Abstract
Vascularization is one of the main challenges in bone tissue engineering (BTE). In this study, vascular endothelial growth factor (VEGF), known for its angiogenic effect, was delivered by our developed sponge, derived from a polyelectrolyte complexes hydrogel between chitosan (CHT) and anionic cyclodextrin polymer (PCD). This sponge, as a scaffold for growth factor delivery, was formed by freeze-drying a homogeneous CHT/PCD hydrogel, and thereafter stabilized by a thermal treatment. Microstructure, water-uptake, biodegradation, mechanical properties, and cytocompatibility of sponges were assessed. VEGF-delivery following incubation in medium was then evaluated by monitoring the VEGF-release profile and its bioactivity. CHT/PCD sponge showed a porous (open porosity of 87.5%) interconnected microstructure with pores of different sizes (an average pore size of 153 μm), a slow biodegradation (12% till 21 days), a high water-uptake capacity (~600% in 2 h), an elastic property under compression (elastic modulus of compression 256 ± 4 kPa), and a good cytocompatibility in contact with osteoblast and endothelial cells. The kinetic release of VEGF was found to exert a pro-proliferation and a pro-migration effect on endothelial cells, which are two important processes during scaffold vascularization. Hence, CHT/PCD sponges were promising vehicles for the delivery of growth factors in BTE.
Highlights
Bone is a dynamic tissue with metabolic, physical, and endocrine roles in the human body [1]
vascular endothelial growth factor (VEGF)-loaded scaffolds were put in a 24-well plate, 1 mL of extracellular matrix (ECM) medium supplemented with 0.5% FBS was added to each well, and the plate was incubated at 37 ◦C
The bioactivity of VEGF released from CHT/PCD sponges was evaluated by its effect on the proliferation and migration of endothelial cells (HUVECs), which is the key step of the angiogenic process
Summary
Bone is a dynamic tissue with metabolic, physical, and endocrine roles in the human body [1]. Among the different methods of hydrogel fabrication, those obtained by gas foaming, solvent casting or freeze-drying, called sponges, exhibit a mechanically stronger architecture similar to that of the extracellular matrix (ECM) and ideally serve as supports for exogenous cells or vehicles for trapping and delivering biomolecules (such as drugs, GF, and cytokines) [27,28,29] to fill large bone defects for tissue regeneration [30,31]. This work further focused on the “derivative” of CHT-PCD hydrogels, sponges, in order to provide sustained delivery and spatial control of bioactive VEGF in bone defects. This sponge was formed by freeze-drying a homogeneous CHT/PCD hydrogel, and thereafter stabilized by a thermal treatment. VEGF was incorporated in the sponge, and VEGF-delivery following incubation in medium was investigated by monitoring the VEGF-release profile and its bioactivity in contact with endothelial cells
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