Hydrogels for osteosarcoma treatment: Bioprinting strategies and local tumor eradication–bone regeneration

Abstract

Osteosarcoma remains a clinically challenging primary bone malignancy because effective postoperative treatment must both eradicate residual tumor cells and restore function after tumor resection. Hydrogel-based platforms have emerged as versatile local therapeutic systems because of their injectability, tunable physicochemical properties, cavity-conforming capacity, high local retention, and ability to integrate antitumor and osteoregenerative functions. This review summarizes recent advances and design principles in hydrogel-based osteosarcoma treatment and bioprinting Strategies, with emphasis on local tumor eradication–bone regeneration. The reviewed platforms include architecturally programmed 3D-printed hydrogel and scaffold–hydrogel hybrid constructs, postoperative locoregional depots, tumor-microenvironment-responsive hydrogels, chemoimmunotherapeutic and sonodynamic systems, photothermally actuated theragenerative platforms, and externally regulated magnetic and piezoelectric depots. Particular attention is given to the complementary clinical roles of injectable hydrogels and patient-specific printed constructs. Hydrogels are thus evolving from passive drug reservoirs into programmable biomaterial systems capable of spatiotemporal treatment control, immune–stromal modulation, molecularly targeted delivery, and functional reconstruction. Key translational barriers include the limited relevance of current preclinical models, normal-tissue safety of field-regulated therapies, degradation and long-term biocompatibility of multifunctional materials, sterilization, quality assurance, regulatory classification, manufacturability, and integration into surgical workflows. Overall, the most clinically realistic direction is a staged and adaptable platform that provides early local tumor control while progressively supporting bone regeneration and structural reconstruction.