Saccharide-Peptide Hybrid Copolymers for Tissue Engineering

用于组织工程的糖-肽杂化共聚物

• 批准号: 7319678
• 负责人: ZHIBIN GUAN
• 金额: $ 29.64万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-10 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7319678
• 关键词: 3-Dimensional; Address; Adhesives; Adsorption; Animals; Benign; Biocompatible; Biocompatible Materials; Biological; Biomimetic Materials; Blood Vessels; Cell Adhesion; Cell Survival; Cell model; Cell physiology; Cells; Cellular biology; Chemicals; Clinical; Communities; Condition; Dental; Development; Diagnostic; Drug Delivery Systems; Extracellular Matrix; Family; Gel; Generations; Healthcare; Human; Hybrids; Hydrogels; Immune response; Implant; In Vitro; Investigation; Laboratories; Measures; Mechanics; Medical Device; Methodology; Modeling; Orthopedics; Peptides; Phenotype; Polymers; Process; Property; Prosthesis; Proteins; Proteolysis; Proteomics; Rattus; Research; Research Personnel; Research Proposals; Resistance; Route; Series; Smooth Muscle Myocytes; Spectrum Analysis; Structure; Surface Plasmon Resonance; Synthesis Chemistry; System; Testing; Tissue Engineering; Tissues; analog; biomaterial compatibility; copolymer; crosslink; cytotoxicity; density; design; in vivo; macromolecule; migration; novel; programs; response; scaffold; sensor; subcutaneous; success

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.

描述（由申请人提供）：拟议的研究旨在开发糖-肽杂化共聚物作为一类全新的多功能聚合生物材料。新一代高功能、明确定义和“交互式”生物材料的开发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，真正新颖的生物材料却很少出现，大多数研究人员都将精力集中在修饰过去 20-30 年研究的材料上。虽然这种方法取得了一定程度的成功，但许多现有材料存在明显的局限性，无法可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。管实验室最近取得的突破导致了一系列源自肽和糖起始材料的新型生物材料。体外测试表明，糖-肽杂化共聚物可以通过蛋白水解作用降解，并且具有较低的细胞毒性。初步动物研究表明这些材料不会引起大鼠的全身免疫反应。这些特性与其多功能性和高功能性相结合，使这些生物材料成为交互式生物材料应用的有希望的候选者。在本提案中，我们将利用关实验室的合成化学专业知识来开发生物交互材料，并利用普特南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。具体来说，我们建议开发新型糖-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。通过拟议的研究，将实现以下具体目标：（1）我们将开发高效且良性的合成路线来制造糖-肽杂化共聚物及其水凝胶； （2）我们将制备并表征一系列具有精确控制的化学和机械性能的明确的水凝胶基质； （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）我们将研究它们的体内相容性和作为细胞递送载体的潜力。