Biomedical materials (Bristol, England)最新文献

It is essential to develop new strategies for wound treatment and skin reconstruction, particularly by scaffolds that replicate the structure and function of native skin. A bilayer scaffold was developed using three-dimensional bioprinting, based on a uniform chitosan-based formulation for both layers, maintaining material uniformity while offering structural support and promoting cell adhesion. The upper chitosan layer, embedded with Newborn Human Epidermal Keratinocytes-Neo, is stiffer and mimics the epidermis, while the softer lower layer contains embedded HFFs and HFSCs, mimicking the dermis. Moreover, the softer layer was infused with recombinant decorin (DCN) proteoglycans for skin repair through controlled release. The scaffold facilitates effective fluid management. Its positive contact angle suggests sufficient wettability. The scaffold layers have high water content and swelling capacity. The epidermis displayed lower compressive strength due to its more protective and less hydrated nature. Rheological analysis confirmed the scaffold's viscoelastic behavior. Chitosan-gel had high cytocompatibility. Chitosan scaffolds supplemented with DCN proteoglycans had enhanced blood entrapment and clotting. The scaffold's timely biodegradation may reduce prolonged material exposure and support safe tissue integration. This scaffold has potential in the treatment of acute and chronic wounds.

Carbon quantum dots (CQDs), owing to their small size, special surface functionalities, and remarkable fluorescence properties, have gained significant attention from researchers in the biomedical field. In the present work, CQDs were synthesized fromBlumea erianthaDC (BEDC) extract using green approach via microwave-assisted technique. The synthesized BEDC-CQDs were characterized using spectroscopic techniques to confirm their formation. Strong absorption peaks at 279.46 nm and 325.41 nm are attributed to the excitation ofπandnelectrons of C=C and C=O groups, respectively, indicating the formation of CQDs. HepG2 cells were treated with varying concentrations of BEDC-CQDs and gauged via MTT assay, flow cytometry, and western blot analysis. Reactive oxygen species (ROS) generation, and expression of p53 and MDM2 proteins were evaluated to determine the cytotoxic mechanism. BEDC-CQDs exhibited bright light-blue fluorescence under UV irradiation, with photoluminescence quantum yield 18.90%. X-ray diffraction peaks reveal the nano-crystalline nature of the BEDC-CQDs. High-resolution transmission electron microscopy analysis revealed that BEDC-CQDs are spherical particles with sizes ranging from 2.19 to 8.95 nm. The MTT assay of BEDC-CQDs on HepG2 cells demonstrated substantial cell cytotoxicity at a concentration of 50 μg ml^-1, with an IC₅₀value of 40.86 μg ml^-1. Flow cytometry results indicated that BEDC-CQDs induced apoptosis in HepG2 cells. Intracellular ROS levels were also found to be significantly increased in HepG2 cells after treatment with BEDC-CQDs. Western blot analysis further disclosed that the expression of p53 and MDM2 were increased by 6.282- and 3.836-fold, respectively, in BEDC-CQD treated HepG2 cells compared to the control. These observations suggest that the synthesized BEDC-CQDs could serve as a viable therapeutic agent against hepatocellular carcinoma and support further exploration of similar nanohybrids with other bioactive compounds.

Chronic wounds stand as a significant challenge to public health due to their high prevalence and complications, such as difficult-to-treat infections. The present study focuses on developing antimicrobial self-healing injectable hydrogels composed of chitosan (CS), collagen (CG), and polyvinyl alcohol (PVA) for the noninvasive treatment of chronic wounds with complex geometries. The hydrogels were synthesized through physical crosslinking via hydrogen bonds and ionic interactions, achieved through the freeze-thaw method and pH variations, resulting in materials with dynamic bonds. This feature endowed hydrogels with self-healing capability, allowing injection, adaptation to wound shapes, and recovery of properties after application. The hydrogels exhibited a vapor transmission rate of around 2500-3500 g m^-2d^-1, a pH range of 5.2-6.2, 40%-110% swelling, and degradation occurring within 4-48 h, which are within ranges known to support wound regeneration. Rheological analysis revealed viscoelastic and pseudoplastic behavior, and a self-healing capacity of up to 83% after deformation. Hydrogels also presented injection forces below 40 N, ensuring ease of handling. Additionally, hydrogels presented suitable blood compatibility and strong antimicrobial properties, achieving over 99% inhibition against microorganisms commonly associated with chronic wounds. Finally, all hydrogels demonstrate low irritability in the primary skin irritation assay, increased skin moisture, and decreased skin temperature, which are features that could support the wound healing process. These results highlight the potential of these materials for chronic wound treatment, offering a unique combination of natural polymer composition, injectability, self-healing, antimicrobial properties, skin-moisturizing effect, and low irritation potential.

Biofilms are surface-attached microbial communities that play vital roles in natural ecosystems and contribute to persistent problems in medicine and industry. These communities exhibit heterogeneous chemical, physical, and physiological properties, which are governed by reciprocal structure-function relationships. Linking structure to function is crucial for understanding biofilm physiology but remains challenging due to the structural complexity of naturally formed biofilms. Bioprinting offers exquisite control over biofilm structure and holds potential for systematically exploring these relationships; however, the microscale colony distributions that emerge within hydrogel-based print resins remain unexplored. To address this, we use light-based bioprinting to create single-layer hydrogel films containing homogeneously dispersedPseudomonas fluorescensbacteria and characterize the spatiotemporal distribution of colonies that develop within these films. We systematically vary the concentration of bacteria over nearly three orders of magnitude, track colony growth using microscopy, and quantify structural features with image analysis. We observe empirical relationships between initial cell concentration and key structural features: colony size, colony volume, total biovolume, and characteristic gradient length scale. This knowledge can be used to print microbial communities with well-defined features, is readily applicable to more complex three-dimensional shapes, and provides a tool for advancing our understanding of microbial communities.

Currently investigated two-dimensional cell culture systems are typically inadequate for large-scale cell expansion and prone to causing altered cell morphology, aberrant differentiation, and distorted protein expression. To overcome these limitations, a glycidyl methacrylate-modified silk fibroin (SFMA)/methacrylic anhydride-modified gelatin (GelMA) interpenetrating polymer network hydrogel (SFMA-GelMA) was developed via microfluidic fabrication for three-dimensional (3D) bone tissue engineering applications. With increased SFMA content, the molecular chains in SFMA-GelMA undergo a structural transformation from random coil toβ-sheet andβ-crystallite, enhancing storage modulus to about 500 Pa and extending degradation duration from about 47.7% to 84.3% mass retention over 7d. The higher GelMA content with the arginine-glycine-aspartic acid sequence in SFMA-GelMA facilitated early cell adhesion, provided interconnected pores (5-80 μm diameter), and promoted the osteogenic differentiation of MC3T3-E1preosteoblasts in 3D culture, as confirmed by alkaline phosphatase activity up to about 45 U mg^-1protein. Overall, SFMA-GelMA shows substantial potential as a 3D cell culture scaffold and injectable material for regenerative medicine, particularly in bone tissue engineering.

In recent years, the incidence of orthopedic diseases has increased significantly, while traditional treatments often face limitations such as limited efficacy and pronounced side effects. The development of nanomedicine technology provides novel strategies for orthopedic disease treatment. As an emerging two-dimensional nanomaterial, black phosphorus nanosheets (BPNSs) demonstrate remarkable potential in the treatment of orthopedic diseases due to their unique physicochemical properties, superior biocompatibility, and the fact that their degradation product-elemental phosphorus-constitutes an essential component of bone tissue. This review systematically summarizes the fundamental properties of BPNS, their preparation methods (mechanical exfoliation, chemical vapor deposition, liquid exfoliation, and electrochemical exfoliation), and functional modification strategies (surface covalent coupling, ion loading, and surface coating). We then focus on analyzing research progress in multiple clinical orthopedic applications including bone regeneration, bone defect repair, treatment of degenerative bone diseases, bone tumor therapy, wound healing promotion and orthopedic image-guided applications. Simultaneously, this review objectively discusses key challenges facing clinical translation of BPNS, including long-term biosafety concerns, large-scale preparation technology limitations, and insufficient mechanistic studies, while proposing future research directions. We believe that with further advancements in materials science, nanotechnology, and biomedical engineering, BPNS will become a novel nanomedicine in orthopedic treatment, offering patients more effective and safer therapeutic options.

Melanoma remains a major global health challenge due to the uncontrolled growth of abnormal skin cells, resistance to conventional therapies, and poor prognosis in advanced cases. Localized, early-stage melanoma, defined as melanoma confined to the skin without regional or distant spread, offers a critical treatment window, as thin lesions are often curable with surgical excision. However, delays in treatment allow progression to lymph node involvement and distant metastasis, which worsen prognosis and limit available therapies. Although surgery and radiotherapy remain standard options, they often struggle with limitations like incomplete melanoma targeting, damage to healthy tissues, and treatment resistance. To address these challenges, we explored a more precise radiotherapy approach aimed at enhancing treatment efficacy while minimizing harm to surrounding tissues. In this study, we investigated the potential of rare-earth-doped nanoparticles (RENPs) as radiosensitizers by integrating them with microneedles (MNs) and shortwave infrared (SWIR) imaging to improve the precision of radiotherapy for localized, early-stage melanoma treatment. RENPs were synthesized using a modified thermal decomposition method and surface-modified them with Tween 20 (Tw) to facilitate their transition into the aqueous phase for biological applications. Incorporating RENP-Tw into MNs enabled precise and localized delivery into melanoma tissue. Meanwhile SWIR imaging, with its deep tissue penetration and high contrast resolution, allowed real-time monitoring of RENP-Tw localization, ensuring optimal radiosensitization at the melanoma site. Ourin vivostudies demonstrated that RENP-Tw/MNs significantly enhanced radiation-induced cell death in melanoma-bearing mice while minimizing systemic toxicity. Moreover, SWIR imaging revealed sustained luminescence of RENP-Tw/MNs at the melanoma site, further supporting precise radiotherapy with improved therapeutic outcomes. This innovative approach addresses the limitations of conventional radiotherapy by improving melanoma specificity, reducing off-target effects, and enhancing radiosensitization efficiency. Overall, our findings suggest that RENP-Tw/MNs hold potential as an effective strategy for advancing localized, early-stage melanoma treatment through precise, imaging-guided radiotherapy.

Targeting glucocorticoid Receptors (GR) induces gluconeogenesis in cancer cells, potentially disrupting their glycolytic dependency and acidic tumor microenvironment (TME), thereby creating an energetically unfavourable state and reducing drug resistance by impairing the acid reflux mechanism. Based on this rationale, we developed a GR-mediated liposomal co-delivery system, D1XP-p53, carrying the tumor suppressor gene, p53, and the chemotherapeutic drug, paclitaxel, to overcome the limitations of conventional anti-cancer therapies and to assess whether wild-type p53 enhances the anti-cancer activity of paclitaxel against Oral Squamous Cell Carcinoma (OSCC).In vitrostudies demonstrated that D1XP-p53 selectively decreased the viability of OSCC cells and significantly inhibited their migration, invasion, and proliferation. Mechanistic investigations revealed an upregulation of the BAX/BCL2 ratio when oral cancer cells were treated with D1XP-p53, indicating the activation of intrinsic apoptotic pathways. The efficacy of D1XP-p53 was further validated in 3D spheroid models using MOC2 and FaDu cell lines, where it significantly reduced spheroid-forming ability and upregulated E-cadherin expression, indicating its potential role in enhancing anti-cancer activity and mitigating cellular migration.In vivoexperiments using a murine model of OSCC with MOC2 cells showed a marked reduction in tumor volume in mice treated with D1XP-p53, with minimal systemic toxicity as assessed by H&E staining and biodistribution analysis. Considering the crucial role of TME components such as tumor-associated macrophages, cancer stem cells, and growth factors in tumor progression and metastasis, we further evaluated the impact of our delivery system, D1XP-p53, on these elements. We observed that D1XP-p53 treatment in mice significantly upregulated the M1/M2 ratios and decreased thec-mycandSOX2expression, indicating the potential role of the delivery system in modulating the TME components. These findings collectively demonstrate that the GR-targeted co-delivery system, D1XP-p53, enhances anti-cancer activity and modulates the TME, offering a promising multi-modal treatment against aggressive oral cancer.

This study presents a novel electrochemical aptasensor utilizing polydopamine-graphene (PDA-G) nanocomposite for VEGF₁₆₅detection. The PDA-G nanocomposite was synthesized through a one-step self-polymerization process and characterized by SEM, XPS, and FTIR, confirming successful PDA coating on graphene sheets with 22.3% C-N bond incorporation. Electrochemical characterization confirmed stepwise increases in charge transfer resistance (Rct), and quantitative detection was based on ΔRct (the change in Rct before vs. after VEGF₁₆₅binding). Under optimized conditions (pH 7.4, 37 °C, 30 min incubation), the sensor demonstrated dual-linear response regions with high sensitivity. Analysis of clinical samples showed minimal matrix effects with a 1:4 dilution ratio, and endogenous VEGF₁₆₅levels in healthy donor serum were determined to be 28.4 ± 3.2 pg ml^-1. The method's practicality was validated through comprehensive interference studies, with common serum proteins generating relative responses below 5.2% compared to the target.

Mineralized keratin (M-keratin) has previously been shown to promote the differentiation of dental pulp stem cells (DPSCs) into odontoblasts; however, thein vivobiological effects and biocompatibility of this material have not yet been illustrated. To investigate this, we first prepared M-keratin (defined as keratin that has been mineralized in Simulated body fluid) nanoparticles, then, implanted these into a femoral injury Sprague-Dawley Rats model. Signs of bone regeneration were observed and/or detected by CT scan, HE stains, Masson stain, and Western blot. We found the regeneration of bone tissue was accelerated in the 28 d following implantation, seen as an up-regulation in the expression of Runx2, ALP, BMP-2, and OSX proteins. GO enrichment analysis and KEGG pathway enrichment analysis showed that cell membrane regulation and calcium ion signaling pathway were significantly activated, and it was revealed that multiple genes served as cross-linking hubs between different signaling pathways to jointly promote bone tissue repair. With this study, we hope to provide a theoretical basis for the clinical treatment of bone defect diseases.