EiR: Thermo-sensitive Therapeutic Laden Hydrogels to Induce Cartilage Tissue Regeneration

EiR：热敏治疗负载水凝胶可诱导软骨组织再生

• 批准号: 1900806
• 负责人: Juana Mendenhall
• 金额: $ 49.99万
• 依托单位: Morehouse College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1900806&HistoricalAwards=false
• 关键词: EiR; Thermo; sensitive; Therapeutic; Laden

Non-Technical: Cartilage is the firm connective tissue found in human joints. The damage attributed to cartilage over time presents a tremendous challenge for millions of Americans, and ultimately fosters the development of osteoarthritis. Given this important need to mitigate the damage to cartilage, it is critical that new therapeutic implantable materials are developed for human joints. In order to discover, understand, and ultimately utilize new biomaterial, fundamental knowledge of the behavior of these materials in a complex mechanical stress and biological environment is required. This award will support graduate and undergraduate training on the preparation and evaluation of new therapeutic materials for cartilage tissue repair and will further our understanding of how they respond under stressed environments that lead to osteoarthritis. Additionally, students at Morehouse College will prepare short films to engage society into learning about biomaterial science while also hosting outreach activities for local Atlanta Public School students. This activity will facilitate the development of a community of learners ranging from K-12, undergraduate, post graduate, to adults. Technical: Articular cartilage is a highly ordered avascular connective tissue that lines the articular joints and is known to withstand enormous biomechanical loads having a frictionless surface for optimal mobility. However, articular cartilage is limited in its ability to repair itself after defects from disease or injury. At the onset of injury or disease, hypoxia (low oxygen) disrupt the avascular architecture giving rise to the presence of reactive oxygen species that prevent healthy articular cartilage cell proliferation throughout the three-dimensional cartilage tissue matrix. Biomaterials that promote healthy 3D cell culture and proliferation under hypoxia are currently not available. The objective of this project focuses on the development of thermo-sensitive therapeutic laden hydrogels and the study of hypoxia on cell viability and hydrogel structure and function prepared from 3D printed bio-inks. This research entails the preparation, characterization, 3D printing, biochemical analysis, and spatial mapping of thermo-responsive therapeutic laden hydrogels that provide a new approach to regenerative tissue engineering. The use of hybrid therapeutic hydrogels to improve cell microenvironments and promote healthy extracellular matrix in 3D culture is of particular interest. The governing hypothesis of this project is driven by formulations of hybrid therapeutic laden hydrogels with robust structural integrity, higher oxygen diffusion coefficients, and the structural mimicry of articular cartilage zones via 3D printed bio-inks to provide cellular-protection under hypoxia towards chondrogenesis. Using hybrid therapeutic laden hydrogels, the Principal Investigator and research team evaluate how hypoxic induced reactive oxygen species mitigate cell fate, ECM amounts, and effect biomaterial properties. The effect of chemical modifications and the impact of structure and function in hybrid therapeutic hydrogels are noted for improved tissue engineering strategies. The research team approaches include using chemical and polymer synthesis of preparation of hybrid therapeutic hydrogels, material characterization, 3D-printing using flow-based direct ink write, static cell culture of articular chondrocytes and mesenchymal stem cells under hypoxia and normoxia, and mechanical stimulation regimes to assess chemical structure phase changes, along with temporal and spatial localization of extra cellular matrix proteins. Finally, new knowledge will be gained from this research by contributions to the development of novel therapeutic hydrogels for cartilage tissue engineering and regeneration by improving biomaterial properties to endure under pathophysiological conditions.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.

非技术性：软骨是人体关节中坚固的结缔组织。随着时间的推移，软骨造成的损伤给数百万美国人带来了巨大的挑战，并最终促进了骨关节炎的发展。鉴于减轻软骨损伤的重要需求，为人类关节开发新的治疗性植入材料至关重要。为了发现、理解并最终利用新的生物材料，需要了解这些材料在复杂的机械应力和生物环境中的行为的基础知识。该奖项将支持研究生和本科生关于软骨组织修复新治疗材料的制备和评估的培训，并将进一步了解它们在导致骨关节炎的压力环境下如何反应。此外，莫尔豪斯学院的学生将制作短片，让社会了解生物材料科学，同时还为当地亚特兰大公立学校的学生举办外展活动。这项活动将促进从 K-12、本科生、研究生到成人的学习者社区的发展。技术：关节软骨是一种高度有序的无血管结缔组织，排列在关节内，可以承受巨大的生物力学负荷，具有无摩擦的表面，可实现最佳的活动性。然而，关节软骨在因疾病或受伤而出现缺陷后自我修复的能力受到限制。在损伤或疾病发生时，缺氧（低氧）会破坏无血管结构，导致活性氧的存在，从而阻止健康的关节软骨细胞在整个三维软骨组织基质中增殖。目前尚无可在缺氧条件下促进健康 3D 细胞培养和增殖的生物材料。该项目的目标重点是开发热敏治疗负载水凝胶，并研究缺氧对细胞活力的影响以及由 3D 打印生物墨水制备的水凝胶结构和功能。这项研究涉及热响应治疗水凝胶的制备、表征、3D 打印、生化分析和空间绘图，为再生组织工程提供了一种新方法。使用混合治疗水凝胶来改善细胞微环境并促进 3D 培养中健康的细胞外基质特别令人感兴趣。该项目的主导假设是由混合治疗负载水凝胶的配方驱动的，该水凝胶具有坚固的结构完整性、更高的氧扩散系数，以及通过 3D 打印生物墨水模拟关节软骨区域的结构，以在缺氧条件下为软骨形成提供细胞保护。首席研究员和研究团队使用混合治疗性负载水凝胶，评估缺氧诱导的活性氧如何减轻细胞命运、ECM 量和影响生物材料特性。混合治疗水凝胶中化学修饰的效果以及结构和功能的影响因改进的组织工程策略而受到关注。 研究团队的方法包括使用化学和聚合物合成制备混合治疗性水凝胶、材料表征、使用基于流动的直接墨水写入的 3D 打印、缺氧和常氧下关节软骨细胞和间充质干细胞的静态细胞培养以及机械刺激方案评估化学结构相变，以及细胞外基质蛋白的时间和空间定位。最后，通过改善生物材料在病理生理条件下的性能，为开发用于软骨组织工程和再生的新型治疗性水凝胶做出贡献，将从这项研究中获得新的知识。该奖项反映了 NSF 的法定使命，并通过评估被认为值得支持利用基金会的智力优势和更广泛的影响审查标准。