Biomedical materials (Bristol, England)最新文献

Additive manufacturing (AM) has rapidly evolved over recent years, offering a multitude of possibilities for the development of highly realistic medical equipment and devices. Each generation of AM technology introduces new features, enhancing its application in the medical field. Three-dimensional (3D) printing, the foundational technology, offers a cost-effective, rapid, and personalized approach for fabricating medical devices. However, its limited ability to produce highly complex geometries restricts its use in certain advanced applications. To overcome these limitations, 4D printing technology has emerged, enabling the production of dynamic structures that can respond to environmental stimuli. This makes it ideal for fabricating scaffolds and implants that closely mimic the behavior of natural tissues, offering significant potential in regenerative medicine. Additionally, 5D printing surpasses traditional 3D printing by employing five axes in the manufacturing process, enabling the production of complex, robust structures with enhanced mechanical strength. The latest innovation, 6D printing, integrates the dynamic capabilities of 4D printing with the multi-axis precision of 5D printing, further enhancing the complexity and functionality of fabricated medical devices. This review explores recent advancements in AM technologies, including 3D, 4D, 5D, and 6D printing. It discusses their transformative potential in medical applications, from tissue engineering to the production of customized implants and prosthetics.

Magnetic fluid hyperthermia (MFH) is emerging as a promising cancer therapeutic modality due to its minimal side effects and targeted approach. This study presents the synthesis and characterization of temperature-sensitive biocompatible MF containing citric acid-coated Mn_0.9Zn_0.1Fe₂O₄nanoparticles, along within vitroinvestigations on the prostate cancer cells LNCaP, to demonstrate the potential of these nanoparticles as a hyperthermic agent for MFH. The biocompatibility of MF was assessed using the MTT assay, which demonstrated no cytotoxic effects at concentrations up to 3 mg ml^-1. Furthermore, rapid internalization of nanoparticles into LNCaP prostate cancer cells was observed within 10 min, as determined by a Prussian blue assay and quantified by inductively coupled plasma mass spectrometry. Upon exposure to an alternating magnetic field of 10 kA m^-1and 332 kHz frequency, the nanoparticles achieved the therapeutic temperature of 42 °C within 27 min, while sustaining a hyperthermic range of 42 °C-45 °C for one hour. Notably, three MFH treatment sessions were identified as requisite for the elimination of LNCaP cells. Apoptosis was detected using Hoechst-Propidium iodide (PI) staining and further quantified by Annexin-V/PI flow cytometry. These findings underscore the potential of citric acid-coated Mn-Zn ferrite nanoparticles as effective biocompatible agents for MFH-based cancer therapy, warranting further detailed investigations to elucidate their therapeutic efficacy.

The rise in wound infections underscores the need for chitosan-based biomaterials, which, when loaded with bioactive agents, provide antibacterial, wound-healing, and effective long-term drug delivery capabilities. In this study, a chitosan-based dressing loaded withα-mangostin was successfully fabricated in the form of an aerogel. The new aerogel, incorporatingα-mangostin prepared as nanoparticles (nanomangostin), exhibited multifunctional activities including wound healing, hemostasis, and antibacterial effects. A crosslinked network structure was created using glutaraldehyde (GA) at a concentration of 14 g g^-1, resulting in a highly hydrophilic matrix that modulates the water absorption capacity of the chitosan aerogel-an essential characteristic for both hemostatic function and wound healing. The cytotoxicity of the aerogel was evaluated on HaCaT cells using the MTT assay. Results showed that aerogel concentrations ranging from 5 to 80 µg ml^-1were non-toxic to HaCaT cells across all 12, 24, and 48 h treatment groups. Interestingly, the aerogel stimulated HaCaT cell migration in a dose- and time-dependent manner. Treatments at 20, 40 and 80 µg ml^-1significantly enhanced HaCaT cell migration at all groups. Notably, the 40 and 80 µg ml^-1group at 48 h displayed the highest migration rate (up to 95.98%) compared to the untreated control (71.43%,p< 0.05). Moreover, the nanomangostin-loaded chitosan aerogel demonstrated clear antibacterial activity. A stronger inhibitory effect was observed againstStaphylococcus aureusATCC 25 923 compared toEscherichia coliATCC 25 922. These findings highlight the potential of nanomangostin-loaded chitosan aerogels for biomedical applications, particularly in wound healing and antimicrobial coatings.

Interface tissues, such as the enthesis connecting ligaments to bone, present multiphasic architectures with continuous gradients in structure, composition, and mechanics. Engineering such complex transitions remains a major challenge in biofabrication. This study aims to develop a hybrid manufacturing and machine learning (ML)-guided design strategy to create functionally graded scaffolds for anterior cruciate ligament (ACL) reconstruction. A hybrid biofabrication platform was used to integrate extrusion-based three-dimensional printing and electrospinning within a single workflow. Polycaprolactone was used as the common biomaterial for both modalities. Four scaffold designs, varying in electrospun midsection length, slit patterning, and core geometry, were fabricated to replicate the native ACL's zonal architecture. Scaffolds were characterized through scanning electron microscopy (SEM) and uniaxial tensile testing. Resulting data were used to train a ML model to predict mechanical performance from geometric features. The model was then used to generate a fifth scaffold design optimized for enhanced performance. The hybrid process successfully fabricated multiscale scaffolds with integrated bone-like, enthesis-like, and ligament-like regions. SEM confirmed morphological integration between printed and electrospun structures. Mechanical testing revealed design-dependent variations in strength and stiffness. The ML model identified slit number and outer diameter as key predictors and guided the design of an optimized scaffold that combined the compliance of slitted geometries with enhanced mechanical strength. The ML-optimized scaffold achieved the highest tensile force among the slitted designs and improved stiffness compared to the other slitted configurations this study demonstrates a predictive and performance-driven biofabrication strategy that integrates hybrid additive manufacturing and ML. The approach enables rational scaffold optimization, reduces empirical iterations, and supports the development of biomimetic constructs for soft-to-hard tissue engineering. While focused on ACL reconstruction, the workflow is adaptable to a wide range of tissue interfaces.

Cancer remains a global health challenge, with conventional treatments limited by toxicity and drug resistance. Propolis, a natural resin with promising anticancer properties but restricted in clinical applications due to low bioavailability and poor solubility. Nanotechnology, offers a potential approach to enhance propolis' therapeutic efficacy through more efficient delivery and improved pharmacokinetics. Propolis-loaded niosomes (PLNs) were prepared using the ethanol injection method, optimized using response surface methodology (RSM) for surfactant type (Tween 80), cholesterol-to-surfactant ratio, and propolis content. Physicochemical properties, including particle size, polydispersity index (PDI), and zeta potential were characterized. Stability was assessed under various storage conditions, and total polyphenol content (TPC) and entrapment efficiency (EE%) were determined. Anticancer activity wasin vitroassessed against MCF7 breast cancer and L929 fibroblast cell lines. The optimized PLN formulation (at a mass ratio 4:1:8 of propolis: cholesterol: Tween 80, respectively) achieved a particle size of 193.5 nm, PDI of 0.123, and zeta potential of -19.6 mV, with a TPC of 21.83 mg GAE g^-1and EE% of 57.82%. Stability studies confirmed optimized formulation's robustness at 4 °C, with minimal changes over 42 d, though higher temperatures induced aggregation. PLNs exhibited superior cytotoxicity against MCF7 cells inhibitory concentration (IC₅₀equivalent to 106.85 µg ml^-1) compared to L929 cells (IC₅₀equivalent to 127.14 µg ml^-1). The formulation's uniformity and moderate stability support its potential for targeted drug delivery. PLNs effectively enhance propolis' anticancer efficacy and bioavailability, offering a promising delivery system for cancer therapy. Future studies should focus on improving zeta potential,in vivovalidation, and encapsulation efficiency to advance clinical translation.

The production of artificial bone constructs using human mesenchymal stem cells (hMSCs) is a promising approach for tissue engineering and regenerative medicine. However, the development of a suitable 3D bioreactor system that can mimic thein vivoenvironment and promote osteogenic differentiation of hMSCs remains a significant challenge. The 3D cell culture system established in this study consists of a bioreactor with an included vascular-mimetic perfusion system for hydrogel cultures and enables to study the effect of different hydrogels and the addition of cell matrix components (in this study Collagen type 1) or the 3D environment itself on the osteogenesis process. Our results show that the 3D bioreactor system can promote osteogenic differentiation of hMSCs, as evidenced by increased expression of osteogenic markers and mineralization of the hydrogel matrix. We also observed a positive effect of collagen type I on cell morphology. The results of this study demonstrate the potential of the 3D bioreactor system for the production of artificial bone constructs using hMSCs and provide a basis for further optimization and scaling up of the system. Our reactor system is an easy and reproducible system that can be used conventionally in laboratories to form or assemble histocompatible tissue substitutes to research artificial bone constructs and could reduce animal experiments in the near future.

Development of biomimetic scaffolds that mimic the complex structures and compositions of extracellular matrices is a promising approach in tissue engineering. This comprehensive review delves into the evolving and advancing field of gradient and hierarchical scaffolds in tissue engineering, with a particular emphasis on electrospinning-based and extrusion-based fabrication techniques, as well as their hybrid methodologies. We first introduce the fundamental concepts of biomimetic scaffold design in tissue engineering. Subsequently, we provide an overview of the design principles, mechanical considerations, and fabrication methods for creating gradient and hierarchical scaffolds that closely mimic the complex structures found in natural tissues. The applications of gradient and hierarchical scaffolds in various areas of tissue engineering, such as bone, cartilage, tendon, ligament, and vascular tissues, are also highlighted. Furthermore, the paper addresses current challenges in the field, including limitations in fabrication techniques, scalability issues, and the integration of smart and stimuli-responsive materials. It concludes by discussing emerging trends and future research directions, emphasizing the potential of these advanced scaffolds to revolutionize tissue engineering and regenerative medicine. This review aims to provide researchers and practitioners with clear insights into recent advancements, current challenges, and prospective directions in gradient and hierarchical scaffold design and fabrication.

The global health crisis posed by antimicrobial resistance and biofilm-protected infections demands urgent development of biocompatible antibacterial materials. The traditional antimicrobial substances are challenged by their higher cytotoxicity, poorer biofilm penetration, or resistance induction. This review highlights the transformative potential of highly biocompatible and antibacterial polymers, which achieve broad-spectrum efficacy while minimizing toxicity. The parameter of selectivity index (SI) is emphasized in assessing the balance between antimicrobial efficacy and biocompatibility of antimicrobial materials. A higher SI value indicates that the material retains potent antimicrobial activity while exhibiting superior biocompatibility. Representative examples of antimicrobial materials with high SI values are also summarized. The polymeric quaternary ammonium salts, chitosan derivatives, polyamino acids such as hyperbranched polylysine, and N-halamine polymers demonstrate synergistic antibacterial actions through membrane destabilization, oxidative stress induction, and biofilm suppression, exhibiting tunable degradation, immune tolerance, and selective targeting, enabling applications in medical devices and tissue materials, encompassing both fundamental research and commercial applications in biomedicine, to serve as a comprehensive reference for relevant researchers. Challenges in scalable manufacturing, regulatory classification, and long-term biosafety assessment, and future perspectives on multifunctional polymer design and smart responsive systems are finally discussed.

Postoperative infection and insufficient osseointegration of orthopedic implants are core challenges leading to surgical failure, and endowing implants with drug storage and release functions has become a key innovative direction to break through this bottleneck. As the core carrier of the drug storage and release system, the size, morphology, and porosity of micro/nano topological structures directly determine the drug-loading efficiency and release kinetics. With its unique advantages of precise controllability and the ability to achieve multi-level topological structure integration in a single step, laser processing technology has received much attention in the integrated application of multifunctional design and drug storage/release for orthopedic implants. This review systematically summarizes the research progress of laser technology in constructing drug storage and release microstructures on the surface of orthopedic implants: first, it introduces the development history of implant surface microstructure design and mainstream preparation methods; then it focuses on the use of ultrafast lasers to construct surface micro/nano topological structures to achieve antibacterial and sustained drug release; it emphasizes the discussion on the preparation of implant scaffolds with complex microstructures and graded porosity by laser additive manufacturing technology, and their application in improving drug-loading capacity and achieving on-demand drug release; finally, it analyzes the existing challenges in this field and looks forward to future development trends and research directions.

The clinical application of injectable hydrogels as drug delivery vehicles is limited by persistent pain and discomfort at the injection site, which are critical issues that affect long-term patient compliance. This pain primarily originates from thein situswelling of the hydrogel within the tissue post-injection. However, the complex biomechanical mechanisms underlying this process remain uncertain. This study utilized the COMSOL Multiphysics platform to construct a multiphysics model that couples the large-deformation swelling of the hydrogel with the poro-viscoelastic interactions of subcutaneous tissue, aiming to investigate the evolution of tissue stress during the quasi-static phase post-injection. The simulation results reproduce the characteristic rise-and-fall dynamics of tissue stress. The stress peaks at approximately 60-100 min post-injection, driven by hydrogel swelling, reaching a peak stress of approximately 10.8 kPa, a level clearly exceeding the reported ∼6-9 kPa threshold for activating nociceptors. Subsequently, it gradually decreased owing to the poro-viscoelastic relaxation effects of the tissue, reaching a stress equilibrium phase after approximately 400 min. Parametric studies further reveal two key design principles for low-pain formulations: (1) An optimal injection depth window exists (6-12 mm in this model) that effectively disperses stress and facilitates the formation of a morphologically regular drug depot, whereas injections that are too shallow or too deep lead to stress concentration due to boundary constraints; (2) A smaller hydrogel radius (volume) can trigger higher local peak stress due to a point-like pressure source effect. This study provided a theoretical foundation for the design of low-pain injectable formulations. By synergistically optimizing parameters such as injection depth and volume, the poromechanical microenvironment induced by hydrogel swelling can be actively managed, thereby enhancing patient comfort and compliance while ensuring therapeutic efficacy.