Biomimetic Nanofibrillar Scaffolds For Cartilage Tissue Engineering

描述(申请人提供)：当关节软骨因老化而损伤或受损时，其再生能力非常有限，采用生物兼容基质或支架的组织工程概念和方法有可能通过在生物兼容支架中种植细胞来生成组织学和功能正常组织，然后将细胞-材料复合体植入修复软骨缺损，从而帮助修复关节软骨缺陷。人们迫切需要设计和开发模仿关节软骨天然ECM的支架，并以生物响应的方式分配应变，以信号播种的软骨细胞来合成和组织ECM，从而产生与自然软骨相似的材料特性。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生软骨，不仅用于移植，而且作为软骨形成对照研究的模型系统。本应用的目的是设计和开发接近关节软骨天然细胞外基质(ECM)的支架，这些支架主要由胶原纳米纤维组成，并在软骨组织工程的范例中评估这些方法的可行性。该项目的创新之处在于，我们能够基于排列的纳米和/或亚微米范围的纤维重复制备具有可调生物力学性能和基质刚性的多孔支架，并评估基质力学、机械应力和其他物理因素对仿生基质中细胞活动的具体贡献。我们预计，本研究中开发的基于亚微米或纳米纤维支架的组织工程学方法将通过提供组织学、生化和力学性能发现的综合研究，为更好地理解组织发育提供工具。本提案中开发的工程方法可能会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.