A programmable shape memory bioscaffold incorporating doxorubicin for postoperative chemotherapy and enhanced bone regeneration

Abstract

The clinical management of bone cancers remains challenging due to the risk of residual tumour cells following surgical resection and the associated complications of systemic chemotherapy. To address this, we developed a shape memory scaffold (SMS) with ion-responsive functionality, designed to enable localised drug delivery and promote bone regeneration postoperatively. Constructed from silk fibroin, carboxymethyl chitosan, alginate, and montmorillonite, the optimised rSCAM scaffold exhibited a porous microarchitecture (93.0 ± 1.2%) and toughness (10.6 ± 0.5 MJ m⁻³), along with rapid shape recovery triggered by bicarbonate ions. rSCAM sustained doxorubicin release over 14 days and showed high drug loading efficiency. In vitro, the scaffold was highly biocompatible, with over 80% cell viability, low ROS induction, and potent anti-osteosarcoma activity, achieving complete tumour cell inhibition within 12 hours. It also supported MC3T3-E1 proliferation, migration, and osteogenic differentiation, as evidenced by elevated MMP2/MMP9 expression, TEER enhancement, and Alizarin Red S staining. CAM assay confirmed neovascularisation and scaffold–host tissue integration. These results demonstrate the multifunctionality of SMS rSCAM as a promising strategy for minimally invasive treatment of postoperative bone cancer, integrating chemotherapeutic delivery and tissue regeneration within a single therapeutic platform.