DNA Molecular Robot for Osteosarcoma Therapy and Bone Regeneration

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

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.

Liver-inspired decellularized hydrogel platform to eradicate osteosarcoma and reconstruct bone defects.

Osteosarcoma (OS), the most prevalent primary malignant bone tumor, presents significant clinical challenges following surgical resection, including irregularly-shaped bone defects, residual microtumors, and inadequate bone regeneration. Inspired by the liver's remarkable regenerative capacity, an injectable hydrogel was fabricated from liver-decellularized extracellular matrix (dECM) by incorporating liposomes co-loaded with gold nanoparticles (GNPs) and doxorubicin (DOX), which was designated as GL/DOX@dECM. Functionally, this hydrogel exhibited prominent thermosensitivity, enabling facile injection and conformity to irregular defects. Under near-infrared laser irradiation, the GNPs-mediated photothermal effect combined with DOX chemotherapy to induce tumor cell apoptosis, effectively suppressing OS growth in subcutaneous models. More importantly, the native liver-specific ECM-enriched GL/DOX@dECM provided osteogenesis-conducive biochemical and biomechanical cues. RNA sequencing confirmed that it markedly enhanced cytoskeletal remodeling and integrin-mediated adhesion, alongside significant enrichment of key osteogenic pathways including mitogen-activated protein kinases and transforming growth factor-β, thereby promoting the in vitro osteogenic differentiation of marrow mesenchymal stem cells. Critically, the GL/DOX@dECM prompted substantial new-bone formation in the cranial defect model, evidenced by a bone volume/total volume ratio of 41.76% ± 11.41% after eight weeks post-implantation. In summary, the liver-inspired injected decellularized hydrogel platform presented a highly-promising strategy for treating refractory bone defects following OS resection.

A multifunctional therapeutic polyurethane platform for minimizing tumor recurrence and metastasis after breast-conserving surgery

Microporous annealed particle scaffold integrated with autologous tumor cells for personalized postsurgical tumor therapy.

Biomaterial scaffolds hold great potential for addressing tumor recurrence and tissue defects following surgical tumor resection; however, personalized therapy remains a critical barrier to their clinical translation. To address this issue, we developed an autologous tumor cell-integrated microporous annealed particle (MAP) scaffold co-delivering an immune adjuvant and an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor for tumor postoperative therapy. This scaffold was fabricated using microfluidic electrospray combined with step-by-step crosslinking technology. The injectable microspheres, prior to annealing, can be directly delivered into the defect site and conform to its shape upon crosslinking, forming a stabilized, porous structure. Featuring interconnected pores that facilitate cell infiltration and proliferation, the scaffold demonstrated effective tissue repair in mice subjected to full-thickness skin excision. Within the scaffold, cryo-inactivated tumor cells and the immune adjuvant recruit and activate dendritic cells (DCs) in situ, stimulating a robust antitumor immune response. This response is further amplified by the IDO1 inhibitor, which reverses immunosuppression by inhibiting regulatory T cells (Tregs). Consequently, the scaffold exhibited remarkable anti-recurrence efficacy and prolonged survival in a melanoma mouse model. These properties highlight the significant potential of our personalized microporous hydrogel particle scaffold for efficient postoperative antitumor therapy and tissue regeneration. STATEMENT OF SIGNIFICANCE: Tumor recurrence and tissue defects represent significant challenges following surgical tumor removal in cancer patients. Meanwhile, a critical barrier to the clinical translation of postoperative biomaterial scaffolds is the lack of personalization for both antitumor therapy and tissue reconstruction. Here, we developed a personalized microporous annealed particle (MAP) scaffold that integrates autologous tumor cells, immune adjuvant, and IDO1 inhibitor to simultaneously address tumor recurrence and tissue defects. Personalized antitumor therapy is achieved by the injectable MAP scaffold through a tumor vaccine formed from autologous tumor-derived cells within the scaffold, eliciting tumor-specific T-cell responses that are further amplified by reversing the local immunosuppressive microenvironment. Personalized tissue repair is also enabled by such scaffold, which conforms to irregular wound shapes and supports cell infiltration. This work establishes a paradigm that unifies personalized immunotherapy with personalized tissue repair, offering substantial promise for postsurgical cancer therapy.

Bone defect repair materials after bone tumour resection: from structural substitutes to biofunctionalized synergistic therapy

Abstract Background Critical-sized bone defects following malignant tumour resection remain among the most difficult challenges in orthopaedic oncology. Conventional substitutes such as autografts or polymethyl methacrylate (PMMA) provide initial stability but often fail to ensure durable integration or prevent recurrence. This review aims to summarize recent progress in bone defect reconstruction materials, with particular attention to strategies that unite structural reliability with biological functionality. Discussion Over the past decade, repair materials have evolved from inert fillers to multifunctional scaffolds capable of combining load-bearing support with local therapeutic action. Current designs integrate chemotherapy, photothermal hyperthermia or magnetic hyperthermia, immunomodulation, antibacterial function, and angiogenic–osteogenic cues. Intelligent drug delivery systems and additive manufacturing enable patient-specific, stimuli-responsive implants, while early clinical use of antibiotic-loaded cements and custom-printed prostheses demonstrates translational potential. Nevertheless, most evidence remains preclinical and heterogeneous, with inconsistent tumour, infection, regeneration, and safety endpoints; long-term safety, manufacturing reproducibility, cost-effectiveness, and regulatory acceptance remain unresolved. Conclusions Reconstruction after bone tumour resection is entering a new era in which implants are expected not only to restore anatomy and stability but also to actively suppress tumour recurrence and foster regeneration. Multifunctional and patient-tailored scaffolds hold promise to redefine limb-salvage surgery, provided that future work delivers robust clinical validation and scalable manufacturing pathways.

Bone-Targeted Nanosystems Induce Multiple Types of Cell Death and Suppress Osteoclasts via Sonodynamic Sensitization Therapy to Treat Bone Metastatic Tumors.

Sonodynamic therapy (SDT) has enormous potential to eradicate tumors in situ and reshape antitumor immunity, but the efficacy of SDT is constrained by sonosensitizer performance and the intensity of the induced immune response. In the present study, a metal-organic framework (MOF) sonosensitizer (PN20@Rx) for treating bone metastases was designed through alendronate sodium (ALN)-mediated defect engineering. This strategy significantly increased sonocatalytic efficiency by narrowing the interstitial spaces and optimizing the sonic-to-electrical energy conversion. Furthermore, PN20@Rx exhibited multiple nanoenzyme activities and bone-targeting properties, simultaneously depleting glutathione (GSH), generating hydroxyl radicals (•OH), and producing oxygen (O2). In a bone metastasis model, upon ultrasound (US) stimulation, PN20@Rx effectively cleared 4T1 cells within mouse tibiae, inhibited tumor-associated bone destruction, and induced multiple regulated cell death (RCD) pathways and immunogenic cell death (ICD). PN20@Rx simultaneously downregulated the expression of the CD47 immune checkpoint protein on tumor cell surfaces, thereby converting the tumor from an immune "cold" state to an immune "hot" state and effectively suppressing lung metastasis. The present study provides a unique sonocatalytically enhanced strategy and novel insights for MOF-based clinical tumor immunotherapy.