Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
J Biomed Mater Res A. 2010 May;93(2):807-16. doi: 10.1002/jbm.a.32769.
Combinatorial polymer syntheses are now being utilized to create libraries of materials with potential utility for a wide variety of biomedical applications. We recently developed a library of photopolymerizable and biodegradable poly(beta-amino ester)s (PBAEs) that possess a range of tunable properties. In this study, the PBAE library was assessed for candidate materials that met design criteria (e.g., physical properties such as degradation and mechanical strength and in vitro cell viability and osteoconductive behavior) for scaffolding in mineralized tissue repair. The most promising candidate, A6, was then processed into three-dimensional porous scaffolds and implanted subcutaneously and only presented a mild inflammatory response. The scaffolds were then implanted intramuscularly and into a critical-sized cranial defect either alone or loaded with bone morphogenetic protein-2 (BMP-2). The samples in both locations displayed mineralized tissue formation in the presence of BMP-2, as evident through radiographs, micro-computed tomography, and histology, whereas samples without BMP-2 showed minimal or no mineralized tissue. These results illustrate a process to identify a candidate scaffolding material from a combinatorial polymer library, and specifically for the identification of an osteoconductive scaffold with osteoinductive properties via the inclusion of a growth factor.
组合聚合物合成现在被用于创建具有广泛生物医学应用潜力的材料库。我们最近开发了一系列可光聚合和可生物降解的聚(β-氨基酯)(PBAE)库,这些 PBAE 具有一系列可调节的特性。在这项研究中,根据设计标准(例如降解和机械强度等物理性质以及体外细胞活力和骨诱导行为)评估了 PBAE 库中候选材料作为矿化组织修复支架的适用性。然后,将最有前途的候选物 A6 加工成三维多孔支架,并皮下植入,仅引起轻度炎症反应。然后将支架植入肌肉内和颅骨临界缺损部位,单独或负载骨形态发生蛋白-2(BMP-2)。在有 BMP-2 的情况下,两个部位的样本均通过 X 光片、微计算机断层扫描和组织学显示出矿化组织的形成,而没有 BMP-2 的样本则显示出很少或没有矿化组织。这些结果说明了从组合聚合物库中鉴定候选支架材料的过程,特别是通过包含生长因子来鉴定具有成骨特性的骨诱导支架。