Biomedical materials (Bristol, England)最新文献

Degenerative disc disease is a leading cause of chronic back pain, and current surgical treatments such as fusion and disc arthroplasty remain limited by implant wear, stress shielding, and mechanical mismatch with the native intervertebral disc (IVD). This study investigates three-dimensional (3D) printed thermoplastic polyurethane (TPU) Gyroid structures as biomimetic disc replacements. Using filaments of varying stiffness, 3D-printed constructs demonstrated high geometric fidelity and mechanical performance within physiological load and deformation ranges. Dynamic compression testing revealed damping coefficients of approximately 16%, closely matching native IVD behavior. Stiffness scaled predictably with structural density, allowing mechanical tuning toward physiological properties. These findings highlight the potential of Gyroid-structured TPU implants to replicate the natural damping and load distribution of human discs, offering a pathway toward customizable, patient-specific disc replacements. Future work will focus on medically approved TPU, biological responses, and multiaxial loading.

Myelination is a critical biological process in which Schwann cells form myelin sheaths around axons to support signal transmission and nerve regeneration. Artificial axon models can provide a useful tool for studying the process of myelination. Here, we present a high-throughput microdevice featuring ordered, suspended polydimethylsiloxane microfibers generated through mechanical stretching of micropillars. The device provides a biocompatible and optically transparent platform that facilitates cell culture, live imaging, and quantification of myelin formation. S42 Schwann cells cultured on the microfibers formed myelin sheaths that were visualized using fluorescence microscopy. Moreover, increased myelination induced by progesterone and IL-12 p80 was observed, demonstrating the potential of the device for drug screening. This three-dimensional myelination culture chip provides a robust and accessible tool for studying peripheral nerve repair and therapeutic development.

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.