Nussenbaum Brian, Krebsbach Paul H
Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, 660 South Euclid Ave., Campus Box 8115, St. Louis, MO 63110, USA.
Adv Drug Deliv Rev. 2006 Jul 7;58(4):577-91. doi: 10.1016/j.addr.2006.03.009.
Basic science advances in bone tissue engineering using osteoinductive protein therapy have already been translated to the use in patients with selected orthopedic problems. The story of the development of bone morphogenetic protein (BMP) osteoinductive therapy, from the discovery of this class of molecules in 1965 to the publication of randomized clinical trials in 2001 for tibial non-unions and 2002 for spinal fusion, is truly fascinating. Both clinical studies showed healing equivalence of the BMP-bioimplant compared to a free non-vascularized bone graft but without the associated donor site morbidity. These advances unfortunately have not lead to rapid application of using BMP osteoinductive protein therapy for reconstructing most craniofacial bone defects, with clinical case series beginning to be reported only for limited small-sized defects. This is a reflection of the complexity and unique characteristics of most craniofacial defects, which will likely require a more robust osteoinductive signal than delivering recombinant protein on a scaffold for clinically meaningful bone regeneration. Gene therapy approaches are promising for overcoming the unique challenges that are characteristic of craniofacial and dental defects.
使用骨诱导蛋白疗法的骨组织工程基础科学进展已转化应用于患有特定骨科问题的患者。骨形态发生蛋白（BMP）骨诱导疗法的发展历程，从1965年这类分子的发现到2001年针对胫骨不愈合以及2002年针对脊柱融合的随机临床试验的发表，着实引人入胜。两项临床研究均表明，与游离的非血管化骨移植相比，BMP生物植入物在促进愈合方面效果相当，但不存在相关供区并发症。遗憾的是，这些进展并未促使BMP骨诱导蛋白疗法迅速应用于大多数颅面骨缺损的修复，临床病例系列报道仅针对有限的小尺寸缺损。这反映出大多数颅面缺损具有复杂性和独特性，可能需要比在支架上递送重组蛋白更强有力的骨诱导信号，才能实现具有临床意义的骨再生。基因治疗方法有望克服颅面和牙齿缺损所特有的独特挑战。
