Biomedical materials (Bristol, England)最新文献

Utilization of cell derived decellularized extracellular matrices (dECM) is a highly versatile way to introduce complex cell specific native-like microenvironment in vitro. While dECMs have been used in various applications, surface functionalization of biomaterials with cell-derived dECMs that maintain their structural integrity for investigating cell behavior is rarely reported. In this study, we developed and characterized a platform combining native bone surface topography mimicked polydimethylsiloxane (BSM PDMS) surfaces with pre-osteoblast derived dECM to mimic both physical and biochemical cues of the bone microenvironment. Decellularized ECM on PDMS and BSM PDMS surfaces preserved their structure and specific matrix components, in addition to having a significant influence on microscale surface topography. Recellularization of BSM PDMS + dECM surfaces supported cell attachment and proliferation of both pre-osteoblasts and adipose derived mesenchymal stem cells (hADMSC). BSM PDMS + dECM surfaces showed significantly elevated glycosaminoglycan (GAG) content, as well as, resulted in induction and topography dependent calcification of hADMSCs. Osteogenic induction and dECM presence on BSM PDMS synergistically increased RUNX2 expression of hADMSCs while keeping YAP expression relatively unaltered. This work provides insights for designing biomimetic platforms integrating biochemical and biophysical cues for advanced bone tissue engineering.

The development of injectable and printable conductive hydrogels is of great importance for tissue engineering, particularly for supporting the regeneration of electrically active or excitable tissues. In this study, a nanocomposite hydrogel was formulated by incorporating reduced graphene oxide (rGO) into a self-healing andin situ-gelling aldehyde-functionalized xanthan gum (AXG) and gelatin (Gel) matrix. The AXG-Gel hydrogels incorporated by 0, 0.5, 1, and 2% w/v rGO were synthesized using Schiff-base chemistry and evaluated for its physicochemical, mechanical, rheological, electrical, and biological properties. The 1% rGO formulation exhibited the highest mechanical modulus (0.315 ± 0.0135 MPa) and self-healing yield (93.18 ± 1.56%), compared to 0.2157 ± 0.0145 MPa and 77.16 ± 5.98% in the 2% rGO formulation. By an increase in rGO content, an increase in porosity was observed, holding values from 90.43% in rGO-free scaffolds to 97.70% in the 2% rGO group. All samples maintained high swelling capacities (>800%), with AXG-Gel-0.5rGO showing the highest (∼940%) and AXG-Gel-2rGO the lowest (∼830%). Conductivity improved significantly in the 1% rGO hydrogel, achieving 4.16 × 10²S/m which was 24% higher than the rGO-free scaffold (3.33 × 10²S m^-1). Impedance spectroscopy showed reduced resistance and higher charge transfer efficiency in rGO-loaded scaffolds. The AXG-Gel-1rGO also exhibited favourable rheological behavior, with a storage modulus of 1.7 kPa at 1 Hz and pronounced shear-thinning. The injectability and printability were confirmed by syringe injection assay and extrusion-based 3D printing of circular structure. MTT and SEM-based cytocompatibility assays confirmed an excellent viability and cell adhesion for AXG-Gel-1rGO scaffolds after 3 d. Overall, the 1% rGO scaffold achieved a balanced combination of conductivity, printability, injectability, porosity, mechanical strength, and cytocompatibility, indicating its potential as a promising candidate for future electrically active tissue engineering applications.

Chemotherapy is an anti-cancer treatment that uses chemical drugs to suppress rapidly growing cancer cells. Nevertheless, low water solubility and poor pharmacokinetics of chemotherapeutic drugs can reduce therapeutic efficacy and limit the duration of drug action due to rapid clearance from the body. Furthermore, systemic chemotherapy can attack not only cancer cells but also normal cells, inducing severe side effects. In this study, Tri-GalNAc-decorated RNA nanoparticles (RNAPs) loaded with doxorubicin (Dox-TG-RNAP) were developed to treat hepatocellular carcinoma (HCC). The surface of RNAP was decorated with avidin and biotin-Tri-GalNAc sequentially using electrostatic and non-covalent interactions. Dox-TG-RNAP had a high loading capacity of Dox and delivered Dox to HCC cells specifically through asialoglycoprotein receptor (ASGPR)-mediated endocytosis. Consequently, Dox-TG-RNAP induced apoptosis selectively in HCC cells expressing ASGPR, while minimizing cytotoxicity in non-ASGPR-expressing cells such as HDF cells. Such ligand-modified RNAPs facilitated targeted drug delivery effectively to a range of tissues through surface functionalization with diverse ligands, thereby mitigating off-target effects.

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.