DOI: 10.3390/polym18212738 ISSN: 2073-4360

Polymer Network Engineering of Hydrogel Bioinks for Skin Regeneration: From Molecular Design to Adaptive Biofabrication

Xuanru Zhu, Jiaxian Zhang, Hongwei Liu, Yuesheng Huang

Three-dimensional (3D) bioprinting offers substantial potential for reconstructing the structural and biological complexity of skin, yet its regenerative performance and clinical translation are constrained by the challenge of concurrently realizing printability, structural stability, and tissue remodeling with hydrogel bioinks. This review integrates bibliometric analysis with a polymer-centric assessment of functional hydrogel bioinks for skin tissue engineering and wound regeneration. Beyond polymer composition alone, we discuss how molecular features, crosslinking chemistry, and network architecture collectively determine bioink performance and regenerative function. Recent studies show that dynamic crosslinking, interpenetrating networks, and hybrid or nanocomposite designs can improve the balance between printability and post-print stability while also regulating transport, degradation, and cell–material interactions. Importantly, these material properties are not independent design targets; they are mechanistically linked to the ability of bioinks to modulate the wound microenvironment, support vascularization, and promote extracellular matrix reconstruction. Although emerging biofabrication strategies extend these functionalities, they impose stricter requirements for precise regulation of polymer rheology, crosslinking kinetics, and dynamic network adaptability. Despite rapid progress, translation to clinical use remains hindered by limited biological fidelity, poor reproducibility, and the lack of standardized manufacturing and regulatory criteria. We therefore propose that future bioink development should shift from empirical formulation toward predictive and adaptive polymer systems in which network design, biological function, and manufacturing requirements are considered simultaneously. This structure–property–function perspective provides a rational framework for developing next-generation polymer bioinks with improved regenerative efficacy and translational potential.

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