ACS Biomaterials Science & Engineering最新文献

The development of poly(lactic-co-glycolic acid) (PLGA)-based microsphere scaffolds with comprehensive osteogenic activity, hydrophilicity, mechanical strength, and biocompatibility remains a significant challenge. Here, we constructed a hexagonal mesoporous silica (HMS)/PLGA composite microsphere scaffold (HP). Subsequently, we further developed a polydopamine (PDA)-modified version of HP (PHP) by applying a PDA coating to its surface. Compared with HP, PHP exhibited improved compressive strength and hydrophilicity while maintaining desirable porosity. In vitro, PHP promoted BMSCs proliferation and osteogenic differentiation, upregulated osteogenic gene expression, and induced macrophage polarization toward the M2 anti-inflammatory phenotype. In a rat calvarial defect model, PHP significantly enhanced bone regeneration, as confirmed by micro-CT and histological analyses, and maintained elevated expression of BMP-2 and VEGF to support osteogenesis and angiogenesis. Immunostaining further demonstrated increased CD163 and decreased iNOS expression, indicating an immunomodulatory effect. All materials showed favorable biocompatibility. This work integrated the surface functionalization of PDA with the structural features of HMS, demonstrating that the ternary composite scaffold achieved simultaneous regulation of the immune microenvironment and osteogenesis, providing a promising strategy for clinically translatable bone repair materials.

Biomimetic gold nanoparticles (Au NPs) were synthesized via a sustainable approach without any additional toxic chemical reagents and fully characterized. It was proven that only whole aqueous extracts of Rosa damascene (RD) and Rosa rugosa (RR) are powerful enough to reduce, graft, and stabilize metallic nanostructures, resulting in the formation of stable, monodisperse nanocolloids (Au@RD NPs and Au@RR NPs) whereas individual constituent molecules were insufficient to yield stable metal NPs. The biological study conducted, both in vitro and in vivo, revealed no acute cytotoxicity (in HaCaT cell lines and zebrafish larval models) but bacteriostatic activity at equivalent doses with potent inhibition of biofilm formation (for a MRSA strain). Noteworthy, the additive antibacterial activity of rose extracts when combined with rifampicin promotes that these attractive inorganic-organic hybrids could be suitable alternatives to combat the acquisition of antimicrobial resistance. This huge application potential was also emphasized by the presence of insignificant changes in the expression of pro-inflammatory cytokine genes (IL-1β, IL-6, and CXCL8) and apoptotic/autophagic associated genes (TP53, MAP1LC3B, and SQSTM1) in treated HaCaT cells at antimicrobial doses. In addition, at the studied doses, the survival of Danio rerio larvae and their proper development (i.e., lack of deformities) endorsed biocompatibility in vivo.

Collagen-glycosaminoglycan (CG) scaffolds are extensively utilized in tissue engineering for their excellent biocompatibility and low immunogenicity; however, their poor mechanical stiffness typically requires further physical or chemical modifications to enhance their structural integrity for clinical applications. We investigate the effects of nonthermal plasma (NTP) treatment; an emerging technology commonly used in the biomedical field for surface modifications, sterilization, and wound healing. A comprehensive analysis is conducted to evaluate the surface characteristics, biophysical properties, and biocompatibility of the 3D CG scaffolds treated with NTP for 2 and 5 min, compared with untreated controls. Histological and SEM analyses demonstrated thickening of the scaffold pore struts and an increase in porosity, while Energy Dispersive X-ray Spectroscopy (EDS) and Fourier transform infrared spectroscopy (FTIR) confirmed that the native chemical composition of the scaffolds remained intact and unchanged following NTP exposure. Post-treatment, the scaffolds exhibited increased hydrophilicity demonstrated by a reduced contact angle. Mechanical testing showed significant improvements in the scaffold's compression modulus, with increases of approximately 16.7% and 14.5% for 2 min and 5 min treatments, respectively (p < 0.05). In vitro biocompatibility assays indicated increased metabolic rates and significantly higher cell numbers in the ADSC-seeded on NTP-treated scaffolds (p = 0.001; p = 0.02, respectively). Following 21 day osteogenic conditions, both 2 min and 5 min NTP-treated scaffolds exhibited significantly elevated expression of key osteogenic markers, with RUNX2 showing a 9-fold increase at 2 min and an 11-fold increase at 5 min (p < 0.001), and Osteocalcin demonstrating increases of 2.5-fold and 2.3-fold, respectively (p < 0.01), compared to untreated controls. The enhanced biocompatibility and ability to serve as a supportive matrix that promotes osteogenic lineage commitment observed in the NTP-treated scaffolds suggest that these materials could be effectively utilized as allogenic osteocyte-loaded biomaterials for bone regeneration. Collectively, these results demonstrate that NTP treatment significantly improves the functional performance and mechanical strength of the 3D CG scaffolds, establishing it as an effective approach for enhancing scaffold performance in regenerative medicine applications.

Poly(vinylidene fluoride) (PVDF) is widely used in neural tissue engineering for its strong piezoelectric response, yet its nonbiodegradability and environmental persistence limit its clinical translation. Neural regeneration demands scaffolds that not only replicate the extracellular matrix but also deliver bioelectrical cues to guide neuronal growth. Here, we introduce aligned electrospun fibers of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and cellulose acetate (CA) as biodegradable, sustainable alternatives to PVDF for studying how piezoelectricity, surface charge, and nanotopography influence neuronal function. Compared to polycaprolactone (PCL) as a nonpiezoelectric control, the PVDF, PHBV, and CA scaffolds exhibited distinct morphologies and progressively decreasing piezoelectric coefficients. All supported robust adhesion and proliferation of B35 neuronal cells; however, piezoelectric fibers significantly enhanced intracellular Ca²⁺ influx, neurite elongation, and β3-tubulin expression. Both PVDF and PHBV activated the WNT/GSK3β signaling pathway and downregulated the pro-apoptotic BAX/BCL-2 ratio, suggesting enhanced neuroprotective capacity. Notably, while PVDF induced strong Ca²⁺-mediated neuronal maturation through piezoelectric stimulation, PHBV elicited additional antiapoptotic effects, likely linked to 3-hydroxybutyrate metabolism. Together, these findings demonstrate that combining nanoscale alignment, surface charge, and intrinsic piezoelectricity generates a bioelectrically active microenvironment conducive to neuronal regeneration. Importantly, PHBV emerges as a sustainable, biodegradable alternative to PVDF, bridging environmental responsibility with functional performance in neural tissue engineering.

Bioinspired scaffolds, designed to mimic natural tissue and provide biological cues for tissue regeneration, are becoming increasingly important in the field of tissue engineering. We previously developed hydrogel scaffolds based on alginate and decellularized Wharton's jelly (DWJ) from an umbilical cord. These scaffolds have proven to be highly effective in promoting the recovery of the lost discogenic phenotype in degenerated intervertebral disc (IVD) cells obtained from patients undergoing discectomy. This prompted us to refine the various steps of the protocol to optimize the development of stable DWJ-based scaffolds with anatomically shaped geometries such as millimeter-scale cylinders (millicylinders) suitable for use in articular cartilage tissue engineering. Particular attention was paid to the handling of the materials used, the reproducibility of data, and the adaptability of the developed system to different experimental needs/conditions, including the transmission of mechanical stimuli and the evaluation of the reactivity of the combined cells. Here, we report the characterization of both the physicochemical properties of the hydrogel produced and its specific biological effects by using IVD cells and macrophages as experimental models. The detailed description of the various steps provides a protocol that aims to facilitate the development of DWJ-based hydrogels that may provide new strategies for addressing joint degeneration.

Osteoarthritis affects over 30 million US adults and is a leading cause of disability, yet no approved therapies halt or reverse disease progression due to cartilage's limited intrinsic repair capacity. Autologous chondrocyte implantation strategies demonstrate some efficacy but are constrained by high costs, donor variability, and limited scalability. Allogeneic juvenile cartilage-derived chondrocyte (JCC) sheets represent a promising "off-the-shelf" alternative, exhibiting strong proliferative and chondrogenic capacity in both preclinical models and a first-in-human trial. However, restricted per-donor yield and dedifferentiation during ex vivo expansion beyond passage 2 (P2) hinder clinical translation. This study investigated how cell sheet layering and coculture with human bone marrow-derived mesenchymal stromal cells (BMSCs) might restore the chondrogenic capacity of high-passage (P4) JCC sheets, thereby improving the scalability of JCC sheet-based therapies. Layered constructs comprising one-, two-, or three-layer P4 JCC sheets, as well as bilayers of P4 JCC and BMSC sheets in both apical and basal layer orientations, were fabricated and evaluated for in vitro chondrogenesis with and without BMP6 media supplementation. When differentiated with BMP6, all cell sheet constructs produced equally mature hyaline-like cartilage rich in sulfated proteoglycans, collagen II, and aggrecan, although the ultimate thickness varied according to the number of layers. Culture in BMP6-deficient differentiation media revealed cell sheet layering-enhanced chondrogenesis, with triple-layer P4 JCC sheets (J3L) demonstrating hyaline-like cartilage formation equivalent to BMP6 media differentiation. Cocultured JCC-BMSC bilayers showed layer-orientation-dependent outcomes when differentiated without BMP6: JCC-apical (JonB) constructs maintained chondrogenesis comparable to that of JCC-only sheets, while BMSC-apical (BonJ) constructs exhibited impaired chondrogenesis and elevated hypertrophy markers. Cell sheet layering enables high-passage JCC sheets to recover therapeutic potency, facilitating enhanced sheet yields per donor nearly 60-fold and addressing a critical production scalability barrier. These findings support layered allogeneic JCC sheets as a clinically feasible and scalable allogeneic strategy for future cartilage regeneration.

Hydrocephalus management generally requires the implantation of a cerebrospinal fluid (CSF) shunt system that includes a ventricular catheter, a mechanical valve to regulate CSF flow, and a distal catheter that diverts the CSF to another site in the body, most commonly the peritoneal cavity. Despite advancements, approximately 40% of these shunts fail within two years, primarily due to catheter occlusion caused by cell attachment and cellular debris. Previous strategies, including polyvinylpyrrolidone (PVP) coatings aimed at reducing bacterial adhesion, have not significantly mitigated occlusion rates in clinical settings. This study explores the development of ventricular shunt catheters with a multilayered fibrous web using electrospinning technique in an effort to mitigate cellular attachment and enhance shunt longevity. Commercial silicone catheters were coated with medical-grade polyurethane material and evaluated for cellular adhesion using human astrocytes and choroid plexus epithelium (ChPE). Cells were visualized through DAPI staining and immunolabeling, and cell counts were quantified using ImageJ. Results demonstrated a significant reduction in cellular adhesion on web-spun catheters compared to uncoated controls, with normalized astrocyte densities decreasing from 37.10 ± 18.44 to 24.39 ± 16.68 [cells/mm²] (p = 0.0329). These findings suggest that web-spun coatings hold promise for improving the reliability and lifespan of shunt systems by mitigating cellular occlusion.

Irregular implants designed using Voronoi tessellation exhibit a high degree of biomimicry with respect to human bone morphology and mechanical behavior. However, conventional irregular structures often suffer from limited controllability of seed point control and excessive randomness, resulting in poor reproducibility and localized mechanical defects. To address these issues, this study proposes a controllable irregular porous structure design method that incorporates Poisson disk sampling to homogenize seed-point distribution, thereby improving structural randomness and mechanical properties. The effects of design parameters on porous structures were systematically investigated, followed by finite element analysis (FEA) to evaluate their mechanical behavior. In addition, 3D-printed porous specimens were fabricated and subjected to compression tests, and the experimental results were compared with simulation predictions. The results demonstrate that irregular porous structures designed by this method exhibit more favorable stress distributions than traditional designs, reduce the elastic modulus, alleviate stress shielding, and satisfy the requirements for biomedical implants. These findings highlight the strong potential of controllable irregular porous structures for future applications in bone implant development.

A novel core-shell hybrid material composed of bioactive glass (BG) nanoparticles and the metal-organic framework (MOF) MIL-100(Fe) (Fe₃O(H₂O)₂OH(BTC)₂·nH₂O, BTC: 1,3,5-benzenetricarboxylate) was synthesized using a layer-by-layer strategy. The formation of the MIL-100(Fe) shell on the BG core was directly confirmed by high-resolution transmission electron microscopy, which revealed a continuous MOF layer with an average thickness of 6.1 ± 0.9 nm. Complementary characterization by infrared spectroscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, N₂ sorption, and synchrotron-based X-ray absorption spectroscopy (XAS) confirmed the coexistence of MIL-100(Fe) and BG components and their structural integrity within the hybrid material. Notably, for the first time, a synchrotron-based technique (XAS) was used to characterize the MOF@BG system, providing unique insight into its local coordination environment and structural evolution. The hybrid material demonstrated favorable cytocompatibility in a long-term (21-day) assay on mouse osteoblast precursor cells (MC3T3) and human dermal fibroblasts (HDF). At the same time, it did not induce ex vivo hemolysis at concentrations up to 1000 μg/mL. The induction of osteogenic differentiation in MC3T3 cells in the presence of MIL-100(Fe)@BG was confirmed by early osteogenic markers, including alkaline phosphatase (ALP) activity and alizarin red staining (ARS). Bioactivity studies in Dulbecco's phosphate-buffered saline (DPBS) and simulated body fluid (SBF) revealed rapid formation of nanohydroxyapatite, beginning within the first hours of incubation. Importantly, under physiological conditions, the MIL-100(Fe) shell undergoes a controlled structural transformation, yielding highly dispersed nanoscale Fe₂O₃ particles. These nanoparticles induce the production of reactive oxygen species (ROS) and contribute to antibacterial activity, thereby inhibiting E. coli and S. aureus without the need for external antimicrobial agents. The combination of bioactivity, osteogenic potential, hemocompatibility, and intrinsic antibacterial functionality positions MIL-100(Fe)@BG as a promising multifunctional platform for bone regeneration and infection control.

Osteosarcoma (OS), a highly malignant primary bone tumor, is a relatively rare cancer with an incidence of about 3.4 cases per million people annually, yet it remains the most common malignant bone tumor in children and adolescents. Current clinical treatments often fail to completely eradicate the tumor, resulting in recurrence and substantial bone loss. To address these challenges, advanced macro-, micro-, and nanoscale bioactive materials are increasingly needed in bone tumor management. These materials must not only replace lost tissue and integrate with host bone but also provide a supportive environment for osteoblast growth and healing. Biomaterial-mediated bone regeneration focuses on designing temporary scaffolds and injectable micro/nanosponges or gels that fill bone defects and replicate the native bone niche. Additionally, such biomaterials should offer therapeutic functions to eliminate residual cancer cells after resection. Enhancing the therapeutic index and treatment efficiency while simultaneously addressing bone loss is necessary for improving clinical outcomes in osteosarcoma management. This review highlights the most advanced strategies and innovative theragenerative nano- and microparticles containing biomaterials investigated for bone cancer management (killing bone tumor cells and/or repairing bone defects) focusing on osteosarcoma.