NSF/DMR-BSF: Ultra-Tough Double-Network Hydrogels for Cartilage Repair

非技术性：这项由宾夕法尼亚大学材料研究部生物材料计划颁发的NSF/DMR-BSF奖项将促进我们对用于软骨修复和再生的生物医用水凝胶的理解。该奖项是由国际科学与工程办公室的全球风险基金共同设立的。软骨损伤占每年进行的近50万次外科手术，但越来越多的证据表明，目前的干预措施提供的长期好处不足。尽管科学家们精确地揭示了如何使用间充质干细胞再生软骨组织，但它们的常规临床应用仍然需要一个强大的植入过程，将细胞保留在需要的地方，并提供促进修复的环境。该项目的总体目标是开发一种可注射水凝胶，可用于包裹间充质干细胞，并能在植入关节后经受住机械要求的环境。为了实现这些目标，这项研究将通过结合两种类型的聚合物网络来设计双网络水凝胶，这两种类型的聚合物网络可以产生坚韧的水凝胶，同时支持活细胞的包裹和分化。该项目将纳入教育项目，并将让不同层次的学生参与研究活动。该项目对科学更广泛的影响是通过设计和研究新型水凝胶来促进科学进步，同时通过改善我们未来可用于生物医学应用的新治疗方法的知识库来促进国民健康。技术：该项目的总体目标是开发双网络水凝胶来包裹和控制间充质干细胞的软骨分化。双网络水凝胶表现出高强度和高韧性，以及在软骨缺损和修复中应用的力学特性。然而，目前还没有既可注射又可生物兼容的水凝胶存在。该项目的具体目标包括：1)合成一系列双网络水凝胶，并阐明其结构与性质的关系；以及2)评估间充质干细胞在双网络水凝胶中的存活和软骨形成。建议的设计包括将基于透明质酸和聚乙二醇的共价交联水凝胶与纤维蛋白原相结合，以实现酶降解，以及基于客体-主体基团修饰的生物聚合物的自组装动态网络，该网络是动态和自我修复的。这种设计结合了所需的刚性和延展性网络，这些网络包含在可基于物理客体-宿主相互作用注入的DN水凝胶中，然后通过光聚合反应进行共价交联。水凝胶的性能将通过改变每个网络的比例和组成来定制，除了理想的水凝胶机械性能外，还将重点关注包裹的间充质干细胞的活性和软骨生成。成功完成后，这项工作将确定对水凝胶技术的基本理解，并开发一种潜在的平移水凝胶，用于基于间充质干细胞的治疗，用于进一步的研究和生物医学应用。

Non-technical: This NSF/DMR-BSF award by the Biomaterials Program in the Division of Materials Research to the University of Pennsylvania will be to advance our understanding of biomedical hydrogels for use in cartilage repair and regeneration. This award is cofounded by the Global Venture Funds in the Office of International Science and Engineering. Cartilage injuries account for nearly half a million surgical procedures performed each year, yet mounting evidence suggests that current interventions provide insufficient long-term benefits. Even as scientists uncover precisely how to regenerate cartilage tissue using mesenchymal stem cells, their routine clinical applications will still require a robust implantation process that retains the cells where desired and provides an environment that promotes repair. The overall goal of this project is to develop an injectable hydrogel that can be used for the encapsulation of mesenchymal stem cells and that can also withstand the mechanically demanding environment after placement in a joint. To accomplish these objectives, this research will be designing double-network hydrogels by incorporating two types of polymer networks that give rise to hydrogels that are tough and at same time support the encapsulation and differentiation of viable cells. The project will incorporate educational programs, and will involve students at various levels in the research activities. The scientific broader impact of the project is to both promote the progress of science through the design and investigation of novel hydrogels and at the same time to advance the national health by improving on our knowledge base of new treatments that can be used for biomedical applications in the future.Technical: The overall goal of this project is to develop double-network hydrogels to encapsulate and control the chondrogenic differentiation of mesenchymal stem cells. Double-network (DN) hydrogels exhibit high strength and toughness, and mechanical features that may be desirable for application in cartilage defects and repair. However, at present there are no hydrogels that exist that are both injectable and bio-compatible. The specific aims of the project include: 1) synthesis of a series of double network hydrogels, and elucidate the structure-property relationships; and 2) assess mesenchymal stem cells survival and chondrogenesis within the double-network hydrogels. The proposed design involves the combination of covalently crosslinked hydrogels based on hyaluronic acid and poly(ethylene glycol) with fibrinogen to permit enzymatic degradability, as well as a self-assembled dynamic network based on biopolymers modified with guest-host groups that are dynamic and self-healing. This design incorporates the requisite rigid and ductile networks that are encompassed within DN hydrogels that are injectable based on the physical guest-host interactions and then covalently crosslinked through a photopolymerization reaction. The hydrogel properties will be tailored through alterations in the ratio and composition of each network with a focus on encapsulated mesenchymal stem cell viability and chondrogenesis as outcomes, in addition to desirable hydrogel mechanical properties. Upon successful completion, this work will identify fundamental understanding of hydrogel technology, as well as develop a potentially translational hydrogel for mesenchymal stem cells-based therapeutics for further investigations and biomedical applications.