CAREER: Polysaccharide-Based Biohybrid Constructs for Engineering of Cartilaginous Tissue

职业：用于软骨组织工程的基于多糖的生物杂交结构

• 批准号: 0747968
• 负责人: Steven Nicoll
• 金额: $ 40万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0747968&HistoricalAwards=false
• 关键词: CAREER; Polysaccharide; Based; Biohybrid; Constructs

0747968NicollArticular cartilage is a thin layer of soft connective tissue that covers the articulating surfaces in moveable joints. The principal function of articular cartilage is to redistribute applied loads and to provide a low friction-bearing surface to facilitate movement within these joints. Annually, over one million procedures involving cartilage replacement are performed in the United States as a result of debilitating ailments affecting articular cartilage. Unlike other connective tissues, cartilage has a limited reparative ability because it is relatively acellular and avascular. Current attempts to engineer articular cartilage are limited by a scarcity of both specialized cartilage-forming cells and biomaterials with appropriate mechanical properties. Therefore, the overall objective of this NSF CAREER research project is to develop alternative biohybrid implants that are readily available and possess appropriate mechanical properties for cartilage reconstruction. The study design will employ a unique mechano-chemical paradigm to differentiate human skin cells into cartilage cells. In addition, novel polysaccharide-based hydrogel materials will be fabricated to allow for the assembly of a functional extracellular matrix by encapsulated cells. Successful completion of the proposed studies may lead to the development of novel living tissue equivalents to restore the function of cartilaginous tissues. In addition, the naturally-derived biomaterials generated from this work will serve as versatile, clinically-relevant platforms to study cellular behavior. The proposed studies bridge multiple disciplines, including cell biology, materials science, and mechanical engineering, and will be integrated with three specific educational objectives: (1) Course development in orthopaedic tissue engineering, (2) Undergraduate student research internships, and (3) Community outreach geared toward mentoring middle school children.

[04:79 . 68]关节软骨是一层薄薄的软结缔组织，覆盖在活动关节的关节表面。关节软骨的主要功能是重新分配施加的载荷，并提供一个低摩擦承载表面，以促进这些关节内的运动。在美国，每年有超过100万例涉及软骨置换的手术是由于影响关节软骨的衰弱性疾病。与其他结缔组织不同，软骨的修复能力有限，因为它相对来说是无细胞和无血管的。由于缺乏专门的软骨形成细胞和具有适当机械性能的生物材料，目前对关节软骨工程的尝试受到限制。因此，这项美国国家科学基金会CAREER研究项目的总体目标是开发可替代的生物杂交植入物，这些植入物易于获得，并具有用于软骨重建的适当机械性能。研究设计将采用一种独特的机械化学模式将人类皮肤细胞分化为软骨细胞。此外，新的基于多糖的水凝胶材料将被制造，以允许由被封装的细胞组装功能的细胞外基质。成功完成所提出的研究可能会导致新的活体组织的发展，以恢复软骨组织的功能。此外，从这项工作中产生的天然衍生生物材料将作为研究细胞行为的多功能临床相关平台。拟议的研究跨越多个学科，包括细胞生物学，材料科学和机械工程，并将与三个特定的教育目标相结合：(1)骨科组织工程课程开发，(2)本科生研究实习，以及(3)面向中学儿童的社区外展指导。