Sulfated hyaluronic acid hydrogels with retarded degradation and enhanced growth factor retention promote hMSC chondrogenesis and articular cartilage integrity with reduced hypertrophy

Publication date: Available online 11 February 2017
Source:Acta Biomaterialia
Author(s): Qian Feng, Sien Lin, Kunyu Zhang, Chaoqun Dong, Tianyi Wu, Heqin Huang, Xiaohui Yan, Li Zhang, Gang Li, Liming Bian
Recently, hyaluronic acid (HA) hydrogels have been extensively researched for delivering cells and drugs to repair damaged tissues, particularly articular cartilage. However, the in vivo degradation of HA is fast, thus limiting the clinical translation of HA hydrogels. Furthermore, HA cannot bind proteins with high affinity because of the lack of negatively charged sulfate groups. In this study, we conjugated sulfate groups to HA. These sulfated HA exhibit significantly slower degradation by hyaluronidase compared to the wild type HA. We hypothesize that sulfation reduces the available HA octasaccharide substrate needed for the effective catalytic action of hyaluronidase. Moreover, the sulfated HA significantly improve the protein sequestration, thereby effectively extending the availability of the proteinaceous drugs in the hydrogels. In the following in vitro study, we demonstrate that the sulfation exerts no negative effect on the viability of human mesenchymal stem cells (hMSCs). Furthermore, the sulfated HA promotes the chondrogenesis and suppresses the hypertrophy of hMSCs both in vitro and in vivo. Moreover, animal research demonstrate that the sulfated HA hydrogels avert the cartilage abrasion and hypertrophy in the animal osteoarthritis joints. Collectively, our findings demonstrate that the sulfated HA is a promising biomaterial for regenerative medicine applications including cartilage repair.Statement of significanceIn this paper, we conjugated sulfate to hyaluronic acid (HA) and demonstrated the slow degradation and growth factor delivery of sulfated HA. Futhermore, in vitro and in vivo culture of hMSCs laden HA hydrogels proved that the sulfation of HA hydrogels not only promotes the chondrogenesis of hMSCs but also suppresses hypertrophic differentiation of the chondrogenically induced hMSCs. The animal OA model study showed that the injected sulfated HA hydrogels significantly reduced the cartilage abrasion and hypertrophy in the animal OA joints. We believe that this study will provide important insights into the design and optimization of the HA-based hydrogels as the scaffold materials for cartilage regeneration and OA treatment in clinical setting.

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