Injectable hydrogels can be useful tools for facilitating wound healing
since they conform to the irregular shapes of wounds, serving as a temporary
matrix during the healing process. However, the lack of inherent pore structures
of most injectable hydrogels prohibits desired interactions with the cells of
the surrounding tissues limiting their clinical efficacy. Here, we introduce a
simple, cost-effective and highly biofunctional injectable macroporous hydrogel
made of gelatin microgels crosslinked by microbial transglutaminase (mTG). Pores
are created by the interstitial space among the microgels. A water-in-oil
emulsion technique was used to create gelatin microgels of an average size of
250μm in diameter. When crosslinked with mTG, the microgels adhered to
each other to form a bulk hydrogel with inherent pores large enough for cell
migration. The viscoelastic properties of the porous hydrogel were similar to
those of nonporous gelatin hydrogel made by adding mTG to a homogeneous gelatin
solution. The porous hydrogel supported higher cellular proliferation of human
dermal fibroblasts (hDFs) than the nonporous hydrogel over two weeks, and
allowed the migration of hDFs into the pores. Conversely, the hDFs were unable
to permeate the surface of the nonporous hydrogel. To demonstrate its potential
use in wound healing, the gelatin microgels were injected with mTG into a cut
out section of an excised porcine cornea. Due to the action of mTG, the porous
hydrogel stably adhered to the cornea tissue for two weeks. Confocal images
showed that a large number of cells from the cornea tissue migrated into the
interstitial space of the porous hydrogel. The porous hydrogel was also used for
the controlled release of platelet-derived growth factor (PDGF), increasing the
proliferation of hDFs compared to the nonporous hydrogel. This gelatin
microgel-based porous hydrogel will be a useful tool for wound healing and
tissue engineering.