A minimally invasive shape-programmable scaffold system for defect conformation and sustained paclitaxel delivery after osteosarcoma resection

Postoperative tumor recurrence and chemoresistance in osteosarcoma treatment highlight the urgent need to develop localized implants, particularly large-scale scaffolds capable of selectively eliminating residual tumor cells, minimizing significant trauma during implantation. In this study, a drug-loaded intelligent scaffold system was designed for minimally invasive surgical implantation, enabling localized sustained release of the anticancer drug paclitaxel (PTX). This material system was fabricated into a three-dimensional porous scaffold via in situ polymerization combined with gas foaming technology. Citrate-functionalized amorphous calcium phosphate (CACP) was incorporated into the polyurethane (PU) scaffold, serving as an antibacterial agent while enhancing osteogenic expression. Following surface modification with polydopamine (PDA), PTX-Lips were covalently immobilized onto the modified scaffold surface. The resulting scaffold exhibited an extracellular matrix-mimicking highly porous structure, provided good mechanical support, and demonstrated excellent shape memory properties at 37°C. Comprehensive in vitro and in vivo studies confirmed that the drug-loaded scaffold exhibited three key functionalities: sustained drug release kinetics; significant tumor cell inhibitory efficacy; and biocompatibility supporting normal cell adhesion. Crucially, animal models unequivocally demonstrated its effectiveness in preventing postoperative local tumor recurrence and suppressing distant metastasis. This scaffold provided an efficient synergistic strategy for postoperative osteosarcoma treatment by integrating localized chemotherapy with tissue regeneration support.