Glycosaminoglycans (GAGs) are linear, negatively charged polysaccharid es 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, and 3) degradation mechanisms of GAGs. GAG-protein interactions can be based on 1) GAG sulfation pattern, 2) GAG carbohydrate conformation, and 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 degenerate or injured tissues.
Mesenchymal stem cells (MSCs) have been previously explored as a part of cell-based therapies for the repair of damaged cartilage. Current MSC chondrogenic differentiation strategies employ large pellets; however, we have developed a technique to form small MSC aggregates (500-1,000 cells) that can reduce transport barriers while maintaining a multicellular structure analogous to cartilaginous condensations. The objective of this study was to examine the effects of incorporating chondroitin sulfate methacrylate (CSMA) microparticles (MPs) within small MSC spheroids cultured in the presence of transforming growth factor (TGF)-β1 on chondrogenesis. Spheroids with MPs induced earlier increases in collagen II and aggrecan gene expression (chondrogenic markers) than spheroids without MPs, although no large differences in immunostaining for these matrix molecules were observed by day 21 between these groups. Collagen I and X were also detected in the extracellular matrix (ECM) of all spheroids by immunostaining. Interestingly, histology revealed that CSMA MPs clustered together near the center of the MSC spheroids and induced circumferential alignment of cells and ECM around the material core. This study demonstrates the use of CSMA materials to further examine the effects of matrix molecules on MSC phenotype as well as potentially direct differentiation in a more spatially controlled manner that better mimics the architecture of specific musculoskeletal tissues.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.