Spatially Controlled Gene Delivery of Morphogenetic Factors from Woven Scaffolds

描述（由申请人提供）：受损或患病骨骼组织的再生仍然是一个重大的临床挑战，也是导致人类残疾和不适的原因。组织工程和再生医学正在成为通过创建由细胞、生物活性因子和可生物降解支架组成的活组织替代物来治疗这些病症的有前景的策略。组织工程在创造均匀的组织，如皮肤和软骨方面特别成功。然而，许多损伤和疾病会影响组织之间的界面，例如骨和软骨之间的过渡。需要开发新的组织工程方法来概括这些双相组织界面的结构和功能。该项目开发了一种在三维支架内以精确的空间模式将生物活性因子递送到细胞的方法。因此，接种在这些支架上的干细胞将被刺激以产生预定义模式的不同组织类型。特别是，我们将通过空间控制的分化因子基因转移，用人间充质干细胞产生骨软骨组织。精确的空间控制将通过生物材料介导的基因递送的创新方法和用于创建3D聚合物支架的微尺度编织技术来实现。这项工作是重要的组织工程策略，创造复杂的结构，概括的异质性和功能的天然组织接口。

DESCRIPTION (provided by applicant): The regeneration of damaged or diseased skeletal tissues remains a significant clinical challenge and cause for human disability and discomfort. Tissue engineering and regenerative medicine are emerging as promising strategies for treating these conditions by creating living tissue substitutes composed of cells, bioactive factors, and a biodegradable scaffold. Tissue engineering has been particularly successful in creating uniform tissues, such as skin and cartilage. However, many injuries and diseases affect the interfaces between tissues, such as the transition between bone and cartilage. New tissue engineering methods need to be developed to recapitulate the structure and function of these biphasic tissue interfaces. This project develops a method to deliver bioactive factors to cells in a precise spatial pattern within a three dimensional scaffold. As a result, stem cells seeded onto these scaffolds will be stimulated to produce different tissue types in predefined patterns. In particular, we will generate osteochondral tissues with human mesenchymal stem cells through spatially controlled gene transfer of differentiation factors. Precise spatial control will be enabled by innovative methods of biomaterial-mediated gene delivery and a microscale weaving technique for creating 3D polymer scaffolds. This work is significant to developing tissue engineering strategies for creating complex structures that recapitulate the heterogeneity and function of native tissue interfaces.