Biomaterials最新文献

Spinal cord injury (SCI) is a debilitating condition that leads to severe motor and sensory dysfunction, largely due to inflammation, neuronal damage, and disrupted neural circuits. In this study, we developed an injectable hydrogel (C/F/Gel) co-loaded with fibroblast growth factor 21 (FGF21) and cannabidiol micelles (CBDm) to enhance SCI repair. The hydrogel, composed of PF127 and α-cyclodextrin (α-CD), provides sustained drug release and improves drug stability at the injury site. Our findings demonstrate that C/F/Gel effectively modulates the inflammatory microenvironment by promoting microglial polarization toward the anti-inflammatory M2 phenotype via cannabinoid receptor 2 (CB2R) activation. Additionally, it regulates the balance between excitatory and inhibitory neurons, and significantly improves motor function in SCI mice. Behavioral assessments, histological analysis, and molecular studies confirmed the superior therapeutic efficacy of C/F/Gel compared to single-agent treatments. These results highlight C/F/Gel as a promising biomaterial-based strategy for SCI repair, offering a synergistic approach that integrates inflammation modulation, neuroprotection, and functional recovery.

Bacterial biofilm eradication and prevention of re-colonization are critical for effective treatment of biofilm-associated infections. Although significant progress has been made in nanovehicle-assisted antimicrobial platforms for biofilm eradication, strategies to address re-colonization remain underdeveloped. In this study, we constructed a versatile antimicrobial delivery platform based on multimodal interaction polyurea nanogels (MIPN). MIPN demonstrated excellent biocompatibility and could effectively load various antimicrobials with high capacity due to the multiple intermolecular interactions between the antimicrobials and nanocarriers, including hydrogen bonding, electrostatic, and hydrophobic interactions. By incorporating self-synthesized quorum sensing inhibitors (QSI) within MIPN, bacteria re-colonization was successfully prevented by blocking the quorum sensing pathway and disrupting surface-associated bacterial motilities. Furthermore, MIPN coloaded with QSI- and antibiotics showed a synergistic effect on biofilm eradication and re-colonization prevention, significantly enhancing the healing of biofilm-associated infections in chronic wounds.

Cuproptosis, a form of copper-dependent programmed cell death, has emerged as a promising therapeutic target for cancer treatment. However, the efficacy of cuproptosis is undermined by metabolic reprogramming, notably the Warburg effect and the overproduction of glutathione stemming from solute carrier family 7 member 11 (SLC7A11) overexpression. Upregulation of the cystine transporter SLC7A11, while providing a survival advantage, also creates a glucose-dependent metabolic vulnerability in cancer cells, offering a new opportunity for cancer treatment through disulfidptosis under glucose deprivation conditions. Herein, we developed copper-based metal-organic framework nanoparticles, CuSS@876-PEG, which exploit metabolic vulnerabilities by consuming glutathione and subsequently releasing copper ions and the glucose transporter inhibitor BAY-876, thereby eliciting cuproptosis and disulfidptosis. This strategy not only enhances cell death but also stimulates immunogenic cell death, activating the antitumor immune response. To summarize, our innovative strategy provides a multifaceted approach to targeting tumors, paving the way for combined cancer therapy.

Junctional hemorrhage is a major prehospital care challenge, causing 67 % of preventable deaths. In addition, the high risk of secondary hemorrhage during transportation remains a challenge for long-term wound protection. Present hemostatic materials can't simultaneously achieve "anti-high-pressure, fast hemostasis and stable blockage". Inspired by coagulation process, positively charged dense cross-linked structure-inherited microgels (PEDM) were prepared. PEDM hybrid blood form quasi-bicontinuous composite structure (Q-Bi CS), utilizing blood realize rapid anti-high-pressure hemostasis and stable protection. PEDM can self-gel within 15 s when contact with blood, mimicking primary hemostasis to form a quick mechanical blockage. Blood cells are concentrated within 50 s, which promotes the Q-Bi CS formed in 120 s. Compared to PEDM-PBS, the compression modulus of PEDM-blood is improved by 5.4 times, achieving robust blockage. Q-Bi CS showed stable dynamic adhesion with strength maintained at 90.1 % after 200 cycles. In the rabbit femoral artery hemorrhage model, PEDM can achieve rapid hemostasis within 61 s and prevent secondary hemorrhage. PEDM even controlled porcine iliac artery hemorrhage within 30 s. In this paper, the self-gelling of PEDM matches with coagulation process, and blood is incorporated as the reinforcing phase into the Q-Bi CS, overcoming the difficulty of junctional hemostasis.

Cell-based therapies offer transformative potential for treating a range of diseases, however, maintaining desirable cell functions under environmental and biochemical stresses remains a major challenge. In the present study, silk ionomer nanoencapsulation using layer-by-layer (LbL) deposition was utilized as a versatile strategy to provide temporary cell protection from these stresses and preserve cell functions for downstream use. Using THP-1 immune cells, tunable encapsulation of the cells with up to 10 bilayers of silk was demonstrated. Characterization by quartz crystal microbalance (QCM-D) and atomic force microscopy (AFM) revealed nonlinear thickness growth (∼800 nm) and peak stiffness of 231 kPa above five bilayers, indicating a transition from rigid initial layer deposition, to softer outer layers. We demonstrate that the silk ionomer coatings preserved cellular functions, including differentiation into M1 and M2 macrophages, the associated cytokine profiles (TNF-α, IL-1β, IL-10, TGF-β), and expression of cell surface markers (CD68, CD206) when compared to the uncoated controls. Notably, these temporary coatings blocked antibody binding to CD14/CD68 receptors and also protected cells from shear stress during extrusion through a 34G needle at 200 μL/min, resulting in greater than a 70 % increase in cell survival compared to the uncoated cells during extrusion. These results establish silk ionomers as a robust biomaterials platform for enhancing the mechanical resilience and immune evasion of cells in advanced applications, such as for 3D bioprinting, adoptive immunotherapy, and regenerative transplantation.

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.