Injectable, In Situ Forming Hydrogels for Craniofacial Tissue Engineering

用于颅面组织工程的可注射原位形成水凝胶

• 批准号: 8648033
• 负责人: Tiffany N Vo
• 金额: $ 4.3万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8648033
• 关键词: Address; Alkaline Phosphatase; Allografting; Autologous Transplantation; Biochemical; Biocompatible; Biocompatible Materials; Biodegradation; Biological Assay; Biology; Body Temperature; Bone Regeneration; Bone Transplantation; Cell Proliferation; Cell Survival; Cell-Matrix Junction; Cells; Chemicals; Chemistry; Clinical; Defect; Deposition; Development; Differential Scanning Calorimetry; Disease; Effectiveness; Encapsulated; Esthetics; Evaluation; Extracellular Matrix; Face; Fellowship; Gel; Gene Expression; Gold; Head; Healed; Hydrogels; Hydrophobicity; In Situ; In Vitro; Injectable; Knowledge; Left; Measures; Mechanics; Mesenchymal Stem Cells; Morbidity - disease rate; Natural regeneration; Operative Surgical Procedures; Organ; Osteogenesis; Outcome; Patients; Physiological; Polymers; Porosity; Procedures; Production; Property; Ptosis; Rattus; Recovery; Regenerative Medicine; Rehabilitation therapy; Research; Shapes; Site; Social Impacts; Spectrum Analysis; Staging; Stem cells; Structure; Surgeon; System; Techniques; Temperature; Testing; Therapeutic; Time; Tissue Engineering; Tissues; Translations; Transplanted tissue; Trauma; Work; Wound Healing; base; biomineralization; bone; craniofacial; craniofacial complex; crosslink; density; design; engineering design; functional group; healing; improved; in vivo; insight; interest; mineralization; minimally invasive; novel; osteogenic; physical property; poly-N-isopropylacrylamide; public health relevance; reconstruction; regenerative; repaired; research study; response; scaffold; soft tissue; stem; tissue regeneration; tomography; tool; wound

Project Summary The rationale for the proposed research is based on the need for minimally invasive strategies to provide functional and aesthetic reconstruction in complex craniofacial defects caused by trauma and disease. The objective of this research is to develop an injectable, in situ forming hydrogel that utilizes a unique dual gelation mechanism to rapidly form gels at physiological temperature, chemically crosslink to maintain hydrogel stability, and biodegrade for full tissue regeneration. The proposed research will test the fundamental hypothesis that the injectable hydrogel will provide a supportive and mineralized substrate for mesenchymal stem cell (MSC) proliferation, enable osteogenic differentiation in vitro, and promote bone regeneration in vivo. The proposed research will be accomplished through three specific aims: 1) To develop and characterize injectable, in situ forming, biodegradable and space-filling hydrogels as an acellular tissue engineering therapeutic; 2) To assess the effectiveness of the injectable, dual-gelling hydrogels to promote the proliferation and osteogenic differentiation of encapsulated MSCs in vitro and bone regeneration in vivo; and 3) To evaluate the effects of cell seeding density and predifferentiation stage on the regenerative capacity of injectable, dual-gelling hydrogels in vivo. The novel macromers with crosslinkable and degradable functional groups will be synthesized and characterized using 1HNMR spectroscopy, differential scanning calorimetry, and rheometry. Cytocompatibility, encapsulated MSC viability and in vitro osteogenic differentiation will be measured via real-time PCR for osteogenic marker gene expression and essential biochemical assays for cell proliferation, mineralized extracellular matrix production and alkaline phosphatase activity. In order to evaluate the capacity of the hydrogels to promote bone regeneration, histological and histomorphometric scoring, microcomputed tomography analysis and mechanical testing will be used to quantify the tissue response and characterize functional bone formation. At the completion of these studies, the expected outcomes are successful fabrication of an in situ forming, injectable hydrogel capable of biodegradation, biomineralization, and stem cell delivery and the extensive evaluation of the system's efficacy for bone regeneration. The proposed work will not only improve the understanding and testing of biomaterials-based therapies for minimally invasive tissue regeneration as viable clinical alternatives, but provide new insights in the rational design of thermosensitive materials and hydrogel biomineralization. Moreover, the proposed system provides a novel platform for composite tissue regeneration and controlled delivery for application in a variety of different tissues.

项目摘要 拟议研究的基本原理是基于微创策略的需要， 为创伤和疾病引起的复杂颅面缺损提供功能和美学重建。 本研究的目的是开发一种可注射的原位形成水凝胶， 在生理温度下快速形成凝胶的凝胶化机制，化学交联以保持水凝胶 稳定性和可生物降解性，用于完全组织再生。拟议的研究将测试基本的 假设可注射水凝胶将为间充质干细胞提供支持性和矿化基质， 干细胞（MSC）增殖，在体外能够成骨分化，并在体内促进骨再生。 建议的研究将通过三个具体目标来实现：1）开发和 表征可注射的、原位形成的、可生物降解的和空间填充的水凝胶作为无细胞组织 工程治疗; 2）评估可注射的双凝胶化水凝胶促进生物相容性的有效性。 包封的MSC在体外的增殖和成骨分化以及在体内的骨再生;以及3） 评价细胞接种密度和预分化阶段对细胞再生能力的影响 可注射的，双胶凝水凝胶在体内。具有可交联和可降解功能的新型大分子单体 将使用1HNMR光谱，差示扫描量热法， 和流变测定法。细胞相容性、包封的MSC活力和体外成骨分化将是 通过实时PCR测量成骨标志物基因表达和细胞基本生化测定， 增殖、矿化的细胞外基质产生和碱性磷酸酶活性。为了评价 水凝胶促进骨再生的能力，组织学和组织形态学评分， 微计算机断层扫描分析和机械测试将用于量化组织反应， 表征功能性骨形成。 在这些研究完成后，预期的结果是成功地制造了一个原位 形成能够生物降解、生物矿化和干细胞递送的可注射水凝胶， 广泛评估该系统对骨再生的功效。这项工作不仅将改善 了解和测试基于生物材料的微创组织再生疗法， 可行的临床替代方案，但在热敏材料的合理设计方面提供了新的见解， 水凝胶生物矿化此外，所提出的系统为复合组织提供了一个新的平台， 再生和受控递送以应用于各种不同的组织。