Bio-inks for skin regeneration: phase-adaptive design, multifunctional platforms, and 4D bioprinting frontiers

Abstract

Chronic wounds and scarring represent major clinical challenges owing to dysregulated tissue repair processes. The emergence of 3D bioprinting offers a promising approach by enabling the fabrication of biomimetic skin substitutes that enhance chronic wound management and facilitate scar modulation. This review provides a phase-oriented framework linking bio-ink properties with the dynamic biological requirements of each wound-healing stage, integrating material engineering, regenerative mechanisms, and translational challenges with a particular focus on establishing phase-specific relationships between bioink properties and wound-healing requirements. By synthesizing recent evidence, we identify a critical gap: phase-specific bio-ink design remains largely underdeveloped and is often only implicitly considered in current analyses of healing phases. Furthermore, we highlight emerging 4D bioprinting strategies and propose that adaptive 4D bio-inks, guided by multi-omics datasets, could facilitate the development of stage-responsive systems capable of adapting therapeutic delivery to the evolving biological requirements of wound repair. Such advancements hold considerable potential to contribute to advancing chronic wound treatment and promote improved scar outcomes.