Biomaterials Science最新文献

Small interfering RNA (siRNA) is a potent method for silencing survivin mRNA within cells, offering a promising option for treating hepatocellular carcinoma (HCC) since survivin is specifically overexpressed in HCC cells. However, the clinical use of gene therapy with siRNA is limited by factors such as rapid enzyme degradation, low cell uptake, and non-specific distribution in the body. In this study, we investigate the use of a specially selected metal-organic framework (MOF) to encapsulate siRNA, with the aim of silencing survivin mRNA in HCC cells and reducing the survivin protein level. The MOF was functionalized with triantennary N-acetylgalactosamine (GalNAc), which has high affinity for asialoglycoprotein receptors that are overexpressed in HCC cells. Both in vitro and in vivo experiments showed that the GalNAc-decorated MOF specifically accumulated in HCC tumor tissue and was effectively endocytosed by HCC cells. The protective properties of the MOF increased the stability of siRNA and allowed for significant downregulation of survivin expression in HCC tumors, contributing to tumor inhibition through the suppression of cell proliferation and the induction of apoptosis. These findings highlight the potential of MOF-based siRNA delivery systems for targeted cancer therapy.

Polyurethane (PU) is a synthetic polymer with a micro-phase separation structure and tunable mechanical properties. Since the first successful application of thermoplastic polyurethane (TPU) in vivo in 1967, PU has become an important biomedical material for various applications in tissue engineering, artificial organs, wound healing, surgical sutures, medical catheters, and bio-flexible electronics. This review summarizes three strategies for regulating the mechanical properties of medical PU elastomers, including monomer design and selection, modification and arrangement of segments, and incorporation of nanofillers. Furthermore, we discuss the feasible strategies to achieve the biodegradability and self-healing properties of polyurethane to meet specific biomedical needs. Finally, this review highlights the latest advancements in functionalized PU for biomedical applications and offers insights into its future development.

Bacterial nanocellulose (BNC) is a versatile natural polymer with unique morphological properties. However, its susceptibility to biofouling limits its utility in healthcare. To address this challenge, this study explores the incorporation of gallic acid, a phenolic acid with potent antimicrobial and antithrombotic properties, into BNC membranes. Additionally, a novel drying method termed gradual freezing is introduced, resulting in a directionally-aligned BNC membrane with enhanced mechanical integrity and high porosity. Using glycerol as a solvent and plasticizer, gallic acid was loaded into air-dried BNC (AD-BNC), freeze-dried BNC (FD-BNC), and gradually-frozen BNC (GF-BNC) membranes. Successful drug-loading into FD-BNC and GF-BNC significantly increased the elasticity of the films, however mechanical testing indicated that GF-BNC and its gallic acid/glycerol loaded counterpart (GF-GG-BNC) achieved overall optimal mechanical strength and elasticity. These samples were selected for further antifouling testing. Antibacterial assays demonstrated the practical efficacy of GF-GG-BNC in inhibiting the proliferation and biofilm formation of E. coli and S. aureus, while favorable antithrombotic behaviour prevented clot formation and red blood cell adhesion on the material's surface when compared to GF-BNC membranes. These findings highlight the potential of GF-GG-BNC as a multifunctional biomaterial for the prevention of biofouling in biomedical applications.

DNA-functionalized gold nanoparticles (DNA-AuNPs) and nanorods (DNA-AuNRs) have emerged as key yet versatile biomaterials for applications in biosensing, diagnostics and programmable assembly. The high cost and sometimes complex procedures of functionalization of DNA onto AuNPs and AuNRs via the Au-thiol interaction may have set a threshold for its expanded application by researchers of diverse fields. Although oligoA-tailed DNA has been introduced as an alternative to thiolated DNA, its extended use has been largely confined to spherical nanoparticles with suboptimal functionalization density. Here we show a rapid and efficient method for high-density functionalization of both AuNPs and AuNRs using oligoA-tailed DNA via butanol dehydration, with the length of oligoA as short as A₂. By preventing secondary structure formation at an elevated temperature, our results demonstrate significantly enhanced DNA adsorption, further allowing for functionalization of a random sequence onto the AuNPs. This yields stable DNA-nanoparticle conjugates with superior stability and durability, suitable for in situ naked-eye loop-mediated isothermal amplification (LAMP) assay of bacterial pathogens and stimuli-responsive self-assembly. This study overcomes long-standing barriers in rapid, simple and low-cost preparation of DNA-AuNPs and DNA-AuNRs, paving the way for cross-disciplinary applications in diverse fields that were previously siloed and beyond.

Uncontrolled inflammation is one of the major causes of various forms of tissue injury, and nanomedicines with immunoregulatory effects are needed. Mesenchymal stromal cell-derived extracellular vesicles (e.g., MSC-EVs) have been proposed as promising therapies, but the highly efficient generation of EVs with desirable properties is still a considerable challenge in this field. Here, we report that preconditioning MSCs with a critical immune process (pyroptosis) is a robust method for improving both the yield and anti-inflammatory potency of MSC-EVs. In brief, pyroptosis-preconditioned MSCs using a combined lipopolysaccharide (LPS) and adenosine triphosphate (ATP) stimulation showed elevated EV yields compared with those of MSCs cultured under normal conditions. Pyroptosis preconditioning upregulated multiple pathways (e.g., cell proliferation, DNA repair, and the immune response) in MSCs, leading to the enrichment of immunoregulatory cargos (e.g., PD-L2 and STC2) in MSC-EVs. In vitro, pyroptosis-preconditioned MSC-EVs (P-EVs) treatment has greater potential to suppress cytokine expression and cell death in pyroptotic macrophages than treatment with normal MSC-EVs (N-EVs). Compared with N-EV treatment, P-EV treatment showed superior potency in attenuating proinflammatory cell infiltration, cytokine/chemokine expression, resident tissue cell death, and the severity of pathological injury in different models of inflammatory diseases (acute lung or kidney injury), and these effects are likely the joint result of diverse functional cargos delivered by such EVs. This study highlights that pyroptosis preconditioning is a promising strategy for the highly efficient production of MSC-EVs with advanced therapeutic potential for treating diverse inflammatory diseases.

The biopharmaceutical industry for engineered protein drugs is rapidly increasing in size but there is a lack of controlled release vehicles to enable targeted delivery for regenerative medicine applications. In this study, we used photocrosslinkable 3-sulfopropyl acrylate potassium salt (SPAK)-poly(ethylene glycol) diacrylate (PEGDA) hydrogels to achieve controlled release of lysozyme for 70 days with zero-order release and tuneable release rate. Scaling down hydrogel volume and protein loading concentration to release Transforming growth factor beta-1 (TGF-β1) and Interleukin-4 (IL-4) resulted in low cumulative release, even without SPAK. Increasing PEGDA molecular weight from 4 kDa to 20 kDa improved TGF-β1 release but it still remained below 10% after 10 days. We observed sustained IL-4 release in the therapeutic ng mL^-1 range for 73 days when loading IL-4 to 5% SPAK-10% PEGDA post photocrosslinking. Released IL-4 maintained bioactivity, promoting M2-like polarisation of THP-1 macrophages with day 53 supernatant, modelling long-term immunomodulation in vitro. We manufactured SPAK-PEGDA hydrogels by projection micro stereolithography, in which 3D printed 5% SPAK-10% PEGDA had an increased lysozyme release rate compared to its cast counterpart. 3D printed 5% SPAK-10% PEGDA with porous 3D design had an increased lysozyme release rate compared to a volume matched non-porous design. These findings highlight the potential of SPAK-PEGDA hydrogels for long-term cytokine delivery and show proof-of-concept for manipulating protein release kinetics with 3D printed hydrogel design.

Chemotherapy and surgery, though effective in cancer treatment, trigger the release of nucleic acid-containing pro-inflammatory compounds from damaged tumor cells, known as nucleic acid-associated damage-associated molecular patterns (NA-DAMPs). This inflammation promotes tumor metastasis, and currently, no effective treatment exists for this treatment-induced inflammation and subsequent tumor metastasis. To address this challenge, we developed a biomimetic liposome complex (Lipo-Rh₂) incorporating a hybrid structure of liposomes and dendritic polymers, mimicking cell membrane morphology. Lipo-Rh₂ leverages the multivalent surface properties of dendritic polymers to clear cell-free nucleic acids while serving as both a structural stabilizer and targeting ligand via embedded ginsenoside Rh₂. Experimental data show that Lipo-Rh₂ effectively reduces free nucleic acids in mouse serum through charge interactions, downregulates Toll-like receptor expression, decreases inflammatory cytokine secretion, and inhibits both primary tumor growth and metastasis. Compared to the current nucleic acid scavenger PAMAM-G3, Lipo-Rh₂ demonstrates stronger antitumor effects, lower toxicity, and enhanced targeting capabilities. This biomimetic liposome-based nucleic acid scavenger represents a novel approach to nucleic acid clearance, expanding the framework for designing effective therapeutic agents.

For tissue engineering, nanocellulose-based three-dimensional hydrogel structures hold potential as biocompatible support materials for biomimetic scaffolds to regenerate damaged tissues. One challenge of this material is that nanocellulose does not degrade in the human body. Therefore, different carriers are needed to locally deliver cellulase in a controlled manner to degrade the scaffold at the same time the cells grow and proliferate. To achieve this, we developed casein microparticles (CMPs) as delivery vehicles as they are non-toxic and have high porosity with a stable structure at physiological pH values. The porosity of the CMPs was first tested by diffusion experiments with fluorescently labelled dextrans of different sizes as model molecules, demonstrating inward diffusion of dextrans up to 500 kDa. The CMPs continuously release active cellulase, resulting in the degradation of the nanocellulose hydrogel over a time of 21 days, supporting 3D cell growth.

The paper proposes a strategy for the accelerated deposition of biomimetic organomineral layers on the surface of dental enamel, utilizing di/tetrahydroquinolinediol (hydroxyquinoline) polymerized in the presence of nanocrystalline hydroxyapatite (nano-cHAp). The mechanisms underlying the formation of dental coatings were elucidated through a combination of structural, microstructural, and spectroscopic analytical methods, including synchrotron infrared nanoimaging. Additionally, the antimicrobial effects of these coatings were investigated. It has been demonstrated that the deposition of an organomineral layer, based on polymerized dihydroxyquinoline, on the surface of natural enamel leads to the agglomeration and orientation of hydroxyapatite nanocrystals within the coating. This process enables the layer to replicate the mechanical properties of natural enamel, resulting in a microhardness value that closely resembles that of natural enamel. Using synchrotron s-SNOM, it has been established that the biomimetic organomineral layer possesses the morphological structure of a poly(2,2,4-trimethyl-1,2-dihydroquinoline-6,7-diol (TMDHQ))/nano-cHAp composite film, which is homogeneously distributed and tightly packed on the enamel surface. Furthermore, it has been demonstrated that the dental coating formed from polydihydroxyquinoline and nanocrystalline hydroxyapatite exhibits inhibitory activity against colonies of Streptococcus spp. The developed technology for the formation of dental biomimetic layers, which exhibit simultaneous antibacterial and mineralizing effects, holds significant potential for future clinical applications.

Synovitis and angiogenesis are two essential pathological factors that synergistically aggravate rheumatoid arthritis (RA), in which the highly inflammatory environment promotes new blood vessel formation while constant angiogenesis renders recruitment of more inflammatory macrophages. Herein, we developed a micelle-embedded dissolvable microneedle to realize both anti-inflammation and anti-angiogenesis effects for enhanced anti-arthritis therapy. Anti-arthritis natural products, berberine (Ber) and sinomenine (Sin), were encapsulated in the reactive oxygen species (ROS)-responsive micelles (B/S-TMs) and self-assembled using thioketal-modified amphiphilic copolymer PLGA-TK-PEG, followed by their integration into a carboxymethyl cellulose-based microneedle to achieve effective transdermal delivery and rapid cargo release. B/S-TMs were accumulated in the RA joint via passive targeting, and they released Ber and Sin through thioketal bond cleavage under a high ROS level environment. Interestingly, Ber or Sin individually exerted anti-inflammatory effect via simultaneously promoting M2 macrophage polarization and anti-angiogenesis effect by decreasing the endothelial cell migration and tube formation. The combined Ber and Sin further amplified these effects. The therapeutic microneedle patch (B/S-TM@MN) significantly decreased the expression of CD68-positive macrophages and CD31-stained blood vessel, attaining improved anti-arthritis efficacy compared with monotherapies in the collagen-induced arthritis (CIA) mouse model. Our work represents a promising strategy for targeting multiple pathological factors for enhanced anti-RA therapy.