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人类残疾和不适的重大临床挑战和原因。组织工程和再生医学是治疗这些疾病的有希望的策略，通过创造由细胞、生物活性因子和可生物降解的支架组成的活组织替代品。组织工程学在创造均匀的组织方面尤其成功，例如皮肤和软骨。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输送到细胞的方法。因此，种植在这些支架上的干细胞将受到刺激，以预定义的模式产生不同的组织类型。特别是，我们将通过空间控制的分化因子基因转移，用人间充质干细胞生成骨软骨组织。通过生物材料介导的基因传递的创新方法和用于创建3D聚合物支架的微型编织技术，精确的空间控制将成为可能。这项工作对于开发组织工程策略以创建复杂结构具有重要意义，这些结构概括了天然组织界面的异质性和功能。

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.