Thermoresponsive Injectable Pluronic Composite Hydrogels: Advances in Filler Integration for Regenerative Medicine

Abstract

Pluronic-based thermoresponsive injectable hydrogels have gained attention in tissue engineering because of their sol–gel transition at physiological temperature and ease of administration. However, rapid degradation, weak mechanical stability, and limited bioactivity affect their clinical translation. This review focuses on the role of fillers in modulating structural, mechanical, and biological properties while addressing advances in gelation, rheology, stability, and functional performance. Natural polymers such as chitosan, alginate, and gelatin enhance cellular compatibility and regenerative potential, while nanofillers like graphene oxide, silica, and clays improve strength, responsiveness, and durability. Metallic nanoparticles, particularly gold and silver, further extend functionality by imparting antibacterial properties, conductivity, and reinforcement. Fillers influence micelle aggregation and crosslinking, leading to improved rheology, controlled drug release, and greater biodegradability. Composite formulations consistently demonstrate superior outcomes in vitro and in vivo, promoting cell growth, differentiation, and mineral deposition, with demonstrated utility in cartilage repair, bone regeneration, wound healing, and cardiovascular applications. Despite these advances, translation remains constrained by instability, dilution effects, and regulatory hurdles. Future efforts should prioritize dual-network stabilization, stimuli-responsive gelation, and immune-compatible modifications to accelerate clinical adoption.