Biomedical materials (Bristol, England)最新文献

Despite their recognized potential for ischemic tissue repair, the clinical use of human mesenchymal stromal cells (hMSC) is limited by the poor viability of cells after injection and the variability of their paracrine function. In this study, we show how the choice of biomaterial scaffolds and the addition of cell preconditioning treatment can address these limitations and establish a proof-of-concept for cryopreservable hMSC-loaded microbeads. Injectable microbeads in chitosan, chitosan-gelatin, and alginate were produced using stirred emulsification to obtain a similar volume moment mean diameter (D[4,3]500 µm). Cell viability was determined through live/dead assays, and vascular endothelial growth factor (VEGF) release was measured by ELISA. Proangiogenic function was studied by measuring the wound closure velocity of endothelial cells (HUVEC) co-cultured with MSC-loaded microbeads. The effect of freeze-thawing on microbeads morphology, porosity, injectability and encapsulated MSC was also studied. hMSC-loaded chitosan-based microbeads were found to release 11-fold more VEGF than alginate microbeads (p˂0.0001) and chitosan-gelatin was chosen for further studies because it presented the best cell viability. Preconditioning with celastrol significantly enhanced the viability (1.12-fold) and VEGF release (1.40-fold) of MSC-loaded in chitosan-gelatin microbeads, as well as their proangiogenic paracrine function (1.2-fold; p˂0.05). In addition, preconditioning significantly enhanced the viability of hMSC after 1 and 3 days in low-serum medium after cryopreservation (p˂0.05). Cryopreserved hMSC-loaded microbeads maintained their mechanical properties, were easily injectable through a 23G needle, and maintained their paracrine function, enhancing the proliferation and migration of scratched HUVEC. This study shows the advantage of chitosan as a scaffold material and concludes that chitosan-gelatin microbeads with celastrol-preconditioned cells form a promising off-the-shelf, cryopreservable allogenic MSC product. In vivo testing is required to confirm their potential in treating ischemic diseases or other clinical applications.

Biphasic calcium phosphate (BCP) has been used as a material to support bone grafting, repair, recovery, and regeneration over the past decades. However, the inherent weakness of BCP is its low porosity, which limits the infiltration, differentiation, and proliferation of bone cells. To address this issue, porous BCP was synthesized using polyethylene glycol (PEG) 1000 with weight ratio ranging from 20%-60% in BCP as the porogen through the powder-forming method. Analytical methods such as Fourier transform infrared spectroscopy, x-ray diffraction, scanning electron microscopy were used to demonstrate the purity, morphology and functional groups on the material surface of the obtained BCP samples. Structurally, the BCP sample with 60% PEG, named B60, possessed the highest porosity of 71% and its pore diameters ranging from 5 to 75 µm. Besides, thein vitrobiocompatibility of B60 material have been demonstrated on the L929 cell line (90% cell viability) and simulated body fluid (apatite formation after 1 d). These results suggested that B60 should be further studied as a promising artificial material for bone regenerating applications.

The voluntary recall of textured breast implants due to their association with breast implant-associated anaplastic large cell lymphoma has resulted in the loss of the primary advantage of the textured surface: positional stability. We have engineered a novel soft gel-filled smooth implant with a surface that promotes positional stability without texture, known as the positionally stable smooth implant (PSSI). Miniature anatomically shaped breast implant shells were fabricated from polydimethylsiloxane using 3D-printed molds. The implant shell design incorporates cylindrical wells 1-4 mm in diameter. Implants were filled with commercial breast implant-derived silicone gel. Smooth and textured implants were also fabricated, serving as controls. Six implants per group were implanted subcutaneously into the bilateral rat dorsum. Rotation was measured every 2 weeks for a total of 12 weeks to assess stability. Animals were sacrificed at 4 and 12 weeks, and implant-capsule units were explanted for histological and Micro-computed tomography (MicroCT) analyzes. Four weeks after implantation, PSSI conditions showed tissue ingrowth and conformation to well dimensions, as assessed by histological staining and MicroCT imaging. Twelve weeks post implantation, textured implants and PSSI conditions with larger widths, depths, and well number demonstrated statistically significant increased stability compared to smooth implants (p< 0.05). Tissue ingrowth into shell features occurred by 4 weeks and remained throughout longer time points. No significant differences were found in capsule thickness or collagen content between groups. These results suggest a promising alternative to textured surfaces for inducing implant positional stability.

The escalating threat of healthcare-associated infections highlights the urgent need for biocompatible antibacterial materials that effectively combat drug-resistant pathogens. In this study, we present a novel fabrication method for triple-helical recombinant collagen (THRC)-silver hybrid nanofibers, specifically designed for anti-methicillin-resistantstaphylococcus aureus(MRSA) applications. Utilizing a silver-mediated crosslinking strategy, we harness a low-power 38 W lamp to enable silver ions (Ag⁺) to mediate crosslinking across various proteins. Mechanistic insights reveal the pivotal role of nine amino acids in facilitating this reaction. The THRC maintains its native structure, forming well-ordered nanofibers, while other globular proteins form a distinctive network-like structure. THRC also serves as a reducing and dispersing agent, facilitating thein situsynthesis of highly dispersed silver nanoparticles (AgNPs) (∼7 nm in diameter) within the nanofibers. Systematic investigation of the reaction conditions between THRC and Ag⁺demonstrates the versatility of this novel approach for nanofiber fabrication. The incorporation of AgNPs imparts exceptional antibacterial activity to the THRC/AgNPs nanofibers, exhibiting a minimum inhibitory concentration of 19.2 mg l^-1and a minimum bactericidal concentration of 153.6 mg l^-1against MRSA. This innovative approach holds significant potential for developing antibacterial protein-based biomaterials for infection management in wound healing and other biomedical applications.

The rise of antimicrobial resistance necessitates innovative strategies to combat persistent infections. Metal-organic frameworks (MOFs) have attracted significant attention as antibiotic carriers due to their high drug loading capacity and structural adaptability. In particular, 2D MOF nanosheets are emerging as a notable alternative to their traditional 3D relatives due to their remarkable advantages in enhanced surface area, flexibility and exposed active region properties. Herein, we synthesized 2D copper 1,4-benzendicarboxylate (CuBDC) nanosheets and utilized them as a carrier and controlled release system for Doxycycline (Doxy@CuBDC), for the first time. The Doxy@CuBDC nanosheets were subsequently incorporated into Poly(lactic-co-glycolic acid) (PLGA) electrospun membranes (Doxy@CuBDC/PLGA). The resultant bioactive fibrous membranes exhibited double-barrier controlled release properties, extending the Doxy release up to ∼9 d at pH 7.4 and 5.5. Significant inhibitory effects againstStaphylococcus aureusandEscherichia coliwere observed. The morphological analyses revealed the deformed bacterial cell structures on Doxy@CuBDC/PLGA membranes that indicates potent bactericidal activity. Furthermore, cytotoxicity assays demonstrated the non-toxic nature of the fabricated membranes, underscoring their potential use for biomedical applications. Overall, the hybrid antibacterial PLGA membranes present a promising strategy for combating microbial infections while maintaining biocompatibility and offer a versatile approach for biomedical material design and surface coatings (e.g. wound dressings, implants).

Early thrombosis following coronary artery bypass grafting (CABG) surgery leads to perioperative myocardial infarction, which causes difficulties for clinicians and patients. Moreover, once perioperative myocardial infarction occurs, the mortality rate is extremely high. In recent years, microneedle (MN) drug delivery systems have become a research hotspot with broad clinical application prospects. These systems are capable of achieving sustained, safe, and painless local drug release. In cardiovascular applications, MNs maximize local anticoagulant effects, inhibit endometrial hyperplasia, and reduce systemic side effects. We speculate that a MN drug delivery system can be used to target transplanted veins to inhibit their thrombosis and reduce the incidence of perioperative myocardial infarction after CABG surgery. Therefore, this study developed a hyaluronic acid MN patch loaded with tirofiban and conducted preliminary physicochemical tests. The safety, efficacy, biocompatibility, and targeting of the MN system were evaluated usingin vitroandin vivoexperiments using a jugular vein transplantation model. The results indicate that the MN system has excellent physical properties, safety, effectiveness, biocompatibility, and strong targeting, which can effectively inhibit early local thrombus formation. In addition, the observation of early postoperative endometrial hyperplasia activation provides a foundation for future research.

Thiol-norbornene photoclick hydrogels are highly efficient in tissue engineering applications due to their fast gelation, cytocompatibility, and tunability. In this work, we utilized the advantageous features of polyethylene glycol (PEG)-thiol-ene resins to enable fabrication of complex and heterogeneous tissue scaffolds using 3D bioprinting and in-air drop encapsulation techniques. We demonstrated that photoclickable PEG-thiol-ene resins could be tuned by varying the ratio of PEG-dithiol to PEG norbornene to generate a wide range of mechanical stiffness (0.5-12 kPa) and swelling ratios. Importantly, all formulations maintained a constant, rapid gelation time (<0.5 s). We used this resin in biological projection microstereolithography (BioPµSL) to print complex structures with geometric fidelity and demonstrated biocompatibility by printing cell-laden microgrids. Moreover, the rapid gelling kinetics of this resin permitted high-throughput fabrication of tunable, cell-laden microgels in air using a biological in-air drop encapsulation apparatus (BioIDEA). We demonstrated that these microgels could support cell viability and be assembled into a gradient structure. This PEG-thiol-ene resin, along with BioPµSL and BioIDEA technology, will allow rapid fabrication of complex and heterogeneous tissues that mimic native tissues with cellular and mechanical gradients. The engineered tissue scaffolds with a controlled microscale porosity could be utilized in applications including gradient tissue engineering, biosensing, andin vitrotissue models.

Coating a titanium (Ti) implant with hydroxyapatite (HA) increases its bioactivity and biocompatibility. However, implant-related infections and biological corrosion have restricted the success of implant. To address these issues, a modified hydroxyapatite nanocomposite (HA/silica-EDTA-AgNPs nanocomposite) was proposed to take advantage of the sustained release of silver nanoparticles (AgNPs) and silicate ions through the silica-EDTA chelating network. As a result, a uniform layer of nanocomposite, compared to HA as the gold standard, was formed on Ti implants without fracture and with a high level of adhesion, using Plasma Electrolytic Oxidation (PEO). Bioactivity assessment evidenced a shift in the surface phase of the Ti implant to generation of beta-tricalcium phosphate (β-TCP), a more bioresorbable material than HA. Metabolic activity assessments using human dental pulp stem cells revealed that Ti surfaces modified by the new nanocomposite are superior to bare and HA-modified Ti surfaces for cell attachment and proliferation in vitro. In addition, it successfully inhibited bacterial growth and induced osteogenesis on the implant surface. Finally, potentiodynamic polarization behavior of Ti implants before and after coating confirmed that a thick oxide interface layer on the modified Ti surface acts as an electrical barrier and protects the substrate layer from corrosion. Therefore, the HA/silica-EDTA/Ag nanocomposite presented here, compared to HA, can better coat Ti dental implants due to its good biocompatibility and osteoinductive activity, along with improved biological stability.

This study aimed to optimize mesalamine (MES)-nanoparticles (NPs) using Box Behnken Design and investigate itsin vivoantioxidant potential in colon drug targeting. The formulation was prepared using oil/water (O/W) emulsion solvent evaporation technique for time dependent colonic delivery. The optimal formulation with the following parameters composition was selected: polymer concentration (% w/w) (A) = 0.63, surfactant concentration (% w/w) (B) = 0.71, sonication duration (min) (C) = 6. The outcomes showed that ethyl cellulose (EC) NP containing MES has particles size of 142 ± 2.8 nm, zeta potential (ZP) of -24.8 ± 2.3 mV, % EE of 87.9 ± 1.6%, and PDI of 0.226 ± 0.15. Scanning electron microscopy revealed NPs has a uniform and spherical shape. Thein-vitrorelease data disclosed that the EC NPs containing MES showed bursts release of 52% ± 1.6% in simulated stomach media within 2 h, followed by a steady release of 93% ± 2.9% in simulated intestinal fluid that lasted for 48 h. The MES release from NP best match with the Korsmeyer-Peppas model (R²= 0.962) and it followed Fickian diffusion case I release mechanism. The formulation stability over six-months at 25 °C ± 2 °C with 65% ± 5% relative humidity, and 40 °C ± 2 °C with 75% ± 5% relative humidity showed no significant changes in colour, EE, particle sizes and ZP. As perin vivoresults, MES-NP effectively increased glutathione, SOD level and reduces the LPO level as compared to other treatment groups. The findings hold promise that the developed formulation can suitably give in ulcerative colitis.

The study aimed to investigate the impact of low-intensity pulsed ultrasound (LIPUS) on human urinary-derived stem cells (hUSCs) viability within three-dimensional (3D) cell-laden gelatin methacryloyl (GelMA) scaffolds. hUSCs were integrated into GelMA bio-inks at concentrations ranging from 2.5% to 10% w/v and then bioprinted using a volumetic-based method. Subsequent exposure of these scaffolds to LIPUS under varying parameters or sham irradiation aimed at optimizing the LIPUS treatment. Assessment of hUSCs viability employed Cell Counting Kit-8 (CCK8), cell cycle analysis, and live&dead cell double staining assays. Additionally, Western blot analysis was conducted to determine protein expression levels. With 3D bio-printed cell-laden GelMA scaffolds successfully constructed, LIPUS promoted the proliferation of hUSCs. Optimal LIPUS conditions, as determined through CCK8 and live&dead cell double staining assays, was achieved at a frequency of 1.5 MHz, a spatial-average temporal-average intensity (ISATA) of 150 mW cm^-2, with an exposure duration of 10 min per session administered consecutively for two sessions. LIPUS facilitated the transition from G0/G1 phase to S and G2/M phases and enhanced the phosphorylation of ERK1/2 and PI3K-Akt. Inhibition of ERK1/2 (U0126) and PI3K (LY294002) significantly attenuated LIPUS-induced phosphorylation of ERK1/2 and PI3K-Akt respectively, both of which decreased the hUSC viability within 3D bio-printed GelMA scaffolds. Applying a LIPUS treatment at an ISATA of 150 mW cm^-2promotes the growth of hUSCs within 3D bio-printed GelMA scaffolds through modulating ERK1/2 and PI3K-Akt signaling pathways.