BETA HAIRPIN PEPTIDE HYDROGELS FOR LIVER REGENERATION

用于肝脏再生的β发夹肽水凝胶

• 批准号: 8168492
• 负责人: DARRIN J POCHAN
• 金额: $ 41.46万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168492
• 关键词: Address; Adopted; Cell Culture Techniques; Cells; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Culture Media; Doctor of Medicine; Encapsulated; Excision; Funding; Gel; Grant; Hepatocyte; Hydrogels; In Vitro; Institution; Kinetics; Liver; Liver Regeneration; Malignant Neoplasms; Malignant neoplasm of liver; Mechanics; Molecular; Molecular Conformation; Muscle Rigidity; Natural regeneration; Operative Surgical Procedures; Peptides; Property; Prunella vulgaris; Rattus; Recovery; Research; Research Personnel; Resected; Resources; Running; Shapes; Site; Solutions; Source; Stimulus; Surgeon; Syringes; Testing; Tissues; United States National Institutes of Health; aqueous; base; biomaterial compatibility; crosslink; design; in vivo; self assembly; shear stress; wound

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We are developing a hydrogelation strategy, based on the triggered self-assembly of peptides, to aid in liver regeneration after cancer resection surgery. We will design hydrogels that can encapsulate cells in vitro that can be subsequently injected in vivo. We have designed peptides that, when dissolved in aqueous solutions, form an ensemble of random coil conformations rendering them fully soluble. However, when we add an exogenous stimulus, such as cell culture media, the peptides fold into a ¿-hairpin conformation. These folded peptides undergo rapid self-assembly forming a highly crosslinked hydrogel. When the selfassembly mechanism triggers hydrogelation in the presence of hepatocytes, gels become impregnated with cells. A unique characteristic of these gels is that when an appropriate shear stress is applied, the gel will shear-thin, becoming a viscous gel. However, after the application of shear has stopped, the viscous gel quickly self-heals producing a gel with mechanical rigidity nearly identical to the original hydrogel before shear-thinning. The gels' material properties, such as the gelation kinetics, mechanical rigidity and recovery kinetics after shear-thinning, will be tuned via peptide design to enable them to be delivered via syringe. With syringe delivery, the resulting gel/cell constructs can be shear-thin-delivered to targeted tissue where they quickly recover, adopting a shape that compliments the wound site. After delivery, the gels remain localized at the point of application (e.g. they do not run). We will investigate the cytocompatibility and biocompatibility of the gels, as well as the ability of the gel/cell constructs to be delivered in a spatially localized manner to rat liver tissue. We will test their ability to aid in the regeneration of resected rat liver. We have assembled the following team to address the aims of this proposal: Cindy Farach-Carson, a cell and molecular biologist, Dr. Joe Bennett M.D., a liver cancer surgeon, Darrin Pochan, an expert in hydrogel materials, and Joel Schneider, an expert in peptide design, synthesis and materials. Collectively, the expertise of the team spans material design, characterization, in vitro cell compatibility, and in vivo biocompatibility.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 我们正在开发一种基于肽触发自组装的水凝胶策略，以帮助切除手术后的肝脏再生。我们将设计可以在体外封装细胞的水凝胶，然后可以将其注射到体内。 ，当溶解在水溶液中时 然而，当我们添加外源刺激物（例如细胞培养基）时，肽会折叠成 ¿ -发夹构象。当自组装时，这些折叠的肽经历快速自组装形成高度交联的水凝胶。 机制在肝细胞存在的情况下引发水凝胶化，凝胶充满细胞，这些凝胶的独特特征是，当施加适当的剪切应力时，凝胶将剪切稀化，成为粘性凝胶。停止后，粘性凝胶会快速自愈，产生机械刚性与剪切稀化前的原始水凝胶几乎相同的凝胶。凝胶的材料特性（例如凝胶化）。剪切稀化后的动力学、机械刚性和恢复动力学将通过肽设计进行调整，使它们能够通过注射器输送，所得的凝胶/细胞结构可以快速剪切稀化输送到目标组织。恢复，采用与伤口部位相适应的形状。交付后，凝胶在应用点保持局部状态（例如，它们不会流动）。凝胶，以及凝胶/细胞构建体在空间中传递的能力 我们将测试它们帮助切除的大鼠肝脏再生的能力，以实现该提案的目标：细胞和分子生物学家 Cindy Farach-Carson 博士。 Bennett M.D.（肝癌外科医生）、Darrin Pochan（水凝胶材料专家）和 Joel Schneider（肽设计、合成和材料专家）总的来说，该团队的专业知识涵盖材料设计、表征和体外。细胞相容性和体内生物相容性。