Biomimetic Dermal Substitutes for Skin Reconstruction: Advances in Scaffold Design, Biological Integration, and Clinical Performance

Reconstructive surgery still faces various challenges when dealing with the reconstruction of complex skin defects, regardless of their origin (e.g., trauma, burns). Split-thickness autologous skin grafts remain the gold standard; however, this technique comes with several limitations, including donor site morbidity, infection, and scarring. Since extensive research on conventional techniques has not provided sufficient long-term results, there has been a shift toward dermal substitutes made from regenerative biomaterials that can aid wound management and support tissue restoration. This structured review will introduce the challenges posed by complex skin defects, the limitations of autologous skin grafts and conventional reconstruction techniques, and the emerging field of dermal substitutes and biomimetic scaffolds. Moreover, the native dermis is presented as a blueprint for biomimetic scaffold design, along with key principles to consider when engineering a dermal scaffold, from architecture and porosity to angiogenic potential. A critical examination of the main classes of available dermal substitutes and their clinical performance is conducted, highlighting their limitations and the translational gaps in current evidence. Although the current pool of biomaterials still faces challenges in accurately mimicking the properties and architecture of natural skin, future perspectives offer promising alternatives that could overcome these limitations.