Assembly of skin substitute by cross-linking natural biomaterials on synthetic biodegradable porous mat for critical-size full-thickness burn wound regeneration

Human skin architecture comprises several interpenetrating macromolecules seen as organized extracellular matrix (ECM). For regeneration of critical-size acute and chronic wounds, substituting the damaged tissue with artificially assembled biomolecules offer an interactive milieu. This study reports development and preclinical evaluation of a biodegradable and immuno-compatible scaffold for regeneration of critical-size (4 x 4 cm(2)) full-thickness rabbit burn wounds. The designed wound care product comprises synthetic terpolymer poly(L-Lactide-co-Glycolide-co-Caprolactone) (PLGC), human clinical-grade fibrin (FIB), and hyaluronic acid (HA), termed as PLGCFIBHA. Here, clotting of fibrinogen concentrate (FC) with excess thrombin in the scaffold create an interpenetrating FIB network harnessed with adhesive molecules like fibronectin and laminin present in FC with exogenous HA to produce ECM-like milieu on porous PLGC. Penetrating into porous PLGCFIBHA, long term study showed a regulated fibroblast growth resulting in non-fibrotic dermal-like tissue in vitro. The freeze-dried PLGCFIBHA with residual thrombin facilitated suture-less, hemostatic matrix adhesion to the wound bed in vivo. By 28 d, mature and scar-less epidermis-dermis formation with skin appendages was evident in the PLGCFIBHA-treated wound area. Both negative (untreated/sham) and positive (commercial matrix-treated) control wounds showed incomplete regeneration. The PLGCFIBHA-treated wounds were comparable to native skin by 56 d. These regenerative outcomes upon single application of PLGCFIBHA confirms its potential translational value for wound care.