Saccharide-Peptide Hybrid Copolymers for Tissue Engineering

描述（由申请人提供）：拟定研究旨在开发糖-肽杂合共聚物，作为一种全新的多功能聚合物生物材料。开发新一代高功能、定义明确和“相互作用”的生物材料对于推动组织工程领域走向可行的临床现实至关重要。尽管如此，很少有真正新颖的生物材料出现，大多数研究人员反而专注于修改过去20-30年来研究的材料。虽然这种方法已经取得了一定程度的成功，但许多现有的材料都受到很大的限制，无法预测地控制细胞功能。作为替代方案，这项多学科研究计划旨在开发和测试真正新颖的聚合物生物材料。Guan实验室最近的突破导致了一系列来自肽和糖起始材料的新型生物材料。体外试验表明，糖肽杂化共聚物可被蛋白水解降解，且具有较低的细胞毒性。初步的动物研究表明，这些材料不会引起大鼠的全身免疫应答。这些特点结合其多功能性和高功能性，使这些生物材料有希望的候选人的互动生物材料的应用。在这项提案中，我们将利用Guan实验室的合成化学专业知识来开发生物相互作用材料，并利用Putnam实验室的细胞生物学专业知识来研究这些新材料作为合成细胞外基质（ECM）类似物。具体而言，我们建议开发新的糖-肽杂化共聚物的有效合成，并测试这些新材料的体外和体内生物相容性。通过这些研究，我们将实现以下具体目标：（1）我们将开发制备糖-肽杂化共聚物及其水凝胶的有效和良性的合成路线;（2）我们将制备和表征一系列具有精确控制的化学和机械性质的定义明确的水凝胶基质;（3）我们将研究这些水凝胶材料作为细胞研究的模型基质的细胞相容性，并解决它们在体外指导细胞表型的能力;最后（4）我们将研究它们作为细胞递送载体的体内相容性和潜力。

DESCRIPTION (provided by applicant): The proposed research is aimed at developing saccharide-peptide hybrid copolymers as a family of fundamentally new versatile polymeric biomaterials. The development of new generations of highly functional, well-defined and "interactive" biomaterials is essential to advance the field of tissue engineering towards a viable clinical reality. Despite this, very few truly novel biomaterials have emerged, with most researchers instead focusing their efforts to modify materials that have been studied for the past 20-30 years. While this approach has achieved certain extent of successes, many of the existing materials suffer from significant limitations and are unable to predictably control cell function. As an alternative, this multi-disciplinary research proposal seeks to develop and test truly novel polymeric biomaterials. Recent breakthroughs in the Guan laboratory led to a series of novel biomaterials derived from peptide and saccharide starting materials. In vitro tests show that the saccharide-peptide hybrid copolymers can be degraded by proteolysis and have low cytotoxicity. Preliminary animal studies indicate these materials do not illicit systemic immune response in rats. These features combined with their versatility and high functionality make these biomaterials promising candidates for interactive biomaterials applications. In this proposal, we will leverage the synthetic chemistry expertise of the Guan laboratory to develop bio-interactive materials, and the cell biology expertise of the Putnam laboratory to investigate these new materials as synthetic extracellular matrix (ECM) analogs. Specifically, we propose to develop efficient synthesis of novel saccharide-peptide hybrid copolymers and test the in vitro and in vivo biocompatibility of these new materials. Through the proposed studies the following specific aims will be accomplished: (1) we will develop efficient and benign synthetic routes for making saccharide-peptide hybrid copolymers and their hydrogels; (2) we will prepare and characterize a series of well-defined hydrogel matrices having precisely controlled chemical and mechanical properties; (3) we will investigate the cytocompatibility of these hydrogel materials as model substrates for cell studies, and address their ability to direct cell phenotype in vitro; and finally (4) we will investigate their in vivo compatibility and potential as cell delivery vehicles.