The effect of desulfation of chondroitin sulfate on interactions with positively charged growth factors and upregulation of cartilaginous markers in encapsulated MSCs

• Authors: Johnna Temenoff, Emory University; Johnna S. Lim, Georgia Institute of Technology
• Journal Title: Biomaterials
• Volume: Volume 34, Number 21
• Publisher: Elsevier Science Ltd. | 2013-07-01, Pages 5007-5018
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.biomaterials.2013.03.037
• Keywords: Science & Technology; Technology; Engineering, Biomedical; Materials Science, Biomaterials; Engineering; Materials Science; Chondroitin sulfate; Glycosaminoglycan; Growth factors; Mesenchymal stem cell; Cartilage tissue engineering; MESENCHYMAL STEM-CELLS; IN-VITRO; HYALURONAN; HYDROGELS; GLYCOL); BINDING; GLYCOSAMINOGLYCANS; DIFFERENTIATION; PROTEOGLYCANS; RELEASE

Abstract

Sulfated glycosaminoglycans (GAGs) are known to interact electrostatically with positively charged growth factors to modulate signaling. Therefore, regulating the degree of sulfation of GAGs may be a promising approach to tailor biomaterial carriers for controlled growth factor delivery and release. For this study, chondroitin sulfate (CS) was first desulfated to form chondroitin, and resulting crosslinked CS and chondroitin hydrogels were examined invitro for release of positively charged model protein (histone) and for their effect on cartilaginous differentiation of encapsulated human mesenchymal stem cells (MSCs). Desulfation significantly increased the release of histone from chondroitin hydrogels (30.6±2.3μg released over 8 days, compared to natively sulfated CS with 20.2±0.8μg), suggesting that sulfation alone plays a significant role in modulating protein interactions with GAG hydrogels. MSCs in chondroitin hydrogels significantly upregulated gene expression of collagen II and aggrecan by day 21 in chondrogenic medium (115±100 and 23.1±7.9 fold upregulation of collagen II and aggrecan, respectively), compared to CS hydrogels and PEG-based swelling controls, indicating that desulfation may actually enhance the response of MSCs to soluble chondrogenic cues, such as TGF-β1. Thus, desulfated chondroitin materials present a promising biomaterial tool to further investigate electrostatic GAG/growth factor interactions, especially for repair of cartilaginous tissues.