Modular Assembly of Interdigitated Osteochondral Interfaces

描述（由申请人提供）：大的全层软骨缺损通常需要细胞或组织移植来促进再生，然而目前的临床治疗受到缺乏组织可用性和移植组织不充分整合的阻碍。组织工程通过创造可用于移植的骨软骨组织提供了一个解决方案。然而，实现工程骨和软骨组织之间的紧密结合是具有挑战性的。这个为期两年的探索性项目的目标是通过使用模块化组织工程方法创建连续的、强大的骨软骨界面来解决这个问题。由细胞外基质材料（胶原蛋白、壳聚糖、羟基磷灰石）制成的离散微珠（直径200-50）将用于包封和控制成人间充质干细胞（hMSC）的表型。成骨和成软骨的微珠群体将分别产生，然后结合形成有凝聚力的多相组织结构。对组件微珠组装的控制提供了一种规定所得界面组织的方法。该项目所基于的一般假设是，可以操纵软骨和成骨微珠之间的界面结构，以促进这两种组织类型的整合，从而产生强大而稳定的骨软骨组织。该项目解决了三个特定的子假设，这些子假设提供了对骨软骨界面形成的几何、规模和时间的影响的见解。这些假设将通过两个具体目标进行测试。在SA1中，我们将通过在层状和连续结构中结合软骨和成骨微珠来创建骨软骨组织和界面。同时，SA2将在选定的时间点全面表征微珠和骨软骨结构，特别强调通过生化、组织学和力学评估界面组织和强度。通过使用水凝胶微珠方法创建3D多相结构，我们期望实现工程骨和软骨组织的增强整合。设计坚固且高度互连的骨-软骨结构的能力可以改善骨软骨缺损的治疗。

DESCRIPTION (provided by applicant): Large, full thickness cartilage defects typically require cell or tissue transplantation to promote regeneration, however current clinical treatments are hampered by a lack of tissue availability and inadequate integration of the transplanted tissue. Tissue engineering offers a solution by creating osteochondral tissues that could be used for transplantation. However, achieving tight integration between engineered bone and cartilage tissues is challenging. The objective of this two-year exploratory project is to address this problem by creating continuous, strong osteochondral interfaces using a modular tissue engineering approach. Discrete microbeads (200-50 in diameter) made from extracellular matrix materials (collagen, chitosan, hydroxyapatite) will be used to encapsulate and control the phenotype of adult human mesenchymal stem cells (hMSC). Osteogenic and chondrogenic populations of microbeads will be created separately and then combined to form cohesive multiphase tissue constructs. Control of the assembly of the component microbeads provides a way to prescribe the organization of the resulting interface. The general hypothesis upon which this project is based is that the architecture of the interface between chondrogenic and osteogenic microbeads can be manipulated to promote integration of these two tissue types, thereby leading to strong and stable osteochondral tissues. This project addresses three specific sub-hypothesis that provide insight into the effects of geometry, scale, and timing of formation of osteochondral interfaces. These hypotheses will be tested through two Specific Aims. In SA1 we will create osteochondral tissues and interfaces by combining chondrogenic and osteogenic microbeads in both layered and continuous architectures. In parallel, SA2 will comprehensively characterize the microbeads and osteochondral constructs at selected time points, with particular emphasis on interfacial organization and strength through biochemical, histological and mechanical assessment. By creating 3D multiphase constructs using the hydrogel microbead approach we expect to achieve enhanced integration of engineered bone and cartilage tissue. The ability to design robust and highly interconnected bone-cartilage constructs could lead to improved treatment of osteochondral defects.