Induction of Angiogenesis by Matrigel Coating of VEGF-Loaded PEG/PCL-Based Hydrogel Scaffolds for hBMSC Transplantation

Abstract

hBMSCs are multipotent cells that are useful for tissue regeneration to treat degenerative diseases and others for their differentiation ability into chondrocytes, osteoblasts, adipocytes, hepatocytes and neuronal cells. In this study, biodegradable elastic hydrogels consisting of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(ε-caprolactone) (PCL) scaffolds were evaluated for tissue engineering because of its biocompatibility and the ability to control the release of bioactive peptides. The primary cultured cells from human bone marrow are confirmed as hBMSC by immunohistochemical analysis. Mesenchymal stem cell markers (collagen type I, fibronectin, CD54, integrin1β, and Hu protein) were shown to be positive, while hematopoietic stem cell markers (CD14 and CD45) were shown to be negative. Three different hydrogel scaffolds with different block compositions (PEG:PCL=6:14 and 14:6 by weight) were fabricated using the salt leaching method. The hBMSCs were expanded, seeded on the scaffolds, and cultured up to 8 days under static conditions in Iscove’s Modified Dulbecco’s Media (IMDM). The growth of MSCs cultured on the hydrogel with PEG/PCL= 6/14 was faster than that of the others. In addition, the morphology of MSCs seemed to be normal and no cytotoxicity was found. The coating of the vascular endothelial growth factor (VEGF) containing scaffold with Matrigel slowed down the release of VEGF in vitro and promoted the angiogenesis when transplanted into BALB/c nude mice. These results suggest that hBMSCs can be supported by a biode gradable hydrogel scaffold for effective cell growth, and enhance the angiogenesis by Matrigel coating.

Synergistic Effects of Vascular Endothelial Growth Factor on Bone Morphogenetic Proteins Induced Bone Formation In Vivo: Influencing Factors and Future Research Directions

“…To overcome these disadvantages, gene delivery [6, 58–63] and material-based delivery system [64–70] have been developed in tissue engineering. There are mainly two strategies used in the codelivery of VEGF and BMPs.…”

Tissue engineering strategies for the induction of angiogenesis using biomaterials

“…These cells have per se potential to modulate the function of blood vessels in different trials. In support of this statement, scientists have strived to exploit the pro-angiogenic ability of EPCs for treating myocardial infarction, ischemic changes, and peripheral vascular disease and wound healing as well [20, 24]. After initiation of ischemic changes, there is an urgent need for the pro-angiogenic activity of transplanted cells on engineered vascular constructs while inhibiting angiostatic pathways [25].…”

In Vitro Study of the Interaction of Innate Immune Cells with Liquid Silicone Rubber Coated with Zwitterionic Methyl Methacrylate and Thermoplastic Polyurethanes

“…A confluent endothelial cell layer on material surfaces is widely considered an approach to improve the biocompatibility of implanted cardiovascular materials. Therefore, VEGF coatings or functionalization have been used to protect stents from in-stent restenosis, induce angiogenesis, or protect small diameter vascular grafts from thrombosis or degeneration by inducing endothelial formation [32][33][34]. However, VEGF can also lead to increased neo-intimal hyperplasia [34], and there are implants where integration with the surrounding tissue should be avoided, such as transvenous pace maker electrodes.…”