Shape-Memory Injectable Cryogels: From Minimally Invasive Delivery to Multifunctional Tissue Regeneration

Injectable cryogels have emerged as a transformative class of biomaterials that combine macroporosity, mechanical resilience, and shape-memory properties to enable minimally invasive therapeutic delivery. Unlike conventional hydrogels, cryogels are fabricated through cryogelation-a sub-zero polymerization process that generates interconnected macropores through ice crystal templating-endowing them with sponge-like elasticity and the ability to withstand extreme compression and recover their original architecture upon injection. Over the past decade, injectable cryogels have evolved from simple porous scaffolds to sophisticated multifunctional platforms incorporating nanocomposites, bioactive molecules, and stimuli-responsive elements for applications spanning bone and cartilage regeneration, stem cell delivery, cancer immunotherapy, and hemostatic wound healing. This review provides a comprehensive and critical analysis of recent advances in shape-memory injectable cryogels, organized around five interconnected themes: (i) the physicochemical mechanisms governing shape-memory behavior and material design strategies, (ii) emerging fabrication approaches including three-dimensional printing-cryogelation hybrids and nanocomposite reinforcement, (iii) cryogel-mediated stem cell delivery and tissue regeneration, (iv) immunomodulatory and vaccine platforms, and (v) hemostatic and wound-healing applications. We critically evaluate how macro-architectural features, mechanical tunability, and biochemical functionalization collectively dictate biological outcomes, and identify key challenges-including scalability, sterilization, regulatory pathways, and clinical translation-that must be addressed to realize the full therapeutic potential of injectable cryogels.