Nanoscale Polymeric Templates for Orthopedic Tissue Engineering

描述（申请人提供）：自体松质骨是目前应用最广泛的骨移植材料。然而，自体松质骨移植存在一些问题，如额外的疤痕组织形成、供体部位发病率、疼痛、长期康复、深度感染、炎症风险增加和可用性受限。这些问题促使人们设计合成骨支架来替代自体松质骨移植物。合成组织工程支架提供了一种仿生结构，它利用天然的生物级联来促进愈合，以及天然组织的整合和再生。随着细胞信号传导及其后续功能在组织工程中的作用越来越清晰，组织工程师正在开发多功能生物活性支架，旨在加速自然愈合过程，同时防止植入后可能发生的病理。理想的支架在生物降解的同时能够呈现一个物理化学的仿生环境，因为原生组织分别整合和积极促进或阻止理想和不理想的生理反应。因此，提出的研究计划的假设和具体目标是：特定目标1：开发用于骨科组织工程应用的高度均匀的微/纳米级支架的最佳制造工艺，这些支架具有可控的几何形状和生物活性。特异性目的3确定微/纳米级支架的体内生物相容性和骨整合特性考虑到目前临界尺寸缺陷的金标准治疗的局限性，可生物降解的合成骨支架在未来的治疗方案中具有很大的前景。因此，合成骨组织工程支架在过去的二十年中得到了积极的研究，现在已经成为修复骨缺损的一种有希望的替代疗法。组织工程背后的基本概念是利用人体对组织损伤的自然生物反应与工程原理相结合。成功的合成骨支架促进祖细胞迁移到支架上（骨传导），支持或诱导成骨分化（骨诱导），最终与宿主组织整合（骨整合）。成功的骨支架的其他关键方面包括生物相容性、临时机械稳定性、生物可降解性、孔隙度和生物活性分子的可控释放，以加速愈合和/或防止不希望的病理。这个提议的项目概述了PCL纳米线表面发展背后的动机和原因。

DESCRIPTION (provided by applicant): Autogenous cancellous bone is currently the most widely used bone graft material. However, there are several problems associated with autogenous cancellous bone grafts such as additional scar tissue formation, donor site morbidity, pain, prolonged rehabilitation, increased risk of deep infection, inflammation and restricted availability. These problems have motivated the design of synthetic bone scaffolds as a replacement for autogenous cancellous bone grafts. Synthetic tissue engineering scaffolds provide a biomimetic construct, which employ natural biological cascades to promote healing, and native tissue integration and regeneration. As the role of cell signaling and subsequent functionality in tissue engineering becomes more clear, tissue engineers are developing multifunctional bioactive scaffolds designed to accelerate the natural healing process, which simultaneously prevent pathologies that may occur post-implantation. Ideal scaffolds are capable of presenting a physiochemical biomimetic environment while biodegrading as native tissue integrates and actively promotes or prevents desirable and undesirable physiological responses respectively. Thus, the hypotheses and specific aims of the proposed research program are: Specific Aim 1 Develop processes for optimal fabrication of highly uniform micro/nano-hierarchal scaffolds of controllable geometry and bioactivity from PCL for orthopedic tissue engineering applications Specific Aim 2 Determine the effect of nanostructured surface morphology (size of nanowires) on the behavior of MSCs (adhesion, viability, morphology, differentiation, phenotype) both short term (days) and long term (several weeks) Specific Aim 3 Determine in vivo biocompatibility and oseointegration properties of micro/nano- hierarchal scaffolds Considering the limitations of the current gold-standard treatment for critical sized defects, biodegradable synthetic bone scaffolds hold a lot of promise for future treatment regimes. Therefore, synthetic bone tissue engineered scaffolds have been aggressively pursued in the last two decades, and now have emerged as a promising alternative to conventional therapies for repairing bone defects. The fundamental concept behind tissue engineering is to utilize the body's natural biological response to tissue damage in conjunction with engineering principles. Successful synthetic bone scaffolds promotes progenitor cell migration on to the scaffold (osteoconduction), support or induce osteogenic differentiation (osteoinduction), and finally integrate with host tissue (osseointegration). Additional critical aspects of successful bone scaffolds include biocompatibility, temporary mechanical stability, biodegradability, porosity, and controlled release of bioactive molecules to accelerate healing and/or prevent undesired pathologies. This proposed project outlines the motivation and reasoning behind the development of the PCL nanowire surfaces. PUBLIC HEALTH RELEVANCE: Autogenous cancellous bone is currently the most widely used bone graft material. However, there are several problems associated with autogenous cancellous bone grafts such as additional scar tissue formation, donor site morbidity, pain, prolonged rehabilitation, increased risk of deep infection, inflammation and restricted availability. These problems have motivated the design of synthetic bone scaffolds as a replacement for autogenous cancellous bone grafts. This proposed project outlines the motivation and reasoning behind the development of the polymeric nanowire surfaces as a bone graft material.