Biomedical materials (Bristol, England)最新文献

Naringenin (NGN) is a plant-derived flavonoid that has attracted significant interest due to its antioxidant and anticancer characteristics. However, its therapeutic applications are limited because of its low solubility in water, instability, and bioavailability at the target site. Therefore, the present study aimed to formulate NGN-encapsulated poly (lactic acid) (PLA)/neem gum (NEG) nanoparticles (NPs) to enhance their anticancer potency against breast cancer cells. The modified solvent evaporation-emulsification technique was followed to formulate NGN-PLA/NEG NPs, and their physicochemical properties, stability, drug release, and cytotoxic potentials were evaluated. The formulated NGN-PLA/NEG NPs showed a semi-crystalline nature, a zeta potential of +0.152 mV, a polydispersity index of 0.234, and a z-average particle size of 44.14 nm with spherical shape. NGN's encapsulation efficiency and loading capacity into PLA/NEG NPs were 77.72 ± 1.38% (w/w) and 8.57 ± 0.4% (w/w), respectively. At pH 5.8, NGN-PLA/NEG NPs released more NGN (78.46 ± 0.96%) than at pH 3.5 and 7.4. The MTT assay showed that NGN-PLA/NEG NPs had a significantly higher cytotoxic efficacy than free-NGN in Michigan Cancer Foundation 7 (MCF-7) cells, with an IC₅₀of 31.51 μg ml^-1. The IC₅₀concentration of NGN-PLA/NEG NPs significantly elevated the intracellular reactive oxygen species level, caspase-3 and -9 activity, and triggered apoptosis in MCF-7 cells. Apoptotic indicators, such as membrane blebbing and nuclear disintegration, have been observed in cancer cells treated with NGN-PLA/NEG NPs. These findings suggested that NGN-PLA/NEG NPs, which target NGN delivery into MCF-7 cells and promote endocytosis, could have potent anticancer activity against breast cancer cells.

Osteoporotic bone presents a compromised regenerative niche, with reduced osteoblast function and an imbalance between bone formation and resorption, limiting the success of conventional defect filling strategies. Injectable biomaterials that conform to irregular defects and provide localized osteogenic cues are particularly relevant. Here, we developed injectable sodium alginate hydrogels (HPs) incorporating 45S5 bioactive glass (HB) or the same glass functionalized with two osteoporosis-relevant osteotropic drugs deliberately selected for distinct mechanisms of action: raloxifene hydrochloride (HBRx; selective estrogen receptor modulation) and strontium ranelate (HBSr; dual action on bone remodeling). Within the scope of this work, we established material feasibility and comparativein vitroperformance through quantitative assessment of microstructure and surface behavior, together with cytocompatibility and osteogenic readouts. Glass incorporation remodeled the scaffold microstructure, increasing mean pore size from 54.0 ± 17.9 µm (HP) to 139.9 ± 51.5 µm (HB), while drug functionalization produced intermediate pores (84.8 ± 26.3 µm for HBRx; 85.5 ± 37.4 µm for HBSr). The increased inorganic contribution in the composites was reflected by higher residual mass at 800 °C (from 33.5% in HP to 45.0%-48.3% in glass-containing groups) and by shifts in wettability, with all formulations remaining hydrophilic (θ< 90°) but differing between functionalizations (44.2 ± 9.1° for HBRx vs 62.4 ± 11.8° for HBSr). All HPs were cytocompatible (day 7 relative viability ⩾70%) and supported osteogenic readouts (protein production, alkaline phosphatase activity, calcium deposition, and mineralized nodules), with HBSr showing the most favorable overall cellular response among the composites. Collectively, these findings indicate that osteoporosis-relevant drug-functionalized 45S5 within injectable alginate HPs provides a quantitative route to tune microstructure and interfacial behavior while preserving cytocompatibility and osteogenic potential. Future work will prioritizein vivovalidation in osteoporotic models to assess bone repair efficacy and determine whether localized delivery mitigates drug-specific drawbacks associated with systemic therapies.

Craniofacial bone deficiencies caused by trauma or disease pose clinical challenges as the shape of the damaged area varies between people. Although bone grafts are effective, they face issues such as poor drug retention and potential immune responses. PLA scaffolds possess therapeutic potential owing to their size, mechanical properties, stability, and biocompatibility. However, PLA scaffolds inherently lack bioactive molecules necessary to promote osteogenesis. HSPG2, also known as perlecan (Pln), are a basement membrane-specific GAG-containing core protein. Pln is a reservoir for heparin-binding growth factors, such as FGF, through GAG chains in domain I. For these reasons, we designed an HSPG2-coated PLA scaffold to enhance FGF delivery and promote cranial bone regeneration. Our results suggested an ideal scaffold with a 0.3 mm pore size and 60% porosity, enabling MG63 cell proliferation and osteogenesis. HSPGs help modulate FGF signaling during MG63 cell differentiation, motivating further studies on the microenvironment involved in neo-bone formation. We used 3D-printed PLA scaffolds coated with HSPG2 to create an osteoconductive environment. Advanced quantitative tests, computed tomography, and confocal microscopy confirmed the efficacy of the scaffold in reducing cranial bone-gap distances. Customized PLA scaffolds repaired diverse bone defects and regulated FGF delivery via HSPG2/FGF signaling, consequently promoting cranial bone regeneration. This study demonstrated promising applications for the treatment of cranial bone defects.

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.