Modular Assembly of Interdigitated Osteochondral Interfaces

描述(申请人提供)：大型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因缺乏组织可获得性和移植组织整合不充分而受到阻碍。组织工程学通过创造可用于移植的骨软骨组织提供了一种解决方案。然而，实现工程化骨和软骨组织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、坚固的骨软骨界面来解决这一问题。由细胞外基质材料(胶原、壳聚糖、羟基磷灰石)制成的离散微珠(直径200-50)将用于包裹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被分开创建，然后结合在一起，形成具有凝聚力的多相组织结构。对组件微珠的组装的控制提供了规定所得界面的组织的方式。这个项目所基于的一般假设是，可以操纵成软骨微珠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，从而产生坚固而稳定的骨软骨组织。这个项目解决了三个具体的子假说，它们提供了对骨软骨界面形成的几何、规模和时间的影响的洞察力。这些假设将通过两个具体目标进行检验。在SA1中，我们将通过将软骨微珠和成骨微珠在分层和连续结构中相结合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、组织学和机械评估的界面组织和强度。通过使用水凝胶微珠方法创建3D多相结构，我们希望实现工程化骨和软骨组织的增强整合。设计坚固且高度相互连接的骨-软骨结构的能力可能会改善骨软骨缺陷的治疗。

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.