Controlled Release of Vascular Endothelial Growth Factor from Heparin-Functionalized Gelatin Type A and Albumin Hydrogels.

Christiane Claaßen,Günter Tovar,Lisa Sewald,Kirsten Borchers

doi:10.3390/gels3040035

Abstract

Bio-based release systems for pro-angiogenic growth factors are of interest, to overcome insufficient vascularization and bio-integration of implants. In this study, we investigated heparin-functionalized hydrogels based on gelatin type A or albumin as storage and release systems for vascular endothelial growth factor (VEGF). The hydrogels were crosslinked using carbodiimide chemistry in presence of heparin. Heparin-functionalization of the hydrogels was monitored by critical electrolyte concentration (CEC) staining. The hydrogels were characterized in terms of swelling in buffer solution and VEGF-containing solutions, and their loading with and release of VEGF was monitored. The equilibrium degree of swelling (EDS) was lower for albumin-based gels compared to gelatin-based gels. EDS was adjustable with the used carbodiimide concentration for both biopolymers. Furthermore, VEGF-loading and release were dependent on the carbodiimide concentration and loading conditions for both biopolymers. Loading of albumin-based gels was higher compared to gelatin-based gels, and its burst release was lower. Finally, elevated cumulative VEGF release after 21 days was determined for albumin-based hydrogels compared to gelatin A-based hydrogels. We consider the characteristic net charges of the proteins and degradation of albumin during release time as reasons for the observed effects. Both heparin-functionalized biomaterial systems, chemically crosslinked gelatin type A or albumin, had tunable physicochemical properties, and can be considered for controlled delivery of the pro-angiogenic growth factor VEGF.

Highlights

Formation of fibrotic encapsulation around implants, as well as insufficient oxygen and nutrient supply in tissue engineering grafts due to poor vascularization remain fundamental limitations for clinical translation [1,2]
Gelatin type A and albumin are bio-based molecules that are already used in biomaterial applications as matrices for tissue engineering, or release systems for drugs
Albumin-based gels generally exhibited lower equilibrium water contents compared to gelatin-based gels, they took up higher amounts of the growth factor vascular endothelial growth factor (VEGF), when dried gels were loaded by swelling in growth factor solution

Summary

Introduction

Formation of fibrotic encapsulation around implants, as well as insufficient oxygen and nutrient supply in tissue engineering grafts due to poor vascularization remain fundamental limitations for clinical translation [1,2]. Hydrogel materials that mimic features of the extracellular matrix (ECM) have been extensively studied as artificial scaffolds for tissue engineering [8,9,10] and for controlled growth factor release [8,9,10]. In this context, approaches based on biopolymers from the native tissue matrix have the advantage of the often inherent biocompatibility and biodegradability of the hydrogel-forming components [11].

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Results

Conclusion