Biomaterials research最新文献

Background: Metabolic-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis (MASH), is a growing health concern characterized by liver inflammation, fibrosis, and endothelial dysfunction. Targeted therapies are essential to address these issues and improve treatment outcomes. Methods: A sialic acid (SA)-modified nanomicelle system (SA-PEG-ALA) was developed to target liver sinusoidal endothelial cells (LSECs) via the E-selectin (SELE). Molecular docking and surface plasmon resonance (SPR) were used to confirm the binding interaction between SA and SELE. In vitro assays using LSECs and steatotic hepatocytes were conducted to evaluate the cellular uptake and therapeutic efficacy of SA-PEG-ALA. In vivo studies using an HFHC-induced MASH mouse model were carried out to evaluate the distribution and therapeutic outcomes of SA-PEG-ALA. Additionally, RNA sequencing was performed to explore the molecular mechanisms underlying its effects. Results: Molecular docking and SPR analyses confirmed that SA effectively binds to SELE, facilitating the targeted delivery of ALA to LSECs. In vitro, SA-PEG-ALA showed substantially higher uptake in LSECs compared to other formulations. In vivo, SA-PEG-ALA demonstrated superior targeting of the liver and showed enhanced therapeutic effects compared to PEG-ALA, significantly alleviating steatosis, liver inflammation, and fibrosis in the MASH model. Mechanistically, SA-PEG-ALA interacted with HSP70, enhancing its stability and promoting the binding of HSP70 to IκBα, which contributed to inhibition of NF-κB signaling pathway. Conclusion: SA-PEG-ALA offers a promising targeted therapeutic strategy for MASLD, with improved liver targeting, anti-inflammatory, and antifibrotic effects, highlighting its potential for treating MASLD.

Cancer patients exposed to chemotherapeutic drugs and whole-body radiation can result in testicular injury and germ cell loss. One of the mechanisms is that these drugs lead to the accumulation of reactive oxygen species (ROS) in the testes, which has been documented to cause testicular damage. Therefore, this highlights the critical need for ROS clearance in testes to preserve male fertility during cancer treatment. The blood-testis barrier (BTB) poses a major challenge, due to the absence of effective pharmaceutical agents that can penetrate this barrier to neutralize ROS effectively. We synthesized nanomaterials based on manganese-superoxide dismutase (PCN-222-Mn), demonstrating the ability to cross BTB and facilitate ROS clearance. Real-time T1-weighted magnetic resonance imaging confirmed the targeted delivery of PCN-222-Mn to the testes in mice. In murine models of testicular injury induced by cyclophosphamide, PCN-222-Mn showed major therapeutic effects by protecting germ cells and associated somatic cells through ROS reduction and autophagy enhancement. Additionally, PCN-222-Mn was demonstrated to penetrate Sertoli cells via clathrin-mediated and caveolae-mediated endocytosis and expelled by exocytosis, facilitating transport across the BTB. This research not only proposes a viable therapeutic approach to preserve male fertility during cancer treatment but also underscores the transformative potential of nanozymes in clinical settings.

Tendinopathy is a musculoskeletal disorder characterized by severe pain that may persist for weeks or months, often resulting in disability. Existing treatments primarily consist of conservative interventions, including rest, nonsteroidal anti-inflammatory medications, localized corticosteroid injections, ultrasound, bracing, and stem cell-based therapies, as well as surgical procedures. However, therapeutic outcomes remain unsatisfactory. Consequently, there is an urgent need for effective strategies in tendinopathy management. As a bioengineered material, the hydrogel has been extensively studied for the treatment of tendinopathy due to its stable physicochemical properties, biocompatibility, degradability, mechanical robustness, injectability, and stimuli-responsive drug delivery capability. Based on the anatomical structure of tendons and therapeutic requirements during disease progression, hydrogels can be designed into various formulations, such as scaffolds, patches, sprays, microspheres, and injectable systems, depending on the raw materials, crosslinking methods, sizes, and morphological configuration. This review provides a comprehensive overview of the pathophysiological process involved in tendon healing and summarizes the considerations in the design of hydrogels in tendinopathy treatment. It emphasizes the therapeutic applications and stimuli-responsive properties of various hydrogel formulations in tendinopathy treatment, advancing the understanding of hydrogel-based strategies for tendinopathy management and focusing on formulation design. Additionally, the opportunities artificial intelligence brings to hydrogel research in design, optimization, and application advancement are also comprehensively discussed. Understanding the advances associated with hydrogel development is crucial for tendinopathy treatment.

Diarrheal infections caused by antibiotic-resistant Escherichia coli pose a serious threat to human and animal health, driving the need for innovative therapeutic strategies. This study introduces a dual-action strategy that integrates bacteriophage EC.W2-6 with bentonite to enhance bacterial clearance and macromolecular toxin removal. Phage EC.W2-6 demonstrated high specificity against enterotoxigenic E. coli (ETEC) H10407, achieving nearly 100% adsorption to host cells within 15 min and a moderate burst size of approximately 80 plaque-forming units per infected cell. Bentonite exhibited substantial dose-dependent binding of ETEC-secreted proteins and outer membrane vesicles (OMVs), with the 30-g treatment showing the highest efficiency. Nanoparticle tracking analysis confirmed a 3.56-fold reduction in OMVs at 5 g bentonite and near-complete removal at 30 g. Physicochemical analysis indicated a stabilizing effect of bentonite, showing that bentonite-phage association partially neutralized the phage surface charge (from -34.2 to -13.4 mV), forming a more stable colloidal complex with an approximately 2-fold decrease in colloidal size. In a murine diarrheal model, single therapy with either EC.W2-6 (multiplicity of infection = 0.1) or 8% bentonite conferred 60% survival, whereas combination treatment provided 100% protection with a synergistic effect. Microbiome analysis revealed that dual therapy restored gut microbial diversity and suppressed Proteobacteria expansion, closely resembling healthy controls. These findings highlight the therapeutic potential of combining bentonite with phage therapy as an integrated macromolecular intervention against ETEC-induced diarrhea and intestinal dysbiosis.

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.