Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Biomaterials. 2010 Mar;31(9):2574-82. doi: 10.1016/j.biomaterials.2009.12.008. Epub 2009 Dec 28.
Healing large bone defects and non-unions remains a significant clinical problem. Current treatments, consisting of auto and allografts, are limited by donor supply and morbidity, insufficient bioactivity and risk of infection. Biotherapeutics, including cells, genes and proteins, represent promising alternative therapies, but these strategies are limited by technical roadblocks to biotherapeutic delivery, cell sourcing, high cost, and regulatory hurdles. In the present study, the collagen-mimetic peptide, GFOGER, was used to coat synthetic PCL scaffolds to promote bone formation in critically-sized segmental defects in rats. GFOGER is a synthetic triple helical peptide that binds to the alpha(2)beta(1) integrin receptor involved in osteogenesis. GFOGER coatings passively adsorbed onto polymeric scaffolds, in the absence of exogenous cells or growth factors, significantly accelerated and increased bone formation in non-healing femoral defects compared to uncoated scaffolds and empty defects. Despite differences in bone volume, no differences in torsional strength were detected after 12 weeks, indicating that bone mass but not bone quality was improved in this model. This work demonstrates a simple, cell/growth factor-free strategy to promote bone formation in challenging, non-healing bone defects. This biomaterial coating strategy represents a cost-effective and facile approach, translatable into a robust clinical therapy for musculoskeletal applications.
治愈大的骨缺损和不愈合仍然是一个重大的临床问题。目前的治疗方法,包括自体和同种异体移植物,受到供体供应和发病率、生物活性不足和感染风险的限制。生物治疗剂,包括细胞、基因和蛋白质,代表了有前途的替代治疗方法,但这些策略受到生物治疗剂传递、细胞来源、高成本和监管障碍等技术障碍的限制。在本研究中,胶原模拟肽 GFOGER 被用于涂覆合成的 PCL 支架,以促进大鼠临界尺寸节段性缺损中的骨形成。GFOGER 是一种合成的三螺旋肽,与涉及成骨的 alpha(2)beta(1)整合素受体结合。GFOGER 涂层在没有外源性细胞或生长因子的情况下被动吸附在聚合物支架上,与未涂层支架和空缺陷相比,显著加速和增加了非愈合股骨缺损中的骨形成。尽管骨体积存在差异,但在 12 周后,扭转强度没有差异,表明在该模型中仅改善了骨量而不是骨质量。这项工作证明了一种简单、无细胞/生长因子的策略,可以促进具有挑战性的、不愈合的骨缺损中的骨形成。这种生物材料涂层策略代表了一种具有成本效益和简单的方法,可以转化为用于肌肉骨骼应用的强大临床治疗方法。