Abstract
Thermal injury trauma can induce a state of immunosuppression causing wounds to become chronic in nature. Stem-cell based therapies represent a promising new approach to treat such wounds due to their capacity to self-renew and their multi-lineage potential. Mesenchymal stem cells (MSCs) are known to secrete endogenous factors that stimulate wound healing by promoting angiogenesis, extracellular matrix (ECM) remodeling, skin re-generation, and by dampening down inflammation. MSC delivery in a biomaterial construct can augment their wound healing capacity by concentrating cells at the burn site and upregulating trophic factor secretion. The work presented is the first to evaluate repair in an in vitro raft thermal injury model using a regenerative, dual cell delivery 3D core/shell (c/s) "living dressing" construct. This previously characterized 3D c/s bioprinted construct, that delivers both MSCs and endothelial cells, was used to treat an in vitro 3D raft skin thermal injury wound model. The mesenchymal stromal cell line (T0523) was encapsulated within a gelatin-based shell bioink, and human um-bilical vein endothelial cells (HUVECs) within a chitosan-based core bioink to biofabricate a living dressing for enhanced thermal injury repair and regeneration. We hypothesized that the cell-laden c/s tissue engineered con-struct (TEC) would strengthen the wound's proangiogenic, anti-inflammatory, and skin regeneration potential. An in vitro thermal injury in a 3D raft skin model showed a slight delay in wound closure in the presence of the c/s TEC but was augmented by corresponding increases in the release of wound healing factors, EGF, MMP-9, TGF-α, PDGF; a decrease in pro-inflammatory factor IL-6, and evidence of neovascularization. Impact statement C/s 3D bioprinted living dressings were used to heal an in vitro thermal injury wound in a 3D raft skin model. The MSC/HUVEC-laden 3D TEC when compared to the untreated control resulted in a slight de-lay in wound closure along with corresponding increases in the secretion of wound healing factors EGF, MMP-9, TGF-α, PDGF; a decrease in pro-inflammatory factor IL-6, and promotion of neovascularization. The present work is the first to evaluate repair and corresponding cytokine response in an in vitro 3D raft thermal injury model using a "living dressing" construct.