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

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.