This review provides a comprehensive analysis of the fundamental mechanisms of thermoresponsive behaviour, major polymer systems and the most significant applications in tissue engineering and highlights future research directions needed to fully exploit the potential of thermoresponsive hydrogels in regenerative medicine.
Abstract
Thermoresponsive hydrogels have gained considerable attention in tissue engineering due to their unique sol–gel transition behaviour near physiological temperatures, enabling minimally invasive administration, in situ scaffold formation, controlled release of therapeutic agents and enhanced integration with host tissues. Their ability to mimic the extracellular matrix (ECM) and encapsulate cells, growth factors or bioactive molecules makes them promising candidates for regeneration of structurally diverse tissues including cartilage, bone, neural, cardiac, skin, corneal and vascular systems. Recent advances in polymer chemistry, nanotechnology and bio-fabrication, particularly 3D and 4D bioprinting have significantly expanded the versatility and functionality of thermoresponsive hydrogels. This review provides a comprehensive analysis of the fundamental mechanisms of thermoresponsive behaviour, major polymer systems and the most significant applications in tissue engineering. It also outlines cutting-edge innovations such as hybrid nanocomposite hydrogels, stimuli-responsive multifunctional scaffolds and their integration with cell therapies and Current limitations—such as mechanical weaknesses, biodegradation challenges and clinical translation barriers—and highlights future research directions needed to fully exploit the potential of thermoresponsive hydrogels in regenerative medicine.
It is suggested that the interdisciplinary convergence of materials science, bioengineering, and regulatory science is necessary to tackle challenges and make injectable hydrogels a standard-of-care regenerative therapeutic.
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The research indicates that pharmaceutical-grade polymer-based hydrogels are promising candidates for skin tissue engineering and drug delivery through 3D bioprinting, and underscores the potential of these formulations to advance bioprinting technologies and related applications.
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