Thiol-Reactive Crosslinkers for Biomaterials

用于生物材料的硫醇反应性交联剂

• 批准号: 6880336
• 负责人: GLENN DOWNES PRESTWICH
• 金额: $ 10万
• 依托单位: CARBYLAN BIOSURGERY, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-20 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6880336
• 关键词: analog; athymic mouse; biomaterial compatibility; biomaterial development /preparation; cell proliferation; chemical kinetics; chemical structure function; chemical synthesis; crosslink; cysteine; extracellular matrix; fibroblasts; gel; hyaluronate; injection /infusion; polyethylene glycols; spectrometry; thiols; tissue /cell culture

DESCRIPTION (provided by applicant): A limited number of cytocompatible crosslinkers are available for the preparation of cell-seeded hydrogels and in vivo biocompatible injectable biomaterials. To expand this selection, Sentrx Surgical, Inc. will synthesize and evaluate a series of thiol-reactive bivalent and polyvalent crosslinkers based on polyethylene glycol (PEG). We will determine the relative reactivity of the new linkers with cysteine-containing peptides that would be covalently immobilized to thiol-modified hyaluronan (HA) or chondroitin sulfate (CS) and then crosslinked into a hydrogel. We will also establish the feasibility of using these new crosslinkers as in situ crosslinkable synthetic mimics of the extracellular matrix (ECM) for cell encapsulation in vitro and tissue regeneration in vivo. Specifically, we will explore five specific aims. First, we will synthesize five bivalent and five polyvalent PEG derivatives. Second, we will determine the pH dependence of the rates of reaction of each these linkers with cysteine and with HA-DTPH, a thiol-modified HA with the bivalent crosslinkers; rates will include comparison with known thiol-reactive PEG crosslinkers. Third, we will select three chemistries to prepare CRGDS clusters for attachment and crosslinking to give three new CRGDS-modified HA-DTPH hydrogels. Fourth, these new materials will be evaluated for cytocompatibility and cell growth in vitro with murine fibroblasts. Finally, selected materials will be seeded with fibroblasts and injected into nude mice for in vivo tissue generation.

描述（由申请人提供）：可用于制备细胞种子水凝胶和体内生物相容性可注射的生物材料的数量有限的细胞相容交联链。为了扩展这种选择，Sentrx Surgical，Inc。将基于聚乙烯甘油（PEG）合成并评估一系列硫醇反应性二价和多价交联。我们将确定新接头与含半胱氨酸的肽的相对反应性，这些肽将共价固定在硫醇改性的透明质酸（HA）或硫酸软骨素（CS）中，然后交联成凝胶。我们还将建立将这些新的交联链链接器作为原位交联的合成模仿（ECM）的可行性，用于体内的细胞和组织再生。具体来说，我们将探讨五个具体目标。首先，我们将合成五个二价和五个多价PEG衍生物。其次，我们将确定每个连接器与半胱氨酸和HA-DTPH的反应速率的pH依赖性，HA-DTPH是二硫化物的HA，具有二动交叉链接器；速率将包括与已知的硫醇反应性PEG交联剂的比较。第三，我们将选择三个化学物质来准备CRGD簇以进行连接和交联，以提供三种新的CRGDS修饰HA-DTPH水凝胶。第四，将评估这些新材料的细胞相容性和细胞生长在体外与鼠成纤维细胞的体外。最后，选定的材料将用成纤维细胞接种，并注入裸鼠，以进行体内组织。

项目成果

Crosslinked hydrogels for tympanic membrane repair.

用于鼓膜修复的交联水凝胶。

• DOI: 10.1016/j.otohns.2006.02.040
• 发表时间: 2006
• 期刊: Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
• 作者: Park,AlbertH;Hughes,CaseyW;Jackson,Adrienne;Hunter,Lisa;McGill,Lawrence;Simonsen,SaraEllis;Alder,StephenC;Shu,XiaoZheng;Prestwich,GlennD
• 通讯作者: Prestwich,GlennD