Biomedical materials (Bristol, England)最新文献

Cell-based therapies are gaining attention as a promising approach for repairing damaged tissues and organs, offering alternatives to invasive treatments like organ transplants and powerful medications. Recent research has shifted towards extracellular vesicles (EVs), membrane-bound particles that can carry therapeutic compounds like DNA, RNA, and proteins, which may offer advantages over cell-based therapies, such as higher potency and reduced immune reactions. A key challenge in EV therapy is ensuring that the vesicles reach their intended target tissues. While EVs are often delivered via injection, systemic administration can result in off-target effects. To address this, we highlight the microfluidic encapsulation of EVs in hydrogel microcapsules that include a CD9 binding peptide (CD9BP), allowing for controlled EV release in response to a shift in environmental pH. By encapsulating CD9+ EVs in CD9BP hydrogel capsules, we demonstrate the release of their contents in acidified environments typical of damaged tissues. This method allows for targeted, localized EV delivery. The approach promises more effective tissue regeneration while reducing the need for broad, non-specific drug delivery.

The global rise in chronic kidney disease necessitates innovative solutions for end-stage renal disease that can help to overcome the limitations of the only available treatment options, transplantation and dialysis. Tissue engineering presents a promising alternative, leveraging decellularized scaffolds to retain the extracellular matrix (ECM). However, optimizing methods for decellularization and recellularization remains a challenge. Here we present novel work which builds on our previous study where we investigated several decellularization protocols. In this study we analyzed the suitability of decellularized scaffolds for recellularization. Precision-cut kidney slices (PCKS) were utilized as a model to explore the impact of different decellularization protocols on scaffold recellularization. PCKS were pretreated physically followed by immersion decellularization in chemicals (CHEM-Imm). Physical pretreatments included high hydrostatic pressure (HHP-Imm) or freezing-thawing cycles (FTC-Imm). Scaffolds were recellularized, with human renal proximal tubular epithelial cells (RPTEC/TERT1). All scaffolds showed cell growth over the 7 d incubation period. Notably, FTC-Imm demonstrated the highest expression of the tight junction protein zonula-occludens-1 (ZO-1). Moreover, as the native kidney is composed of up to 30 different cell types, we utilized artificial neural networks to investigate the distribution and attachment patterns of RPTEC/TERT1 cells to determine if decellularized scaffolds retain cell specific attachment sites. It was revealed that, at least 97% of RPTEC/TERT1 cells were attached outside the Bowman capsules, potentially showing a clear tendency to attach to their original tubular sites. This suggests that the ECM retains instructive cues guiding the migration and attachment of the cells. Overall, our scoring system identified FTC-Imm as the most effective method.

β-Tricalcium phosphate (β-TCP) is widely used as a material for bone implants due to its excellent biocompatibility, biodegradability, and osteoconductivity, as well as its osteoinductive properties. Here, we demonstrate that the regenerative potential of this material can be significantly enhanced when incorporated into a matrix of inorganic polyphosphate (polyP), a physiological, metabolically active polymer composed of phosphate residues linked by high-energy phosphoanhydride bonds. A 3D-printable hydrogel was developed containing suspendedβ-TCP and amorphous calcium-polyP nanoparticles (Ca-polyP-NP; the water-insoluble depot form of polyP), as well as NaH₂PO₄as the monomeric precursor of the polymeric, water-soluble Na-polyP. Heating the printed scaffold to 700 °C causes condensation of NaH₂PO₄, resulting in the formation of a Na-polyP glass melt that embeds the Ca-polyP-NP andβ-TCP particles. The final scaffolds exhibited the necessary porosity, with pore sizes ranging from 10 to 100 µm (average 84 µm), which are suitable for bone ingrowth, along with the required mechanical stability. The morphogenetically active polyP component is released from the 3D-printed porous scaffolds in appropriate amounts, significantly increasing both the proliferation and energy-dependent differentiation of mesenchymal stem cells (MSCs) into mineralizing osteoblasts compared to polyP-freeβ-TCP scaffolds. Moreover, enhanced formation of collagen fibers and hydroxyapatite deposits on the cell surface, as well as accelerated microvessel tube formation, were observed in MSCs seeded on polyP-containing scaffolds. These results d`emonstrate that the novel strategy of integratingβ-TCP with polyP as an energy-supplying, regeneration-promoting component imparts superior functional properties toβ-TCP scaffolds, making them a promising material for future bone implant applications.

Leukaemia is a haematopoietic system malignancy depicted by the infiltration of the bone marrow, blood and other tissues by proliferative and abnormally differentiated cells of the haematopoietic system. The available therapies aim to induce cell death of these poorly differentiated cells by various means. The anthracycline doxorubicin (DOX) regime remains the standard first-line treatment for leukaemia. DOX has potent anticancer activity at higher dosage concentration and imparts cardiac, renal and hepatic toxicity. The disulfiram metabolite complex zinc diethyldithiocarbamate (Zn-DDC) has potent anticancer efficacy; however, it has a short half-life due to its instability in gastric juice and the blood stream. The present study employed a thin-film hydration method to synthesise liposomal nanoparticles encapsulating DOX (DOX-NPs), Zn-DDC (Zn-DDC-NPs) and both Zn-DDC and DOX (Zn-DDC + DOX-NPs).In vitrocytotoxicity and antioxidant assays were performed to assess their cytotoxicity and antioxidant activity. The liposomes were evaluated against leukaemia in Wistar rats. After leukaemia induction through benzene, haematological and serological assays, morphological and histological examinations were conducted to evaluate treatment approaches. All liposomal formulations overcame their limitations, improved the blood parameters (p> 0.05), restored the hepatic and renal enzyme levels (p> 0.05), and reduced the blast cells in blood and tissues. However, in co-encapsulated liposomes, Zn-DDC reduced the cytotoxicity caused by DOX and provided results more analogous to normal.

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.