Investigation of Vasculogenesis Inducing Biphasic Scaffolds for Bone Tissue Engineering

Abstract

Vascularization is the main obstacle for the bone tissue engineering strategies since the defect size is generally large. Incorporation of angiogenic factors is one of the strategies employed in order to accelerate vascularization and improve bone healing. In this study, a biphasic scaffold consisting of fibrous poly­(lactide-co-glycolide) (PLGA) and poly­(lactide-co-glycolide)-block-poly­(ethylene glycol)-block-poly­(lactide-co-glycolide) (PLGA–PEG–PLGA) hydrogel loaded with vascular endothelial growth factor-A (VEGF) inducer, GS4012, was constructed. Mesenchymal stem cells isolated from rat bone marrow (rBMSCs) were used for differentiation into osteogenic cells, and endothelial cells isolated from rat peripheral blood (rPBECs) were used to test the in vitro endothelial cell recruitment. The biphasic scaffold was tested for cell proliferation, ALP expression, VEGF induction, expression of osteogenic genes by rBMSCs, and recruitment of rPBECs in vitro and for improved bone healing and vascularization in vivo on critical size rat cranial defects. Endothelial migration through porous insert and VEGF induction were obtained in vitro in response to GS4012 as well as the upregulation of ALP, Runx2, Col I, and OC gene expressions. The biphasic scaffold was also shown to be effective in improving endothelial cell recruitment, vascularization, and bone healing in vivo. Thus, the proposed design has a great potential for the healing of critical size bone defect in tissue engineering studies according to both in vitro and in vivo investigations.

Surface Modification Progress for PLGA-Based Cell Scaffolds

“…In addition, studies have shown that the body’s ability to recognize and bind with anti-PEG antibodies may be a challenge for PEG-functionalized PLGA stents in vivo in the long term [ 62 ]. Various elements such as cells [ 63 ], cytokines [ 64 ], therapeutic drugs [ 65 ], or inorganic nanomaterials [ 7 ] can be wrapped into the hydrogel in the sol-to-gel state to regulate the physiological functions of cells and enhance cell–tissue communication and integration while these elements are delivered to cells.…”

Drug delivery systems based on polyethylene glycol hydrogels for enhanced bone regeneration

“…In addition, PEG-based hydrogels can also load a variety of growth factors to obtain different functions. As osteogenesis and angiogenesis are coupled and interact with each other in the repair process of bone defects, a drug delivery system with dual functions of promoting angiogenesis and osteogenesis will have good application prospects ( Pekozer et al, 2021 ). VEGF and BMP-2 co-loaded into PEG-based hydrogel matrix can endow the gel with angiogenesis and osteogenesis functions.…”

Biofunctionalization of hydrogel-based scaffolds for vascular tissue regeneration

“…In vitro, it was shown that the hydrogel induces cell proliferation, VEGF induction, and expression of Runx2, Col I, OC, and ALP genes in rat bone marrow mesenchymal stem cells (rBMSCs) promoters of osteogenesis. In vivo in a rat calvaria defect model, it was demonstrated that the biomaterial containing GS4012 improved vascular endothelial cell recruitment, increased vascularity, and allowed rapid and orderly bone healing (Gurel Pekozer et al, 2021).…”