Pub Date : 2026-01-31DOI: 10.1016/j.bioadv.2026.214756
Luis F O Silva
{"title":"Technical discussion on the methodological and interpretative aspects of \"mineralized extracellular matrix composite scaffold incorporated with salvianolic acid a enhances bone marrow mesenchymal stem cell osteogenesis and promotes calvarial bone regeneration\".","authors":"Luis F O Silva","doi":"10.1016/j.bioadv.2026.214756","DOIUrl":"https://doi.org/10.1016/j.bioadv.2026.214756","url":null,"abstract":"","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"183 ","pages":"214756"},"PeriodicalIF":6.0,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114678","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 : 2026-01-30DOI: 10.1016/j.bioadv.2026.214752
Xin Chen, Song Chen, Yi Hou
Periodontitis is caused by dental plaque that triggers the host immune responses by the dysregulation of reactive oxygen species (ROS), leading to the destruction of local tissues such as gingiva, periodontal ligament, and alveolar bone. With its high prevalence, periodontitis impacts the oral health of billions worldwide. Clinical therapy for periodontitis relies on mechanical debridement and adjunctive antibiotics, strategies that often result in incomplete efficacy and a high recurrence rate. The development of cerium oxide nanoparticles (nanoceria), which exhibits enzyme-like catalytic activity and biocompatibility, enables targeted redox modulation to restore ROS balance, showing promise for clinical treatment. Based on above, this article focuses on the pathogenesis of periodontitis and the regulatory functions of ROS, and summarizes the design principles, functional engineering, and therapeutic mechanisms of nanoceria for periodontal therapy. Furthermore, the review outlines preventive strategies against periodontitis based on nanoceria. It then discusses the associated clinical challenges and future prospects. Overall, this work provides a comprehensive overview of nanoceria as the redox-based strategy for periodontal management.
{"title":"Nanoceria-mediated redox modulation for periodontal management: Mechanisms, applications, and challenges.","authors":"Xin Chen, Song Chen, Yi Hou","doi":"10.1016/j.bioadv.2026.214752","DOIUrl":"https://doi.org/10.1016/j.bioadv.2026.214752","url":null,"abstract":"<p><p>Periodontitis is caused by dental plaque that triggers the host immune responses by the dysregulation of reactive oxygen species (ROS), leading to the destruction of local tissues such as gingiva, periodontal ligament, and alveolar bone. With its high prevalence, periodontitis impacts the oral health of billions worldwide. Clinical therapy for periodontitis relies on mechanical debridement and adjunctive antibiotics, strategies that often result in incomplete efficacy and a high recurrence rate. The development of cerium oxide nanoparticles (nanoceria), which exhibits enzyme-like catalytic activity and biocompatibility, enables targeted redox modulation to restore ROS balance, showing promise for clinical treatment. Based on above, this article focuses on the pathogenesis of periodontitis and the regulatory functions of ROS, and summarizes the design principles, functional engineering, and therapeutic mechanisms of nanoceria for periodontal therapy. Furthermore, the review outlines preventive strategies against periodontitis based on nanoceria. It then discusses the associated clinical challenges and future prospects. Overall, this work provides a comprehensive overview of nanoceria as the redox-based strategy for periodontal management.</p>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"183 ","pages":"214752"},"PeriodicalIF":6.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138120","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}
3D bioprinting is a promising strategy for engineering in vitro tumor models. However, replicating the intratumoral parenchyma-stroma heterogeneity remains challenging due to the poor formability of biomimetic bioinks. In this study, we developed a method to enable the direct extrusion of low-concentration gelatin-methacrylate (GelMA)/Matrigel by overcoming its rheological limitations. The bioink was then incorporated within a coaxial bioprinting system to engineer a defined tumor parenchyma-stroma interface. The coaxial lung cancer model featured a dual-layer tubular structure. In this structure, the inner microsphere bioink was designed to mimic the tumor parenchyma, and the surrounding HAMA/Fibrin hydrogel was used to reproduce the stroma. The model not only established the spatial heterogeneity but also recapitulated biological function such as fibroblast-driven angiogenesis, as demonstrated by a 3.4-fold increase in microvascular density and a 2.3-fold extension in total vessel length. Furthermore, the model exhibited 50-fold increase in drug resistance compared to two-dimensional (2D) cultures. Additionally, the long-term cryopreservation stability and scalability endowed the model with the potential to be a tool for on-demand use. This work provides a potential platform for drug screening and mechanistic investigation of tumor biology.
{"title":"Coaxial bioprinting of microsphere bioink to engineer heterogeneous vascularized lung cancer model","authors":"Qiulei Gao , Zhongwei Guo , Shiqiang Zhang , Jingjing Xia , Junfu Li , Tianying Yuan , Jiyu Chen , Yongcong Fang , Jingjiang Qiu , Ronghan Wei","doi":"10.1016/j.bioadv.2026.214741","DOIUrl":"10.1016/j.bioadv.2026.214741","url":null,"abstract":"<div><div>3D bioprinting is a promising strategy for engineering in vitro tumor models. However, replicating the intratumoral parenchyma-stroma heterogeneity remains challenging due to the poor formability of biomimetic bioinks. In this study, we developed a method to enable the direct extrusion of low-concentration gelatin-methacrylate (GelMA)/Matrigel by overcoming its rheological limitations. The bioink was then incorporated within a coaxial bioprinting system to engineer a defined tumor parenchyma-stroma interface. The coaxial lung cancer model featured a dual-layer tubular structure. In this structure, the inner microsphere bioink was designed to mimic the tumor parenchyma, and the surrounding HAMA/Fibrin hydrogel was used to reproduce the stroma. The model not only established the spatial heterogeneity but also recapitulated biological function such as fibroblast-driven angiogenesis, as demonstrated by a 3.4-fold increase in microvascular density and a 2.3-fold extension in total vessel length. Furthermore, the model exhibited 50-fold increase in drug resistance compared to two-dimensional (2D) cultures. Additionally, the long-term cryopreservation stability and scalability endowed the model with the potential to be a tool for on-demand use. This work provides a potential platform for drug screening and mechanistic investigation of tumor biology.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"183 ","pages":"Article 214741"},"PeriodicalIF":6.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081867","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 : 2026-01-29DOI: 10.1016/j.bioadv.2026.214740
Yinan Wang, Ziyang Liu, Xiaoxuan Wu, Lei Zhang, Jinwen Wang, Yiran Zhao, Lijun Fan, Yiming Sun, Lu Lv, Zhen Yang, Huan Zhou, Lei Yang
Intraoperative bleeding associated with bone defects often impairs surgical outcomes. Traditional hemostatic bone wax acts as a passive, non-degradable barrier, whose biological inertness typically triggers inflammation and hinders bone regeneration. To overcome the limitations of bioinert bone wax, absorbable alternatives composed of bioceramic particles and absorbable polymer matrices have been attempted. However, in clinical practice such as endoscopic orthopedic procedures, the applied hemostatic agent needs to resist washout in dynamic aqueous environments, adhere firmly to bleeding bone surfaces, and form an in situ physical matrix for dual hemostatic and osteogenic functions. To address this need, we prepared a self-setting, fluid-resistant composite candidate: magnesium phosphate-based bone putty (MPP). This material is formulated with magnesium oxide (MgO) and dipotassium hydrogen phosphate (K₂HPO₄) dispersed in a pregelatinized starch-polyethylene glycol (PEG) matrix. MPP can undergo rapid acid-base reactions in aqueous environments to form a magnesium phosphate matrix in situ, which converts the putty-like paste into a bone-like solid in the bleeding area. In vitro tests such as underwater adhesion, liquid sealing, hemocompatibility, and cytocompatibility verified the prospects of MPP in dynamic aqueous environments. Moreover, the as-formed matrix degraded gradually, with mass loss increasing from 22.44 ± 1.97% on day 1 to 34.52 ± 2.55% on day 7. Besides, MPP exhibited stronger coagulation activation than bone wax, along with a low hemolysis rate of 3.24 ± 1.36% and enhanced osteoblast adhesion, proliferation, and alkaline phosphatase (ALP) expression. In vivo rat models further confirmed that MPP outperformed commercial bone wax in intraoperative hemostasis and postoperative bone regeneration. Ultimately, MPP is highlighted for its immediate bleeding control and sustained osteogenesis, capable of serving as a promising orthopedic hemostatic agent for clinical applications.
{"title":"A self-setting magnesium phosphate bone putty for effective hemostasis and osteogenesis in bleeding bone defect.","authors":"Yinan Wang, Ziyang Liu, Xiaoxuan Wu, Lei Zhang, Jinwen Wang, Yiran Zhao, Lijun Fan, Yiming Sun, Lu Lv, Zhen Yang, Huan Zhou, Lei Yang","doi":"10.1016/j.bioadv.2026.214740","DOIUrl":"https://doi.org/10.1016/j.bioadv.2026.214740","url":null,"abstract":"<p><p>Intraoperative bleeding associated with bone defects often impairs surgical outcomes. Traditional hemostatic bone wax acts as a passive, non-degradable barrier, whose biological inertness typically triggers inflammation and hinders bone regeneration. To overcome the limitations of bioinert bone wax, absorbable alternatives composed of bioceramic particles and absorbable polymer matrices have been attempted. However, in clinical practice such as endoscopic orthopedic procedures, the applied hemostatic agent needs to resist washout in dynamic aqueous environments, adhere firmly to bleeding bone surfaces, and form an in situ physical matrix for dual hemostatic and osteogenic functions. To address this need, we prepared a self-setting, fluid-resistant composite candidate: magnesium phosphate-based bone putty (MPP). This material is formulated with magnesium oxide (MgO) and dipotassium hydrogen phosphate (K₂HPO₄) dispersed in a pregelatinized starch-polyethylene glycol (PEG) matrix. MPP can undergo rapid acid-base reactions in aqueous environments to form a magnesium phosphate matrix in situ, which converts the putty-like paste into a bone-like solid in the bleeding area. In vitro tests such as underwater adhesion, liquid sealing, hemocompatibility, and cytocompatibility verified the prospects of MPP in dynamic aqueous environments. Moreover, the as-formed matrix degraded gradually, with mass loss increasing from 22.44 ± 1.97% on day 1 to 34.52 ± 2.55% on day 7. Besides, MPP exhibited stronger coagulation activation than bone wax, along with a low hemolysis rate of 3.24 ± 1.36% and enhanced osteoblast adhesion, proliferation, and alkaline phosphatase (ALP) expression. In vivo rat models further confirmed that MPP outperformed commercial bone wax in intraoperative hemostasis and postoperative bone regeneration. Ultimately, MPP is highlighted for its immediate bleeding control and sustained osteogenesis, capable of serving as a promising orthopedic hemostatic agent for clinical applications.</p>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"183 ","pages":"214740"},"PeriodicalIF":6.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101103","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}
Bone defects with irregular geometries and high infection risk remain a major clinical challenge. Injectable bone grafts (IBGs) offer minimally invasive and moldable solutions, yet conventional β-tricalcium phosphate (β-TCP)-based formulations often lack sufficient mechanical strength and antimicrobial activity. Here, a dual-functional β-TCP-based putty-form IBG was developed by combining powdered and sintered granules at optimized ratios to enhance mechanical stability, osteogenic potential, and handling properties. Antimicrobial peptides (AMPs), KR-12 and its anti-MRSA analog KR-12-a5, were covalently immobilized onto β-TCP surfaces via cold atmospheric plasma (CAP), which created reactive sites without compromising structural integrity to ensure stable peptide conjugation and sustained antimicrobial activity. The AMP-functionalized IBGs demonstrated potent anti-biofilm activity against Staphylococcus aureus, Escherichia coli, multidrug-resistant Pseudomonas aeruginosa, and MRSA with KR-12-a5, while KR-12 more effectively promoted human mesenchymal stem cell (hMSC) viability, osteogenic differentiation, and extracellular matrix deposition. Osteogenic markers were analyzed using alkaline phosphatase (ALP) activity and collagen deposition to assess protein levels, and the expression of OCN, OPN, COL1, ALP and RUNX2 genes was evaluated by quantitative PCR (qPCR). To our knowledge, this is the first injectable bone graft that simultaneously integrates osteogenic and broad-spectrum anti-biofilm functionalities for treating complex, infection-prone, and irregularly shaped bone defects.
{"title":"Dual-functional β-TCP based injectable bone grafts functionalized with peptides for enhanced osteogenesis and broad-spectrum biofilm inhibition","authors":"Eda Bilgiç , Şevval Özkaya , Duygu Gençer , Ozan Karaman , Günnur Pulat","doi":"10.1016/j.bioadv.2026.214739","DOIUrl":"10.1016/j.bioadv.2026.214739","url":null,"abstract":"<div><div>Bone defects with irregular geometries and high infection risk remain a major clinical challenge. Injectable bone grafts (IBGs) offer minimally invasive and moldable solutions, yet conventional β-tricalcium phosphate (β-TCP)-based formulations often lack sufficient mechanical strength and antimicrobial activity. Here, a dual-functional β-TCP-based putty-form IBG was developed by combining powdered and sintered granules at optimized ratios to enhance mechanical stability, osteogenic potential, and handling properties. Antimicrobial peptides (AMPs), KR-12 and its anti-MRSA analog KR-12-a5, were covalently immobilized onto β-TCP surfaces via cold atmospheric plasma (CAP), which created reactive sites without compromising structural integrity to ensure stable peptide conjugation and sustained antimicrobial activity. The AMP-functionalized IBGs demonstrated potent anti-biofilm activity against <em>Staphylococcus aureus</em>, <em>Escherichia coli</em>, multidrug-resistant <em>Pseudomonas aeruginosa</em>, and MRSA with KR-12-a5, while KR-12 more effectively promoted human mesenchymal stem cell (hMSC) viability, osteogenic differentiation, and extracellular matrix deposition. Osteogenic markers were analyzed using alkaline phosphatase (ALP) activity and collagen deposition to assess protein levels, and the expression of OCN, OPN, COL1, ALP and RUNX2 genes was evaluated by quantitative PCR (qPCR). To our knowledge, this is the first injectable bone graft that simultaneously integrates osteogenic and broad-spectrum anti-biofilm functionalities for treating complex, infection-prone, and irregularly shaped bone defects.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"183 ","pages":"Article 214739"},"PeriodicalIF":6.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081884","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 : 2026-01-28DOI: 10.1016/j.bioadv.2026.214738
Kanzal Abbas, Aimen Masaud Khan, Muhammad Shahbaz Nawaz, Tayyba Sher Waris, Aamir Razaq, Anwarul Hasan, Sheila MacNeil, Muhammad Yar
This study reports the development of dual-functional, dissolvable microneedle array patches (MN) integrating chitosan, polyvinyl alcohol (PVA), tetraethyl orthosilicate (TEOS), 2-deoxy-d-ribose (2dDR), and zinc oxide (ZnO) for chronic wound healing applications. The developed MN arrays were characterized using FTIR and SEM, which confirmed the successful incorporation of all components without any undesired chemical reactions, as well as the maintenance of sharp structural integrity of the MNs. Drug release studies demonstrated rapid 2dDR delivery, along with successful penetration into goat ear pinna skin, while antibacterial assays showed concentration-dependent inhibition of S. aureus, E. coli, P. aeruginosa, and Methicillin-Resistant S. aureus by ZnO-containing MNs. Biocompatibility and regenerative potential were assessed through cell viability, fibroblast migration, and CAM assays, indicating enhanced angiogenesis and cell proliferation. In Vivo evaluation using a Sprague-Dawley rat full-thickness wound model revealed that the D1Z-MN formulation (0.1% ZnO) achieved the highest wound closure rate (95% by day 11), superior neovascularization, reduced inflammation, greater re-epithelialization (78.33%), and increased collagen deposition (82.33%) compared to other groups. These results demonstrate that combining 2dDR with an optimal concentration of ZnO in MN patches offers a multifunctional, minimally invasive strategy for infection control, angiogenesis stimulation, and tissue regeneration in wounds.
{"title":"Development of 2-deoxy-d-ribose and zinc oxide loaded microneedle array patches of chitosan and PVA to stimulate angiogenesis and reduce infection and promote wound healing.","authors":"Kanzal Abbas, Aimen Masaud Khan, Muhammad Shahbaz Nawaz, Tayyba Sher Waris, Aamir Razaq, Anwarul Hasan, Sheila MacNeil, Muhammad Yar","doi":"10.1016/j.bioadv.2026.214738","DOIUrl":"https://doi.org/10.1016/j.bioadv.2026.214738","url":null,"abstract":"<p><p>This study reports the development of dual-functional, dissolvable microneedle array patches (MN) integrating chitosan, polyvinyl alcohol (PVA), tetraethyl orthosilicate (TEOS), 2-deoxy-d-ribose (2dDR), and zinc oxide (ZnO) for chronic wound healing applications. The developed MN arrays were characterized using FTIR and SEM, which confirmed the successful incorporation of all components without any undesired chemical reactions, as well as the maintenance of sharp structural integrity of the MNs. Drug release studies demonstrated rapid 2dDR delivery, along with successful penetration into goat ear pinna skin, while antibacterial assays showed concentration-dependent inhibition of S. aureus, E. coli, P. aeruginosa, and Methicillin-Resistant S. aureus by ZnO-containing MNs. Biocompatibility and regenerative potential were assessed through cell viability, fibroblast migration, and CAM assays, indicating enhanced angiogenesis and cell proliferation. In Vivo evaluation using a Sprague-Dawley rat full-thickness wound model revealed that the D1Z-MN formulation (0.1% ZnO) achieved the highest wound closure rate (95% by day 11), superior neovascularization, reduced inflammation, greater re-epithelialization (78.33%), and increased collagen deposition (82.33%) compared to other groups. These results demonstrate that combining 2dDR with an optimal concentration of ZnO in MN patches offers a multifunctional, minimally invasive strategy for infection control, angiogenesis stimulation, and tissue regeneration in wounds.</p>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"183 ","pages":"214738"},"PeriodicalIF":6.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121140","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}
Advancements in bone tissue engineering have increased interest in 3D-printed scaffolds for bone regeneration. Polylactic acid (PLA), a biocompatible and biodegradable polyester, is a promising candidate for bone scaffold materials. Reinforcing PLA with inorganic nanotubes of tungsten disulfide (INT-WS2) offers new possibilities for scaffold design. INT-WS2 is an innovative material known for its chemical stability, non-toxicity, and favorable mechanical properties. Integrating PLA with INT-WS2 marks a pioneering development in bone scaffold technology, providing a safer, more effective alternative to other nanofillers, such as TiO₂ nanoparticles and carbon nanotubes, which face challenges related to cytotoxicity and dispersion. This study adds an important aspect to the characterization of this material by investigating the cytocompatibility and hydrolytic degradation effects on 3D-printed samples of PLA reinforced with 0.5 wt% INT-WS2. The samples are proposed as structurally suitable candidate for load-bearing 3D-printed bone scaffolds, with the femur chosen as the upper-limit mechanical benchmark. Controlled hydrolytic degradation of PLA/INT-WS2 samples was conducted over 12 weeks under human-body simulated conditions. Results demonstrated that the material underwent bulk degradation while maintaining mass and surface hardness. Although the ultimate tensile strength progressively decreased to two-thirds of its initial value, potentially allowing gradual loading of the growing bone, it remained significantly higher than the maximum stress experienced by the human femur during normal walking. Furthermore, the PLA/INT-WS2 nanocomposite exhibited non-toxic behavior, promoting cell viability and proliferation. Despite the need for a longer experiment to fully assess the degradation rate, these findings support PLA/INT-WS2 as a promising candidate for tailored 3D-printed bone scaffolds designed for individual patients.
{"title":"Biocompatibility and degradation of PLA reinforced with tungsten disulfide nanotubes for 3D-printed bone scaffold.","authors":"Ofek Golan, Noa Granada, Lin Lemesh, Salome Azoulay-Ginsburg, Francesca Netti, Vania Altobelli, Roey J Amir, Lihi Adler-Abramovich, Noa Lachman","doi":"10.1016/j.bioadv.2026.214736","DOIUrl":"https://doi.org/10.1016/j.bioadv.2026.214736","url":null,"abstract":"<p><p>Advancements in bone tissue engineering have increased interest in 3D-printed scaffolds for bone regeneration. Polylactic acid (PLA), a biocompatible and biodegradable polyester, is a promising candidate for bone scaffold materials. Reinforcing PLA with inorganic nanotubes of tungsten disulfide (INT-WS<sub>2</sub>) offers new possibilities for scaffold design. INT-WS<sub>2</sub> is an innovative material known for its chemical stability, non-toxicity, and favorable mechanical properties. Integrating PLA with INT-WS<sub>2</sub> marks a pioneering development in bone scaffold technology, providing a safer, more effective alternative to other nanofillers, such as TiO₂ nanoparticles and carbon nanotubes, which face challenges related to cytotoxicity and dispersion. This study adds an important aspect to the characterization of this material by investigating the cytocompatibility and hydrolytic degradation effects on 3D-printed samples of PLA reinforced with 0.5 wt% INT-WS<sub>2</sub>. The samples are proposed as structurally suitable candidate for load-bearing 3D-printed bone scaffolds, with the femur chosen as the upper-limit mechanical benchmark. Controlled hydrolytic degradation of PLA/INT-WS<sub>2</sub> samples was conducted over 12 weeks under human-body simulated conditions. Results demonstrated that the material underwent bulk degradation while maintaining mass and surface hardness. Although the ultimate tensile strength progressively decreased to two-thirds of its initial value, potentially allowing gradual loading of the growing bone, it remained significantly higher than the maximum stress experienced by the human femur during normal walking. Furthermore, the PLA/INT-WS<sub>2</sub> nanocomposite exhibited non-toxic behavior, promoting cell viability and proliferation. Despite the need for a longer experiment to fully assess the degradation rate, these findings support PLA/INT-WS<sub>2</sub> as a promising candidate for tailored 3D-printed bone scaffolds designed for individual patients.</p>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"183 ","pages":"214736"},"PeriodicalIF":6.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121134","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 : 2026-01-26DOI: 10.1016/j.bioadv.2026.214734
Cong Wang , Ke Che , Qi Zheng , Guanglei Zhang , Gaocheng Shi , Huihui Meng , Hao Yu , Junsong Wang
Current therapies for ischemic stroke lack the capacity to simultaneously restore metabolic homeostasis, repair the neurovascular unit, and deliver hydrophobic neuroprotectants across the blood-brain barrier.
Here, we demonstrate that extracellular vesicles derived from Ligusticum sinense chuanxiong (CXEVs)—nanoscale particles of 167.1 ± 3.3 nm—are naturally enriched in phthalides (∼60%), including ligustilide and butylphthalide derivatives. Following systemic administration, CXEVs efficiently cross the blood-brain barrier, accumulating in ischemic brain tissue with peak concentration at 12 h. In photothrombotic stroke mice, CXEVs dose-dependently improved motor coordination and reduced anxiety-like behaviors. Untargeted metabolomics revealed that CXEVs reprogrammed 30 key metabolites across seven pathways, notably restoring arginine–proline, methionine, purine, and tyrosine metabolism—thereby mitigating ammonia toxicity, oxidative stress, and energy failure. Concurrently, CXEVs activated VEGF signaling by upregulating VEGFA and NOS3 while normalizing KDR and MAPK1 expression, driving endothelial migration, tube formation in vitro, and vascular regeneration in zebrafish. To enhance therapeutic potency, we engineered G3702-loaded CXEVs (G3702@CXEVs) with optimal loading efficiency (1:2 w/w), exceptional stability over 30 days, and sustained release without burst effect. Critically, G3702@CXEVs outperformed either free G3702 or blank CXEVs alone in promoting functional recovery, preserving cortical architecture, and synergistically enhancing both neurogenesis (BrdU+/DCX+ cells) and angiogenesis (BrdU+/CD31+ microvessels).
CXEVs represent a novel, multifunctional nanoplatform that integrates intrinsic phytochemical-mediated metabolic reprogramming with innate brain-targeting capability. When loaded with G3702, they form a synergistic “therapy-and-delivery” system that concurrently rescues neuronal and vascular injury after stroke. This work establishes plant-derived EVs as a low-cost, scalable, and dual-action nanomedicine platform for complex neurological disorders.
{"title":"Plant-derived extracellular vesicles as a dual-function nanoplatform for synergistic neurovascular repair in ischemic stroke","authors":"Cong Wang , Ke Che , Qi Zheng , Guanglei Zhang , Gaocheng Shi , Huihui Meng , Hao Yu , Junsong Wang","doi":"10.1016/j.bioadv.2026.214734","DOIUrl":"10.1016/j.bioadv.2026.214734","url":null,"abstract":"<div><div>Current therapies for ischemic stroke lack the capacity to simultaneously restore metabolic homeostasis, repair the neurovascular unit, and deliver hydrophobic neuroprotectants across the blood-brain barrier.</div><div>Here, we demonstrate that extracellular vesicles derived from <em>Ligusticum sinense</em> chuanxiong (CXEVs)—nanoscale particles of 167.1 ± 3.3 nm—are naturally enriched in phthalides (∼60%), including ligustilide and butylphthalide derivatives. Following systemic administration, CXEVs efficiently cross the blood-brain barrier, accumulating in ischemic brain tissue with peak concentration at 12 h. In photothrombotic stroke mice, CXEVs dose-dependently improved motor coordination and reduced anxiety-like behaviors. Untargeted metabolomics revealed that CXEVs reprogrammed 30 key metabolites across seven pathways, notably restoring arginine–proline, methionine, purine, and tyrosine metabolism—thereby mitigating ammonia toxicity, oxidative stress, and energy failure. Concurrently, CXEVs activated VEGF signaling by upregulating VEGFA and NOS3 while normalizing KDR and MAPK1 expression, driving endothelial migration, tube formation in vitro, and vascular regeneration in zebrafish. To enhance therapeutic potency, we engineered G3702-loaded CXEVs (G3702@CXEVs) with optimal loading efficiency (1:2 w/w), exceptional stability over 30 days, and sustained release without burst effect. Critically, G3702@CXEVs outperformed either free G3702 or blank CXEVs alone in promoting functional recovery, preserving cortical architecture, and synergistically enhancing both neurogenesis (BrdU<sup>+</sup>/DCX<sup>+</sup> cells) and angiogenesis (BrdU<sup>+</sup>/CD31<sup>+</sup> microvessels).</div><div>CXEVs represent a novel, multifunctional nanoplatform that integrates intrinsic phytochemical-mediated metabolic reprogramming with innate brain-targeting capability. When loaded with G3702, they form a synergistic “therapy-and-delivery” system that concurrently rescues neuronal and vascular injury after stroke. This work establishes plant-derived EVs as a low-cost, scalable, and dual-action nanomedicine platform for complex neurological disorders.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214734"},"PeriodicalIF":6.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078211","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 : 2026-01-26DOI: 10.1016/j.bioadv.2026.214733
Wenyi Huang, Tongshan Su, Jiacheng Fan, Xianxian Chen, Sen Ye, Xianjie Chen, Yu Li, Qian Shen, Miaochun Huang, Hui Li, Yu Yan, Chun Li
This study aimed to elucidate the mechanism through which luteolin/polyvinyl alcohol/sodium alginate (Lut/PVA/SA) hydrogel promotes the healing of pressure injury (PI), thereby offering optimized strategies for clinical management. Four formulations of PVA/SA hydrogel were synthesized using chemical cross-linking combined with freeze-thaw cycles. The optimal formulation was then selected based on its physicochemical properties to construct the Lut/PVA/SA drug delivery system. The characterization and biocompatibility of the materials were evaluated by CCK-8 assay, PI/Calcein-AM double staining, and Fourier transform infrared spectroscopy. A stage II PI model was established in Sprague-Dawley (SD) rats to evaluate therapeutic efficacy and histopathological changes. Network pharmacology identified potential targets of Lut, with KEGG enrichment analysis and systematic literature review predicting the underlying mechanisms. RT-qPCR, Western blotting and immunofluorescence were performed to assess anti-inflammatory, antioxidant and anti-apoptotic effects of the hydrogel. The result showed that Lut/PVA/SA hydrogel exhibited superior physicochemical properties and significantly accelerated wound healing. Treatment with the hydrogel enhanced collagen deposition and increased expression of α-SMA and Collagen I. Compared with model group, treatment with Lut/PVA/SA hydrogel activated the NRF2/HO-1 signaling pathway, upregulated the level of SOD and CAT, while downregulated the level of MDA. Additionally, in the Lut/PVA/SA hydrogel groups, the expression of pro-apoptotic proteins BAX and Caspase 3 were downregulated, the expression of anti-apoptotic protein BCL2 was upregulated, resulting in the restoration of the BAX/BCL2 ratio. The expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) were significantly suppressed. In conclusion, Lut/PVA/SA hydrogel can effectively promote the healing of stage II PI in SD rats. Its therapeutic effect may be attributed to the enhanced antioxidant capacity by activating the NRF2/HO-1 pathway, regulating the BAX/BCL2 ratio to inhibit fibroblast apoptosis, further alleviating the inflammatory microenvironment. These actions collectively promote collagen synthesis to facilitate wound repair.
{"title":"Luteolin/polyvinyl alcohol/sodium alginate hydrogel enhances fibroblast-mediated tissue repair and facilitates pressure injury healing.","authors":"Wenyi Huang, Tongshan Su, Jiacheng Fan, Xianxian Chen, Sen Ye, Xianjie Chen, Yu Li, Qian Shen, Miaochun Huang, Hui Li, Yu Yan, Chun Li","doi":"10.1016/j.bioadv.2026.214733","DOIUrl":"https://doi.org/10.1016/j.bioadv.2026.214733","url":null,"abstract":"<p><p>This study aimed to elucidate the mechanism through which luteolin/polyvinyl alcohol/sodium alginate (Lut/PVA/SA) hydrogel promotes the healing of pressure injury (PI), thereby offering optimized strategies for clinical management. Four formulations of PVA/SA hydrogel were synthesized using chemical cross-linking combined with freeze-thaw cycles. The optimal formulation was then selected based on its physicochemical properties to construct the Lut/PVA/SA drug delivery system. The characterization and biocompatibility of the materials were evaluated by CCK-8 assay, PI/Calcein-AM double staining, and Fourier transform infrared spectroscopy. A stage II PI model was established in Sprague-Dawley (SD) rats to evaluate therapeutic efficacy and histopathological changes. Network pharmacology identified potential targets of Lut, with KEGG enrichment analysis and systematic literature review predicting the underlying mechanisms. RT-qPCR, Western blotting and immunofluorescence were performed to assess anti-inflammatory, antioxidant and anti-apoptotic effects of the hydrogel. The result showed that Lut/PVA/SA hydrogel exhibited superior physicochemical properties and significantly accelerated wound healing. Treatment with the hydrogel enhanced collagen deposition and increased expression of α-SMA and Collagen I. Compared with model group, treatment with Lut/PVA/SA hydrogel activated the NRF2/HO-1 signaling pathway, upregulated the level of SOD and CAT, while downregulated the level of MDA. Additionally, in the Lut/PVA/SA hydrogel groups, the expression of pro-apoptotic proteins BAX and Caspase 3 were downregulated, the expression of anti-apoptotic protein BCL2 was upregulated, resulting in the restoration of the BAX/BCL2 ratio. The expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) were significantly suppressed. In conclusion, Lut/PVA/SA hydrogel can effectively promote the healing of stage II PI in SD rats. Its therapeutic effect may be attributed to the enhanced antioxidant capacity by activating the NRF2/HO-1 pathway, regulating the BAX/BCL2 ratio to inhibit fibroblast apoptosis, further alleviating the inflammatory microenvironment. These actions collectively promote collagen synthesis to facilitate wound repair.</p>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"183 ","pages":"214733"},"PeriodicalIF":6.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127413","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}
Corneal neovascularization (CNV) is a sight-threatening pathological process that poses the challenge of controlling inflammation, preventing infection, and thereby inhibiting angiogenesis. To address this, we developed a novel pH-responsive smart micelle-integrated hydrogel, termed LEV@DG-HPMC. This system is composed of a three-dimensional network formed by dipotassium glycyrrhizinate (DG) and hydroxypropyl methylcellulose (HPMC) for the delivery of levofloxacin (LEV). The hydrogel network is formed by physical cross-linking. Within this system, LEV provides potent antibacterial activity, while DG contributes inherent anti-inflammatory properties. The LEV@DG-HPMC hydrogel demonstrated excellent biocompatibility and significantly prolonged ocular surface retention. Its unique pH-responsive drug release profile closely matched the temporal pH changes in the pathological microenvironment post-alkali injury. Crucially, the hydrogel exhibited synergistic therapeutic effects, combining potent antibacterial activity with the ability to significantly downregulate key inflammatory cytokines and suppress pro-angiogenic factors, such as such as interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, nuclear factor-κB, vascular endothelial growth factor A, matrix metalloproteinase-9. Consequently, it effectively inhibited CNV progression, reduced corneal opacity, and promoted corneal repair. This multifunctional smart hydrogel represents a highly promising strategy for the treatment of CNV.
{"title":"Micelle-integrated hydrogel combined with pH-response boosts eye burns therapy by inhibiting neovascularization, regulating inflammation and bacteriostasis.","authors":"Yahong Li, Xinyuan Wang, Meina Wu, Jieying Ren, Yanan Wang, Chaochao Wen, Xia Sen, Qingjun Tian, Yijie Wang, Yumeng Guo, Jian Xue, Yajian Duan, Tao Gong, Baofeng Yu","doi":"10.1016/j.bioadv.2026.214732","DOIUrl":"https://doi.org/10.1016/j.bioadv.2026.214732","url":null,"abstract":"<p><p>Corneal neovascularization (CNV) is a sight-threatening pathological process that poses the challenge of controlling inflammation, preventing infection, and thereby inhibiting angiogenesis. To address this, we developed a novel pH-responsive smart micelle-integrated hydrogel, termed LEV@DG-HPMC. This system is composed of a three-dimensional network formed by dipotassium glycyrrhizinate (DG) and hydroxypropyl methylcellulose (HPMC) for the delivery of levofloxacin (LEV). The hydrogel network is formed by physical cross-linking. Within this system, LEV provides potent antibacterial activity, while DG contributes inherent anti-inflammatory properties. The LEV@DG-HPMC hydrogel demonstrated excellent biocompatibility and significantly prolonged ocular surface retention. Its unique pH-responsive drug release profile closely matched the temporal pH changes in the pathological microenvironment post-alkali injury. Crucially, the hydrogel exhibited synergistic therapeutic effects, combining potent antibacterial activity with the ability to significantly downregulate key inflammatory cytokines and suppress pro-angiogenic factors, such as such as interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, nuclear factor-κB, vascular endothelial growth factor A, matrix metalloproteinase-9. Consequently, it effectively inhibited CNV progression, reduced corneal opacity, and promoted corneal repair. This multifunctional smart hydrogel represents a highly promising strategy for the treatment of CNV.</p>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"183 ","pages":"214732"},"PeriodicalIF":6.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127378","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}