Injectable tissue adhesive composite hydrogel with fibroblasts for treating skin defects

Abstract

In this work, an injectable composite hydrogel was synthesized via a unique way of crosslinking glycol chitosan (GC) with silica nano-particles (SiNP) through non-chemical interactions, and was then applied as a kind of wound dressing. Gelation was achieved through the incorporation of SiNPs with the GC segments in aqueous solution, therefore strictly confining the movement of the solubilized polymer chains. Rheology tests showed that the sol–gel transition and the moduli of the hydrogel were influenced by the composition of the two components, the size of the nano-particles and the conformation of the polymers. Using such a strategy, tissue adhesion properties of GC were well-preserved in the GC/SiNP hydrogel and therefore it gains gluey properties toward biological tissues as demonstrated through the adhesion of two pieces of mouse skin, obtaining a lap-shear stretching force of ca. 90 kPa. This characteristic, together with the injectability, allowed the hydrogel to be administrated directly on the wound site and to fill the wound area. Meanwhile, the hydrogel also works as a carrier of protein and cells. The in situ encapsulation of fibroblasts enabled the promising properties of the GC/SiNP hydrogel to be used for treating full-thickness skin defects in a mouse model, resulting in the favorable growth of hair follicles and microvessels, hence reducing the risk of scar formation.