Biomaterials research最新文献

Diabetic wounds represent a critical public health challenge due to impaired healing processes driven by chronic inflammation, infection, and biomechanical deficiencies. Despite advances in wound dressings and negative-pressure therapy, current treatments often fail to provide sufficient mechanical support or to fully resolve inflammatory responses, resulting in prolonged ulceration and high risk of complications. To address these limitations, a photocrosslinkable chitosan quaternary ammonium salt (CQS) derivative (methacrylated CQS [CQS-MA]) was developed to accelerate gelation and improve structural integrity. We then used ultraviolet-initiated copolymerization of CQS-MA with gelatin methacrylate (GelMA) and type I collagen to fabricate a ternary composite hydrogel encapsulating fibroblast growth factor 21 (FGF-21), termed G/C-CS@FGF-21. This composite hydrogel synergistically combined FGF-21's early-stage inflammation-resolving activity, CQS's sustained antimicrobial function, GelMA's tunable mechanical resilience, and collagen's native cell-adhesive ligands, which could promote all phases of wound repair. In vitro, G/C-CS@FGF-21 promoted macrophage polarization toward the anti-inflammatory M2 phenotype and enhanced fibroblast proliferation and migration. In a full-thickness diabetic mouse wound-healing model, treatment with G/C-CS@FGF-21 accelerated wound closure by mitigating inflammation and promoting reepithelialization and angiogenesis. These findings suggest that the G/C-CS@FGF-21 hydrogel holds strong potential for future clinical translation in diabetic wound management.

Colorectal cancer (CRC) is a lethal disease characterized by its propensity to metastasize to distant organs. Despite advances in surgery and chemotherapy, CRC remains a major clinical challenge, with high recurrence rates following treatment. The complexity of CRC is further compounded by the limitations of current preclinical models, which often fail to accurately recapitulate the human tumor microenvironment. This underscores the need for improved experimental systems to evaluate novel therapeutic strategies. This study investigates a multimodal second-line treatment strategy using a 3-dimensional (3D), patient-derived CRC tumoroid model that more faithfully mimics the in vivo tumor microenvironment. We evaluated the therapeutic efficacy of a combinatorial approach integrating recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL), artesunate-eluting microspheres (ART-EMs), and mild hyperthermia at 42 °C using a water bath. rhTRAIL selectively induces apoptosis in CRC tumoroids, ART-EMs impose ferroptotic stress, and hyperthermia enhances the crosstalk between these mechanisms. This multitargeted approach is designed to trigger synergistic cell death through the convergence of apoptotic and ferroptotic signaling pathways. Synergistic interactions among rhTRAIL, ART-EMs, and hyperthermia were demonstrated using propidium iodide staining assay, immunoblotting assay, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, JC-1 assay, and dichlorofluorescein assay. Our findings indicate that the multimodal treatment induces greater tumor cell death than individual monotherapies, primarily through amplification of death signaling pathways in tumoroids. The integration of rhTRAIL, ART-EMs, and hyperthermia represents a promising second-line therapeutic strategy for CRC. By harnessing apoptosis-ferroptosis synergy within a clinically relevant 3D model, this approach has the potential to reduce recurrence and improve patient outcomes.

Chronic kidney disease (CKD) involves inflammation, fibrosis, and impaired regeneration. We developed a biofunctional hybrid scaffold (PMEAR/MM/uEV) combining a porous poly(lactic-co-glycolic acid)-porcine extracellular matrix, ricinoleic acid-modified magnesium hydroxide, metanephric mesenchyme-like cells, and ureteric bud-derived extracellular vesicles, with resveratrol and adapalene to confer antioxidant and pro-regenerative properties. The scaffold exhibited uniform porosity, pH-buffering, and reactive oxygen species-scavenging activity. In vitro, it accelerated epithelial wound closure, reduced oxidative stress, and shifted cytokine profiles toward an anti-inflammatory state by increasing interleukin-4 while decreasing tumor necrosis factor-alpha, interleukin-6, and interleukin-8. In a 5/6 nephrectomy mouse model, PMEAR/MM/uEV reduced collagen deposition, improved blood urea nitrogen and creatinine, and up-regulated podocyte markers synaptopodin, nephrin, and podocin, as well as the renal developmental marker Pax2. mRNA sequencing revealed activation of angiogenesis, extracellular matrix remodeling, oxidative defense, and immune modulation, with Kyoto Encyclopedia of Genes and Genomes enrichment in tumor necrosis factor and interleukin-17 signaling and nuclear factor kappa B-associated pathways. These findings establish PMEAR/MM/uEV as an effective, multimodal platform for kidney regeneration.

Immunotherapy offers a promising paradigm for cancer treatment, but its efficacy is often constrained by tumor heterogeneity and the immunosuppressive tumor microenvironment. Herein, we constructed a multifunctional nanoplatform (termed MD1a NP) designed to elicit personalized antitumor immunity and overcome tumor immunosuppression by co-assembling a hypochlorous acid (HOCl)-responsive methylene blue (MB)-doxorubicin (DOX) dimer prodrug with a stimulator of interferon genes (STING) agonist (1a). Following intravenous administration, elevated intratumoral HOCl triggers the activation and release of MB and DOX, inducing nanoparticle disassembly and facilitating the liberation of 1a. Upon near-infrared laser irradiation, MB-mediated photodynamic therapy synergizes with DOX-induced chemotherapy to eradicate tumor cells and amplify immunogenic cell death, thereby enhancing the release of tumor antigens and damage-associated molecular patterns. This cascade promotes dendritic cell maturation, which is further reinforced by 1a-mediated STING activation. Moreover, MD1a NP treatment decreases regulatory T-cell populations, alleviates T-cell suppression, and promotes memory T-cell formation. Consequently, MD1a NP combined with laser irradiation remodels the immunosuppressive tumor microenvironment and effectively inhibits both primary and distant tumor growth while preventing lung metastasis in orthotopic 4T1 breast cancer models. This study provides insights into the design of tumor-activatable nanoplatforms for multimodal therapy against immune-desert cancers.

The integration of biomaterials and additive manufacturing (AM) has revolutionized the design, manufacturing, and clinical applications of permanent and bioresorbable implants. AM offers design flexibility and potential for mass customization but poses challenges for scalable manufacturing. Unlike other high-commodity implantable devices that are already clinically approved, stent AM is still in the early phases of research and development. Here, following the recent Food and Drug Administration approval of Abbott's Esprit stent for below-the-knee use, we examine the current prospects for AM of polymeric stents, specifically focusing on polymeric bioresorbable stent geometry, material composition and mechanical properties, and surface quality, predominantly intended for cardiovascular applications. The advancement of bioresorbable polymeric stents is shown through a comparison with metallic stents commonly used in clinical practice. The different AM techniques used for stent fabrication and the level of currently fabricated bioresorbable stents are reviewed. A road map for translating AM stents from the research laboratory to the clinic is proposed.

Advances in cancer therapy, delayed parenthood, and an increasing number of reproductive disorders have intensified the need for the effective preservation of fertility. However, current clinical strategies such as ovarian tissue cryopreservation, transplantation, and hormonal stimulation remain limited in scope and efficacy. Biomaterials have emerged as powerful tools to overcome these limitations, enabling fertility preservation and functional restoration of reproductive and endocrine systems. Recent progress has included the development of hydrogel-based systems for in vitro follicle maturation, bioengineered scaffolds for ovarian tissue support, and artificial ovaries capable of hormone secretion and oocyte development. These platforms are increasingly incorporating immunomodulatory features to address rejection and enhance graft integration. Beyond preservation, biomaterials are also being harnessed to repair reproductive damage caused by conditions such as primary ovarian insufficiency, intrauterine adhesions, and endometriosis. Through tunable biochemical and mechanical properties, materials can direct tissue regeneration, modulate inflammation, and restore physiological functions. Emerging technologies, including biofabrication with reproductive-specific bioinks, organoid models, hormone-responsive systems, and artificial intelligence-driven biomaterial designs, are accelerating innovation toward translational applications. Collectively, these developments represent a paradigm shift in reproductive medicine from passive preservation to active regenerative strategies. This review highlights the state-of-the-art biomaterial-enabled fertility restoration and outlines future directions toward personalized, functional, and clinically viable solutions.

Osteoarthritis (OA) is the fastest-growing cause of physical disability worldwide, yet no therapy currently halts its age-dependent progression. Increasing evidence suggests that reactive oxygen species (ROS) are central drivers of cartilage degradation and OA progression. Therefore, the clearance of ROS is critical for mitigating OA progression and developing effective therapeutic strategies. In this study, we report a bioinspired copper-manganese zeolitic imidazolate framework (CuMn-ZIF) that integrates catalase (CAT) and superoxide dismutase (SOD)-mimetic activities within a single nanoplatform. By simultaneously scavenging H₂O₂ and superoxide anions, the CuMn-ZIF nanozyme rebalances redox status in human OA chondrocytes, suppressing PI3K-AKT-mTOR signaling and restoring lysosomal-autophagic flux. An intra-articular injection in destabilized medial meniscus (DMM) mice markedly ameliorated cartilage deterioration and subchondral bone loss, showing a 1.5-fold increase in bone mineral density (BMD), a 2.1-fold greater bone volume/tissue volume (BV/TV), and a 2-fold increase in trabecular number compared to DMM controls. Comprehensive in vitro and in vivo analyses validated the CuMn-ZIF nanozyme as a potent therapeutic agent, demonstrating exceptional catalytic activity and reproducible disease-modifying effects in OA. This work establishes a scalable blueprint for ROS-targeting, enzyme-mimetic nanomedicines that can potentially be translated to treat OA and other ROS-dependent diseases.

Cryopreservation is a crucial procedure to maintain quality of stem cell spheroids (SCSs) for a long period. It is affected by spheroid size because only internalized cryoprotectants can effectively play their roles within SCSs. Here, small, medium, and large SCSs with diameters of 30 to 80, 80 to 150, and 100 to 200 μm, respectively, were prepared using tonsil-derived stem cells. SCSs were preincubated in the presence of poly(ethylene glycol)s (PEGs) (10.0 wt % in a medium) with molecular weights of 200, 400, or 600 Da at 37 °C for 2 h, and then cryopreserved at -196 °C for 7 d. SCS recovery rate from cryopreservation was significantly affected by their size as well as molecular weight of PEGs; excellent recovery was observed for the small SCSs that were preincubated in PEG200 solutions. Population density of PEGs in the SCSs was 2.0 to 4.5 times higher in small SCSs than in large SCSs, which contributed to the survival of the SCSs during cryopreservation. The small SCSs recovered from cryopreservation showed innate activities of stem cells including fusion, proliferation, and differentiation much better than medium or large SCSs. The small SCSs employing the PEG200 preincubation protocol exhibited a cell recovery rate of >60% for 1 month of cryopreservation. These findings provide valuable insights into size-dependent cryopreservation strategies for high-level complex cellular systems.

Bacterial-infected wounds impose a substantial burden worldwide, with polymicrobial infections exacerbating the complexity of healing through dysregulated pH environments and gelatinase-mediated matrix degradation. Herein, we developed a microenvironment-responsive microneedle (MN) patch utilizing a "dynamic warning-graded intervention" strategy. The patch incorporates (a) a bromothymol blue-based pH visual warning system that detects acid-base changes during both acute and chronic infections, (b) a gelatin methacryloyl and exosome matrix material that enables enzyme-triggered release of human bone marrow mesenchymal stem cell-derived exosomes, responding to pathological gelatinase for spatiotemporal drug delivery, and (c) triple therapeutic payloads [hemostasis (halloysite nanotubes)/antibacterial and anti-inflammatory (antimicrobial peptides)/scar reduction (salvianolic acid B)]. In vitro validation demonstrated a bacterial clearance rate exceeding 95% against methicillin-resistant Staphylococcus aureus/imipenem-resistant Pseudomonas aeruginosa, with biofilm inhibition and disruption rates both surpassing 90%. In vivo experiments demonstrated that MNs showed observable changes in wound color within 8 h in both infectious acute and chronic wounds. In acute wounds, nearly complete healing was achieved within 10 d. By coordinating hemostasis (platelet activation within 60 s), controlling inflammation (62.07% down-regulation of tumor necrosis factor-α), and promoting angiogenesis (2.51-fold up-regulation of CD31), the healing rate of diabetic ulcers was accelerated by 9.20% compared to clinical dressings. This platform provides a foundation for integrating real-time diagnosis and treatment in complex wound management.

Colorectal cancer (CRC) remains a major clinical challenge owing to its immunosuppressive tumor microenvironment and limited targeting therapeutic efficiency. Developing innovative strategies that integrate immune activation with enhanced tumor-targeting ability is urgently needed. Herein, we reported a bioengineered exosome drug delivery nanoplatform (Apatinib-Exo^aPD-L1), in which HEK293T-derived exosomes were surface functionalized with anti-PD-L1 antibody (aPD-L1) and encapsulated the tyrosine kinase inhibitor Apatinib, aiming to enhance the tumor-targeted immunotherapy against CRC. Apatinib-Exo^aPD-L1 exhibited efficient tumor-targeting capability and prolonged systemic circulation, attributed to aPD-L1 modification, resulting in markedly enhanced antitumor efficacy without evident body toxicity. Mechanistically, Apatinib was efficiently delivered and internalized by tumor cells, where it triggered immunogenic cell death (ICD) and promoted dendritic cell maturation. This immune activation cascade facilitated the infiltration and activation of cytotoxic T cells within the tumor microenvironment. Furthermore, Apatinib-Exo^aPD-L1 reduced the population and suppressive function of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), thereby effectively reversing immune suppression and amplifying the antitumor immune response. Collectively, our findings demonstrated that Apatinib-Exo^aPD-L1 is a safe and effective exosome-based therapeutic platform, offering a promising strategy to convert immunologically "cold" tumors into "hot" ones and improve clinical outcomes in CRC.