Biomedical materials (Bristol, England)最新文献

Antibiotic-loaded PMMA (polymethylmethacrylate) bone cement (ALBC) is widely used to prevent and treat periprosthetic joint infections (PJIs), yet its clinical efficacy is limited by issues like burst release and short release duration. To address these challenges, this study developed a composite bone cement (HV-PMMA) loaded with vancomycin-functionalized halloysite nanotubes (HNTs-Van). The results showed that HV-PMMA optimized antibiotic elution: it avoided initial burst release, and the drug elution amount of HV-PMMA was superior to that of traditional ALBC with vancomycin formulation. The addition of HNTs-Van slightly reduces the compressive strength of the bone cement. Importantly, HV-PMMA maintained good biocompatibility, with a hemolysis rate below 5% and no acute systemic toxicity. This nano-scale physical drug-loading strategy effectively solves the limitations of traditional ALBC, providing an efficient and safe approach for designing antibacterial bone cements to prevent and treat PJIs.

Mechanotransduction refers to the cellular mechanism by which mechanical cues from the extracellular matrix (ECM) are sensed and transduced into biochemical signals, playing a critical role in regulating stem cell differentiation. In degenerative intervertebral disc (IVD) disease, the mechanical microenvironment undergoes pathological alterations, most notably a marked increase in ECM stiffness. This aberrant mechanical milieu disrupts cellular fate decisions and poses a critical barrier to successful endogenous regeneration. To address this limitation, poly(acrylamide-co-acrylic acid) (P(AAm-co-AA)) microgels with tunable elastic moduli were synthesized via inverse emulsion polymerization. These microgels were subsequently functionalized with polydopamine (PDA) to enhance cellular adhesion, thereby facilitating cytoskeletal remodeling and activation of mechanotransductive signaling pathways. Notably, a compliant matrix with an elastic modulus of approximately 2 kPa was found to enhance nucleus pulposus (NP)-like differentiation of adipose-derived mesenchymal stem cells in differentiation-inducing medium, as evidenced by significantly upregulated expression of NP marker genes (COL2, ACAN, SOX9). This effect was correlated with the translocation of yes-associated protein 1 (YAP).In vivostudies demonstrated that implantation of these microgels into degenerated discs led to restoration of disc height and increased ECM deposition within the NP region, as demonstrated by imaging and immunohistochemical results. Collectively, this work highlights the potential of microgel-based delivery platforms with tunable mechanical properties as a promising strategy to facilitate stem cell differentiation and promote IVD regeneration.

Three-dimensional (3D)-printed breast scaffolds have attracted increased attention for soft tissue reconstruction. However, the polymeric porous scaffolds commonly cause fibrous tissue ingrowth due to their limited immunomodulatory capabilities. In this study, we integrated polycaprolactone (PCL) scaffolds with adipose-derived mesenchymal stem cell (ADSC) exosome-laden Gelatin Methacrylate (GelMA) hydrogels (Exos@GelMA+PCL) to promote macrophage M2 polarization and adipose regeneration. The biohybrid scaffolds exhibited sustained Exo release, with a cumulative release of >80% by day 14. Internalized Exos enhanced RAW264.7 macrophage M2 polarizationin vitro, as confirmed by immunofluorescence and real-time quantitative PCR. Conditioned medium from scaffold-macrophage cocultures enhanced the proliferation, migration, and adipogenic differentiation of ADSCs.In vivo, Exos@GelMA+PCL biohybrid scaffolds significantly increased the proportion of M2 macrophages compared to controls (GelMA+PCL and PCL scaffolds). At 12 weeks, the biohybrid scaffolds achieved markedly higher adipose tissue area percentages (46.26 ± 4.55%) compared to GelMA+PCL scaffolds (23.76 ± 1.90%) and PCL scaffolds (26.14 ± 2.55%). This strategy offers an innovative immunomodulatory approach to enhance soft tissue regeneration in breast reconstruction by regulating the microenvironment.

In this study, we prepared a series of chitosan/gelatin (CS/GEL) cryogels containingVerbascum thapsus(V. thapsus) leaf extract and identified a lead formulation for noncompressible hemorrhage (NCH). Cryogels with average pore diameters ranging from 225 to 478 µm were fabricated through cryogelation at various CS/GEL ratios. C15 was chosen as the base scaffold due to its homogeneous pore distribution, with a pore size coefficient of variation (CV) of approximately 0.22. Extract loading was 1%, 5%, 10%, and 20% w/v. Functional porosity was reported by the relative accessible void index (RAVI). In PBS, the values relative to neat C15 were 1.00, 0.27, 0.20, 0.13, and 0.09 for concentrations of 0%, 1%, 5%, 10%, and 20% w/v, respectively. In citrated blood, the series was 1.00, 0.29, 0.12, 0.14, and 0.09. After loading, equilibrium swelling decreased and the compressive modulus increased, consistent with partial pore filling in a fixed network. The cryogels maintained an interconnected macroporous network and showed swelling from 300% to 3600% in blood and PBS. Antibacterial activity reached 89% inhibition, and cell viability remained above 80%. Hemolysis was low and within acceptance limits. Clotting improved in whole blood as the blood clotting index decreased from 11.9 to 6.5, and the clotting time was approximately 6 min. The 5% w/v group provided the optimal balance of clotting, antibacterial effects, and biocompatibility. This study presents a novel hemostatic CS/GEL cryogel containingV. thapsusleaf extract that holds strong potential for future applications in NCH management.

Mechanobiology drives many important cell biological behaviors such as stem cell differentiation, cancer drug resistance and cell migration up stiffness gradients, a process called durotaxis. The development of 3D hydrogel systems with tunable 2D mechanical gradient patterns affords the ability to study these mechanosensitive cell behaviors to understand cancer invasion or enhance wound healing through directed migration. In this paper, we developed an approach to spatially imprint within alginate hydrogels, gradients in mechanical properties that can be used to probe mechanobiology. Stencils were easily designed and fabricated using a common craft cutter to control the presentation of a calcium crosslinking solution to alginate gels. Different stencil shapes result in different gradients in opacity that can be imprinted into both thick and thin alginate gels of arbitrary 2D shape. The steepness of the opacity gradient as well as the maximum opacity can be controlled based on reproducible crosslinking kinetics regulated through calcium concentration and gradient developing time. Calcium crosslinking results in both opacity changes as well as increases in elastic modulus in the bulk hydrogel. Opacity correlates with elastic modulus over a range of elastic moduli, allowing it to be used as a proxy for local elastic modulus. Functionalized alginate gels with collagen and imprinted stiffness gradients within them resulted in cell invasion that was spatially dependent, where stiffer regions facilitated deeper invasion of breast cancer cells. Consequently, this stenciling approach represents a facile way to control stiffness gradients in alginate gels in order to study mechanosensitive cellular behavior.

Cancer is among the major causes of mortality, responsible for approximately 15% of all deaths worldwide. Despite remarkable progress in modern medicine, it remains a significant global health challenge. Nevertheless, conventional therapies such as chemotherapy and radiotherapy target healthy and malignant tissues, leading to adverse side effects, including hair loss, fatigue, and nausea, which significantly reduce patients' quality of life. Even more critically, the therapeutic response varies from patient to patient, which reduces the effectiveness of treatment. Therefore, cancer tissue engineering has evolved as a novel interdisciplinary field, aiming to develop structures that mimic the tumor microenvironment to elucidate cancer development mechanisms and devise effective treatment methods. However, producing a fully synthetic biosimilar matrix by assembling all individual ECM components remains unfeasible due to the heterogeneity and complex structure of tumor tissues, as well as the necessity of highly advanced micro- and nanoengineering techniques. Consequently, decellularization techniques have recently been applied to cancer tissues to produce biomimetic tumor models. In this review, we provided a comprehensive overview of the extracellular matrix (ECM) architecture and its role in tumor progression. We also discussed the structural differences between normal and malignant tissues. We briefly reviewed decellularization techniques and analytical approaches for ECM characterization. Emphasizing the cutting-edge research, we categorized developments into three groups: decellularized tumor-derived ECM (dT-ECM), hydrogels, and bioinks. Subsequently, we critically assessed the benefits, limitations, and potential future developments of dT-ECM-based strategies. Finally, we envision that tumor tissue engineering will provide preventive treatment approaches by developing patient-specific predictive and personalized cancer models through integrating advanced biomaterials with artificial intelligence and machine learning.

The inert surface of titanium (Ti) leads to inadequate osseointegration and bacterial infection, which are critical factors contributing to the failure of Ti implants. Micro-arc oxidation (MAO) technology enables the formation of a biocompatible porous TiO₂coating on Ti surfaces, offering advantages such as a simple fabrication process, strong adhesion to the substrate, and the ability to incorporate functional ions (e.g. Ag⁺, Cu²⁺, Sr²⁺). This modification significantly enhances cellular adhesion and osteogenic activity. However, the TiO₂produced via MAO exhibits a wide bandgap (3.2 eV), responding primarily to ultraviolet light, which results in low photothermal conversion efficiency in the near-infrared (NIR) region with greater tissue penetration, thereby limiting its application in photothermal therapy (PTT). This study was based on Sr²⁺-doped TiO₂coating, and its NIR photothermal efficiency was improved through surface modification with a metal-polyphenol network (MPN). Additionally,ϵ-poly-L-lysine (EPL) antimicrobial peptides were grafted onto the surface to establish a synergistic photothermal-chemical antibacterial system. Experimental results demonstrated that the TiO₂-MPN-EPL composite coating exhibited high-efficiency photothermal conversion under 808 nm laser irradiation, with the synergistic action of EPL providing targeted membrane disruption of bacteria. This system achieved a high bactericidal rate againstStaphylococcus aureusandEscherichia coliwhile mitigating the thermal damage risks associated with standalone PTT. Furthermore, it promoted the proliferation of MC3T3-E1 osteoblasts.

Hydrogels, as three-dimensional (3D) hydrophilic polymer networks, have gained widespread attention in tissue engineering (TE) due to their high-water content, porosity, biocompatibility, and structural similarity to the native extracellular matrix. Injectable andin situforming hydrogels offer additional advantages by enabling minimally invasive delivery directly to injury sites, reducing patient discomfort, and improving clinical accessibility. Among these, tyramine (Tyr)-modified hydrogels have emerged as a promising class of biomaterials, combining enhanced biocompatibility, bioactivity, and mechanical properties through the incorporation of phenolic groups. This functionalization enables enzymatic and light-mediated cross-linking under mild physiological conditions, providing precise control over hydrogel stiffness, degradation, and cell-interacting properties. This review comprehensively covers recent advances in the synthesis, modification, and cross-linking strategies of Tyr-conjugated polymers, particularly enzymatic methods mediated by horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂), as well as light-mediated methods, and their impact on the properties of hydrogels. It also further explores the broad applications of Tyr-modified hydrogels in TE, including bone and cartilage regeneration, wound healing, vascular and cardiac repair, and 3D bioprinting. Finally, it discusses current challenges and future perspectives for Tyr-modified hydrogels in regenerative medicine.

The employment of metal nanoparticles for biomedical applications is gaining visibility as a result of their excellent properties. Niobium oxide (Nb₂O₅) possesses interesting physicochemical properties that can be modified for its use in prosthetic coatings. However, there are only a limited number of studies in the literature concerning its characterization as a pure powder, its surface modification and their cytotoxicity. Therefore, the purpose of this study was to evaluate nine different Nb₂O₅samples synthesized using the microwave technique, each with a different surfactant. x-ray diffraction results indicated that all samples were amorphous, and the addition of surfactants did not seem to cause any alterations, as indicated by Raman and FTIR. Scanning electron microscopy (SEM) images revealed that the particles tended to form aggregates; modification of parameters such as surface area and acid sites was also observed, with pure Nb₂O₅having the highest area (230.4 m²g^-1) and NbSDS5 having the highest total acidity (3141 µmol g^-1). We assessed the cytotoxicity in sheep's erythrocytes and the Zebrafish Liver (ZF-L) cell line. Pure Nb₂O₅exhibited high cytotoxicity at 10 mg ml^-1in red blood cells with an erythrocyte survival rate of 15%. The MTT assay that revealed that NbCA1 showed only 27.1% cell viability, while NbSDS1 was able to increase cell proliferation (101.1%) even at a lower pH. Compounds were also able to interfere with the intrinsic coagulation pathway, with several samples exceeding the clotting time (>120 s). Nb ions leaching to the medium does not seem to directly affect cytotoxicity. Pearson's correlation does not indicate a direct relationship between surface area, acid sites, and cytotoxicity assays.

Vascular tissue engineering endeavors to design, fabricate, and validate biodegradable and bioabsorbable small-diameter vascular scaffolds engineered with bioactive molecules, capable of meeting the challenges posed by commercial vascular prostheses. A comprehensive investigation of these engineered scaffolds in a bioreactor (BR) is deemed essential as a prerequisite before anyin vivoexperimentation in order to gather information regarding their behavior under physiological conditions and predict the biological activities they may exhibit. This study focuses on an innovative electrospun scaffold made of poly(caprolactone) and poly(glycerol sebacate), integrating quercetin (Q), which is able to modulate inflammation, and gelatin (G), which is necessary to reduce permeability. A custom-made BR was used to assess the performance of the scaffolds maintained under different pressure regimes, covering the human physiological pressure range. As a result, the 3D microfibrous architecture of the scaffolds was notably influenced by the release of bioactive molecules, while retaining the properties required forin vivoregeneration. Furthermore, the scaffolds exhibited mechanical properties comparable to those of native human arteries. The release of Q was effective in counteracting post-surgical inflammation, whereas the amount of released G was adequate to avoid blood leakage and useful to make the material porous during the testing period. This study showcases the successful validation of an engineered scaffold in a BR, supporting its potential as a promising candidate for vascular substitutes inin vivoapplications. Our approach represents a significant leap forward in the field of vascular tissue engineering, offering a multifaceted solution to the complex challenges associated with small-diameter vascular prostheses.