Biomaterials最新文献

Current injectable biomaterials for vocal fold disorders suffer from fast degradation and require frequent re-injection. Decellularized extracellular matrix (dECM) hydrogels are a tissue-derived, injectable biomaterial with intrinsic regenerative capacity. However, dECM hydrogels often exhibit mechanical instability and share the same problems with degradation as existing vocal fold biomaterials. In this work, we developed a composite dECM-alginate hydrogel with bioorthogonal click tetrazine ligation with improved stability, biocompatibility and regenerative capacity. dECM was extracted from two sources: tissue-specific vocal fold mucosa and scalable small intestinal submucosa for comparative analysis. Click dECM hydrogels from both sources were tunable and matched mechanical properties of native human vocal folds. The click dECM hydrogels showed capacity to resist contraction and modulate bioactive molecule secretion by fibroblasts, as well as stimulate the initial endothelial cell elongation phase of vasculogenesis. When injected subcutaneously into rats, both gels exhibit a strong initial immune response, followed by integration with the surrounding tissue by day 21. Overall, our click dECM hydrogels showed improved stability over previous dECM hydrogels and their performance was independent of tissue source.

The unique design of low molecular weight hydrogels (LMWH) without carriers has sparked great interest in biomedical applications, yet the construction of binary LMWH remains elusive due to the lack of a theoretical framework linking structure and assembly. Hence, we proposed an innovative theoretical framework, in which a subtle -OH change in parent structures triggers the interconversion of nanoparticles and nanofibers. This framework hinges on a pair of hydrophobic planar small molecules with only one -OH difference, self-assembling into binary LMWH at 1:1 ratio. Notably, LMWH featuring coptisine and chrysin exhibits superior antifungal efficacy against multidrug-resistant Candida auris compared to the clinical first-line drug fluconazole. By electrostatic adsorption, Candida auris with negative charges can specifically adhere to LMWH with positive charges, facilitating the further exertion of LMWH's pharmacological effects. This leads to the activation of the CWI-MAPK pathway, disrupting the polysaccharide components in the fungal cell wall, inhibiting cell wall biosynthesis, and exerting an antifungal effect. Subsequently, this process reduces inflammation and promotes wound healing. This carrier-free, environmentally friendly strategy has significantly enhanced our understanding of the intricate relationship between structure and assembly, and has paved the way for the theory-guided construction of binary LMWH functional biomaterials with antifungal properties.

The integration of ultrasensitive smart human-machine interaction and well skin-like healing capabilities into the biomaterials-based dressing still remains great challenges. Herein, a sort of novel multifunctional lignocellulose dressing is proposed by combining ammonia-oxygen pretreatment with papermaking strategy, which promotes wound healing and achieves synchronous and resolvable self-powered quadruple sensing. In-situ aminated lignin within lignocellulose skeleton and the incorporated foreign natural tea polyphenols (TP) on outer wall synergistically enhanced the polarity of the lignocellulose, the optimized lignocellulose/TP TENG displayed the highest output performance, with the maximum output power of 210.43 mW/m², 890.72 % higher than that of pristine lignocellulose. Benefiting from the reinforced triboelectricity and abundant polar groups, the as-constructed bio-dressing is highly responsive to multiple stimuli with the assistance of machine learning, including pressure, humidity, and material types. Moreover, the unique three-dimensional interwoven networks of fibers and phenolic hydroxyl on TP endows the bio-dressing with high air permeability of 4.5 mm s^-1, excellent antibacterial and antioxidant properties, and high mechanical strength. After coating the lignocellulose-dressing, the wound recovery can be significantly accelerated within 12 days and the wound healing state can be monitored in single-electrode model. Our findings offered a reliable strategy to design and fabricate advanced biomaterials, boosting the development of future point-of-care applications.

Current gel dressings face significant challenges in seawater-immersed wound management due to their marine-intolerance, poor bioadhesion and non-antibacterial properties. Herein, we develop a multifunctional gel that integrates marine-tolerance, wet adhesion, non-invasive detachment, good antibacterial properties to resist bleeding and promote wound healing in marine environments. Our design strategy employs solvent-exchange-induced self-assembly of hydrophobic segments to engineer hydrophobic microdomains, coupled with the synergistic effects of hydrogen/ionic/coordination bonds as multicrosslinked networks, resulting in a marine-tolerant hydrogel with a "hydrophobic microdomain-multicrosslinked" network structure. An "interfacial drainage-multivalent bonding" dual-effect adhesion strategy is proposed: the interfacial drainage effect induced by silicone oil and hydrophobic microdomains enables tight tissue-gel anchoring, while the cooperative interactions of hydrogen/carbon-nitrogen/carbon-sulfur bonds synergistically achieve strong interfacial adhesion, achieving stable wet adhesion in marine environments. Furthermore, glutathione can cleave the disulfide bonds within the gel and the carbon-sulfur bonds between the gel and tissue, facilitating non-invasive detachment. Besides, the incorporation of zinc oxide nanoparticles provides broad-spectrum antibacterial functionality. Comparative animal experiments demonstrate superior performance over commercial glue in hemostatic efficiency and wound regeneration under marine conditions. This multifunctional hydrogel system establishes a new paradigm for developing advanced marine medical biomaterials through the rational integration of structural engineering and functional components.

Portal vein tumor thrombus (PVTT) is a common and severe indicator in advanced hepatocellular carcinoma (HCC), characterized by a poor prognosis and limited response to existing therapies. Cancer-associated fibroblasts (CAFs) play an important role in promoting HCC metastasis and contribute to resistance against sorafenib (SOR) resistance, which is a standard treatment for advanced HCC. The data from single-cell RNA sequencing highlights the critical role of C-X-C motif chemokine ligand 12 (CXCL12) in the activation of CAFs. To address these challenges, we develop a PVTT-targeted nanocarrier designed to co-deliver small interfering RNA (siRNA) and a multikinase inhibitor, aiming to enhance therapeutic outcomes for PVTT. This novel lipid-coated polylactide-co-glycolide nanoparticle system effectively downregulate CXCL12 expression in CAFs, leading to their inactivation and subsequent reshaping of the tumor microenvironment. The resulting modulation of the tumor microenvironment significantly suppress tumor cell migration, invasion, and resistance to SOR, thereby demonstrating potent anti-tumor effects in orthotopic mouse models of PVTT. Furthermore, RNA sequencing reveals key regulatory pathways and genes associated with the inhibition of SOR resistance and PVTT formation mediated by these nanoparticles. These findings suggest that modulating the tumor microenvironment, combined with targeted anti-tumor therapies, offers a promising strategy for treating HCC patients with PVTT.

The senescence of mesenchymal stem cells (MSCs) leads to the significant change of their metabolic activity and physiological behaviors. In the context of orthopedic treatment, the osteointegration of titanium implant is largely affected by MSC aging, imposing considerable limitations on its long-term application. In this study, a surface modification on titanium implants was designed to enhance osteointegration by effectively regulating the functions of senescent MSC: A typical micro-nano topological structure was established on the implant surface to improve the osteogenic differentiation of MSCs. Then a functional hydrogel coating was covalently modified to the implant surface through a poly-dopamine layer. For senescent MSCs, firstly, the coating can eliminate the activation of senescence-associated secretory phenotype (SASP) of senescent MSCs by micro-nano topological structure, and it accelerated the proliferation of non-senescent MSCs by the reactive oxygen species (ROS) scavenging. With the degradation of the hydrogel coating, the composition of stem cell pool around the implant interfaces gradually rejuvenated, as the number of non-senescent MSCs increased and senescent MSCs decreased. Meanwhile, the exposed micro-nano topological structure showed significant effect on the osteogenic differentiation of MSCs, and ultimately promoted the osteointegration in aging rats. These results provided promising insights for the design and application of orthopedic titanium implants for aging patients.

Chronic diabetic wounds are characterized by hypoxia, persistent microbial infection, and impaired healing, posing significant challenges to conventional therapies. Herein, we present a novel sprayable double-network hydrogel platform designed to achieve efficient antimicrobial activity and accelerated wound repair under hypoxic conditions by leveraging a type I photodynamic therapy (PDT) and immune-metabolic regulatory strategy. Specifically, we employ salvianolic acid B (SAB) to form a self-assembled hydrogel (SAB-gel) and incorporate fibrin to construct a robust and acidic double-network SAB/F-gel with enhanced mechanical strength and acidic environment. Concurrently, thymoquinone (TQ) and chlorin e6 (Ce6) are self-assembled via hydrophobic interactions to form TQ/Ce6 nanoparticles (TQ/Ce6 NPs) and embedded in the SAB/F-gel, to fabricate the TQ/Ce6@SAB/F-gel. Under low-oxygen conditions, TQ acts as an electron-transfer mediator, enabling Ce6 to generate abundant superoxide anions (·O₂^-) via type I PDT under red light (RL) irradiation. These ·O₂^- are subsequently converted into hydrogen peroxide (H₂O₂) and hydroxyl radicals (·OH) in the acidic environment provided by acidic SAB/F-gel, thereby reducing the dependence on oxygen and maintaining potent antimicrobial efficacy against MRSA, Pseudomonas aeruginosa (Pa), Acinetobacter baumannii (Ab), Escherichia coli (E. coli) and Candida albicans (Ca). In vitro experiments demonstrated that TQ/Ce6@SAB/F-gel regulates macrophage M2 polarization and promotes endothelial cell proliferation, migration, and tube formation via the immune-metabolic regulatory pathways. When applied to MRSA-infected diabetic wounds in mice, the hydrogel in combination with RL completely eradicated bacteria, promoted collagen deposition and angiogenesis, and significantly accelerated wound closure, as demonstrated by histological examination and transcriptome sequencing. This work offers a versatile, biocompatible, and oxygen-independent PDT-based hydrogel system for the treatment of refractory infected diabetic wounds, offering potential for clinical translation and improved patient outcomes.

Osteoarthritis (OA), a prevalent degenerative joint disease, currently lacks effective therapeutic options beyond symptomatic relief. Persistent inflammation and impaired cartilage repair accelerate the disease progression. The enzyme inducible nitric oxide synthase (iNOS) contributes to OA by producing nitric oxide (NO), which intensifies inflammation and inhibits cartilage regeneration. Traditional iNOS inhibitors have demonstrated limited efficacy due to inadequate targeted release and uncoordinated control over inflammation. In this study, we developed a self-supported DNAzyme-based DNA hydrogel using rolling circle amplification (RCA) technology to deliver iNOS-targeting DNAzymes and bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) in response to inflammation. The hydrogel incorporates triglycerol monostearate nanoparticles (TGMS NPs), which degrade under high matrix metalloproteinase (MMP) levels in OA joints, thereby triggering the release of the DNAzymes and exosomes with precision. This targeted delivery modulates the inflammatory microenvironment by reducing pro-inflammatory NO production and supports chondrogenesis by promoting M2 macrophage polarization. In vitro and in vivo analyses reveal that the hydrogel significantly reduces inflammatory cytokine levels, enhances chondrocyte proliferation, and restores extracellular matrix integrity, ultimately slowing OA progression. This smart hydrogel offers a promising ambidextrous strategy for microenvironment modulation and cartilage regeneration, potentially advancing OA treatment.

Cancer progression is driven by the dynamic interplay between metabolic reprogramming and immune evasion. A central mechanism is aerobic glycolysis, which fuels tumor growth while simultaneously impairing antitumor immunity. To address recurrent metastatic triple-negative breast cancer (TNBC), we developed a biomimetic nanoplatform (3BP@CP NPs) composed of high-affinity programmed death-1 (PD-1)-modified cell-membrane nanovesicles encapsulating 3-bromopyruvate (3BP)-loaded nanoparticles. The optimized nanoparticles exhibit enhanced pharmacokinetics with prolonged circulation, enabling dual programmed death-ligand 1 (PD-L1)-targeted tumor homing and checkpoint inhibition. The glycolytic inhibitor 3BP specifically inhibits hexokinase II (HK₂) activity, triggering metabolic collapse and immunogenic cell death while reversing immunosuppression in the tumor microenvironment (TME). This synergistic metabolic-immunological intervention elicits robust systemic antitumor responses, curtailing tumor recurrence and metastasis while extending survival in aggressive TNBC models. Collectively, this study establishes a therapeutic paradigm combining immune checkpoint receptor-modified cell-membrane nanovesicles (ICB CVs) with metabolic modulators to enhance immunotherapy efficacy in recurrent metastatic TNBC, providing a clinically translatable approach for PD-L1-expressing malignancies.

Objectives: Fracture hematoma (FH) initiates fracture healing and is key in the inflammatory phase. Neutrophils, the first infiltrating cells, play a dual role in this process. The discovery of pro-inflammatory N1 and regenerative N2 neutrophil phenotypes provides new insights into their functions. This study aims to investigate the presence, dynamics, and osteogenic effects of N1 and N2 neutrophils in human FH.

Methods: Human neutrophils were polarized into N1 and N2 phenotypes in vitro. CD15 and CD16 served as general markers, while CD54, CD95, and CD182 expression and TNF-α, IL-8, MCP-1, and SDF-1α secretion characterized N1/N2 polarization. After validation, 15 FH samples (4-14 days post-trauma) were analyzed by flow cytometry and immunofluorescence to determine the N2/N1 ratio and its temporal trend. Functional assays assessed their influence on human BMSC osteogenesis in co-culture.

Results: In vitro, N1 neutrophils expressed high CD54 and CD95 and secreted elevated TNF-α, IL-8, MCP-1, and SDF-1α, whereas N2 cells showed increased CD182 and SDF-1α. Both phenotypes were detected in human FH, with a rising N2/N1 ratio over time, indicating a shift from inflammation to regeneration. Functionally, N1 neutrophils counteracted N0-induced inhibition of early osteogenesis but reduced cell metabolism, while N2 neutrophils alleviated N0-mediated suppression of late mineralization.

Conclusions: Our findings provide the first evidence of the coexistence and temporal evolution of N1 and N2 neutrophils within human fracture hematoma, consistent with their polarization characteristics observed in vitro. Moreover, these phenotypes exert distinct effects on osteogenesis, in alignment with the progressive increase of the N2/N1 ratio in vivo, supporting the gradual transition from inflammation to regeneration during the human fracture-healing cascade. Collectively, this study advances the understanding of neutrophil heterogeneity in bone regeneration and bridges fundamental immunobiological mechanisms with potential clinical translation.