Jul 2026· International Journal of Bioprinting· 0 citations
TL;DR
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.
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.
Postoperative osteosarcoma (OS) treatment remains challenging due to local recurrence, pulmonary metastasis, chemoresistance, and critical-sized bone defects that cannot self-repair. Although hydrogel-based biomaterials have emerged as promising localized therapeutic platforms, existing reviews primarily focus on individual hydrogel types or therapeutic strategies without critically evaluating their translational potential. Here, we comprehensively summarize recent advances in drug-eluting, ion-releasing, micro/nanogel, composite, surface-functionalized, and cell-laden hydrogels for postoperative OS management. Particular emphasis is placed on biomaterial design, controlled therapeutic delivery, bone regeneration, and emerging biofabrication approaches, including 3D/4D bioprinting and biomimetic constructs. More importantly, this review critically compares the therapeutic mechanisms, regenerative performance, and translational readiness of these hydrogel systems, highlighting key challenges related to mechanical performance, degradation control, metastasis management, manufacturing scalability, and long-term clinical feasibility. Finally, we discuss future design strategies required to develop clinically translatable multifunctional hydrogel platforms for postoperative osteosarcoma treatment.
H. Diwan, Sumitra Behera, Sumit Murab· Frontiers in Biomaterials Sc...· 0 citations
One of the main issues in oncology is tumor recurrence following resection, which is responsible for a large number of patient deaths and treatment failures in a variety of malignancies. Despite advancements in adjuvant chemotherapy and radiation, residual disease that remains inside or close to the resection cavity and is difficult for systemic therapies to eradicate is the cause of further local recurrence. Hydrogel-nanoparticle (HNP) composites are a new class of therapeutic platforms that emerged from the recent convergence of biomaterial science and nanomedicine. Their specific goals are to fill the surgical gap, provide long-term localized drug release, and energetically remodel the post-surgical tumor microenvironment (TME). This paper includes the biological foundations of localized post-surgical therapy, important physicochemical considerations of the hydrogel matrix and nanoparticle carrier design, and a compilation of mechanistic and preclinical evidence for HNP hybrid platforms. Immunomodulatory strategies, stimuli-responsive release mechanism engineering, and novel techniques, including combination immunotherapy and 3D-printed customized scaffolds, are all given special attention. Examples of translational challenges are also addressed, such as manufacturing repeatability, biocompatibility, and regulatory classification. When considered collectively, the data demonstrate that HNP platforms are a convincing, practically feasible approach to reducing post-surgical recurrence rates and enhancing patient outcomes.
Bogdan Mircea Măciuceanu Zărnescu, Denisa Nicoleta Mușat, Adelina-Gabriela Niculescu et al.· Nanomaterials· 2 citations
Osteosarcoma (OS) is one of the most prevalent primary malignant bone tumours, with a poor prognosis in metastatic cases due to its aggressive nature, high metastatic potential and frequent resistance to conventional therapies. A most crucial approach for investigating drug resistance, metastasis and tumour progression is the recapitulation of the complex tumour microenvironment (TME), which is limited in traditional 2D cell cultures. Sophisticated 3D in vitro models developed via recent advances in materials sciences and cancer biology including cell spheroids, organoids and scaffold-based and hydrogel-based systems more precisely mimic the tumour microenvironment, thus offering deeper insights into tumour biology and therapeutic responses. Hydrogels inherently provide biomimetic cues that promote cell adhesion, proliferation & differentiation, particularly their porous and hydrated characteristics closely replicate the native extracellular matrix. Most importantly, hydrogels can be used for OS therapy both as a depot for therapeutic agents and scaffolds for bone tissue regeneration. This approach could be particularly promising for adjuvant therapy of tumours, as it provides options for both treatment and tissue regeneration. This review explores the emerging innovations in hydrogel-based OS in vitro models, their fabrication methods and applications in drug screening and adjuvant therapies. Furthermore, the challenges in clinical translation and advancing OS models for clinical applications are discussed. Finally, the challenges and future perspectives are outlined by emphasizing the need for multidisciplinary collaboration to advance OS research and therapy.
Satish Kanna Murali, D. Shaji, A. V. Sochilina et al.· Biomaterials Science· 0 citations
Breast cancer treatment still faces challenges including local recurrence, systemic toxicity, tumor heterogeneity, drug resistance, and immunosuppression. Conventional systemic administration provides limited exposure at the tumor site and exhibits significant toxicity. Injectable hydrogels, combining the properties of minimally invasive administration, in situ gelation, local retention, and sustained release, have become a key platform for local precision drug delivery. Compared with nanomedicines or free drugs, hydrogels can both prolong drug retention time and achieve on-demand release through the modulation of crosslinking density, degradation rate, and responsive chemical bonds. This review is organized around the material logic of such systems. Injectable hydrogels are first classified into natural, synthetic, hybrid, supramolecular, nanocomposite, and self-healing systems, the in situ gelation chemistries available to each are compared, and network parameters such as crosslinking density, mesh size, swelling, porosity, modulus, and rheology are related to release kinetics and intratumoral retention. Current research is primarily advancing along two directions: one is the construction of pH-, enzyme-, redox/ROS-, hypoxia-, ATP-, glucose-or thermo-responsive hydrogels; the other is achieving active targeting by integrating functionalized hydrogels with targets such as CD44, folate receptor, integrins, EGFR, transferrin receptor, and HER2 or with biomimetic cell-membrane coatings. On this basis, hydrogels have been extended to cancer vaccines, immune checkpoint modulation, local delivery of CAR-T/CAR-NK, as well as combination therapies involving chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, sonodynamic therapy, radiosensitization, gene therapy, and theranostics. The constraints imposed on hydrogel design by different payload classes, including small molecules, natural products, proteins and peptides, nucleic acids, antibodies, exosomes, and gene-editing machinery, are further examined, and imaging-integrated theranostic gels are discussed together with the emerging role of machine learning and digital fabrication in hydrogel optimization. Based on the biological foundations of breast cancer, this review summarizes advances in the material design, microenvironment-responsive release, targeting strategies, immunomodulation, and combination therapy of hydrogels, critically evaluates the limitations of each strategy, and aims to provide a reference for the design of mechanistically well-defined and translatable hydrogel delivery systems for breast cancer.
Resection of bone-metastatic tumors is often accompanied by severe bone erosion and structural defects. Three‐dimensional (3D) printed hydrogel scaffolds with tailorable architectures and mechanical robustness are increasingly employed to restore bone integrity after tumor removal. Here, a 3D-printed sodium alginate/GelMA hydrogel scaffold is engineered to remodel the local microenvironment for simultaneous tumor ablation and bone repair, aiming to overcome the persistent challenge of functionally modifying hydrogel scaffolds to achieve both effective tumor eradication and bone regeneration. The scaffold encapsulates dendritic cell-derived exosomes loaded with the STING agonist Cyclic dinucleotide (Dex-CDN), together with methacrylated osteogenic growth peptide (OGP-MA), while a dopamine–manganese coordination nanozyme (DM) forms a mussel‐inspired catalytic coating on the surface. Under the acidic tumor milieu, DM exhibits peroxidase‐like activity to trigger Fenton reactions, deplete glutathione, and induce oxidative stress–mediated tumor cell death. Under physiological conditions, DM displays superoxide dismutase‐ and catalase‐like activities, scavenging reactive oxygen species and maintaining redox homeostasis to promote osteogenesis. Sustained Dex‐CDN release activates STING signaling and elicits potent antitumor immunity, whereas OGP‐MA triggers BMP/Smad‐mediated osteogenic differentiation. This integrated scaffold unites catalytic therapy, immune activation, and osteoinduction, offering a promising strategy for localized tumor control and bone regeneration following bone metastatic tumor resection.
Jiachen He, Jianjun Wu, Lin Wang et al.· Advanced Composites and Hybr...· 0 citations
In vivo animal experiments show that the drug-loaded scaffold significantly inhibits tumor recurrence and distant metastasis while exhibiting low chemotherapy drug toxicity and causing no damage to healthy tissues, making it a novel candidate for post-mastectomy prognosis in breast tumors and effective cancer treatment.
Jiaqi Chen, Hanliu Gu, Ziqi Wang et al.· Journal of Materials Science· 0 citations
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