Crosslinkable Hydrogels for Growth Factor Release

用于生长因子释放的可交联水凝胶

• 批准号: 6954717
• 负责人: Robert A. Peattie
• 金额: $ 14.81万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6954717
• 关键词: angiogenesis; bioengineering /biomedical engineering; biomaterial development /preparation; biomimetics; drug delivery systems; enzyme linked immunosorbent assay; extracellular matrix; fibroblast growth factor; gel; gelatin; gene expression; growth factor; heparin; hyaluronate; implant; laboratory mouse; polyethylene glycols; slow release drug; vascular endothelial growth factors

DESCRIPTION (provided by applicant): The goal of the proposed project is to develop and evaluate novel hyaluronic acid (HA)-based hydrogel films optimized for controlled release of desired peptide growth factors (GFs) while simultaneously providing an advantageous environment for pre-seeded cell growth. Synthetic extracellular matrices (sECMs) fabricated from such biopolymer networks can serve as the foundation for tissue and organ growth both in vitro and in vivo. However, at present the clinical utility of most synthetic matrices is limited by poor regulation of the specific coordinated sequences of GF releases that typically drives tissue maturation in vivo. In the proposed project, an sECM containing small amounts of heparin (Hp), which has been shown to substantially improve control of the time course of release of sequestered GFs, will be fabricated from chemically modified HA, or HA and gelatin (Gtn). Conjugate addition chemistry will be employed to crosslink mixtures of HA-DTPH, Gtn-DTPH and Hp-DTPH, using polyethylene glycol diacrylate (PEGDA) as crosslinking agent. Vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) will be added to the HA-DTPH solution non-covalently prior to crosslinking. The relation between Hp concentration and rate of in vitro GF release from these matrices will be investigated by ELISA. Subsequently, gel samples fabricated with a minimal amount of Hp consistent with sustained GF release will be implanted in a series of mouse ear pinnas, and the angiogenic activity of released GF in vivo quantified by measurement of elicited new microvessel growth. In addition, the potential for controlling tissue phenotypic response at the gene expression level with these imlants will be studied in the same mouse model. Tissue samples will be retrieved at a series of time points post implant, and expression changes due to controlled growth factor release determined by microarray and RT-PCR analysis.

描述（由申请人提供）：拟议项目的目的是开发和评估新型的透明质酸（HA）基于基于基于所需肽生长因子（GFS）的释放的基于基于的水凝胶膜，同时为预种植的细胞生长提供了有利的环境。由此类生物聚合物网络制造的合成细胞外基质（SECM）可以作为体外和体内组织和器官生长的基础。然而，目前，大多数合成基质的临床实用性受到对通常在体内驱动组织成熟的GF释放的特定协调序列的调节。 在拟议的项目中，含有少量肝素（HP）的SECM将通过化学修饰的HA或HA和Gelatin（GTN）制造，该SECM已证明可以实质上改善对隔离GFS释放时间的控制。结合添加化学将使用聚乙烯乙二醇二丙烯酸酯（PEGDA）作为交联剂，将化学作用用于HA-DTPH，GTN-DTPH和HP-DTPH的交联混合物。在交联之前将血管内皮生长因子（VEGF）或基本成纤维细胞生长因子（BFGF）添加到HA-DTPH溶液中。 ELISA将研究HP浓度与体外GF释放速率之间的关系。随后，用最少与持续GF释放一致的HP制造的凝胶样品将植入一系列小鼠耳朵pinnas中，并通过测量引起的新微粒生长的生长来定量释放的GF的血管生成活性。此外，将在同一小鼠模型中研究在基因表达水平上控制组织表型反应的潜力。组织样品将在植入物后的一系列时间点上检索，并且由于微阵列和RT-PCR分析确定的受控生长因子释放而引起的表达变化。