Hee-Woong Yun1,2, Byung Hyune Choi3, Do Young Park4, Long Hao Jin5, Byoung-Hyun Min6,7,8. 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. 6. Department of Molecular Science and Technology, Ajou University, San 5, Wonchon-dong, Youngtong-gu, Suwon, 16499, Republic of Korea. bhmin@ajou.ac.kr. 7. Cell Therapy Center, Ajou University School of Medicine, San 5, Wonchon-dong, Youngtong-gu, Suwon, 16499, Republic of Korea. bhmin@ajou.ac.kr. 8. Department of Orthopedic Surgery, Ajou University School of Medicine, San 5, Wonchon-dong, Youngtong-gu, Suwon, 16499, Republic of Korea. bhmin@ajou.ac.kr.
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.
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.
Entities:
Keywords:
Anti-angiogenesis; Cartilage; Enzymatic digestion; Extracellular matrix (ECM); Water dispersible
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