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

0747968 Nicoll关节软骨是一层薄薄的软结缔组织，覆盖活动关节的关节面。 关节软骨的主要功能是重新分配所施加的载荷，并提供低摩擦支承表面以促进这些关节内的运动。 每年，由于影响关节软骨的衰弱性疾病，在美国进行超过一百万例涉及软骨置换的手术。 与其他结缔组织不同，软骨具有有限的修复能力，因为它相对无细胞和无血管。 目前工程关节软骨的尝试受到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的限制。 因此，NSF CAREER研究项目的总体目标是开发替代生物混合植入物，这些植入物易于获得并具有适当的软骨重建机械性能。 该研究设计将采用独特的机械化学范式将人类皮肤细胞分化为软骨细胞。 此外，将制造新型的基于多糖的水凝胶材料，以允许通过封装的细胞组装功能性细胞外基质。 拟议研究的成功完成可能会导致开发新的活组织等同物，以恢复软骨组织的功能。 此外，从这项工作中产生的天然生物材料将作为研究细胞行为的多功能临床相关平台。拟议的研究桥接多个学科，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，以及（3）面向指导中学生的社区外展。

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.