Molecular engineering of glycosaminoglycan chemistry for biomolecule delivery

• Type of Material: Article
• Authors: Tobias Miller, Georgia Institute of Technology; Melissa C. Goude, Georgia Institute of Technology; Todd McDevitt, Emory University; Johnna Temenoff, Emory University
• Language: English
• Date: 2014-04-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Acta Materialia Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.actbio.2013.09.039
• Title of Journal or Parent Work: Acta Biomaterialia
• ISSN: 1742-7061
• Volume: 10
• Issue: 4
• Start Page: 1705
• End Page: 1719
• Grant/Funding Information: The authors are supported by funding from the NIH (R01 AR062006) and NSF (DMR 1207045).
• Keywords: HEPARIN-BASED HYDROGEL; Engineering, Biomedical; Protein binding; BONE MORPHOGENETIC PROTEINS; CROSS-LINKED COLLAGEN; Materials Science, Biomaterials; Engineering; CONJUGATED POLYMERIC MICELLE; FIBROBLAST-GROWTH-FACTOR; Glycosaminolgycan; Growth factor; VESSEL WALL INJURY; DERMATAN SULFATE; CHONDROITIN SULFATE-E; Science & Technology; MESENCHYMAL STEM-CELLS; Technology; Chemistry; HYALURONIC-ACID HYDROGELS; Materials Science; Controlled release
• Research Categories: Engineering, Biomedical

Abstract

Glycosaminoglycans (GAGs) are linear, negatively charged polysaccharides that interact with a variety of positively charged growth factors. In this review article the effects of engineering GAG chemistry for molecular delivery applications in regenerative medicine are presented. Three major areas of focus at the structure-function-property interface are discussed: (1) macromolecular properties of GAGs; (2) effects of chemical modifications on protein binding; (3) degradation mechanisms of GAGs. GAG-protein interactions can be based on: (1) GAG sulfation pattern; (2) GAG carbohydrate conformation; (3) GAG polyelectrolyte behavior. Chemical modifications of GAGs, which are commonly performed to engineer molecular delivery systems, affect protein binding and are highly dependent on the site of modification on the GAG molecules. The rate and mode of degradation can determine the release of molecules as well as the length of GAG fragments to which the cargo is electrostatically coupled and eventually released from the delivery system. Overall, GAG-based polymers are a versatile biomaterial platform offering novel means to engineer molecular delivery systems with a high degree of control in order to better treat a range of degenerated or injured tissues.