Excellence in Research: Biodegradable Functional Hydrogels for Bone Loss Applications

第一部分： 非技术概述水凝胶作为生物材料显示出巨大的前景，然而，它们的应用仍然有限。该奖项旨在为骨丢失应用的水凝胶输送系统的设计原理提供基础知识。从这项研究中获得的结果将提高我们目前的理解水凝胶基生物材料使用基础科学和工程技术。这项调查的跨学科性质将促进整个校园和校外的新的合作。该奖项将为高中生，本科生和博士后研究员提供关于水凝胶基质制造和表征的培训，指导和研究经验，从而加强学生和研究员STEM培训，并为STEM领域的高等教育和职业做好准备。 完成这些研究将为未来开发直接解决骨丢失问题的水凝胶干预措施提供强有力的循证原则证明。技术总结：该奖项支持开发一种机械稳定的功能性水凝胶，用于包封和持续递送以双膦酸盐（BP）和间充质干细胞（MSC）为代表的抗吸收剂。本研究旨在确定BP抑制破骨细胞活性和MSC分化成骨细胞形成新骨与降解水凝胶共存的可行性。本研究还将评价和表征BP-涂层HA与MSC在水凝胶基质中的分散沿着。本研究中使用的方法将包括以下内容：使用机械试验、释放研究、生物化学和细胞测定、组织学、定量逆转录聚合酶链反应（qRT-PCR）和实验统计设计制造和表征水凝胶基质。该提案将扩大旨在用于与生物系统接触的应用的水凝胶基生物材料的领域。它还将有助于开发一种潜在的翻译水凝胶，用于基于间充质干细胞的治疗，以进一步研究骨丢失和其他生物医学应用。该奖项还将为高中生、本科生和博士后研究员提供研究经验，从而为他们在STEM领域接受高等教育和职业生涯做好准备。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

PART 1: NON-TECHNICAL SUMMARYHydrogels show great promise as biomaterials however, their use is still limited. This award seeks to provide foundational knowledge in the design principles of hydrogel delivery systems for bone loss application. The results obtained from this study will improve our current understanding of hydrogel-based biomaterials using basic science and engineering techniques. The transdisciplinary nature of this investigation will foster new collaborations across the campus and off-campus. This award will provide high school students, undergraduates, and a postdoctoral fellow training, mentoring, and research experience on the fabrication and characterization of the hydrogel matrix, thus enhancing students and fellow STEM training and preparing them for higher education and careers in the STEM field. Completing these studies will provide robust evidence-based proof of principle for the future development of hydrogel-based interventions that directly address bone loss concerns. TECHNICAL SUMMARY:This award supports the development of a mechanically stable, functional hydrogel tailored for encapsulating and providing sustained delivery of both anti-resorptive agents typified by the bisphosphonates (BPs) and mesenchymal stem cells (MSCs). This proposed study aims to determine the feasibility of the co-existence of BP’s to inhibit osteoclasts activities and MSCs to differentiate into osteoblasts forming neo bone with the degrading hydrogel. This study will also evaluate and characterize BP-coated HA's dispersion along with MSCs in the hydrogel matrix. The methods used in this investigation will include the following: fabrication and characterization of hydrogel matrix using mechanical testing, release studies, biochemical and cell assays, histology, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and statistical design of experiments. This proposal will expand the field of hydrogel-based biomaterials intended for applications in contact with biological systems. It will also contribute to developing a potentially translational hydrogel for mesenchymal stem cell-based therapeutics for further investigations in bone loss and other biomedical applications. The award will also provide high school students, undergraduates, and a postdoctoral fellow with research experiences, thus preparing them for higher education and careers in STEM fields.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.