Inhibitory Effect of Topical Cartilage Acellular Matrix Suspension Treatment on Neovascularization in a Rabbit Corneal M
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ORIGINAL ARTICLE
Inhibitory Effect of Topical Cartilage Acellular Matrix Suspension Treatment on Neovascularization in a Rabbit Corneal Model Hee-Woong Yun1,2 • Byung Hyune Choi3 • Do Young Park4 • Long Hao Jin5 Byoung-Hyun Min1,2,4
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Received: 15 April 2020 / Revised: 13 May 2020 / Accepted: 14 May 2020 Ó The Korean Tissue Engineering and Regenerative Medicine Society 2020
Abstract BACKGROUND: The extracellular matrix (ECM) of articular cartilage has an inhibitory effect on vascularization, yet clinical utilization has been technically challenging. In this study, we aimed to fabricate a biologically functional ECM powder suspension from porcine articular cartilage that inhibits neovascularization (NV). METHODS: The digested-cartilage acellular matrix (dg-CAM) was prepared by sequential processes of decellularization, enzymatic digestion and pulverization. Physicochemical properties of dg-CAM were compared with that of native cartilage tissue (NCT). Cellular interactions between human umbilical vein endothelial cells (HUVECs) and dg-CAM was evaluated with proliferation, migration and tube formation assays compared with that of type I collagen (COL) and bevacizumab, an anti-angiogenic drug. We then investigated the therapeutic potential of topical administration of dg-CAM suspension on the experimentally induced rabbit corneal NV model. RESULTS: The dg-CAM released a significantly larger amount of soluble proteins than that of the NCT and showed an improved hydrophilic and dispersion properties. In contrast, the dg-CAM contained a large amount of collagen, glycosaminoglycans and anti-angiogenic molecules as much as the NCT. The inhibitory effect on NV of the dg-CAM was more prominent than that of COL and even comparable to that of bevacizumab in inhibiting the HUVECs. The therapeutic potential of the dg-CAM was comparable to that of bevacizumab in the rabbit corneal NV model by efficiently inhibiting neovessel formation of the injured cornea. CONCLUSION: The current study developed a dg-CAM having anti-angiogenic properties, together with water-dispersible properties suitable for topical or minimally invasive application for prevention of vessel invasion. Keywords Cartilage Extracellular matrix (ECM) Water dispersible Enzymatic digestion Anti-angiogenesis
& Byoung-Hyun Min [email protected] 1
Department of Molecular Science and Technology, Ajou University, San 5, Wonchon-dong, Youngtong-gu, Suwon 16499, Republic of Korea
2
Cell Therapy Center, Ajou University School of Medicine, San 5, Wonchon-dong, Youngtong-gu, Suwon 16499, Republic of Korea
3
Department of Biomedical Sciences, Inha University College of Medicine, 100, Inha-ro, Michuhol-gu, Incheon 22212, Republic of Korea
4
Department of Orthopedic Surgery, Ajou University School of Medicine, San 5, Wonchon-dong, Youngtong-gu, Suwon 16499, Republic of Korea
5
Department of Orthopedic Surgery, Yanbian University Medical School, 977 Gongyuan Rd, Yanji, Yanbian, China
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Tissue Eng Regen Med
1 Introduction Decellulari
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