Injectable and reversible preformed cryogels based on chemically crosslinked gelatin methacrylate (GelMA) and physically crosslinked hyaluronic acid (HA) for soft tissue engineering

Abstract

Hydrogels are a promising choice for soft tissue (cartilage, skin and adipose) engineering and repair. However, lack of interconnected porosity and poor mechanical performance have hindered their application, especially in natural polymer-based hydrogels. Cryogels with the potential to overcome the shortcomings of hydrogels have drawn attention in the last few years. Thus, in this study, highly porous and mechanically robust cryogels based on interpenetrating polymer network (IPN) of gelatin methacrylate (GelMA) and hyaluronic acid (HA) were fabricated for soft tissue engineering application. Cryogels have a constant amount of GelMA (3% wt) with different concentrations of HA (from 5% to 20 % w/w). In fact, crosslinking through cryogelation in subzero temperature facilitates the formation of interconnected pores with 90 % porosity percentage without external progen. On the other hand, high mechanical stability (no failure up to 90 % compression) was achieved due to the cryogelation and chemical crosslinking of GelMA as well as physical crosslinking of HA. Furthermore, the porous and hydrophile nature of the cryogels resulted in shape memory properties under compression, which can reverse to initial shape after retaining the water. Although increasing the HA concentration followed by the density of physical crosslinking boosted the mechanical performance of cryogels under compression, it limited the reversibility properties. Nevertheless, all cryogels with different HA concentrations showed acceptable gel strength and Young's modulus (G-H-20, E = 6kPa) and had appropriate pore size for cell infiltration and nutrient transportation with good cell adhesion and high cell viability (more than 90 %). The unique property of fabricated cryogels that facilitate less invasive delivery makes them a promising alternative for the soft tissue application.

Keywords: Gelatin methacrylate; Hyaluronic acid; Injectable cryogels; Interpenetrating polymer network (IPN); Ionic crosslinking; Physical crosslinking; Shape memory properties; Soft tissue engineering.