Jisoo Shin1, Jung Seung Lee1, Changhyun Lee1, Hyun-Ji Park1, Kisuk Yang1, Yoonhee Jin1, Ji Hyun Ryu2, Ki Sung Hong3, Sung-Hwan Moon3, Hyung-Min Chung3, Hee Seok Yang4, Soong Ho Um5, Jong-Won Oh1, Dong-Ik Kim6, Haeshin Lee2 and Seung-Woo Cho1,7,*
1 Department of Biotechnology, Yonsei University, Seodaemun-gu, Seoul, South Korea
2 The Graduate School of Nanoscience and Technology, Department of Chemistry, Korea Advanced Institute of Science and Technology, Yuseong-gu, Daejeon, South Korea
3 Department of Stem Cell Biology, Konkuk University School of Medicine, Gwangjin-gu, Seoul, South Korea
4 Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Dongnam-gu, Cheonan, South Korea
5 School of Chemical Engineering and SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Jangan-gu, Suwon, South Korea
6 Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, South Korea
7 Department of Neurosurgery, Yonsei University College of Medicine, Seoul, South Korea
J.S., J.S.L., and C.L. contributed equally to this work.
Current hyaluronic acid (HA) hydrogel systems often cause cytotoxicity to encapsulated cells and lack the adhesive property required for effective localization of transplanted cells in vivo. In addition, the injection of hydrogel into certain organs (e.g., liver, heart) induces tissue damage and hemorrhage. In this study, we describe a bioinspired, tissue-adhesive hydrogel that overcomes the limitations of current HA hydrogels through its improved biocompatibility and potential for minimally invasive cell transplantation. HA functionalized with an adhesive catecholamine motif of mussel foot protein forms HA-catechol (HA-CA) hydrogel via oxidative crosslinking. HA-CA hydrogel increases viability, reduces apoptosis, and enhances the function of two types of cells (human adipose-derived stem cells and hepatocytes) compared with a typical HA hydrogel crosslinked by photopolymerization. Due to the strong tissue adhesiveness of the HA-CA hydrogel, cells are easily and efficiently transplanted onto various tissues (e.g., liver and heart) without the need for injection. Stem cell therapy using the HA-CA hydrogel increases angiogenesis in vivo, leading to improved treatment of ischemic diseases. HA-CA hydrogel also improved hepatic functions of transplanted hepatocytes in vivo. Thus, this bioinspired, tissue-adhesive HA hydrogel can enhance the efficacy of minimally invasive cell therapy.
Keywords : adhesive hydrogels; catechol; cell therapy; hyaluronic acid; tissue reconstruction