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经 BMP-2 缓慢释放功能化的去蛋白牛骨修复绵羊的临界尺寸骨缺损。

Deproteinized bovine bone functionalized with the slow delivery of BMP-2 for the repair of critical-sized bone defects in sheep.

机构信息

Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Research Institute MOVE, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands.

出版信息

Bone. 2013 Sep;56(1):110-8. doi: 10.1016/j.bone.2013.05.017. Epub 2013 Jun 1.

DOI:10.1016/j.bone.2013.05.017
PMID:23732874
Abstract

As an alternative to an autologous bone graft, deproteinized bovine bone (DBB) is widely used in the clinical dentistry. Although DBB provides an osteoconductive scaffold, it is not capable of enhancing bone regeneration because it is not osteoinductive. In order to render DBB osteoinductive, bone morphogenetic protein 2 (BMP-2) has previously been incorporated into a three dimensional reservoir (a biomimetic calcium phosphate coating) on DBB, which effectively promoted the osteogenic response by the slow delivery of BMP-2. The aim of this study was to investigate the therapeutic effectiveness of such coating on the DBB granules in repairing a large cylindrical bone defect (8 mm diameter, 13 mm depth) in sheep. Eight groups were randomly assigned to the bone defects: (i) no graft material; (ii) autologous bone; (iii) DBB only; (iv) DBB mixed with autologous bone; (v) DBB bearing adsorbed BMP-2; (vi) DBB bearing a coating but no BMP-2; (vii) DBB bearing a coating with adsorbed BMP-2; and (viii) DBB bearing a coating-incorporated depot of BMP-2. 4 and 8 weeks after implantation, samples were withdrawn for a histological and a histomorphometric analysis. Histological results confirmed the excellent biocompatibility and osteoconductivity of all the grafts tested. At 4 weeks, DBB mixed with autologous bone or functionalized with coating-incorporated BMP-2 showed more newly-formed bone than the other groups with DBB. At 8 weeks, the volume of newly-formed bone around DBB that bore a coating-incorporated depot of BMP-2 was greatest among the groups with DBB, and was comparable to the autologous bone group. The use of autologous bone and BMP-2 resulted in more bone marrow formation. Multinucleated giant cells were observed in the resorption process around DBB, whereas histomorphometric analysis revealed no significant degradation of DBB. In conclusion, it was shown that incorporating BMP-2 into the calcium phosphate coating of DBB induced strong bone formation around DBB for repairing a critical-sized bone defect.

摘要

脱蛋白牛骨(DBB)作为自体骨移植物的替代品,广泛应用于临床牙科。虽然 DBB 提供了一个骨传导支架,但由于它没有成骨诱导性,因此不能增强骨再生。为了使 DBB 具有成骨诱导性,先前已经将骨形态发生蛋白 2(BMP-2)掺入 DBB 的三维储库(仿生钙磷酸盐涂层)中,通过缓慢释放 BMP-2 有效地促进了成骨反应。本研究旨在研究这种涂层对 DBB 颗粒在修复绵羊大圆柱形骨缺损(8 毫米直径,13 毫米深度)中的治疗效果。将 8 组随机分配到骨缺损中:(i)无移植物材料;(ii)自体骨;(iii)仅 DBB;(iv)DBB 与自体骨混合;(v)DBB 吸附 BMP-2;(vi)DBB 带涂层但不含 BMP-2;(vii)DBB 带吸附 BMP-2 的涂层;(viii)DBB 带涂层结合 BMP-2 储存库。植入后 4 周和 8 周,取出样本进行组织学和组织形态计量学分析。组织学结果证实了所有测试移植物的优异生物相容性和骨传导性。在 4 周时,与其他 DBB 组相比,DBB 与自体骨混合或经涂层功能化的 DBB 显示出更多的新骨形成。在 8 周时,DBB 带涂层结合 BMP-2 储存库的新骨形成体积在所有 DBB 组中最大,与自体骨组相当。使用自体骨和 BMP-2 可促进更多骨髓形成。在 DBB 周围的吸收过程中观察到多核巨细胞,而组织形态计量学分析显示 DBB 没有明显降解。总之,结果表明,将 BMP-2 掺入 DBB 的钙磷酸盐涂层中可诱导 DBB 周围的强烈骨形成,用于修复临界尺寸的骨缺损。

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