Combination keratinocytes and fibroblasts cell-based therapy in wound healing: a literature review

Skin grafting, a conventional treatment for wound management, is associated with significant limitations including donor-site morbidity, scarring, incomplete functional restoration, and limited efficacy in extensive or chronic wounds. Cell-based therapies, especially those involving combination therapy of keratinocytes and fibroblast, are an emerging and promising alternative. This review discusses the biological roles of keratinocytes and fibroblasts in skin homeostasis and wound repair, focusing on their crosstalk that regulate inflammation, extracellular matrix remodeling, angiogenesis, and re-epithelialization. It examines the principles of cell-based skin regeneration, comparing autologous and allogeneic therapeutic strategies, stem cell sources, and delivery platforms including scaffolds, hydrogels, and bioengineered skin substitutes. Clinical evidence demonstrates that bilayered constructs have superior clinical outcomes compared with monotherapies, in burn care and chronic wound management.The review seeks to highlight current limitations and future directions, including scaffold optimization and appendage regeneration, to advance the development of more functional and durable skin substitutes for wound healing.