Next-generation 3D-printed bioengineered skin grafts: From experimental validation to clinical implementation

Dandoulakis, Emmanouil (2025) Next-generation 3D-printed bioengineered skin grafts: From experimental validation to clinical implementation. World Journal of Biology Pharmacy and Health Sciences, 23 (1). pp. 369-380. ISSN 2582-5542

Bioengineering Three-dimensional (3D) bioprinting has revolutionized tissue engineering by enabling the 3D printing of bioengineered skin grafts with a tissue architecture similar to that of native skin. These grafts, composed of layered cellular constructs containing keratinocytes, fibroblasts, and bioactive hydrogels, have indeed provided an alternative to traditional autografts and allografts, addressing the issues of donor source morbidity and immune rejection. The article provides a detailed overview of the achievements observed by 3D-printed skin grafts on their way to clinical use. Similar to experimental models, the viability of cells is high, differentiation is robust, and cells can be integrated with preclinical models without loss of functionality, with only minor improvements in vascularization and appendage engraftment. Regulation, scale, and graft durability, however, are some of the challenges to clinical translation. The critical outcomes were the practical wound-healing effects on animals and a pilot clinical trial, particularly in the treatment of burns and chronic wounds. The development direction emphasizes progress in the in situ bioprinting method and the improvement of graft optimisation according to Artificial Intelligence and patient-specific grafts as one way to increase the rates of treatment success. The article highlights the future of 3D-printed skin grafts as a revolutionary development in regenerative medicine. It facilitates interdisciplinary cooperation and standardisation of procedures, as well as the level of responsibility and access, to reduce the gap between laboratory innovations and clinical standards.