Biomedical materials (Bristol, England)最新文献

Polylysine-based composites have emerged as promising materials in biomedical applications due to their versatility, biocompatibility, and tunable properties. In drug delivery, polylysine-based composites furnish a novel platform for targeted and controlled release of therapeutic agents. Their high loading capacity and capability to encapsulate diverse drugs make them ideal candidates for addressing challenges such as drug stability and controlled release kinetics. Additionally, their biocompatibility ensures minimal cytotoxicity, vital for biomedical applications. They also hold substantial potential in tissue engineering by providing a scaffold with tunable mechanical characteristics and surface properties, and can support cell adhesion, proliferation, and differentiation. Furthermore, their bioactive nature facilitates cellular interactions, promoting tissue regeneration and integration. Wound healing is another area where polylysine-based composites show promise. Their antimicrobial properties help prevent infections, while their ability to foster cell migration and proliferation accelerates the wound healing procedure. Incorporation of growth factors or other bioactive molecules further enhances their therapeutic effectiveness. In biosensing applications, they serve as robust substrates for immobilizing biomolecules and sensing elements. Their high surface area-to-volume ratio and excellent biocompatibility improve sensor sensitivity and selectivity, enabling accurate detection of biomarkers or analytes in biological samples. Polylysine-based composites offer potential as contrast agents in bioimaging, aiding in diagnosis and monitoring of diseases. Overall, polylysine-based composites represent a versatile platform with diverse applications in biomedical research and clinical practice, holding great promise for addressing various healthcare challenges. .

Adipose tissue engineering (ATE) has been gaining increasing interest over the past decades, offering promise for new and innovative breast reconstructive strategies. Animal-derived gelatin-methacryloyl (Gel-MA) has already been applied in a plethora of TE strategies. However, due to clinical concerns, related to the potential occurrence of immunoglobulin E-mediated immune responses and pathogen transmission, a shift towards defined, reproducible recombinant proteins has occurred. In the present study, a recombinant protein based on human collagen type I, enriched with arginine-glycine-aspartic acid was functionalized with photo-crosslinkable methacryloyl moieties (RCPhC1-MA), processed into 3D scaffolds and compared with frequently applied Gel-MA from animal origin using an indirect printing method applying poly-lactic acid as sacrificial mould. For both materials, similar gel fractions (>65%) and biodegradation times were obtained. In addition, a significantly lower mass swelling ratio (17.6 ± 1.5 versus 24.3 ± 1.4) and mechanical strength (Young's modulus: 1.1 ± 0.2 kPa versus 1.9 ± 0.3 kPa) were observed for RCPhC1-MA compared to Gel-MA scaffolds.In vitroseeding assays showed similar cell viabilities (>80%) and a higher initial cell attachment for the RCPhC1-MA scaffolds. Moreover, the seeded adipose-derived stem cells could be differentiated into the adipogenic lineage for both Gel-MA and RCPhC1-MA scaffolds, showing a trend towards superior differentiation for the RCPhC1-MA scaffolds based on the triglyceride and Bodipy assay. RCPhC1-MA scaffolds could result in a transition towards the exploitation of non-animal-derived biomaterials for ATE, omitting any regulatory concerns related to the use of animal derived products.

Nanocarriers for drugs have been investigated for decades, yet it is still challenging to achieve sustained release from nanomaterials due to drug loading inefficiency and burst release. In this study, we developed novel functional carbon dots (CDs) and investigated the therapeutic efficacy by studying the loading efficiency and release behavior of the anticancer drug doxorubicin (DOX). CDs were successfully synthesized using a one-step pyrolysis method with varying concentrations of citric acid (CA) and thiourea (TU). Functional groups, morphology, particle size, and zeta potential of synthesized CT-CDs and DOX loaded CT-CDs were investigated by UV-visible, Fluorescence, dynamic light scattering, Zeta Potential measurements, FTIR, and transmission electron microscopy. The zeta potential data revealed DOX loading onto CT-CDs by charge difference, i.e. -24.6 ± 0.44 mV (CT-CDs) and 20.57 ± 0.55 mV (DOX-CT-CDs). DOX was loaded on CDs with a loading efficiency of 88.67 ± 0.36%.In vitrodrug release studies confirmed pH-dependent biphasic drug release, with an initial burst effect and sustained release of DOX was found to be 21.42 ± 0.28% (pH 5), 13.30 ± 0.03% (pH 7.4), and 13.95 ± 0.18% (pH 9) even after 144 h at 37 °C. The CT-CDs were non-toxic and biocompatible with L929 Fibroblasts cells. The cytotoxic effect of DOX-CT-CDs showed a concentration-dependent effect after 48 h with Glioblastoma U251 cells. Flow cytometry was used to examine the cellular uptake of CT-CDs and DOX-CT-CDs in L929 and U251 cells. It was observed that the maximum CT-CDs uptake was around 75% at the end of 24 h. This study showed that the synthesized fluorescent CT-CDs demonstrated a high drug loading capacity, pH-dependent sustained release of DOX, and high cellular uptake by mammalian cells. We believe this work provides practical and biocompatible CDs for chemotherapeutic drug delivery that can be applied to other drugs for certain therapeutic aims.

The extracellular matrix (ECM) plays a crucial role in maintaining cell morphology and facilitating intercellular signal transmission within the human body. ECM has been extensively utilized for tissue injury repair. However, the consideration of factor gradients during ECM preparation has been limited. In this study, we developed a novel approach to generate sheet-like ECM with a continuous gradient of stromal cell-derived factor-1 (SDF1α). Briefly, we constructed fibroblasts to overexpress SDF1αfused with the collagen-binding domain (CBD-SDF1α), and cultured these cells on a slanted plate to establish a gradual density cell layer at the bottom surface. Subsequently, excess parental fibroblasts were evenly distributed on the plate laid flat to fill the room between cells. Following two weeks of culture, the monolayer cells were lyophilized to form a uniform ECM sheet possessing a continuous gradient of SDF1α. This engineered ECM material demonstrated its ability to guide oriented migration of human umbilical cord mesenchymal stem cells on the ECM sheet. Our simple yet effective method holds great potential for advancing research in regenerative medicine.

Anterior uveitis is one of the most prevalent forms of ocular inflammation caused by infections, trauma, and other idiopathic conditions if not treated properly, it can cause complete blindness. Therefore, this study aimed to formulate and evaluate dexamethasone sodium phosphate (DSP) loaded polyelectrolyte complex (PEC) nanoparticles (NPs) for the treatment of anterior uveitis. DSP-loaded PEC-NPs were formed through complex coacervation by mixing low molecular weight chitosan and the anionic polymer carboxy methyl cellulose (CMC). The formulations were optimized using Box-Behnken design and evaluated the effect of independent variables: Chitosan concentration, CMC concentration, and pH of chitosan solution on the dependent variables: particle size (PS), Polydispersity Index (PDI), pH of the formulation, and % entrapment efficacy (%EE). The PS, PDI, zeta potential, and pH of the optimized formulation were found 451 ± 82.0995 nm, 0.3807 ± 0.1862, +20.33 ± 1.04 mV and 6.8367 ± 0.0737 respectively. The %EE and drug loading of formulation were 61.66 ± 4.2914% and 21.442 ± 1.814% respectively.In vitrodrug release studies of optimized formulation showed the prolonged release up to 12 h whereas, the marketed formulation showed the burst release 85.625 ± 4.3062% in 1 h and 98.1462 ± 3.0921% at 6 h, respectively. Fourier transform infrared studies suggested the effective incorporation of the drug into the PEC-NPs formulation whereas differential scanning calorimetry and x-ray diffraction studies showed the amorphized nature of the drug in the formulation. Transmission electron microscopy study showed self-assembled, nearly spherical, core-shell nanostructures. The corneal permeation study showed higher permeation of the drug from PEC-NPs compared to the marketed formulation. Hen's Eggs test-Chorioallantoic Membrane test of the optimized formulation revealed non-irritant and safe for ocular administration. Therefore, DSP-loaded PEC-NPs are an effective substitute for conventional eye drops due to their ability to increase bioavailability through longer precorneal retention duration and sustained drug release.

Polyetheretherketone (PEEK), a high-performance special engineering plastic, has gradually been used in bone substitutes due to its wear resistance, acid and alkali resistance, non-toxicity, radiolucency, and modulus close to that of human bone. However, its stable biphenyl structure determines strong biological inertness, thus artificial interventions are required to improve the biological activity of fabricated PEEK parts for better clinical applications. This study developed a novel strategy for grafting bioactive glass (BAG) onto the surface of PEEK through sulfonation reaction with concentrated sulfuric acid (H2SO4), aiming to improve the bioactivity of printed porous bone scaffolds manufactured by fused deposition modeling (FDM) to meet clinical individual needs. In vitro biological study was conducted on sulfonated polyetheretherketone-bioactive glass (SPEEK-BAG) scaffolds obtained by this strategy. The results demonstrated that the optimal modification condition was a 4-hour sulfonation reaction with 1 mol/L concentrated H2SO4 at high temperature and high pressure. The scaffold obtained under this condition showed minimal cytotoxicity, and the Ca/P molar ratio, yield compressive strength, and compressive modulus of this scaffold were 2.94 ± 0.02, 62.78 MPa, and 0.186 GPa respectively. The hydrophilicity and the biomineralization ability of PEEK modified by the proposed strategy were substantially improved. The SPEEK-BAG bone scaffolds exhibited excellent biocompatible properties, suggesting that the sulfonation reaction and BAG effectively enhanced the proliferation and differentiation of osteoblasts. The presented method provides an innovative, highly effective, and customized strategy to improve the biocompatibility and bone repair ability of printed PEEK bone scaffolds for virous biomedical applications.

Stem cell derived small extracellular vesicles (sEVs) have emerged as promising nanomaterials for the repair of bone defects. However, low retention of sEVs affects their therapeutic effects. Clinically used natural substitute inorganic bovine bone mineral (Bio-Oss) bone powder lacks high compactibility and efficient osteo-inductivity that limit its clinical application in repairing large bone defects. In this study, a poly ethylene glycol/hyaluronic acid (PEG/HA) hydrogel was used to stabilize Bio-Oss and incorporate rat bone marrow stem cell-derived sEVs (rBMSCs-sEVs) to engineer a PEG/HA-Bio-Oss (PEG/HA-Bio) composite scaffold. Encapsulation and sustained release of sEVs in hydrogel scaffold can enhance the retention of sEVs in targeted area, achieving long-lasting repair effect. Meanwhile, synergistic administration of sEVs and Bio-Oss in cranial defect can improve therapeutic effects. The PEG/HA-Bio composite scaffold showed good mechanical properties and biocompatibility, supporting the growth of rBMSCs. Furthermore, sEVs enhancedin vitrocell proliferation and osteogenic differentiation of rBMSCs. Implantation of sEVs/PEG/HA-Bio in rat cranial defect model promotedin vivobone regeneration, suggesting the great potential of sEVs/PEG/HA-Bio composite scaffold for bone repair and regeneration. Overall, this work provides a strategy of combining hydrogel composite scaffold systems and stem cell-derived sEVs for the application of tissue engineering repair.

Gene therapy often fails due to enzyme degradation and low transfection efficiency, and single gene therapy usually cannot completely kill tumor cells. Several studies have reported that tripartite motif-containing protein 37 (TRIM37) plays a significant role in promoting the occurrence and development of triple negative breast cancer (TNBC). Herein, we constructed siTRIM37 and IR780 co-loaded nanobubbles (NBs) to achieve the combination of gene therapy and sonodynamic therapy (SDT) against TNBC. On the one hand, ultrasound irradiation causes siRNA@IR780 NBs rupture to produce ultrasound targeted NB destruction effect, which promotes the entry of IR780 and siTRIM37 into cells, increasing the local concentration of IR780 and gene transfection efficiency. On the other hand, under the stimulation of ultrasound, IR780 generates reactive oxygen species to kill TNBC cells. Mechanism studies reveal that TRIM37 is an anti-apoptotic gene in TNBC, and inhibiting TRIM37 expression can induce cell death through the apoptotic pathway. And the combination of siTRIM37 and SDT can aggravate the degree of apoptosis to increase cell death. Therefore, siRNA@IR780 NBs-mediated combination therapy may provide a new treatment approach for TNBC in the future.

Adequate simulation mimicking a tissue's native environment is one of the elemental premises in tissue engineering. Although various attempts have been made to induce human mesenchymal stem cells (hMSC) into an osteogenic pathway, they are still far from widespread clinical application. Most strategies focus primarily on providing a specific type of cue, inadequately replicating the complexity of the bone microenvironment. An alternative multifunctional platform for hMSC osteogenic differentiation has been produced. It is based on poly(vinylidene fluoride) (PVDF) and cobalt ferrites magnetoelectric microspheres, functionalized with collagen and gelatin, and packed in a 3D arrangement. This platform is capable of performing mechanical stimulation of piezoelectric PVDF, mimicking the bones electromechanical biophysical cues. Surface functionalization with extracellular matrix biomolecules and osteogenic medium complete this all-round approach. hMSC were cultured in osteogenic inducing conditions and tested for proliferation, surface biomarkers, and gene expression to evaluate their osteogenic commitment.

Objective: This study investigates the efficacy of the combination of extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) and vacuum sealing drainage (VSD) on chronic wounds.

Methods: From February 2021 to February 2022, 20 patients with chronic wounds were recruited and were divided into experimental and control groups, with 10 patients in each group. Following debridement, we applied various treatments to all cases for 2 weeks. Subsequently, we observed the changes in the wound area and calculated the rate of wound healing. Simultaneously, the wound margin tissues were collected for histological analysis, and the inflammatory cell infiltration within the wound was assessed using HE staining. Masson staining was used to observe the collagen deposition on the wound surface, and CD31 immunohistochemistry was used to count the number of microvessels to evaluate the angiogenesis (Clinical trial registration number: ChiCTR-INR-17013540).

Results: The therapeutic outcomes for all cases included in this study were favorable after a 2-week treatment period, and the wound area was smaller than before. The experimental group exhibited a significantly higher rate of wound healing compared to the control group. In the experimental group as revealed by HE staining, there was a marked reduction in the infiltration of inflammatory cells in the dermis. Masson staining demonstrated that the deposition of collagen fibers in the experimental group was more than the control group. CD31 immunohistochemistry showed an increased number of new blood vessels in the experimental group compared to the control group. Additionally, ECM/SVF-gel extract significantly enhanced the fibroblast proliferation and migration in vitro.

Conclusion: The application of ECM/SVF gel combined with VSD in chronic wounds can accelerate wound healing by reducing inflammatory reaction, increasing collagen fiber deposition, and promoting angiogenesis. Therefore, the combination of ECM/SVF gel and VSD can be used as a simple, safe, and effective therapeutic method for chronic wounds.