Skin bioprinting for burn reconstruction: from stem cell integration to in situ smart regenerative systems

The bioprinting of smart skin is emerging as a versatile platform not only for the coverage of wounds, but for potential sensory regeneration, monitoring of structures in real time, and tissue repairs. This review presents a coherent road map to bridge the biofabrication science and clinical translation. We discuss the investigation into piezoelectric scaffolds, conductive polymers and stimuli-responsive inks in preclinical environments to produce functional features such as thermal and tactile sensing. Early clinical case reports have proven the concept of in vitro skin bioprinting strategies, such as skin patches printed for patient-specific applications with minimally manipulated autologous extracellular matrix or umbilical cord mesenchymal stem cells-laden hydrogels, for the management of chronic wounds. In parallel, several preclinical in situ bioprinting studies with handheld or microfluidic-assisted devices have shown promising results in full-thickness diabetic and burn wound models in terms of enhanced re-epithelisation and neovascularization. We also present inherent differences between in vitro bioprinting of autologous dermo-epithelial substitutions and in situ strategies based on AI-guided print path generation and wound topography mapping. Although sensor-equipped bioprinted grafts with promising results, they are still at an early development stage and await validation in large-scale clinical trials. Nevertheless, integration of stem cell technologies, smart biomaterials, and bio-intelligent control systems may eventually be used to support bioprinted skin constructs not only as replacement tissue, but also as potential living, sensing interfaces. This broad multidisciplinary convergence may be helpful in redefining skin repair by allowing dynamic interaction between engineered skin grafts and skin host tissue physiology.