Injectable multifunctional microgel encapsulating outgrowth endothelial cells and growth factors for enhanced neovascularization.
Recent cell-based therapy approaches have employed both nanotechnologies and other biomedical technologies to enhance their therapeutic potential. A combined strategy using therapeutic stem/progenitor cells and angiogenic proteins is attractive for the treatment of vascular disease. In this study, we developed an injectable multifunctional micro-sized gel system (microgel), composed of arginine-glycine-aspartic acid (RGD)-conjugated alginate, for the delivery of both cells and growth factors in vivo. The microgels encapsulated with outgrowth endothelial cells (OECs) and growth factors (vascular endothelial growth factor, VEGF, and hepatocyte growth factor, HGF) were formed via electrospraying. Cells encapsulated within the microgel exhibited a time-dependent proliferation with enhanced cell viability, and the size-controlled microgels resulted in sustained release of growth factors for enhanced new vessel formation by tube formation and rat aorta sprouting in vitro. Increased angiogenesis was also estimated in mice treated with RGD-microgel containing OECs and growth factors. Furthermore, injection of the multifunctional microgel into a hindlimb ischemia model improved blood flow perfusion and increased the capillary density by histological analysis. Compared with hydrogel system, injectable microgel system was shown to be superior with no toxicity. Overall, our injectable multifunctional microgel system can be attributed to deliver potential therapeutic agents/cells for the treatment of vascular diseases.
Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
Pyung-Hwan
PH
Kim
School of Chemical and Biological Engineering, Seoul National University, Seoul, South Korea.
Hyun-Gu
HG
Yim
Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
Young-Jin
YJ
Choi
Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
Byung-Jae
BJ
Kang
Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
Joohyun
J
Kim
Department of Physiology, School of Medicine, Pusan national University, Yangsan, South Korea.
Sang-Mo
SM
Kwon
School of Chemical and Biological Engineering, Seoul National University, Seoul, South Korea.
Byung-Soo
BS
Kim
School of Chemical and Biological Engineering, Seoul National University, Seoul, South Korea.
Nathaniel S
NS
Hwang
Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea. Electronic address: jeycho@snu.ac.kr.
Je-Yoel
JY
Cho
D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001011:Aorta / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002478:Cells, Cultured; D042783:Endothelial Cells; D005121:Extremities / Q000098:blood supply; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000737:chemistry; D005782:Gels; D020723:Glucuronic Acid / Q000737:chemistry; D057809:HEK293 Cells; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage; D006603:Hexuronic Acids / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007267:Injections; D007511:Ischemia / Q000188:drug therapy; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009842:Oligopeptides / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
D000464:Alginates; D005782:Gels; D006603:Hexuronic Acids; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; D012710:Serum Albumin, Bovine; D017228:Hepatocyte Growth Factor; C047981:arginyl-glycyl-aspartic acid; D020723:Glucuronic Acid; D016650:Fluorescein-5-isothiocyanate
Cell therapy; Electrospraying; Neovascularization; Outgrowth endothelial cells; RGD-conjugated microgel