Catechol-Functionalized Hyaluronic Acid Hydrogels Enhance Angiogenesis and Osteogenesis of Human Adipose-Derived Stem Cells in Critical Tissue Defects.
Over the last few decades, stem cell therapies have been highlighted for their potential to heal damaged tissue and aid in tissue reconstruction. However, materials used to deliver and support implanted cells often display limited efficacy, which has resulted in delaying translation of stem cell therapies into the clinic. In our previous work, we developed a mussel-inspired, catechol-functionalized hyaluronic acid (HA-CA) hydrogel that enabled effective cell transplantation due to its improved biocompatibility and strong tissue adhesiveness. The present study was performed to further expand the utility of HA-CA hydrogels for use in stem cell therapies to treat more clinically relevant tissue defect models. Specifically, we utilized HA-CA hydrogels to potentiate stem cell-mediated angiogenesis and osteogenesis in two tissue defect models: critical limb ischemia and critical-sized calvarial bone defect. HA-CA hydrogels were found to be less cytotoxic to human adipose-derived stem cells (hADSCs) in vitro compared to conventional photopolymerized HA hydrogels. HA-CA hydrogels also retained the angiogenic functionality of hADSCs and supported osteogenic differentiation of hADSCs. Because of their superior tissue adhesiveness, HA-CA hydrogels were able to mediate efficient engraftment of hADSCs into the defect regions. When compared to photopolymerized HA hydrogels, HA-CA hydrogels significantly enhanced hADSC-mediated therapeutic angiogenesis (promoted capillary/arteriole formation, improved vascular perfusion, attenuated ischemic muscle degeneration/fibrosis, and reduced limb amputation) and bone reconstruction (mineralized bone formation, enhanced osteogenic marker expression, and collagen deposition). This study proves the feasibility of using bioinspired HA-CA hydrogels as functional biomaterials for improved tissue regeneration in critical tissue defects.
Department of Biotechnology, Yonsei University , Seoul 120-749, Republic of Korea.
Hyun-Ji
HJ
Park
Department of Biotechnology, Yonsei University , Seoul 120-749, Republic of Korea.
Yoonhee
Y
Jin
Department of Biotechnology, Yonsei University , Seoul 120-749, Republic of Korea.
Jisoo
J
Shin
Department of Biotechnology, Yonsei University , Seoul 120-749, Republic of Korea.
Kisuk
K
Yang
Department of Biotechnology, Yonsei University , Seoul 120-749, Republic of Korea.
Changhyun
C
Lee
Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 330-714, Republic of Korea.
Hee Seok
HS
Yang
Department of Biotechnology, Yonsei University , Seoul 120-749, Republic of Korea.|Department of Neurosurgery, Yonsei University College of Medicine , Seoul 120-752, Republic of Korea.
Seung-Woo
SW
Cho
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002396:Catechols / Q000737:chemistry* / Q000494:pharmacology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006259:Craniocerebral Trauma / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000494:pharmacology; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology; D007511:Ischemia / Q000628:therapy; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D012886:Skull / Q000187:drug effects / Q000293:injuries; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D054457:Tissue Scaffolds / Q000737:chemistry
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D002396:Catechols; D020100:Hydrogels; D006820:Hyaluronic Acid; C034221:catechol