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

关节软骨是一层薄薄的软结缔组织，覆盖在可移动关节的关节表面。关节软骨的主要功能是重新分配所施加的载荷，并提供一个低摩擦的表面，以促进这些关节内的运动。每年，在美国，由于影响关节软骨的衰弱疾病，涉及软骨置换的手术超过100万例。与其他结缔组织不同，软骨的修复能力有限，因为它是相对无细胞和无血管的。目前工程化关节软骨的努力受到专门的软骨形成细胞和具有适当机械性能的生物材料的匮乏的限制。因此，NSF职业研究项目的总体目标是开发替代的生物杂化植入物，该植入物容易获得并具有适当的力学性能用于软骨重建。这项研究设计将使用一种独特的机械力-化学范式将人类皮肤细胞分化为软骨细胞。此外，还将制造基于多糖基的新型水凝胶材料，以允许被包裹的细胞组装成具有功能的细胞外基质。成功完成拟议的研究可能会导致开发新的活组织等价物来恢复软骨组织的功能。此外，从这项工作中产生的自然衍生生物材料将成为研究细胞行为的通用、临床相关的平台。拟议的研究跨越了多个学科，包括细胞生物学、材料科学和机械工程，并将与三个具体的教育目标相结合：(1)骨科组织工程课程开发，(2)本科生研究实习，(3)旨在指导中学生的社区推广。

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.