Formation of a Novel Heparin-Based Hydrogel in the Presence of Heparin-Binding Biomolecules

• Published in: Biomacromolecules Vol. 8; no. 6; pp. 1979 - 1986
• Main Authors: Tae, Giyoong, Kim, Yang-Jung, Choi, Won-Il, Kim, Mihye, Stayton, Patrick S, Hoffman, Allan S
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.06.2007
• Subjects: Animals; Antithrombins - chemistry; Applied sciences; Biocompatible Materials - chemistry; Biological and medical sciences; Carbodiimides - chemistry; Cell Proliferation; Cross-Linking Reagents - chemistry; Exact sciences and technology; Gels; General pharmacology; Heparin - chemistry; Hydrogels - chemistry; Kinetics; Macromolecular Substances; Medical sciences; Mice; Models, Chemical; Natural polymers; NIH 3T3 Cells; Organic polymers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Properties and characterization; Solution and gel properties; Starch and polysaccharides; Sulfhydryl Compounds; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Technology. Biomaterials. Equipments; Cell proliferation; Injectable form; Adsorption capacity; Amidation; Ethylene oxide polymer; Colloidal gel; Biomaterial; Framework; Michael addition; Delivery system; Swelling; Liquid solid adsorption; Tissue engineering; Control release polymer; Gelation; Crosslinking; Ethylene oxide copolymer; Experimental study; Sulfur copolymer; Protein; Chemical modification; Preparation; Prepolymer; Aminothiol; Kinetics; Heparin; Fibroblast
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm0701189

An injectable, heparin-based hydrogel system with the potential to be gelled with cells was developed. First, heparin was modified to have thiol groups by the modification of carboxylic groups of heparin with cysteamine using carbodiimide chemistry. Thiol functionalization of heparin carboxylic groups was controlled from 10% to 60% of the available COOH groups, and the retained bioactivity of the modified heparin, characterized by its binding affinity to antithrombin III, decreased with increasing functionalization. Then, the thiol-functionalized heparin was reacted with poly(ethylene glycol) diacrylate to form a hydrogel. The gelation kinetics and mechanical properties of the final gel state could be tuned by controlling cross-link density. Fibroblast cell encapsulation using this hydrogel revealed the nontoxicity of the present system. Cell proliferation inside the hydrogel was observed, and it was significantly enhanced (more than 5-fold) by the addition of fibrinogen into the hydrogel during gelation.