Tissue Eng Regen Med.  2020 Oct;17(5):625-640. 10.1007/s13770-020-00275-3.

Inhibitory Effect of Topical Cartilage Acellular Matrix Suspension Treatment on Neovascularization in a Rabbit Corneal Model

Affiliations
  • 1Department of Molecular Science and Technology, Ajou University, San 5, Wonchon-dong, Youngtong-gu, Suwon 16499, Republic of Korea
  • 2Cell Therapy Center, Ajou University School of Medicine, San 5, Wonchon-dong, Youngtong-gu, Suwon 16499, Republic of Korea
  • 3Department of Biomedical Sciences, Inha University College of Medicine, 100, Inha-ro, Michuhol-gu, Incheon 22212, Republic of Korea
  • 4Department of Orthopedic Surgery, Ajou University School of Medicine, San 5, Wonchon-dong, Youngtong-gu, Suwon 16499, Republic of Kore
  • 5Department of Orthopedic Surgery, Yanbian University Medical School, 977 Gongyuan Rd, Yanji, Yanbian, China

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.

Keyword

Cartilage; Extracellular matrix (ECM); Water dispersible; Enzymatic digestion; Anti-angiogenesis
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