Chondrogenesis in Enzymatically Degradable Hydrogels

描述(由申请人提供)：这个K22学者发展和教师过渡职业发展奖的总体目的是在推进软骨组织工程的光可聚合水凝胶领域为首席研究员提供额外的(1年)博士后指导和支持，此外还支持(4年)作为独立教师继续在该领域的研究。这项研究的提出是为了补充首席研究员的背景，开发用于骨组织工程的新型光交联型生物材料，长期目标是开发用于颅面应用的骨和软骨界面的复合材料。首席研究员的总体目标是发展一个国际公认的研究实验室，将新材料的合成和修饰作为开发临床相关疗法的平台。本提案中概述的拟议研究和职业发展计划是由麻省总医院和麻省理工学院的首席调查员和导师为实现这一目标而制定的。 可光聚合水凝胶具有许多有益于软骨组织工程的特性，包括：在体内形成的能力，以潜在的粘附性和集成性来填充复杂的缺陷，对聚合过程的空间和时间控制，以及生物信号很容易被整合到网络中来控制细胞分化和组织形成。这些特性对于颅面重建中软骨的再生将是非常有利的。考虑到这些好处，拟议研究的主要目标是： 。合成并表征可通过酶降解过程吸收的光聚合共聚水凝胶网络， 。研究被包裹在水凝胶网络中的软骨细胞形成的组织的数量、分布和类型作为水凝胶组成的函数， 。将信号整合到水凝胶网络中以控制光囊化间充质干细胞的软骨分化；以及 。分析这些技术临床应用所必需的光聚合结构的关键问题。

DESCRIPTION (provided by applicant): The overall purpose of this K22 Scholar Development and Faculty Transition Career Award is to provide additional (1 year) postdoctoral mentorship and support to the principle investigator in the area of advancing photopolymerizable hydrogels for cartilage tissue engineering in addition to support (4 years) as an independent faculty member to continue research in this field. The proposed research originated to complement the principle investigator's background in the development of novel photocrosslinkable biomaterials for bone tissue engineering with a long-term objective of developing complex materials at the interface of bone and cartilage for craniofacial applications. It is the general goal of the principle investigator to develop an internationally recognized research laboratory that uses the synthesis and modification of novel materials as a platform for the development of clinically relevant therapeutics. The proposed research and career development program outlined in this proposal were developed by the principle investigator and Mentors from both the Massachusetts General Hospital and Massachusetts Institute of Technology in an effort to achieve this goal. Photopolymerizable hydrogels have many properties that are beneficial for cartilage tissue engineering including: the ability to form in vivo to fill complex defects with potential adhesive and integrative properties, both spatial and temporal control over the polymerization process, and biological signals are readily incorporated into the networks to control both cellular differentiation and tissue formation. These properties would be extremely beneficial for the regeneration of cartilage in craniofacial reconstruction. With these benefits in mind, the primary aims of the proposed research are to: . synthesize and characterize photopolymerizable copolymer hydrogel networks that resorb via an enzymatic degradation process, . investigate the quantity, distribution, and type of tissue formed by chondrocytes encapsulated in hydrogel networks as a function of hydrogel composition, . incorporate signals into hydrogel networks to control the chondrogenic differentiation of photoencapsulated mesenchymal stem cells, and . analyze critical issues of the photopolymerized constructs necessary for clinical application of these techniques.