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）：有限数量的细胞相容性交联剂可用于制备细胞接种的水凝胶和体内生物相容性可注射生物材料。为了扩大这一选择，Sentrx Surgical, Inc. 将合成并评估一系列基于聚乙二醇 (PEG) 的硫醇反应性二价和多价交联剂。我们将确定新接头与含半胱氨酸肽的相对反应性，这些肽将共价固定到硫醇修饰的透明质酸（HA）或硫酸软骨素（CS）上，然后交联成水凝胶。我们还将确定使用这些新型交联剂作为细胞外基质（ECM）的原位交联合成模拟物用于体外细胞封装和体内组织再生的可行性。具体来说，我们将探讨五个具体目标。首先，我们将合成五种二价和五种多价 PEG 衍生物。其次，我们将确定这些连接体与半胱氨酸和 HA-DTPH（一种带有二价交联剂的硫醇修饰 HA）反应速率的 pH 依赖性；速率将包括与已知的硫醇反应性 PEG 交联剂的比较。第三，我们将选择三种化学物质来制备用于附着和交联的 CRGDS 簇，从而得到三种新的 CRGDS 修饰的 HA-DTPH 水凝胶。第四，将评估这些新材料与鼠成纤维细胞的细胞相容性和体外细胞生长。最后，将选定的材料接种成纤维细胞并注射到裸鼠体内进行体内组织生成。

项目成果

Crosslinked hydrogels for tympanic membrane repair.

用于鼓膜修复的交联水凝胶。

• 发表时间: 2006-12
• 作者: Park, Albert H;Hughes, Casey W;Jackson, Adrienne;Hunter, Lisa;McGill, Lawrence;Simonsen, Sara Ellis;Alder, Stephen C;Shu, Xiao Zheng;Prestwich, Glenn D
• 通讯作者: Prestwich, Glenn D

Cross-linked hydrogels for middle ear packing.

用于中耳填充的交联水凝胶。

• 发表时间: 2006-12
• 作者: Park, Albert H;Jackson, Adrienne;Hunter, Lisa;McGill, Lawrence;Simonsen, Sara Ellis;Alder, Stephen C;Shu, Xiao Zheng;Prestwich, Glenn
• 通讯作者: Prestwich, Glenn

Synthesis and characterization of novel thiol-reactive poly(ethylene glycol) cross-linkers for extracellular-matrix-mimetic biomaterials.

用于细胞外基质模拟生物材料的新型硫醇反应性聚乙二醇交联剂的合成和表征。

• DOI: 10.1021/bm0703564
• 发表时间: 2007-08-11
• 期刊: Biomacromolecules
• 影响因子: 6.2
• 作者: Janssen L V;erhooft;erhooft;B. Mann;G. Prestwich
• 通讯作者: G. Prestwich