Pioneering 3D and 4D bioprinting strategies for advanced wound management: from design to healing

Abstract

Chronic and complex wounds pose a major clinical challenge due to the intricate skin architecture and the multifactorial nature of healing. Conventional wound care often fails to restore native skin function and structure. Advances in 3D and 4D bioprinting have transformed wound management by enabling customized, biomimetic skin substitutes that enhance healing. This review outlines skin complexity and the sequential phases of repair, while addressing limitations of current therapies. The progression of 3D bioprinting is discussed, from basic additive manufacturing (AM) to precise biomaterial and cell deposition for skin reconstruction. Special focus is given to bioinks, including natural polymers, synthetic hydrogels, decellularized extracellular matrix (dECM), and composite formulations, all designed to mimic native skin properties. The emerging field of 4D bioprinting is highlighted, incorporating smart, stimuli-responsive materials capable of dynamic structural and functional adaptation to complex wound environments. Key cellular components and bioprinting techniques for multilayered constructs are reviewed, along with personalized approaches such as in situ handheld bioprinting and artificial intelligence (AI) assisted biofabrication. Finally, challenges in clinical translation, manufacturing, and scalability are addressed, with future perspectives on robotics, AI, and innovative biomaterials in regenerative wound care