Biopolymer-Mimetic Worm-like Micelle Tissue Scaffolds

生物聚合物模拟蠕虫状胶束组织支架

基本信息

批准号：
6787659
负责人：
ROBERT T TRANQUILLO
金额：
$ 20.7万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-30 至 2006-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6787659
关键词：
Biopolymer Mimetic Worm like Micelle

项目摘要

DESCRIPTION (provided by applicant): We propose to develop a novel fibrillar scaffold for artificial tissue growth that combines the key attributes of synthetic biomaterials and fibrillar biopolymers, Synthetic biomaterials allow for defined composition tailored for selective cell adhesion with no risk of viral or pathogen transmission. Fibrillar biopolymer gels, such as type I collagen and fibrin, allow cellularity to be obtained directly by cell entrapment during self-assembly and are conducive to structural and compositional remodeling. For the preparation of worm-like micelle (WLM) scaffolds we will use block copolymers that contain at least three distinct regions: a crosslinkable hydrophobic core, a hydrophilic corona, and a cell adhesion peptide. The hydrophobic core will be degradable under physiological conditions (e.g., polyaliphatic esters). Polyethylene oxide (PEO) will be used as the hydrophilic component and simple cell adhesion peptides will be conjugated to the PEO terminus. After formation of a cell suspension with the WLM in aqueous solution, the hydrophobic cores of the WLMs will be chemically fixed through simple catalytic cross linking, allowing direct cell entrapment into an entangled network of stable but ultimately degrading WLMs, analogous to the fibrillar bi0polymers. Rheometry, cryo-TEM, and SAXS will be used to verify the integrity of the WLM network and to characterize physical properties relevant to cell-network mechanical interactions that lead to network contraction and alignment when a mechanical constraint is applied. The molecular parameters of the amphiphilic block copolymers will be systematically tuned to control the WLM formation, crosslinking density, degradation rates and ultimate mechanical behavior. Efforts to approximate the relevant material properties of the biopolymer gels will be emphasized. With cells entrapped into a cross-linked WLM network, cell induced network compaction and alignment will be analyzed using quantitative polarized light microscopy, and the evolving WLM degradation and ECM deposition characterized using biochemical and histological analyses. Molecular weights and cross-link density will be adjusted accordingly, and various degradable cores will be pursued as necessary, if degradation and deposition occur on disparate time scales. Cell viability and polymer degradation will be monitored. Ultimate mechanical properties, ECM composition, and ECM structure of the artificial tissues following in vitro incubation will be compared to soft connective tissues. The resultant artificial tissues will be assayed in a rat subcutaneous implantation model to assess biocompatibility.

描述（由申请人提供）：我们建议开发一种用于人工组织生长的新型纤维状支架，它结合了合成生物材料和纤维状生物聚合物的关键属性，合成生物材料允许为选择性细胞粘附定制特定的成分，而没有病毒或病原体传播的风险。纤维状生物聚合物凝胶，例如 I 型胶原蛋白和纤维蛋白，可以在自组装过程中通过细胞捕获直接获得细胞结构，有利于结构和成分重塑。为了制备蠕虫状胶束 (WLM) 支架，我们将使用包含至少三个不同区域的嵌段共聚物：可交联的疏水核、亲水冠和细胞粘附肽。疏水核心在生理条件下可降解（例如，聚脂族酯）。聚环氧乙烷 (PEO) 将用作亲水成分，简单的细胞粘附肽将缀合至 PEO 末端。在水溶液中与 WLM 形成细胞悬浮液后，WLM 的疏水核心将通过简单的催化交联进行化学固定，从而允许细胞直接陷入稳定但最终降解的 WLM 的纠缠网络中，类似于纤维状生物聚合物。流变测量、冷冻 TEM 和 SAXS 将用于验证 WLM 网络的完整性，并表征与细胞网络机械相互作用相关的物理特性，这些机械相互作用会在施加机械约束时导致网络收缩和对齐。两亲性嵌段共聚物的分子参数将被系统地调整，以控制 WLM 的形成、交联密度、降解速率和最终的机械行为。将强调近似生物聚合物凝胶的相关材料特性的努力。随着细胞被捕获到交联的 WLM 网络中，将使用定量偏振光显微镜分析细胞诱导的网络压实和排列，并使用生化和组织学分析来表征不断演变的 WLM 降解和 ECM 沉积。如果降解和沉积发生在不同的时间尺度上，则分子量和交联密度将进行相应调整，并且将根据需要寻求各种可降解核心。将监测细胞活力和聚合物降解。体外孵化后的人造组织的最终机械性能、ECM 成分和 ECM 结构将与软结缔组织进行比较。所得的人造组织将在大鼠皮下植入模型中进行分析，以评估生物相容性。