同种异体骨移植的研究进展

同种异体骨移植是目前临床广泛使用于治疗各种骨缺损和促进脊柱融合的方法。根据处理方式的不同,同种异体骨可以分为：新鲜异体骨、深冻骨、冷冻干燥骨（fresh frozen allograft, FFA）和脱钙骨基质（demineralized bone matrix, DBM）。同种异体骨与新鲜的自体骨的愈合机制有着本质不同,其主要依靠“爬行替代”实现与宿主骨的融合,因此愈合速度慢、愈合质量差,容易发生骨不连和移植骨骨折,故存在较高的失败率。而复合生长因子、复合间充质干细胞以及红骨髓等方法可以提高异体骨愈合的速度。利用组织工程的原理与方法,采用复合移植的方法使异体骨得到活化,是今后异体骨移植研究与应用的发展方向。     

Bone regeneration: new findings and potential clinical applications.

Bone is a biologically privileged tissue in that it has the capacity to undergo regeneration as part of a repair process. Fracture healing is the most common and recognizable form of bone regeneration, but several other examples of bone regeneration have been observed in humans, suggesting that the ability to regulate bone regeneration as a therapeutic tool should be possible. Historically, efforts at limb lengthening have led to procedures for regenerating bone, such as the method of Ilizarov. This procedure, known as distraction osteogenesis, has applications in a variety of skeletal conditions, including the restoration of large skeletal defects, the transport of bone in cases of severe trauma with bone loss, and the correction of skeletal deformities. Fibrodysplasia ossificans progressiva is an example of how an abnormal metabolic condition can be viewed as evidence for the capacity of humans to regenerate large amounts of bone if the cellular and molecular signaling events are altered. Elucidation of the cellular and molecular basis for bone regeneration in humans - particularly the role of the human genome in relation to the expression of various growth factors and cytokines, such as the bone morphogenetic proteins - offers great potential for the treatment of orthopaedic conditions. Development of specific bone morphogenetic proteins as therapeutic substances to induce bone regeneration in patients is well under way. As methods for enhancing fracture healing, distraction osteogenesis, and other procedures are refined, the development of protein- and gene-based therapies for regulating bone formation should lead to a new era of orthopaedic practice.     

组织工程引导骨再生膜修复节段性骨缺损

目的　将组织工程技术和引导性骨再生技术相结合修复长骨节段性缺损。方法　兔 2 7只 ,动物模型均为桡骨 1 2cm节段性骨 骨膜缺损 ,分成 3组 ,A组 :利用体外构建的细胞 材料复合物膜修复 ;B组 :利用单纯的膜材料进行修复 ;C组 :断端不作任何处置作空白对照。分别观察 3、 6、 12周后进行X线观察和组织学观察。结果　A组的骨愈合优于B组 ,在 12周时已经完成骨缺损的修复 ,B组在术后 12周仍处于塑形改建之中 ;C组 12周形成典型的骨不连。结论　将组织工程的技术与引导性骨再生技术相结合 ,可以比单纯的引导性骨再生更好地修复长骨节段性缺损。     

Bone morphogenetic proteins in orthopaedic surgery

Bone morphogenetic proteins (BMPs) are growth factors which induce new bone formation. They are an increasingly important adjunct in the treatment of certain musculoskeletal disorders. Their underlying basic science and role in bone healing is explained. Delivery systems, safety issues and current evidence-based clinical applications of BMPs in orthopaedic surgery are described.     

Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction Osteogenesis via Endochondral Bone Formation

Background

Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction.

Methods

The immature rabbit tibial DO model (20 mm length-gain) was used. Twenty-eight animals received DBM 100 mg percutaneously at the end of distraction. Another 22 animals were left without further procedure (control). Plain radiographs were taken every week. Postmortem bone dual-energy X-ray absorptiometry and micro-computed tomography (micro-CT) studies were performed at the third and sixth weeks of the consolidation period and histological analysis was performed.

Results

The regenerate bone mineral density was higher in the DBM group when compared with that in the saline injection control group at the third week postdistraction. Quantitative analysis using micro-CT revealed larger trabecular bone volume, higher trabecular number, and less trabecular separation in the DBM group than in the saline injection control group. Cross-sectional area and cortical thickness at the sixth week postdistraction, assessed using micro-CT, were greater in the regenerates of the DBM group compared with the control group. Histological evaluation revealed higher trabecular bone volume and trabecular number in the regenerate of the DBM group. New bone formation was apparently enhanced, via endochondral ossification, at the site and in the vicinity of the injected DBM. DBM was absorbed slowly, but it remained until the sixth postoperative week after injection.

Conclusions

DBM administration into the distraction gap at the end of the distraction period resulted in a significantly greater regenerate bone area, trabecular number, and cortical thickness in the rabbit tibial DO model. These data suggest that percutaneous DBM administration at the end of the distraction period or in the early consolidation period may stimulate regenerate bone formation and consolidation in a clinical situation with delayed bone healing during DO.     

骨形态发生蛋白在颅颌面外科的应用及展望

面部骨骼发育畸形、骨缺损、骨不连等的修复重建是颅面外科的主要内容。目前,颅面部骨骼修复重建治疗的手段不外乎手术截骨重排结合骨修复材料植入。随着细胞生物学研究的不断深入,及对颅面部骨骼生长发育的深入认识,越来越多的研究表明生长因子在骨骼修复重建中广泛参与骨骼组织再生重建的局部调节,其中骨形态发生蛋白家族(Bone Morphogenetic Proteins,BMPs)是研究热点之一。本文对BMPs概况、促成骨作用机制、动物实验、初步临床应用等方面进行综述,为今后BMPs在颅面骨骼修复重建领域的进一步研究和应用提供一定的理论依据。     

Skeletal homeostasis in tissue-engineered bone.

Tissue-engineering strategies to stimulate bone regeneration may offer an alternative approach to conventional orthopaedic and maxillofacial surgical therapies. Over the last decade, significant advances have been accomplished in developing biomimetic matrices, growth factors, cell transplantation and gene delivery therapeutics to support new bone growth. However, it is not known if tissue-engineered bone recapitulates the biology of normal skeletal tissue in response to physiologic cues. Here, we report that bone formed by the differentiation of transplanted murine bone marrow stromal cells (BMSCs) responds to a systemically delivered calciotropic hormone. Ectopic ossicles in mice exposed to catabolic doses of parathyroid hormone (PTH) had increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts as compared to control mice. In contrast, treatment with anabolic doses of PTH promoted a marked increase in trabecular bone mass as analyzed by microcomputed tomography and histomorphometry. Our findings demonstrate that bone formed from transplanted BMSCs is responsive to normal physiologic signals, and can be augmented by the addition of a systemic anabolic agent. Because multiple and distinct ossicles can be generated in a single animal, this versatile system may be used to: (a) elucidate cellular/molecular mechanisms in bone regeneration; (b) study cell-to-cell interactions in the bone marrow microenvironment in health and disease; and (c) evaluate the efficacy of osteotropic agents that modulate bone turnover in vivo.     

Bone substitutes

Summary Biocompatible calcium phosphate ceramics has been used for several years in orthopeadic surgery. We have been using two new synthetic biphasic calcium phosphate ceramics (BCP) since September 1996 for bone defect filling in any orthopaedic or trauma operation where autograft use was not possible or even wanted. The first, Eurocer 400® has 300 to 500 micron wide macropores with a totally interconnected porosity. This salt seed like product can be used in bone defect filling, when solidity is not a major concern. The second, Eurocer 200® has not totally interconnected 200 micron large pores. Its main characteristic is a mechanical resistance up to 30 Mpa. We use it in any case of weight-bearing surgery. Different sizes and presentation forms are available and will be chosen according to the recipient site shape. We report one hundred and fifty cases with a six to thirty month follow-up. In one third of the patients hip revision surgery was addressed. Another third concerned recent trauma or sequelae cases,.whereas the last third involved cold orthopaedic procedures. General principles are the need of a living and non-infected site after thorough debridement if necessary. Osteocompatibility of calcium phosphate ceramic is confirmed by our results. We report no mechanical failure. In all cases X-rays show a progressive integration, with new bone formation. Our substitutes have been histologically studied in nine cases, four to fifteen months after implantation. New bone formation around and in the substitute is impressive. Indeed, their good mechanical properties without loss of biological quality is the most relevant feature of these BCPs, leading to a wider indication field; therefore we have now abandoned the use of any bony auto, allo or xenograft.Paper presented at the 1998 meeting of GECO (Arc 1800, Bourg-Saint-Maurice, France)     

胶原膜与复合自体骨髓的自体骨引导骨再生的实验研究

目的　观察胶原膜引导骨再生的效果 ,探讨胶原膜的理化特性、自体骨髓、膜下空间的维持在引导性骨再生中的作用。方法　建立兔双侧桡骨缺损模型 ,实验组移植胶原膜与复合自体骨髓的自体骨 ,对照组仅移植复合自体骨髓的自体骨 ,并行大体标本、组织学、生物力学检查。结果　实验组新骨生长及成熟骨替代过程较对照组快 ,且有增生的小血管及神经纤维。结论胶原膜是一种理想的骨移植材料 ,它能有效地发挥阻隔及引导的作用     

Growth factors in bone repair

The role of growth factors (GF) in bone repair is widely recognised, particularly for bone morphogenetic proteins (BMPs), fibroblast growth factor (FGF), insulin-like growth factors (IGFs), platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF). GF are usually stored in the extracellular matrix (ECM), but after injury are actively released by ECM, cells and platelets. In this paper, the use of different recombinant GF for bone repair stimulation is summarised in experimental research and clinical applications. Drug delivery systems, including carriers, cell or gene therapy, are needed to ensure a sustained local release of the factors, but efficacy and potential side effects of such systems require additional research prior to clinical applications. Current sources for delivery of a GF mixture into the site of bone repair are platelet gel and demineralised bone matrix. Nevertheless, the levels of GF in such preparations are affected by variability among donors and differences in preparation. Autogenous GF, produced by the patient himself during the bone repair process, potentially interfere with prosthetic devices or even have a role in implant loosening due to the periprosthetic tissue reaction. In conclusion, GF are key components of functional bone regeneration: screening of basic research results and controlled clinical trials are accelerating the development of GF in orthopaedic surgery.