Engineered models of skin fibrosis: from biomaterial-free to biomaterial-based in vitro systems.

Skin fibrosis is a complex and progressive disorder characterized by excessive extracellular matrix deposition, persistent fibroblast activation and pathological tissue stiffening. Its clinical manifestations such as keloids, hypertrophic scars and systemic sclerosis, can lead to functional impairment, aesthetic disfigurement and significant psychosocial burden. Unfortunately, there are currently no efficient therapies that can halt or reverse skin fibrosis, largely due to our incomplete understanding of the dynamic molecular and cellular mechanisms driving fibrosis progression. Here, we review the advances on bioengineered models of skin fibrosis and discuss their emerging role in elucidating fibrotic pathways and enabling the identification and screening of therapeutic targets. We examine how multicellular and three-dimensional complexity, biochemical cues, mechanomodulatory biomaterials and advanced biofabrication strategies contribute to enhancing the human biomimicry of engineered models. Finally, we outline the challenges and future directions for the development of next-generation in vitro models that better recapitulate skin fibrosis dynamics and enhance translational relevance.