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，与自体松质骨移植相关的几个问题，如额外的瘢痕组织形成、供区发病率、疼痛、长期康复、深度感染风险增加、炎症和可获得性限制。这些问题促使了合成骨支架的设计，作为自体松质骨移植的替代品。合成组织工程支架提供了一种仿生结构，它利用自然的生物级联来促进愈合，以及自然组织的整合和再生。随着细胞信号和后续功能在组织工程中的作用变得越来越清楚，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变化。理想的支架能够呈现出一种物理化学的仿生环境，而生物降解作为天然组织整合并积极促进或阻止期望的和不期望的生理反应。因此，所提出的研究计划的假设和具体目标是：具体目标1开发用于骨科组织工程应用的用于从PCL优化制造几何形状和生物活性可控的高度均匀的微/纳米层级支架的方法。具体目标2确定纳米结构表面形态(纳米线的尺寸)对MSCs行为(粘附性、活性、形态、分化、表型)的影响短期(几天)和长期(几周)具体目标3考虑到当前对严重尺寸缺陷的黄金标准治疗的局限性，确定微/纳米层级支架的体内生物相容性和离子整合特性，可生物降解的合成骨支架为未来的治疗方案带来了很大的希望。因此，合成骨组织工程支架在过去的二十年里受到了积极的追求，现在已经成为修复骨缺损的传统疗法的一种有前途的替代方案。组织工程学背后的基本概念是结合工程学原理利用人体对组织损伤的自然生物反应。成功的人工骨支架可以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、暂时的机械稳定性、生物降解性、孔隙率以及生物活性分子的受控释放，以加速愈合和/或防止不良病理。这项拟议的项目概述了PCL纳米线表面开发背后的动机和理由。 公共卫生相关性：自体松质骨是目前应用最广泛的骨移植材料。然而，与自体松质骨移植相关的几个问题，如额外的瘢痕组织形成、供区发病率、疼痛、长期康复、深度感染风险增加、炎症和可获得性限制。这些问题促使了合成骨支架的设计，作为自体松质骨移植的替代品。这项拟议的项目概述了聚合物纳米线表面作为骨移植材料开发背后的动机和理由。

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.