Hydroxyapatite (HA) coating on orthopedic implants is known to promote osteogenesis and improve bone-implant integration, yet its molecular basis remains to be investigated. Here, transcriptomic profiling of osteoblasts on nano-HA (nHA)-coated surfaces revealed increased expression of key osteogenic and angiogenic molecules. These findings provide the first molecular mechanistic insight into how nHA coatings accelerate osteogenesis and bone healing.
{"title":"Transcriptomic profiling of osteoblasts on hydroxyapatite-coated-metal-surface reveals enhanced osteogenic and angiogenic processes relevant to accelerated bone healing","authors":"Yuki Ogawa , Kosuke Arita , Takayuki Nonoyama , Kano Sato , Ryota Watanabe , Liyile Chen , Tsutomu Endo , Taiki Tokuhiro , Hend Alhasan , Daisuke Takahashi , Norimasa Iwasaki , M. Alaa Terkawi","doi":"10.1016/j.bioadv.2025.214672","DOIUrl":"10.1016/j.bioadv.2025.214672","url":null,"abstract":"<div><div>Hydroxyapatite (HA) coating on orthopedic implants is known to promote osteogenesis and improve bone-implant integration, yet its molecular basis remains to be investigated. Here, transcriptomic profiling of osteoblasts on nano-HA (nHA)-coated surfaces revealed increased expression of key osteogenic and angiogenic molecules. These findings provide the first molecular mechanistic insight into how nHA coatings accelerate osteogenesis and bone healing.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214672"},"PeriodicalIF":6.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145842858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.bioadv.2025.214669
Yinuo Li , Peng Sun , Wenyi Xu, Huanhuan Li, Hongming Yang, Baolong Zhou
Bacterial wound infections pose a serious clinical threat, often leading to impaired healing and severe complications. To address this challenge, we developed CNT@Por-Cu-MOF, a heterojunction material constructed via in situ growth of Cu(I)–carbon-bonded porphyrin-based metal organic framework (Por-Cu-MOF) as a nano-layer on carbon nanotubes (CNTs). The hierarchical porous structure of the composite enhances therapeutic performance by improving the diffusion of reactive substrates and facilitating the conversion of photonic energy into cytotoxic effects. Under light irradiation, this design enables a self-reinforcing therapeutic cycle that synergistically amplifies antibacterial efficacy through three interconnected mechanisms. Specifically, photothermal conversion elevates local temperature and accelerates enzymatic catalytic kinetics. Hybrid type I/II photodynamic reactions that generate multiple reactive oxygen species (ROS), breaking the hypoxia-induced limitations of conventional phototherapy. Dual enzyme-mimetic catalytic activities, including the peroxidase (POD)- and glutathione peroxidase (GPx)-like behavior that convert endogenous H2O2 into •OH while depleting glutathione (GSH), thereby disrupting the redox balance in bacteria. At only 100 μg/mL, CNT@Por-Cu-MOF not only completely eradicates Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), but effectively removes their biofilms. In a murine wound infection model, the combination of the material, H2O2, and laser irradiation significantly accelerated wound healing through integrated photothermal ablation, photodynamic penetration, and catalytic oxidative stress. By leveraging and reprogramming the infected microenvironment, this study introduces a pioneering approach to creating antibacterial platforms with low dosage, broad-spectrum coverage, and hypoxia resistance.
{"title":"Heterojunction-engineered CNT–MOF hybrid platform for synergistic amplified therapy of bacterial-infected wounds","authors":"Yinuo Li , Peng Sun , Wenyi Xu, Huanhuan Li, Hongming Yang, Baolong Zhou","doi":"10.1016/j.bioadv.2025.214669","DOIUrl":"10.1016/j.bioadv.2025.214669","url":null,"abstract":"<div><div>Bacterial wound infections pose a serious clinical threat, often leading to impaired healing and severe complications. To address this challenge, we developed CNT@Por-Cu-MOF, a heterojunction material constructed via in situ growth of Cu(I)–carbon-bonded porphyrin-based metal organic framework (Por-Cu-MOF) as a nano-layer on carbon nanotubes (CNTs). The hierarchical porous structure of the composite enhances therapeutic performance by improving the diffusion of reactive substrates and facilitating the conversion of photonic energy into cytotoxic effects. Under light irradiation, this design enables a self-reinforcing therapeutic cycle that synergistically amplifies antibacterial efficacy through three interconnected mechanisms. Specifically, photothermal conversion elevates local temperature and accelerates enzymatic catalytic kinetics. Hybrid type I/II photodynamic reactions that generate multiple reactive oxygen species (ROS), breaking the hypoxia-induced limitations of conventional phototherapy. Dual enzyme-mimetic catalytic activities, including the peroxidase (POD)- and glutathione peroxidase (GPx)-like behavior that convert endogenous H<sub>2</sub>O<sub>2</sub> into •OH while depleting glutathione (GSH), thereby disrupting the redox balance in bacteria. At only 100 μg/mL, CNT@Por-Cu-MOF not only completely eradicates <em>Staphylococcus aureus</em> (<em>S. aureus</em>) and <em>Escherichia coli</em> (<em>E. coli</em>), but effectively removes their biofilms. In a murine wound infection model, the combination of the material, H<sub>2</sub>O<sub>2</sub>, and laser irradiation significantly accelerated wound healing through integrated photothermal ablation, photodynamic penetration, and catalytic oxidative stress. By leveraging and reprogramming the infected microenvironment, this study introduces a pioneering approach to creating antibacterial platforms with low dosage, broad-spectrum coverage, and hypoxia resistance.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214669"},"PeriodicalIF":6.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.bioadv.2025.214673
Ke Wu , Zhenyu Shen , Jie Wu , Zhiwei Chen , Yun Yang , Qiaoling Huang
Although it is widely believed that the antibacterial adhesion resistance of superhydrophobic surfaces stems from trapped air layers, the specific contributions of surface microstructure and trapped air layers in preventing bacterial adhesion remain unclear. In this study, four hydrophobic titanium dioxide (TiO₂) materials with different nanostructures were prepared, and ultrasonication was used to effectively remove trapped air, enabling a direct comparison of the hydrophobic materials with variations in surface morphology and trapped air. The results demonstrated that for the superhydrophilic samples, a large number of bacteria adhered to the surfaces, and no significant differences were observed among the various nanostructures. In sharp contrast, all four hydrophobic materials significantly reduced bacterial adhesion, with no significant differences observed among surfaces with different topographies. Millimeter scale, macroscopically visible air bubbles at the solid-liquid interphase greatly suppressed the bacterial adhesion, and the bubbles disappeared or decreased with the elapsed time. In contrast, invisible small bubbles (micrometer- or nanometer-scale) cannot decrease bacterial adhesion compared with the ultrasonicated sample (without trapped air). Therefore, the main reason for the significant reduction in bacterial adhesion on various hydrophobic surfaces is the fluorosilane surface modification. Air at the solid–liquid interface can only suppress the bacterial adhesion when it forms millimeter scale, visible bubbles. This work gives new ideas to the antibacterial application of superhydrophobic materials and is of great significance for the design of biomaterial surfaces with anti-adhesive properties.
{"title":"Effect of surface chemistry and structure on bacterial adhesion on titanium dioxide materials with extreme wetting","authors":"Ke Wu , Zhenyu Shen , Jie Wu , Zhiwei Chen , Yun Yang , Qiaoling Huang","doi":"10.1016/j.bioadv.2025.214673","DOIUrl":"10.1016/j.bioadv.2025.214673","url":null,"abstract":"<div><div>Although it is widely believed that the antibacterial adhesion resistance of superhydrophobic surfaces stems from trapped air layers, the specific contributions of surface microstructure and trapped air layers in preventing bacterial adhesion remain unclear. In this study, four hydrophobic titanium dioxide (TiO₂) materials with different nanostructures were prepared, and ultrasonication was used to effectively remove trapped air, enabling a direct comparison of the hydrophobic materials with variations in surface morphology and trapped air. The results demonstrated that for the superhydrophilic samples, a large number of bacteria adhered to the surfaces, and no significant differences were observed among the various nanostructures. In sharp contrast, all four hydrophobic materials significantly reduced bacterial adhesion, with no significant differences observed among surfaces with different topographies. Millimeter scale, macroscopically visible air bubbles at the solid-liquid interphase greatly suppressed the bacterial adhesion, and the bubbles disappeared or decreased with the elapsed time. In contrast, invisible small bubbles (micrometer- or nanometer-scale) cannot decrease bacterial adhesion compared with the ultrasonicated sample (without trapped air). Therefore, the main reason for the significant reduction in bacterial adhesion on various hydrophobic surfaces is the fluorosilane surface modification. Air at the solid–liquid interface can only suppress the bacterial adhesion when it forms millimeter scale, visible bubbles. This work gives new ideas to the antibacterial application of superhydrophobic materials and is of great significance for the design of biomaterial surfaces with anti-adhesive properties.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214673"},"PeriodicalIF":6.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.bioadv.2025.214666
Wenge Lv , Liangcheng Gu , Xingyu Lin , Chun Mao , Ya Guan , Mimi Wan
Conventional drug therapies face significant limitations in complex physiological environments, including poor targeting efficiency, passive diffusion mechanisms, and systemic toxicity. Inspired by the immune system, where immune cells are actively navigated by chemotactic gradients to reach infection sites, researchers have developed nanorobots capable of autonomous, microenvironment-responsive drug delivery. These nanorobots convert endogenous biochemical cues (e.g., pH, enzymes, reactive oxygen species) into directed motion and structure or shape changes, enabling deep tissue penetration and lesion-specific drug release. This review categorizes microenvironment-responsive nanorobots into three functional classes—locomotion, degradation, and deformation—based on their response behaviors to pathological signals. We critically analyze their design principles, biomedical applications in different diseases, and translational challenges. By bridging bioinspired strategies with engineered nanorobotics, this work provides a roadmap for next-generation precision therapeutics.
{"title":"Microenvironment-responsive nanorobots for biomedical applications","authors":"Wenge Lv , Liangcheng Gu , Xingyu Lin , Chun Mao , Ya Guan , Mimi Wan","doi":"10.1016/j.bioadv.2025.214666","DOIUrl":"10.1016/j.bioadv.2025.214666","url":null,"abstract":"<div><div>Conventional drug therapies face significant limitations in complex physiological environments, including poor targeting efficiency, passive diffusion mechanisms, and systemic toxicity. Inspired by the immune system, where immune cells are actively navigated by chemotactic gradients to reach infection sites, researchers have developed nanorobots capable of autonomous, microenvironment-responsive drug delivery. These nanorobots convert endogenous biochemical cues (e.g., pH, enzymes, reactive oxygen species) into directed motion and structure or shape changes, enabling deep tissue penetration and lesion-specific drug release. This review categorizes microenvironment-responsive nanorobots into three functional classes—locomotion, degradation, and deformation—based on their response behaviors to pathological signals. We critically analyze their design principles, biomedical applications in different diseases, and translational challenges. By bridging bioinspired strategies with engineered nanorobotics, this work provides a roadmap for next-generation precision therapeutics.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214666"},"PeriodicalIF":6.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.bioadv.2025.214664
Nicole Fratini , Carolina Castillo , Roberta Grillo , Stefania D'Amone , Luca Pacini , Maddalena Grieco , Maria Grazia Lolli , Sara Maria Giannitelli , Francesco Brasili , Ornella Ursini , Claudia Bearzi , Roberto Rizzi , Barbara Cortese
The tumour microenvironment of glioblastoma (GBM) as defined by mechanical heterogeneity, hypoxia, and hyaluronic acid (HA)–rich extracellular matrix (ECM), is a highly dynamic milieu which influences tumour progression and therapeutic resistance. Yet, how these cues converge to regulate mechanosensitive pathways in 3D remains poorly understood. Here, we engineered agar-based porous hydrogels functionalized with HA to independently tune stiffness and ECM composition, creating biomimetic 3D niches for GBM cells. The presence of HA coating showed to increase hydrogel stiffness, promote YAP/TAZ nuclear localisation, and elevate total LATS1/2 expression, consistent with Hippo pathway feedback regulation. Over time, however, hypoxic niches emerged that destabilised this feedback, enabling sustained YAP nuclear activity. HA also modulated OCT4 and Sox2 localisation and attenuated HIF-1α nuclear accumulation, indicating that HA also modulates the spatial distribution and nuclear accumulation of HIF-1α. Also, a cooperative regulation through the HA–CD44–CXCR4 axis, showed integrated biochemical and mechanical signals to reinforce YAP/HIF crosstalk. Together, these results reveal a dynamic interplay between ECM stiffness, HA signalling, and hypoxia in shaping YAP/HIF crosstalk and stem-like phenotypes in GBM and establish our hydrogel platform as a powerful tool to dissect and therapeutically exploit these interactions.
{"title":"The extracellular matrix HA promotes the YAP/hypoxia axis of glioblastoma cells on 3D agar/HA scaffolds","authors":"Nicole Fratini , Carolina Castillo , Roberta Grillo , Stefania D'Amone , Luca Pacini , Maddalena Grieco , Maria Grazia Lolli , Sara Maria Giannitelli , Francesco Brasili , Ornella Ursini , Claudia Bearzi , Roberto Rizzi , Barbara Cortese","doi":"10.1016/j.bioadv.2025.214664","DOIUrl":"10.1016/j.bioadv.2025.214664","url":null,"abstract":"<div><div>The tumour microenvironment of glioblastoma (GBM) as defined by mechanical heterogeneity, hypoxia, and hyaluronic acid (HA)–rich extracellular matrix (ECM), is a highly dynamic milieu which influences tumour progression and therapeutic resistance. Yet, how these cues converge to regulate mechanosensitive pathways in 3D remains poorly understood. Here, we engineered agar-based porous hydrogels functionalized with HA to independently tune stiffness and ECM composition, creating biomimetic 3D niches for GBM cells. The presence of HA coating showed to increase hydrogel stiffness, promote YAP/TAZ nuclear localisation, and elevate total LATS1/2 expression, consistent with Hippo pathway feedback regulation. Over time, however, hypoxic niches emerged that destabilised this feedback, enabling sustained YAP nuclear activity. HA also modulated OCT4 and Sox2 localisation and attenuated HIF-1α nuclear accumulation, indicating that HA also modulates the spatial distribution and nuclear accumulation of HIF-1α. Also, a cooperative regulation through the HA–CD44–CXCR4 axis, showed integrated biochemical and mechanical signals to reinforce YAP/HIF crosstalk. Together, these results reveal a dynamic interplay between ECM stiffness, HA signalling, and hypoxia in shaping YAP/HIF crosstalk and stem-like phenotypes in GBM and establish our hydrogel platform as a powerful tool to dissect and therapeutically exploit these interactions.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214664"},"PeriodicalIF":6.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Articular cartilage has limited self-healing capacity, driving the need for biomaterial scaffolds that replicate its hierarchical architecture and mechanical resilience. In this study, we present a dual-crosslinked hydrogel system for 3D bioprinting, composed of gellan gum (GG), oxidized GG (OGG), decellularized human amniotic membrane (dHAM), and aminolyzed polycaprolactone nanofibers (A-PCL NFs). Schiff base linkages between OGG aldehydes and amine groups in dHAM/A-PCL NFs, combined with Ca2+-mediated ionic gelation, provided a reinforced hydrogel network with tunable physicochemical properties. The resulting scaffolds exhibited high structural fidelity, a compressive modulus of 232.6 kPa, controlled swelling, and sustained degradation (30 % mass loss over 21 days). The integration of A-PCL NFs significantly enhanced mechanical performance and stabilized the hydrogel matrix, while dHAM supplied native extracellular matrix (ECM) cues. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) encapsulated in the bioink showed >85 % viability after 7 days and underwent robust chondrogenic differentiation, as confirmed by histology and increased glycosaminoglycan deposition. This biomimetic design—combining dynamic crosslinking, ECM-derived bioactivity, and NF reinforcement—demonstrates how structural and biochemical synergies can be harnessed to advance functional cartilage scaffolds. The platform shows strong potential for translational application in articular cartilage repair and may be extended to other load-bearing tissues requiring both mechanical integrity and biological functionality.
{"title":"3D-bioprinted dual-crosslinked oxidized gellan gum-decellularized human amniotic membrane hydrogels reinforced with aminolyzed electrospun nanofibers for cartilage regeneration","authors":"Fariba Hashemi-Afzal , Fatemeh Bagheri , Ebrahim Vasheghani-Farahani , Mahmoud Azami , Lobat Tayebi , Mohamadreza Baghaban Eslaminejad","doi":"10.1016/j.bioadv.2025.214654","DOIUrl":"10.1016/j.bioadv.2025.214654","url":null,"abstract":"<div><div>Articular cartilage has limited self-healing capacity, driving the need for biomaterial scaffolds that replicate its hierarchical architecture and mechanical resilience. In this study, we present a dual-crosslinked hydrogel system for 3D bioprinting, composed of gellan gum (GG), oxidized GG (OGG), decellularized human amniotic membrane (dHAM), and aminolyzed polycaprolactone nanofibers (A-PCL NFs). Schiff base linkages between OGG aldehydes and amine groups in dHAM/A-PCL NFs, combined with Ca<sup>2+</sup>-mediated ionic gelation, provided a reinforced hydrogel network with tunable physicochemical properties. The resulting scaffolds exhibited high structural fidelity, a compressive modulus of 232.6 kPa, controlled swelling, and sustained degradation (30 % mass loss over 21 days). The integration of A-PCL NFs significantly enhanced mechanical performance and stabilized the hydrogel matrix, while dHAM supplied native extracellular matrix (ECM) cues. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) encapsulated in the bioink showed >85 % viability after 7 days and underwent robust chondrogenic differentiation, as confirmed by histology and increased glycosaminoglycan deposition. This biomimetic design—combining dynamic crosslinking, ECM-derived bioactivity, and NF reinforcement—demonstrates how structural and biochemical synergies can be harnessed to advance functional cartilage scaffolds. The platform shows strong potential for translational application in articular cartilage repair and may be extended to other load-bearing tissues requiring both mechanical integrity and biological functionality.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214654"},"PeriodicalIF":6.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteoarthritis (OA) is a chronic degenerative joint disease characterised by progressive functional impairment due to erosion of the articular cartilage, remodelling of the subchondral bone and inflammation of the synovial tissue. In addition to mechanical and metabolic alterations, there is increasing evidence highlighting the pivotal role of macrophages in OA pathophysiology. The imbalance between pro-inflammatory M1 and anti-inflammatory M2 phenotypes drives joint inflammation, extracellular matrix degradation, chondrocyte apoptosis and impaired tissue repair. Therefore, modulating macrophage polarization appears to be an attractive therapeutic target for preventing OA progression. In recent years, nanomaterials have emerged as an innovative approach to tackling this challenge. Their tunable size, morphology, and surface properties enable both direct immunomodulation and the delivery of therapeutic agents. This systematic review examined preclinical studies published between 2021 and 2025 that investigated the potential of various developed nanomaterials to polarize macrophages towards the M2 phenotype, thereby reducing joint inflammation and promoting cartilage protection and repair. Consistent results from both in vitro and in vivo included studies demonstrated their ability to reduce pro-inflammatory mediators related to M1-type macrophages while enhancing the expression of anti-inflammatory ones linked to M2-type macrophages, despite their differences in physicochemical properties. This suggested that nanomaterials could reprogram macrophages to suppress the inflammatory microenvironment of OA and slow down disease progression by lowering synovitis and cartilage damage. By influencing macrophage polarization and fostering a regenerative environment, nanotechnology may pave the way for more effective, targeted strategies in OA management.
{"title":"Nanomaterial-based strategies to modulate macrophage polarization in osteoarthritis: A systematic review","authors":"Giorgia Codispoti , Luca Cavazza , Melania Carniato , Gabriele Bilancia , Gianluca Giavaresi , Matilde Tschon","doi":"10.1016/j.bioadv.2025.214662","DOIUrl":"10.1016/j.bioadv.2025.214662","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a chronic degenerative joint disease characterised by progressive functional impairment due to erosion of the articular cartilage, remodelling of the subchondral bone and inflammation of the synovial tissue. In addition to mechanical and metabolic alterations, there is increasing evidence highlighting the pivotal role of macrophages in OA pathophysiology. The imbalance between pro-inflammatory M1 and anti-inflammatory M2 phenotypes drives joint inflammation, extracellular matrix degradation, chondrocyte apoptosis and impaired tissue repair. Therefore, modulating macrophage polarization appears to be an attractive therapeutic target for preventing OA progression. In recent years, nanomaterials have emerged as an innovative approach to tackling this challenge. Their tunable size, morphology, and surface properties enable both direct immunomodulation and the delivery of therapeutic agents. This systematic review examined preclinical studies published between 2021 and 2025 that investigated the potential of various developed nanomaterials to polarize macrophages towards the M2 phenotype, thereby reducing joint inflammation and promoting cartilage protection and repair. Consistent results from both <em>in vitro</em> and <em>in vivo</em> included studies demonstrated their ability to reduce pro-inflammatory mediators related to M1-type macrophages while enhancing the expression of anti-inflammatory ones linked to M2-type macrophages, despite their differences in physicochemical properties. This suggested that nanomaterials could reprogram macrophages to suppress the inflammatory microenvironment of OA and slow down disease progression by lowering synovitis and cartilage damage. By influencing macrophage polarization and fostering a regenerative environment, nanotechnology may pave the way for more effective, targeted strategies in OA management.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214662"},"PeriodicalIF":6.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study presents a novel porous bone scaffold system (PBCMH) fabricated by melt blending and supercritical CO2 (scCO2) foaming, incorporating nano-hydroxyapatite (nHA), chitosan, polylactic acid (PLA), and polybutylene succinate (PBS). Four formulations with varying nHA content (0 %, 10 %, 20 %, 30 %) were evaluated to optimize the balance of structure, mechanical properties, and osteogenic bioactivity for bone regeneration. The scaffolds demonstrated interconnected porous networks with tunable pore sizes and mechanical strengths (57.2–184.3 μm). The PBCMH3 group (30 % nHA) exhibited the smallest average pore size, highest surface hydrophilicity (61.1°), and the best mechanical properties (elastic modulus ~4.26 MPa), resembling cancellous bone. Physicochemical analysis confirmed uniform dispersion of components and strong interfacial interactions. In vitro studies demonstrated that PBCMH3 significantly promoted rBMSC proliferation and osteogenic differentiation, as indicated by enhanced cytoskeletal organization, elevated alkaline phosphatase (ALP) activity, and increased mineral deposition. These in vitro findings were further supported by in vivo results: in a rat calvarial defect model, micro-CT and histological analyses confirmed superior bone regeneration in the PBCMH3 group, characterized by extensive new bone formation and the presence of mature lamellar bone. Importantly, no signs of systemic toxicity or pathological changes were observed in major organs, validating the biosafety of the scaffold. Together, these results underscore the potential of PBCMH3 as a promising scaffold for clinical bone tissue engineering, offering a comprehensive solution to the challenges of bone regeneration.
{"title":"Supercritical CO2-foamed hierarchically porous PLA/PBS-based scaffold for advanced bone regeneration","authors":"Shan Tang , Guobin Huang , Chengyong Li , Zhongming Li , Yuhui Xie , Feng Wu , Delong Xie , Dong Feng","doi":"10.1016/j.bioadv.2025.214663","DOIUrl":"10.1016/j.bioadv.2025.214663","url":null,"abstract":"<div><div>This study presents a novel porous bone scaffold system (PBCMH) fabricated by melt blending and supercritical CO<sub>2</sub> (scCO<sub>2</sub>) foaming, incorporating nano-hydroxyapatite (nHA), chitosan, polylactic acid (PLA), and polybutylene succinate (PBS). Four formulations with varying nHA content (0 %, 10 %, 20 %, 30 %) were evaluated to optimize the balance of structure, mechanical properties, and osteogenic bioactivity for bone regeneration. The scaffolds demonstrated interconnected porous networks with tunable pore sizes and mechanical strengths (57.2–184.3 μm). The PBCMH3 group (30 % nHA) exhibited the smallest average pore size, highest surface hydrophilicity (61.1°), and the best mechanical properties (elastic modulus ~4.26 MPa), resembling cancellous bone. Physicochemical analysis confirmed uniform dispersion of components and strong interfacial interactions. In vitro studies demonstrated that PBCMH3 significantly promoted rBMSC proliferation and osteogenic differentiation, as indicated by enhanced cytoskeletal organization, elevated alkaline phosphatase (ALP) activity, and increased mineral deposition. These in vitro findings were further supported by in vivo results: in a rat calvarial defect model, micro-CT and histological analyses confirmed superior bone regeneration in the PBCMH3 group, characterized by extensive new bone formation and the presence of mature lamellar bone. Importantly, no signs of systemic toxicity or pathological changes were observed in major organs, validating the biosafety of the scaffold. Together, these results underscore the potential of PBCMH3 as a promising scaffold for clinical bone tissue engineering, offering a comprehensive solution to the challenges of bone regeneration.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214663"},"PeriodicalIF":6.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-13DOI: 10.1016/j.bioadv.2025.214658
G. Dei Rossi , F. Buccino , E. Longo , G. Tromba , L.M. Vergani
Effective bone regeneration requires scaffolds capable of guiding and supporting new mineralized matrix formation. In this study, silk fibroin constructs cultured with human mesenchymal stem cells (hBMSCs) in the presence of either Fetal Bovine Serum (FBS) or Human Platelet Lysate (hPL) are evaluated for their osteogenic potential. A distinctive aspect of this work is the combined use of synchrotron X-ray imaging and a convolutional neural network for high-resolution in situ three-dimensional scaffold osteogenic potential assessment. This approach enables precise evaluation of bone matrix arrangement within the scaffold architecture. Two-dimensional analysis reveals increased mineralization in pores with an average radius of ~115 μm, area of ~4.0 × 104 μm2, and eccentricity of ~0.7 in hPL construct. The subsequent three-dimensional analysis extends these findings by quantifying the spatial distribution and connectivity of the mineralized matrix across the scaffold volume. It identifies pores with an equivalent radius between 110 and 120 μm, high surface area, and moderate sphericity (0.65–0.75) as optimal not only for mineral deposition but also for uniform 3D matrix propagation. Moreover, unsupervised clustering analysis also identifies optimal geometric interdependencies between pore size, surface area, and sphericity, offering new insights for rational design of high-performance scaffolds. The study demonstrates both the efficacy of silk fibroin scaffolds cultured with hPL in promoting bone regeneration and the relevance of a combined synchrotron imaging-artificial intelligence approach in quantitatively correlating three-dimensional porous geometry with regenerative outcomes.
{"title":"Sustainable silk fibroin scaffolds for bone repair: assessing their osteogenic potential via AI-enhanced synchrotron imaging workflow","authors":"G. Dei Rossi , F. Buccino , E. Longo , G. Tromba , L.M. Vergani","doi":"10.1016/j.bioadv.2025.214658","DOIUrl":"10.1016/j.bioadv.2025.214658","url":null,"abstract":"<div><div>Effective bone regeneration requires scaffolds capable of guiding and supporting new mineralized matrix formation. In this study, silk fibroin constructs cultured with human mesenchymal stem cells (hBMSCs) in the presence of either Fetal Bovine Serum (FBS) or Human Platelet Lysate (hPL) are evaluated for their osteogenic potential. A distinctive aspect of this work is the combined use of synchrotron X-ray imaging and a convolutional neural network for high-resolution in situ three-dimensional scaffold osteogenic potential assessment. This approach enables precise evaluation of bone matrix arrangement within the scaffold architecture. Two-dimensional analysis reveals increased mineralization in pores with an average radius of ~115 μm, area of ~4.0 × 10<sup>4</sup> μm<sup>2</sup>, and eccentricity of ~0.7 in hPL construct. The subsequent three-dimensional analysis extends these findings by quantifying the spatial distribution and connectivity of the mineralized matrix across the scaffold volume. It identifies pores with an equivalent radius between 110 and 120 μm, high surface area, and moderate sphericity (0.65–0.75) as optimal not only for mineral deposition but also for uniform 3D matrix propagation. Moreover, unsupervised clustering analysis also identifies optimal geometric interdependencies between pore size, surface area, and sphericity, offering new insights for rational design of high-performance scaffolds. The study demonstrates both the efficacy of silk fibroin scaffolds cultured with hPL in promoting bone regeneration and the relevance of a combined synchrotron imaging-artificial intelligence approach in quantitatively correlating three-dimensional porous geometry with regenerative outcomes.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214658"},"PeriodicalIF":6.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-13DOI: 10.1016/j.bioadv.2025.214655
Zhiping Fang , Yonghao Xiao , Jubo Li , Hailei Li , Xin Wu , Lin Ye , Zenggguo Feng
A double layer small diameter vascular graft (SDVG) was fabricated by sequential electrospinning. The inner layer was composed by three kinds of biodegradable poly (ε-caprolactone) (PCL) fibers with three different molecular weights to induce endothelial regeneration and the outer layer comprised non-degradable thermoplastic polyurethane (TPU) fibers and PCL fibers with the numerical molecular weight of 80,000 g/mol to provide long-term mechanical support. The SDVG was further heparinized through “erosion and graft” strategy. The surface heparin content, the clotting time and the mechanical properties were evaluated in vitro. Then, the double layer SDVG was implanted into the sheep for six months as the arteriovenous fistula connecting carotid artery and jugular vein. The Doppler ultrasonic measurement and angiography showed the patency of the transplanted SDVGs and the in situ puncture test exhibited the potential of the SDVG for hemodialysis. H&E and Masson staining characterized the remodeling of the inner layer, whereas Safranin O and von Kossa staining demonstrated the regeneration of extracellular matrix and the absence of the calcification in the implanted SDVG. More importantly, the perfect regeneration of endothelium on the lumen of the SDVG was proven by CD31 staining. Consequently, the as-prepared SDVG showed the potential to be the artificial arteriovenous fistula in the clinic.
{"title":"Semi-degradable biomimetic double-layer small diameter vascular graft for arteriovenous fistula in large animals","authors":"Zhiping Fang , Yonghao Xiao , Jubo Li , Hailei Li , Xin Wu , Lin Ye , Zenggguo Feng","doi":"10.1016/j.bioadv.2025.214655","DOIUrl":"10.1016/j.bioadv.2025.214655","url":null,"abstract":"<div><div>A double layer small diameter vascular graft (SDVG) was fabricated by sequential electrospinning. The inner layer was composed by three kinds of biodegradable poly (ε-caprolactone) (PCL) fibers with three different molecular weights to induce endothelial regeneration and the outer layer comprised non-degradable thermoplastic polyurethane (TPU) fibers and PCL fibers with the numerical molecular weight of 80,000 g/mol to provide long-term mechanical support. The SDVG was further heparinized through “erosion and graft” strategy. The surface heparin content, the clotting time and the mechanical properties were evaluated in vitro. Then, the double layer SDVG was implanted into the sheep for six months as the arteriovenous fistula connecting carotid artery and jugular vein. The Doppler ultrasonic measurement and angiography showed the patency of the transplanted SDVGs and the in situ puncture test exhibited the potential of the SDVG for hemodialysis. H&E and Masson staining characterized the remodeling of the inner layer, whereas Safranin O and von Kossa staining demonstrated the regeneration of extracellular matrix and the absence of the calcification in the implanted SDVG. More importantly, the perfect regeneration of endothelium on the lumen of the SDVG was proven by CD31 staining. Consequently, the as-prepared SDVG showed the potential to be the artificial arteriovenous fistula in the clinic.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214655"},"PeriodicalIF":6.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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