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<p>Poly(N-isopropylacrylamide) (PNIPAM)-based hydrogels are widely recognized as thermoresponsive biomaterials exhibiting a reversible volume phase transition near physiological temperature. Despite their extensive exploration in biomedical applications, their clinical translation remains fundamentally constrained not only by intrinsic limitations such as insufficient mechanical robustness, limited biodegradability, and bio-inert interfaces, but also by the often-overlooked coupling effects among these properties. This review moves beyond a descriptive summary of modification strategies and instead provides a critical analysis of how mechanical reinforcement, degradability regulation, and bioactivity enhancement are interconnected and sometimes mutually constrained. Recent advances in network engineering, hybrid material design, and functional modification are examined within a unified structure–property-function framework, emphasizing the need for coordinated optimization rather than isolated property enhancement. By clarifying these interdependencies and identifying key limitations in current approaches, this review offers a more analytical perspective on the rational development of PNIPAM-based hydrogels and outlines future directions toward more predictable, tunable, and clinically translatable systems.</p> Graphical Abstract <p></p>

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PNIPAM-based hydrogels for biomedical applications: structure–property-function integration in mechanical, degradable, and bioactive design

  • 期刊论文

  • 发表日期：

    2026年7月13日

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  • Yi Wei,
  • Dan Zheng,
  • Yali Xu,
  • Zhonglian Yang

摘要

Poly(N-isopropylacrylamide) (PNIPAM)-based hydrogels are widely recognized as thermoresponsive biomaterials exhibiting a reversible volume phase transition near physiological temperature. Despite their extensive exploration in biomedical applications, their clinical translation remains fundamentally constrained not only by intrinsic limitations such as insufficient mechanical robustness, limited biodegradability, and bio-inert interfaces, but also by the often-overlooked coupling effects among these properties. This review moves beyond a descriptive summary of modification strategies and instead provides a critical analysis of how mechanical reinforcement, degradability regulation, and bioactivity enhancement are interconnected and sometimes mutually constrained. Recent advances in network engineering, hybrid material design, and functional modification are examined within a unified structure–property-function framework, emphasizing the need for coordinated optimization rather than isolated property enhancement. By clarifying these interdependencies and identifying key limitations in current approaches, this review offers a more analytical perspective on the rational development of PNIPAM-based hydrogels and outlines future directions toward more predictable, tunable, and clinically translatable systems.

Graphical Abstract