, and recombinant human BMP-2 in each defect (BMP/Polymer/TCP group). In the remaining five dogs, the same material without rhBMP-2 (control group) was implanted. In the BMP/Polymer/TCP group, new radiopaque shadows began to appear 4 weeks after surgery at the defects around the hip prostheses on both the femoral and acetabular sides. At 12 weeks, the defects were completely filled with new bone in contact with the prosthesis. On histology, the rhBMP-2/Polymer/beta-TCP composite putty implants had been completely resorbed and replaced by new bone. Repair of the bone defects was not seen in the control group. The ability of this material to restore bone effectively eliminates the dependency on bone grafts of autogeneic or allogeneic origin for revision hip arthroplasty and thus opens up a potential new treatment approach in hip cases requiring this type of surgery.     

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.     

The evaluation of a biphasic calcium phosphate ceramic for use in grafting long-bone diaphyseal defects

The effectiveness of a sintered hydroxyapatite-tricalcium phosphate (HA-TCP) ceramic in bridging large diaphyseal defects in the canine ulna was studied. One-hundred percent morselized HA-TCP, a 50:50 mixture of morselized HA-TCP, and autogenous cancellous bone, and 100% autogenous cancellous bone were used to bridge 2.5-cm defects in the left ulnae of three groups of six dogs each. At 24 weeks the ulnae were explanted and studied by radiography, microradiography, mechanical testing, and histology. Pure HA/TCP was not osteoinductive, and four of six ulnae in this group progressed to a fibrous nonunion. The HA/TCP-cancellous bone mixture and pure cancellous bone were approximately equal in effect, leading to good callus formation at 4 weeks and strong bony union by 24 weeks, with no evidence of bioincompatibility. Morselized HA/TCP promises to be useful as a graft extender when mixed with autogenous cancellous bone.     

Evaluation of bovine-derived bone protein with a natural coral carrier as a bone-graft substitute in a canine segmental defect model

The efficacy of a bone-graft substitute (bovine-derived bone protein in a carrier of natural coral) in the healing of a segmental defect of a weight-bearing long bone was evaluated. Twenty dogs, divided into two groups, underwent bilateral radial osteotomies with creation of a 2.5 cm defect. On one side of each dog, the defect was filled with autogenous cancellous bone graft. Contralateral defects received, in a blinded randomized fashion, cylindrical implants consisting of natural coral (calcium carbonate) or calcium carbonate enhanced with a standard dose of bovine-derived bone protein (3.0 mg/implant; 0.68 mg bone protein/cm³). The limbs were stabilized with external fixators, and all animals underwent monthly radiographs. They were killed at 12 (group 1) or 24 (group 2) weeks, and regenerated bone was Studied by biomechanical testing and histology. Radiographic union developed in all 20 radii with autogenous cancellous bone grafts and in all 10 of the radii with the composite implants. None of the radii with implants of calcium carbonate alone showed radiographic evidence of union. This represented a statistically significant difference between implant types. In addition, calcium carbonate implants both with and without bone protein demonstrated radiographic evidence of near total resorption of the radiodense carrier by 12 weeks. This resorption facilitated radiographic evaluation of healing. Mean values for. biomechanical parameters of radii with the composite implants exceeded those for the contralateral controls at 12 and 24 weeks; the difference was statistically significant at 12 weeks. Histology revealed scant residual calcium carbonate carrier at either time in the defects with calcium carbonate implants; however, a moderate amount was present in defects with the composite implants. In these specimens, the residual carrier was completely surrounded by newly formed bone that may have insulated the calcium carbonate from further degradation. The present study used a carrier of granular calcium carbonate reconstituted with bovine type-I collagen to deliver an osteoinductive protein to the defect site. This carrier is of nonhuman origin (eliminating the risk of disease transmission or antigenicity) and resorbs rapidly. In this model, bovine-derived bone protein in a natural coral carrier performed consistently better than the gold standard autogenous cancellous bone graft in terms of the amount of bone formation and strength of the healed defect. This may have implications for removal of hardware or resumption of weight-bearing in certain clinical situations. These data also indicate that coralline calcium carbonate alone. represents a poor option as a bone-graft substitute in this critical-sized segmental defect model.     

Autogeneic bone marrow and porous biphasic calcium phosphate ceramic for segmental bone defects in the canine ulna.

The purpose of this study was to evaluate a porous biphasic hydroxyapatite-calcium phosphate ceramic as a modifier and extender of an autogeneic marrow graft for filling a 2.5-cm segmental bony defect. Twenty adult mongrel dogs were surgically treated to create diaphyseal defects in the left ulnae. The defects were (1) filled with autogeneic bone marrow mixed with granular hydroxyapatite-tricalcium phosphate ceramic (granular ceramic); (2) grafted with a solid block of ceramic soaked in autogeneic bone marrow (block ceramic); (3) received no graft (no implant); or (4) were grafted with autogeneic bone marrow alone (bone marrow). All animals were followed clinically and roentgenographically for 24 weeks and then killed. Repair of diaphyseal defects with the block ceramic led to three solid unions and three fibrous unions; with the granular ceramic implants and marrow, the defects of five dogs formed solid unions, and one progressed to a fibrous union. Defects in all five dogs grafted with autogeneic bone marrow united. The three dogs with no implant formed nonunions. Histology showed normal marrow and only a light immune reaction. Complete bridging of the defect in the dogs treated with the granular ceramic occurred significantly earlier than bridging in the dogs grafted with bone marrow alone. Histomorphometry, performed on the block ceramic implants indicated active resorption of ceramic. Clinically, addition of ceramic to a marrow graft improved the handling characteristics of the graft material and accelerated healing according to roentgenographic evaluation.     

Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect

BACKGROUND: Mesenchymal stem cells from adult bone marrow are multipotent cells capable of forming bone, cartilage, and other connective tissues. In a previous study, we demonstrated that autologous mesenchymal stem cells could repair a critical-sized bone defect in the dog. The objective of this study was to determine whether the use of allogeneic mesenchymal stem cells could heal a critical-sized bone defect in the femoral diaphysis in dogs without the use of immunosuppressive therapy. METHODS: A critical-sized segmental bone defect, 21 mm in length, was created in the mid-portion of the femoral diaphysis of twelve adult dogs that weighed between 22 and 25 kg. Each defect was treated with allogeneic mesenchymal stem cells loaded onto a hollow ceramic cylinder consisting of hydroxyapatite-tricalcium phosphate. A complete mismatch between donor stem cells and recipient dogs was identified by dog leukocyte antigen typing prior to implantation. The healing response was evaluated histologically and radiographically at four, eight, and sixteen weeks after implantation. The radiographic and histological results at sixteen weeks were compared with the historical data for the control defects, which included defects that had been treated with a cylinder loaded with autologous mesenchymal stem cells, defects treated with a cylinder without mesenchymal stem cells, and defects that had been left untreated (empty). The systemic immune response was evaluated by the analysis of recipient serum for production of antibodies against allogeneic cells. RESULTS: For defects treated with allogeneic mesenchymal stem cell implants, no adverse host response could be detected at any time-point. Histologically, no lymphocytic infiltration occurred and no antibodies against allogeneic cells were detected. Histologically, by eight weeks, a callus spanned the length of the defect, and lamellar bone filled the pores of the implant at the host bone-implant interface. Fluorescently labeled allogeneic cells were also detected. At sixteen weeks, new bone had formed throughout the implant. These results were consistent with those seen in implants loaded with autologous cells. Implants loaded with allogeneic or autologous stem cells had significantly greater amounts of bone within the available pore space than did cell-free implants at sixteen weeks (p < 0.05). CONCLUSIONS: The results of this study demonstrated that allogeneic mesenchymal stem cells loaded on hydroxyapatite-tricalcium phosphate implants enhanced the repair of a critical-sized segmental defect in the canine femur without the use of immunosuppressive therapy. No adverse immune response was detected in this model.     

Treatment of congenital pseudarthrosis of the tibia with native bovine BMP: a case report

Bone morphogenetic proteins (BMP) have been shown to induce bone formation and union in long bone defects and nonunions. We report a case of congenital pseudarthrosis of the tibia treated with a composite implant consisting of a biocoral frame, collagen carrier, and native bovine BMP extract. A six-year-old boy had persisting congenital proximal tibial pseudarthrosis despite six prior operations. At surgery, the sclerotic surfaces of both fragments were excised, fixation was performed using Ilizarov's device, and the composite implant and an autograft were applied to the nonunion site. Three months after the operation, radiographs showed union, and at four months, the Ilizarov device was removed. Two years later, the proximal pseudarthrosis remained clinically and radiologically united. It is concluded that BMP may contribute to the healing of congenital tibial pseudarthrosis of the tibia.     

Healing in peri‐implant gap with BMP‐2 and systemic bisphosphonate is dependent on BMP‐2 dose—A canine study

The bone–implant interface of cementless orthopedic implants can be described as a series of uneven sized gaps with discontinuous areas of direct bone–implant contact. Bridging these voids and crevices by addition of an anabolic stimulus to increase new bone formation can potentially improve osseointegration of implants. Bone morphogenetic protein 2 (BMP‐2) stimulates osteoblast formation to increase new bone formation but also indirectly stimulates osteoclast activity. In this experiment, we investigate the hypothesis that osseointegration, defined as mechanical push‐out and histomorphometry, depends on the dose of BMP‐2 when delivered as an anabolic agent with systemic administration of the anti‐resorptive agent zoledronate to curb an increase in osteoclast activity. Four porous coated titanium implants (one with each of three doses of surface‐applied BMP‐2 (15 µg; 60 µg; 240 µg) and untreated) surrounded by a 0.75 mm empty gap, were inserted into the distal femurs of each of twelve canines. Zoledronate IV (0.1 mg/kg) was administered 10 days into the observation period of 4 weeks. Bone–implant specimens were evaluated by mechanical push‐out test and histomorphometry. The 15 µg implants had the best fixation on all mechanical parameters and largest surface area covered with new bone compared to the untreated, 60 and 240 µg implants, as well as the highest volume of new bone in the implant gap compared to 60 and 240 µg implants. The results in a canine implant model demonstrated that a narrow range of BMP‐2 doses have opposite effects in bridging an empty peri‐implant gap with bone, when combined with systemic zoledronate. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1406–1414, 2018.

     

骨形成蛋白-脱钙骨基质颗粒-骨水泥复合材料修复狗股骨微波灭活骨缺损后的长期观察

目的 :探讨骨形成蛋白 (BMP) 脱钙骨基质颗粒 (DBM ) -骨水泥 (BC)复合材料修复狗股骨微波灭活骨缺损后的生物学过程和归宿。方法 :对BMP DBM BC复合材料进行综合评价和植入动物体内进行了初步观察后 ,进一步对实验动物进行X射线照相、99Tcm MDP骨显像、大体标本观察、组织学观察、土霉素荧光标记和印度墨汁灌注染色观察。结果 :X射线照相 :术后随时间延长复合材料与宿主骨边界模糊程度增加。99Tcm MDP骨显像 :术后 18个月时实验侧同位素浓集仍略高于正常骨组织。大体标本 :初期可见复合材料处有充血炎性反应 ,至 9个月时炎性反应消退。组织学观察 :随时间延长 ,材料内部新生骨增多 ,“生物铆定”增强。土霉素荧光标记 :复合材料内大部分DBM所在部位呈现较强的黄色荧光。印度墨汁灌注 :复合材料内有大量的墨染血管。结论 :BMP DBM BC复合材料修复狗股骨微波灭活骨缺损后能够诱导新骨形成 ,复合材料与宿主骨最终形成“生物铆定”。     

Quantitative comparisons of healing in cranial fresh autografts, frozen autografts and processed autografts, and allografts in canine skull defects

Adult dog skull defects larger than 17 mm do not spontaneously heal. A quest for a potentially viable, cosmetically, mechanically, and technically acceptable template for human cranial reconstruction prompted a comparison of processed autogeneic and allogeneic bone implants with a fresh autograft control in the dog. Quantitative reproducible observations demonstrated that fresh calvarial bone autografts were superior to the nonviable implants in volume percent defect filled, mm2 new cortical bone, mm2 new and old cortical bone, and cortical bone porosity. Frozen autografts achieved 75%, antigen-extracted, autolyzed, partially demineralized auto- and allografts, 50% of the overall efficiency of fresh autografts. Fresh cancellous bone added to allografts did not improve long-term repair. Remodeling of all grafts appeared consistent with osteoconductive invasion by peripheral host endosteal and diploic elements; host external periosteum and dura contributed less. Central osteoinductive recruitment of mesenchymal cells from muscle or dura seemed not to occur in the adult dog. Partially demineralized dog calvarial grafts were resorbed without acting as a template for new bone formation. Surface demineralization, antigen extraction, and autolytic digestion of autografts and allografts, with or without fresh iliac bone, did not improve calvarial bone regeneration in adult dogs.     

羟基磷灰石/超高分子聚乙烯复合材料的组织相容性及骨传导性实验研究

目的　旨在证实羟基磷灰石 超高分子聚乙烯 (hydroxyapatite ultra highmolecularweightpolyethtlene ,HA UHMWPE)复合物具有HA的良好生物性能和骨传导性 ,又保留有超高分子聚乙烯的可塑性。方法　分别对 2 4只新西兰白兔行HA、HA UHMWPE、UHMWPE材料眶上缘置入 ,于术后 1、4、8、12周行大体、光镜组织学和电镜检查。结果　置入物无脱出、移位。组织学检查显示 ,HA组植入物在术后 1周即有新生血管长入和成纤维细胞活跃增殖 ,在术后 8周时可见骨细胞 ,术后 12周可见钙盐呈板状骨样沉积。而在HA UHMWPE组中材料的边缘反应同HA组。UHMWPE组在术后 1周有薄层纤维结缔组织包裹。电镜检查 ,在HA及HA UHMWPE组未见骨细胞 ,UHMWPE组见其包膜胶原纤维排列清晰。结论　HA UHMWPE复合物具有HA的良好生物活性及骨传导性 ,因此此复合物有望成为一种较理想的骨替代材料 ,尤其是眶骨整复的替代材料。     

Reindeer BMP extract in the healing of critical-size bone defects in the radius of the rabbit

Background?Native BMP extracts from reindeer effectively induce ectopic new bone formation in vivo, but their bone healing properties have not yet been evaluated. We investigated the effect of reindeer BMP extracts on the healing of long bone defects.

Methods?The implants tested contained 5?mg or 10?mg of unsterilized BMP extract from reindeer and 10?mg of gamma-sterilized BMP extract administered with collagen carrier (Lyostypt, B. Braun, Germany). 70 μg of rhBMP-2 with collagen carrier (InductOs; Wyeth Europa) served as positive control, and collagen implants (Lyostypt) and untreated defects served as negative controls. New Zealand White rabbits with 1.5?cm of critical-size radius bone defects were used, with 8 weeks of follow-up.

Results?Radiographic analysis showed bone formation (BF) to be higher in all groups containing BMPs than in the untreated controls. BF was also higher in the rhBMP-2 group, and marginally higher in the group treated with 10?mg of unsterilized reindeer BMP extract (p = 0.06) as compared to the collagen controls. Bone union (BU) was better in the unsterilized BMP extract groups and rhBMP-2 group than in the untreated controls. BU was also better in the implants with 10?mg of unsterilized reindeer BMP extract and rhBMP-2 than in the collagen-treated implants. The mean area of new bone at the site of the defect proved to be higher in all implants containing BMP than in the untreated defects. It was also higher in the groups with 10?mg of unsterilized reindeer BMP extract and rhBMP-2 than in the collagen-treated controls. Mechanical tests showed torsional stiffness of the bones to be higher in the group with 10?mg of unsterilized BMP extract than in the collagen group. The mean cross-sectional bone area measured by pQCT densitometry was higher in the rhBMP-2 group than in the collagen group. The mean bone density at the defect area was higher in the group with 10?mg of unsterilized BMP than in the rhBMP-2 group.

Interpretation?We conclude that both reindeer BMP extract and rhBMP-2 induced improved healing of the rabbit radius bone defects at the doses used. Gamma sterilization of reindeer BMP extract reduced osteoinductivity slightly, but not significantly.