Recent Advances in Stem Cell-Based Therapies for Skin Regeneration

Abstract: Severe deep tissue injuries, including extensive traumatic injuries, burns, physicochemical damage, or other primary skin loss conditions, continue to present significant clinical challenges. Skin tissue engineering provides promising solutions by developing bioengineered skin substitutes that promote tissue regeneration and enhance patient care. This review paper aims to examine recent advancements and innovations in skin tissue engineering (STE) by exploring traditional treatments and capitalizing on their weaknesses, utilizing stem cell-based therapies in conjunction with biomaterials and scaffolds to enhance skin regeneration. Conventional treatments often lead to the scarring of tissue. The emergence of advanced skin tissue engineering techniques, which integrate stem cells with biomaterial scaffolds to create bio-inks and are printed using inkjet bioprinting, has the potential to provide solutions to current traditional treatments by promoting angiogenesis, paracrine signaling, and extracellular matrix deposition in wound treatment. Stem cells, including mesenchymal (MSCs), epidermal (EpSCs), and induced pluripotent stem cells (iPSCs), have all demonstrated regenerative potential in independent preclinical studies. These studies have identified limitations, including donor variability, short in vivo survival, and immune response. Hybrid hydrogels combine natural and synthetic hydrogels, such as hyaluronic acid methacrylate (HAMA) and gelatin methacrylate (GelMA), to create a scaffold with both mechanical strength and biocompatibility. Recent progress in 3D bioprinting, particularly ink-jet-based bioprinting, has the potential to overcome the limitations of regenerating vascular networks and skin appendages. Collectively, these clinical applications of stem cells provide a pathway for creating fully functional skin through skin tissue engineering, which restores function, structure, and its appendages.