Gel scaffold for corneal wound healing and tissue engineering

Researchers in Prof. David Myung's laboratory have developed a bio-compatible, crosslinking gel that can be used for in situ repair of damaged cornea or as a three-dimensional scaffold for keratocyte-keratinocyte tissue culture. This click chemistry technology uses bio-orthogonal SPAAC (strain-promoted azide-alkyne cycloaddition) crosslinking to provide a corneal stromal substitute based on collagen type I. The viscous injectable material could be safely applied to a wounded cornea where it reacts to form a gel scaffold able to promote tissue repair without sutures or a human donor. The gel recapitulates the thickness and smooth, continuous surface of the cornea so it can be used as a three-dimensional acellular scaffold or a scaffold that encapsulates cultured cells (keratocytes). In research applications, the scaffold could be used for three-dimensional tissue culture to synthesize lamellar substitutes or to study keratocyte-keratinocyte interactions. In wound healing applications, this technology is a promising candidate for in situ lamellar and defect reconstruction of corneal stromal tissue in cases of deep corneal ulcers to rapidly stabilize wounds or to replace a section of the cornea.

SPAAC gel performance in organ culture model of sutureless in situ-forming anterior lamellar keratoplasty. (A) Schematic of lamellar keratectomy and SPAAC gel treatment with keratocyte as an in situ-forming corneal stromal substitute. (B) Photographs of rabbit corneal tissue with lamellar keratectomy and SPAAC gel application.

Stage of Research
The inventors have characterized the transparency and mechanical properties of the crosslinked gel (transmittance: 84.58 +/- 1.44%; storage modulus: 112.03 +/- 3.94 Pa). Using a rabbit cornea organ culture model, they demonstrated that the SPAAC gels promoted multi-layer re-epithelialization as well as good apposition and adherence to the host tissues.