Aug 2026· Biomaterials· Vol 337, pp.
124567
· 0 citations· 64 references
Medicine
TL;DR
The liver-inspired injected decellularized hydrogel platform presented a highly-promising strategy for treating refractory bone defects following OS resection, thereby promoting the in vitro osteogenic differentiation of marrow mesenchymal stem cells.
Abstract
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.
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
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
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.
Xiaonan Wang, Aobo Zhang· International Journal of Bio...· 0 citations
Bone regeneration is a highly coordinated, multistep process governed by interactions among skeletal cells, immune components, and the vascular system. Although bone exhibits an intrinsic capacity for self-repair, critical-sized defects caused by trauma, tumor resection, infection, or chronic diseases often exceed this regenerative potential and necessitate therapeutic intervention. Conventional bone tissue engineering strategies have predominantly focused on promoting osteogenesis and angiogenesis; however, their limited clinical translation indicates that essential regulatory mechanisms remain insufficiently addressed. Advances in osteoimmunology have revealed that immune responses-particularly the initiation, intensity, and resolution of early inflammation-play an instructive role in determining bone healing outcomes. In parallel, exosomes have emerged as mediators of intercellular communication, capable of transferring bioactive cargos that regulate immune cell polarization, angiogenesis, and osteogenic differentiation. Integrating exosomes with biomaterial scaffolds has led to the concept of osteoimmunoengineering, in which scaffolds are designed not only to provide mechanical support but also to modulate the immune microenvironment in a spatiotemporally controlled manner. This review systematically discusses how exosome-functionalized biomaterials can reprogram immune responses to enhance bone regeneration. We outline the immune landscape of bone healing, highlighting key immune cell populations and cytokine signaling pathways involved in inflammation resolution and tissue reconstruction. We also examine immunomodulatory mechanisms of exosomes, material-based strategies for regulating exosome immobilization and release kinetics, and major translational challenges, including exosome heterogeneity, manufacturing standardization, and clinical product classification.
Asrin Emami, I. Oskouie· Biotechnology and Bioenginee...· 0 citations
Osteosarcoma remains one of the most aggressive bone malignancies, with limited advances in effective therapies. Herein, we developed injectable, in situ gel-forming hydrogels based on gellan gum (GG, 0.75% and 1.25% w/v), naturally extracted melanin nanoparticles (MNPs, 0-500 μg/mL), and Doxorubicin (Dox, 20 μg/mL) for localized chemo-photothermal therapy. Therapeutic efficacy was assessed using a physiologically relevant 3D osteosarcoma model mimicking post-surgical bone defects, generated by encapsulating Saos-2 cells within collagen hydrogels. Cells fully colonized the constructs within 7 days, remaining viable, proliferative, and expressing osteoblastic markers (Runx-2 and ALP). GG concentration modulated hydrogel rheology, injectability, water uptake, and degradation. Upon near-infrared (NIR) irradiation, MNP-loaded hydrogels reached temperatures above 60 °C within 5 min, reducing tumor cell viability to 43% after 24 h. Dox release profiles depended on MNP incorporation: GG(Dox) exhibited a burst release (~30% within 1 h), whereas GG(Dox-MNPs) enabled sustained release (~20% over 48 h). After 7 days of treatment, GG(Dox) reduced tumor viability to 11%, while GG(Dox-MNPs) achieved 27%. Overall, these hydrogels demonstrate strong chemo- and photothermal antitumor efficacy in a 3D osteosarcoma model, offering a versatile platform adaptable through controlled NIR irradiation and drug delivery.
Mariana Caldas, L. P. da Silva, I. Kwon et al.· Biomaterials Advances· 0 citations
Osteoporotic rotator cuff tears represent a major clinical challenge owing to impaired tendon-bone interface (TBI) healing. To address this issue, we engineered an injectable Zein-based composite hydrogel (ZDC hydrogel) using electron-beam irradiation and, incorporated niacin-loaded mesoporous carbon nanospheres to achieve photothermal regulation and niacin release. The ZDC hydrogel exhibited favorable self-assembly, mechanical properties, photothermal performance, degradability, and biosafety. In vitro, ZDC hydrogel extracts enhanced the osteogenic differentiation of MC3T3-E1 cells and the tenogenic differentiation of tendon-derived stem cells (TDSCs). Mechanistically, ZDC hydrogel extracts increased intracellular nicotinamide adenine dinucleotide levels, suppressed p16 and p21 expression, and reduced cytosolic and mitochondrial reactive oxygen species (ROS) accumulation in MC3T3-E1 cells. In the osteoporotic rat rotator cuff repair model, ZDC hydrogels combined with near-infrared irradiation (NIR) enhanced new bone formation within the humeral head bone tunnel, improved fibrocartilaginous TBI reconstruction, and strengthened biomechanical properties of the repaired tendon-bone complex. Furthermore, in a rat skin wound model, ZDC hydrogels combined with NIR increased the expression of vascular endothelial growth factor (VEGF) and CD31 while reducing tumor necrosis factor-α levels, indicating enhanced angiogenesis and attenuated inflammatory responses. Collectively, these findings suggest that the injectable ZDC hydrogel is a promising strategy for osteoporotic rotator cuff tear repair.
Kai Ye, P. Ding, Zhenyou Dong et al.· Small Methods· 0 citations
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