Biomimetic Nanofibrillar Scaffolds For Cartilage Tissue Engineering

描述（申请人提供）：关节软骨的再生能力在因老化而受伤或受损时非常有限，采用生物相容性基质或支架的组织工程概念和方法具有通过在生物相容性支架中接种细胞然后植入细胞产生组织学和功能性正常组织来帮助修复关节软骨缺陷的潜力。修复软骨缺损的材料复合物存在设计和开发支架的动力，所述支架模拟关节软骨的天然ECM，并以生物响应的方式分布应变以向接种的软骨细胞发出信号以合成和组织ECM，从而产生在天然软骨范围内的材料性质。我们研究的长期目标是产生具有适当生物力学特性的组织工程化新软骨，不仅用于移植应用，而且作为软骨形成的受控研究的模型系统。本申请的目的是设计和开发与关节软骨的天然细胞外基质（ECM）（主要由胶原纳米纤维组成）非常接近的支架，并评估这些方法在软骨组织工程范例中的可行性。在这个项目中的创新是我们的能力，可重复地制备多孔支架的基础上对齐的纳米和/或亚微米范围的纤维与可调的生物力学性能和基板刚度，并评估基板力学，机械应力和其他物理因素对细胞活性的仿生矩阵的具体贡献。我们预计，在这项研究中开发的亚微米或微米级的支架的组织工程方法将提供工具，通过提供组织学，生物化学和机械性能的研究结果相结合，以提高对组织发育的理解。本提案中开发的工程方法可能对组织工程的其他表面的制造产生更广泛的影响。

DESCRIPTION (provided by applicant): The regenerative capabilities of articular cartilage are very limited when injured or damaged by aging, tissue engineering concepts and methodologies that employ biocompatible matrices or scaffolds have the potential to help repair defects in articular cartilage by generating histological and functional normal tissue by seeding cells in a biocompatible scaffold and then implanting the cell-material complex to repair chondral defects There is an impetus to design and develop scaffolds that mimic the native ECM of articular cartilage, and distribute strain in a bioresponsive manner to signal seeded chondrocytes to synthesize and organize ECM to result in material properties that are in range of natural cartilage. The long-term goal of our research is to generate tissue-engineered neocartilage with appropriate biomechanical properties, not only for graft applications, but also as a model system for controlled studies of chondrogenesis. The objective of this application is to design and develop scaffolds that closely approximate the native extracellular matrices (ECM) of articular cartilage, which are primarily composed of collagen nanofibers, and to evaluate the feasibility of these approaches within the paradigm of cartilage tissue engineering. The innovation in this project is our ability to reproducibly prepare porous scaffolds based on aligned nano- and/or submicron-range fibers with tunable biomechanical properties and substrate rigidity, and to evaluate the specific contributions of substrate mechanics, mechanical stress, and other physical factors on cellular activity in biomimetic matrices. We anticipate that tissue-engineering approaches with submicron- or nanofiber based scaffolds developed in this study will provide tools for an improved understanding of tissue development, by providing a combined study of histologic, biochemical, and mechanical property findings. The engineering methodology developed in this proposal may have broader impacts on the manufacturing of other surfaces for tissue engineering.