Acta biomaterialia最新文献

{"title":"Structure and material composition of oral disc structures in selected Anuran tadpoles (Amphibia).","authors":"Leonie Dreger, Stanislav N Gorb, Pedro Henrique Dos Santos Dias, Wencke Krings","doi":"10.1016/j.actbio.2025.04.051","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.051","url":null,"abstract":"<p><p>This study investigates the material composition of the keratinous teeth and jaw sheaths of Anuran tadpoles, for the first time. Using scanning electron microscopy (SEM), confocal laser scanning microscopy (CSLM), and energy dispersive X-ray spectroscopy (EDX), the oral discs of eight species were analysed. SEM analysis revealed structural diversity, including different tooth microstructures, which may reflect functional adaptations to different mechanical loads. CSLM imagining documented consistent autofluorescence patterns across species, with notable interspecific differences in tooth composition. EDX analysis identified a wide variety of elemental compositions, suggesting possible correlations with ecological or/and dietary factors. This study is the first on the composition of tadpole mouth parts and provides a foundation for future research on the functional morphology and biomechanics of these structures and their interplay with feeding ecology. STATEMENT OF SIGNIFICANCE: This study marks the first detailed exploration of the material composition of keratinous teeth and jaw sheaths in Anuran tadpoles, unveiling significant structural and compositional diversity. Using SEM, CSLM, and EDX analyses, it highlights interspecific differences in microstructure, autofluorescence, and elemental composition, with potential links to ecological and dietary adaptations. Notably, SEM revealed multi-layered tooth structures likely reducing abrasion, while CSLM indicated species-specific autofluorescence variations possibly linked to element distribution. Elemental analysis identified differences in sulphur, aluminium, and silicon content across species. These findings provide a critical foundation for advancing research into the functional morphology, biomechanics, and ecological roles of tadpole oral structures, paving the way for deeper understanding of their evolution and adaptive mechanisms.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-polymerized metal-phenolic ionogel with multifunctional properties towards theranostic wearable electronics.","authors":"Lanbo Shen, Tingting Kong, Jiahao Yu, Fuchun Nan, Zilong Wu, Bin Li, Jianhua Li, William W Yu","doi":"10.1016/j.actbio.2025.04.053","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.053","url":null,"abstract":"<p><p>With the rapid development of wearable technology toward integrated diagnostics and therapy, wearable electronic materials are required to possess a range of properties, such as stretchable, compressible, conductive, anti-freezing, biocompatible, and antimicrobial properties. Metal-phenolic dual-network ionogel (MP-DN ionogel) was thus prepared by using Fe^III-tannic acid and H₂O₂ as dual self-catalysis system to trigger the polymerization of hydrophilic ionic liquid monomer and hydrophobic acrylamide glycidyl ester monomer. The prepared ionogel showed well-rounded properties including high conductivity, good self-healing, anti-freezing (remains ice-free at -20 °C), anti-swelling, effective antibacterial property (anti-bacterial ratio > 99.9 %), and good cell and tissue biocompatibility. The ionogel exhibited the capability of recording electrocardiogram (ECG), electromyography (EMG), monitoring motion of finger bending and promoting wound healing. The present work provides a simple one-pot strategy to prepare multifunctional ionogels, to meet various application conditions for the next-generation theranostics wearable electronic devices. STATEMENT OF SIGNIFICANCE: 1. A dual-network ionogel with tuned mechanical properties was prepared using a simple one-pot method. 2. The ionogel exhibited superior conductivity, antifreeze, anti-swelling, good adhesion and antibacterial properties. 3. The prepared ionogel demonstrated good performance in rat ECG and EMG signal and high sensitivity to finger bending motions. 4. The ionogel could promote the healing of infected wounds. 5. Offer valuable guidance for the theranostic wearable electronics.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCL-PEtOx-based Crystalline-core Micelles for the Targeted Delivery of Paclitaxel and Trabectedin in Ovarian Cancer Therapy.","authors":"Zixiu Du, Wei Wei, Shuli Lu, Hao Wang, Chenxu Feng, Yinuo Li, Xinyi Cui, Jianan Zhe, Kuo Sun, Kuai Liu, Qiong Fan, Donglei Sun, Wei Bao","doi":"10.1016/j.actbio.2025.04.050","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.050","url":null,"abstract":"<p><p>Ovarian cancer (OC), which primarily metastasizes through ascites, is both invasive and fatal. Despite its toxicity and drug resistance, the platinum-based chemotherapy Taxol®+Carboplatin has been the first-line standard treatment for decades. Trabectedin (TBD) is a recently developed, highly effective antitumor drug that is also capable of regulating tumor-associated macrophages (TAMs), however, its severe side-effects hinder further clinical application. Here, we developed safe and efficient pH-responsive crystalline-core micelles for the combined treatment of OCs, exploiting parallel delivery of paclitaxel (PTX) and TBD. PCL-PEtOx-COOH was selected as the optimal carrier to encapsulate PTX or TBD, which self-assemble into micelles with internal crystalline cores. The carboxyl group exposed on the surface of the micelles was utilized to react with the amines of Herceptin and hyaluronic acid cross-linked polymer (Herceptin-HA) to form PTX(Target). Similarly, TBD(Target) was formed by reaction with the CD206-targeted peptide mUNO. The low critical micelle concentrations of PTX(Target) and TBD(Target) stabilize the micelles in the bloodstream and normal tissues to prevent drug release. In an acidic microenvironment, the tertiary amide group on PEtOx chain of micelles ionizes, causing disassembly and pH-responsive release. Compared with Taxol®+Carboplatin, the combination therapy displayed dramatically improved safety and efficacy, as evidenced by the elimination of peritoneal tumor spheroids and reduced expression of NOX4, a gene that is overexpressed in most OC tissues. Furthermore, in human tissues, the ROS-response gene NOX4 is linked to the development of M2-type TAMs. Collectively, this study provides a safe and effective non-platinum-based chemotherapy for OC, offering an alternative to traditional Taxol®+Carboplatin. STATEMENT OF SIGNIFICANCE: (1) Significance: This work reports a new approach for ovarian cancer (OC) treatment. We utilized trabectedin (TBD) which a recently developed, highly effective antitumor drug that is also capable of regulating tumor associated macrophages (TAMs) combined with paclitaxel (PTX) to replace platinum-based chemotherapy Taxol®+Carboplatin (TC regimen). Compared to the clinical formulations, Yondelis® and Taxol®, pH-responsive PCL-PEtOx-based crystalline-core micelles were utilized for targeted independent delivery of TBD and PTX to TAMs and tumor cells, which maintained safe and efficient transport, overcoming the challenges posed by TAMs and carboplatin resistance. The system capabilities have also been confirmed in organoid and PDX models. (2) This is the first report demonstrating that this approach simultaneously overcomes the abdominal metastasis and carboplatin resistance of OC.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-targeted manganese-based mesoporous silica nanoplatforms trigger cGAS-STING activation and sensitize anti PD-L1 therapy in triple-negative breast cancer.","authors":"Nan Zhong, Ziyue Zu, Yishi Lu, Xuan Sha, Yang Li, Yang Liu, Shangyu Lu, Xi Luo, Yan Zhou, Jun Tao, Feiyun Wu, Zhaogang Teng, Yuxia Tang, Shouju Wang","doi":"10.1016/j.actbio.2025.04.040","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.040","url":null,"abstract":"<p><p>Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway could effectively initiate antitumor immunity in triple-negative breast cancer. However, current nuclear DNA-mediated activation of STING pathway remains constrained by the tight protection of nuclear membrane and histones, highlighting the need for new strategies to enhance its efficacy. Mitochondrial DNA (mtDNA), in contrast, is more vulnerable to damage. Herein, our nanoplatforms exploited the high glutathione (GSH) environment characteristic of tumors to release abundant Mn^b+, which induced mitochondrial dysfunction and the release of endogenous mtDNA. The released mtDNA, in conjunction with Mn^b+ itself functioning as a strong cGAS agonist, effectively activated cGAS-STING pathway. Consequently, the cGAS-STING-dependent secretion of type I interferon successively enhanced the maturation of dendritic cells and cross-priming of CD8⁺ T cells. In a poorly immunogenic 4T1 tumor model, TPP-MMONs efficiently primed systemic antitumor immunity and significantly enhanced the therapeutic efficacy of αPD-L1 therapy, suppressing tumor growth in both localized and metastatic tumor models. These findings provided an innovative and straightforward strategy to enhance TNBC immunogenicity by targeting mitochondrial damage to induce mtDNA-mediated cGAS-STING activation, thereby sensitizing tumors to immune checkpoint inhibitor therapy. STATEMENT OF SIGNIFICANCE: The cGAS-STING pathway is a promising target for overcoming immunoresistance in TNBC. However, current nuclear DNA-based activation strategies are limited by the tight protection of nuclear membrane and histones. Herein, we reported novel manganese-rich, mitochondria-targeting nanoplatforms (TPP-MMONs), which can release abundant Mn²⁺ and significantly induce mitochondrial dysfunction, leading to the release of mtDNA. As a result, the nanoplatforms can effectively stimulate the cGAS-STING pathway, thereby enhancing immune responses and improving the therapeutic efficacy of αPD-L1 therapy, offering new insights into TNBC treatments.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Situ-Formed Tissue-Adhesive Macroporous Scaffolds Enhance Cell Infiltration and Tissue Regeneration.","authors":"Farnoosh Saeedinejad, Fatemeh Alipanah, Steven Toro, Noah Pereira, Delaram Ghanbariamin, Ivan Jozic, Tannin Schmidt, Elmira Arab-Tehrany, Yu Shrike Zhang, Ali Tamayol, Mohamadmahdi Samandari","doi":"10.1016/j.actbio.2025.04.049","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.049","url":null,"abstract":"<p><p>Macroporous hydrogels have shown significant promise in tissue engineering and regenerative medicine. However, conventional macroporous scaffold fabrications are complex and incompatible with in situ customization and fabrication. Here, we propose a highly translational approach for the in situ formation of adhesive macroporous scaffolds through microfluidic homogenization of gas into a self-crosslinkable gelatin transglutaminase (TG) mixture using a double syringe system. Using this strategy, the tissue defect can be evaluated, and the precursor, with the desired composition and volume, foamed and administered in situ. The TG-induced crosslinking stabilizes the pores, leading to strong tissue adhesion and accurate defect geometry approximation. We demonstrate precise control over the porosity, by changing the foaming parameters, and crosslinking kinetics, by adjusting the concentration of gelatin and TG. The resulting foam scaffolds offer controlled pore distribution, flexibility, tissue adhesion, stability, sustained protein release profile, and cell permissibility, with a faster biodegradation profile compared to bulk hydrogel compartments. Consequently, enhanced cell infiltration and reduced fibrous capsule formation are observed upon subcutaneous injection of foams compared to bulk hydrogels. Finally, the scaffolds demonstrate significant improvements in the rate and quality of the healing compared to the bulk hydrogels for the treatment of full-thickness cutaneous wounds in mice. STATEMENT OF SIGNIFICANCE: A highly translational method is presented for the in situ formation of tissue-adhesive macroporous scaffolds through microfluidic homogenization of gas into a self-crosslinkable hydrogel precursor using a double syringe system. This approach allows precise control over porosity and pore size, facilitating cell infiltration, tissue integration, and improved wound healing compared to bulk hydrogels, highlighting their potential in regenerative medicine.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual delivery of agmatine and microRNA-126b using agmatine-mediated DNA nanotube assemblies for acute lung injury therapy.","authors":"Chunfa Chen, Quan Li, Beinuo Wang, Qian Liu, Zi Wang, Bihang Zhang, Lu Wang, Yujuan Zou, Ziye Mou, Chengshan Ren, Zaichun You, Bin Wang, Zhi Xu, Hang Qian","doi":"10.1016/j.actbio.2025.04.044","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.044","url":null,"abstract":"<p><p>Acute lung injury (ALI) is characterized by widespread inflammation and oxidative stress, leading to impaired gas exchange and significant morbidity. In this study, we propose a potential approach using a magnesium-free DNA self-assembly strategy to assemble a DNA nanotube that carries agmatine and microRNA-126b mimics (NT^AGM-126). Agmatine not only reduces electrostatic repulsion between DNA helices, thereby facilitating the folding of the DNA nanotube, but also serves as a drug that inhibits iNOS signaling. The microRNA-126b mimics restore the downregulated microRNA-126b in macrophages and suppress inflammation by targeting high mobility group box 1 (HMGB1). Preliminary results indicated that agmatine can effectively facilitate the assembly of the DNA nanotube, improve serum stability, and enhance the cellular uptake efficiency of NT^AGM-126. Further in vitro and in vivo results demonstrate that NT^AGM-126 effectively reduces oxidative stress and inflammation by downregulating iNOS and HMGB1, providing a combined therapeutic effect in ALI. This study highlights the potential of agmatine-facilitated DNA nanostructures as a versatile drug delivery platform for treating inflammatory diseases, broadening the application of DNA nanotechnology in biomedical research. STATEMENT OF SIGNIFICANCE: This study introduces a promising therapeutic approach using a magnesium-free DNA self-assembly strategy to create a DNA nanotube (NT^AGM-126) that carries agmatine and microRNA-126b mimics. The agmatine not only aids in the assembly and stability of the DNA nanotube but also inhibits iNOS signaling, while the microRNA-126b mimics restore downregulated microRNA-126b in macrophages and suppress inflammation by targeting HMGB1. Preliminary and further results demonstrate that NT^AGM-126 effectively reduces oxidative stress and inflammation, providing a combined therapeutic effect in ALI. This study underscores the potential of agmatine-facilitated DNA nanostructures as a versatile drug delivery platform, broadening the application of DNA nanotechnology in the treatment of inflammatory diseases and advancing biomedical research.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-velocity impact resistance of bio-inspired interlayer hybrid composite laminates with a gradient waviness structure.","authors":"Shicai Zhao, Deyuan Zhang","doi":"10.1016/j.actbio.2025.04.046","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.046","url":null,"abstract":"<p><p>This study explores a bio-inspired design methodology for interlayer layups in hybrid carbon fiber reinforced polymer composites to enhance impact resistance. An impact-resistant and damage tolerance gradient waviness structure is discovered in the rapid mandible strike of trap-jaw ants. Inspired by this natural design, a gradient waviness structure was incorporated into fiber interlayer formation to improve impact resistance. Bio-inspired interlayer hybrid laminates, combining unidirectional fibers with multiple woven fabric arrangements, were fabricated using a mold press forming technique. The results demonstrate that the bio-inspired gradient waviness structure plays a crucial role in limiting crack propagation and generating large in elastic deformation. The 3K-PUP laminate exhibited a 10.2 % increase in peak contact force, an impressive 80.7 % reduction in damage area upon impact, and a 46.2 % increase in energy dissipation compared to traditional laminates. Additionally, the hybrid laminates displayed superior load-bearing capacity, with the 3K-PUP laminate achieving a 6.6 % increase in residual compressive strength. The bio-inspired laminates effectively provided crack tip shielding and enhanced fracture resistance mechanisms, significantly improving damage tolerance against through-the-thickness diffusion of impact damage. STATEMENT OF SIGNIFICANCE: An impact-resistant and damage tolerance gradient waviness structure is discovered in the rapid mandible strike of trap-jaw ants. Inspired by this natural design, a gradient waviness structure was incorporated into fiber interlayer formation to improve impact resistance. Bio-inspired interlayer hybrid laminates, combining unidirectional fibers with multiple woven fabric arrangements, were fabricated using a mold press forming technique. The results demonstrate that the bio-inspired gradient waviness structure plays a crucial role in limiting crack propagation and generating large in elastic deformation. The bio-inspired laminates effectively provided crack tip shielding and enhanced fracture resistance mechanisms, significantly improving damage tolerance against through-the-thickness diffusion of impact damage.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shape-adaptive, deformable and adhesive hydrogels enable stable closure of long incision wounds.","authors":"Xiaojun Zeng, Wenguang Dou, Shuzhuang Zhu, Ye Zhu, Weijun Ji, Mingxue Sun, Jin Zhao, Xubo Yuan, Hongliang Liu, Yansheng Li, Yonglin Gao, Sidi Li","doi":"10.1016/j.actbio.2025.04.045","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.045","url":null,"abstract":"<p><p>Effective closure of long incision wounds is crucial in clinical practice but remains challenging for existing bioadhesives due to the deformations of the long incisions. Herein, we propose a concept of shape-adaptive adhesion and achieve it by designing a class of shape-adaptive, deformable adhesive hydrogels (DAHs) for long incision wound closure. The design strategy is facile yet universally applicable, which involves aldehyde polysaccharides as adhesive primers and microgel-type gelators as building blocks. We demonstrate that the microgel-type gelators are responsible for the integration of a deformable matrix in situ, and aldehyde polysaccharides enhance the adhesive performance of the matrix at cost of a little deformability. Optimization of the flexibility of DAH network is effective in balancing the adhesive and deformable properties, thus developing DAHs featured with the adaptability to irregular shapes, robust adhesive properties, and appropriate deformability. As a result, DAHs achieve shape-adaptive adhesion by effectively bonding the long incision and deforming with it without failure. In vivo results clearly show that DAHs stably close the 4 cm-long incision wounds on the backs and the more dynamic incisions on the napes of rats. The shape-adaptive adhesion achieved by DAHs may provide an alternative way for long incision wound treatment. STATEMENT OF SIGNIFICANCE: Bioadhesive is emerging as an effective tool in clinical wound treatment. However, the closure of severe long incision wounds by currently available bioadhesives is still challenging. In this work, we proposed a concept of shape-adaptive adhesion and accordingly developed a bioadhesive building strategy for long incision wound closure. The strategy is universally applicable, which involves aldehyde polysaccharide as an adhesive primer and microgel-type gelators as building blocks. The results showed that the strategy is effective in developing bioadhesives (DAHs) that simultaneously possess shape-adaptive properties, robust adhesive properties and appropriate deformability, thus overcoming the limitations of most existing bioadhesives. With these features, DAHs successfully achieved shape-adaptive adhesion and stable closure of long incision wounds, providing an effective way for wound treatment.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained ROS Scavenging and Pericellular Oxygenation by Lignin Composites Rescue HIF-1α and VEGF Levels to Improve Diabetic Wound Neovascularization and Healing.","authors":"Jangwook P Jung, Oluyinka O Olutoye, Tanuj J Prajati, Olivia S Jung, Lane D Yutzy, Kenny L Nguyen, Stephen W Wheat, JoAnne Huang, Benjamin W Padon, Fayiz Faruk, Sonya S Keswani, Phillip Kogan, Aditya Kaul, Ling Yu, Hui Li, Shiyanth Thevasagayampillai, Mary E Guerra, Walker D Short, Preethi H Gunaratne, Swathi Balaji","doi":"10.1016/j.actbio.2025.04.047","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.047","url":null,"abstract":"<p><p>Although delayed wound healing is an important clinical complication in diabetic patients, few targeted treatments are available, and it remains a challenge to promote diabetic wound healing. Impaired neovascularization is one of the prime characteristics of the diabetic phenotype of delayed wound healing. Additionally, increased levels of reactive oxygen species (ROS) and chronic low-grade inflammation and hypoxia are associated with diabetes, which disrupts mechanisms of wound healing. We developed lignosulfonate composites with several wound healing properties, including sustained oxygen release through calcium peroxide nanoparticles and reactive oxygen species and free radical scavenging by thiolated lignosulfonate nanoparticles. Sustained release of oxygen and ROS-scavenging by these composites promoted endothelial cell (EC) branching and characteristic capillary-like network formation under high glucose conditions in vitro. Gene co-expression network analysis of RNA-sequencing results from ECs cultured on lignin composites showed regulation of inflammatory pathways, alongside the regulation of angiogenic hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth (VEGF) factor pathways. In vivo, lignosulfonate composite treatment promoted VEGF expression and angiogenesis in full thickness skin wounds in diabetic mice, a model of delayed wound healing. Treatment of diabetic wounds with lignosulfonate composites also promoted faster epithelial gap closure and increased granulation tissue deposition by day 7 post-wounding, with a higher presence of pro-healing type macrophages. Our findings demonstrate that lignosulfonate composites promote diabetic wound healing without requiring additional drugs. This highlights the potential of functionalized lignosulfonate for wound healing applications that require balanced antioxidation and controlled oxygen release. STATEMENT OF SIGNIFICANCE: The lignosulfonate composites developed in this study offer a promising solution for delayed wound healing in diabetic patients. By effectively addressing key factors contributing to the multifaceted pathophysiology of the diabetic wounds, including impaired neovascularization, increased ROS levels, and chronic inflammation and wound proteolysis, these composites demonstrate significant potential for promoting wound repair and reducing the complications associated with diabetic wounds. The unique combination of pro-angiogenic, oxygen-releasing, ECM remodeling and antioxidant properties in these lignosulfonate-based materials highlights their potential as a valuable therapeutic option, providing a multi-pronged approach to diabetic wound healing without the need for additional drugs.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-activated microspheres for enhanced chemoembolization of hepatocellular carcinoma by blocking the adenosine A2A receptor.","authors":"Minjiang Chen, Yaning Chen, Weiqian Chen, Xiaoxiao Chen, Xiaoju Guo, Junchao Yu, Xinyu Guo, Mengyuan Wang, Xinyu Zhang, Qin Hu, Shiji Fang, Liyun Zheng, Zhongwei Zhao, Yongzhong Du, Gaofeng Shu, Jiansong Ji","doi":"10.1016/j.actbio.2025.04.042","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.042","url":null,"abstract":"<p><p>Transcatheter arterial chemoembolization (TACE) stands as the frontline strategy for unresectable hepatocellular carcinoma (HCC), effectively eliminating cancer cells through direct cytotoxicity and immunogenic cell death (ICD). However, TACE triggers rapid tumor apoptosis, which promotes the release of intracellular ATP into the extracellular space. This ATP is sequentially hydrolyzed to adenosine (ADO) by ectonucleotidases (CD39 and CD73) overexpressed in the tumor microenvironment (TME), resulting in ADO accumulation. The ensuing ADO pathway-mediated immunosuppression via adenosine 2A receptors (A2AR) signaling severely limits TACE-induced ICD efficacy, resulting in poor prognosis. To address this, we developed gelatin microspheres co-loaded with doxorubicin (DOX) and the A2AR antagonist SCH-58,261, in which SCH-58,261 was loaded into solid lipid nanoparticle (SLNP) due to its poor water solubility. The microspheres (SLNP-SCH/DOX@MS) showed an average size of 49 ± 13 μm, with the capable of complete tumor vascular embolization, and sustained release profiles of both DOX and SCH-58,261 over 30 days. In vitro and in vivo studies indicated that SLNP-SCH/DOX@MS not only enhanced tumor cell apoptosis but also amplified ICD-mediated dendritic cell maturation and antigen presentation. Moreover, SCH-58,261 counteracted TACE-triggered ADO accumulation by competitively binding to A2AR on immune cells, thereby reversing dendritic cell dysfunction and CD8⁺T cell exhaustion. This dual-action strategy synergized ICD-driven immunostimulation with ADO pathway blockade, reshaping the TME. Our findings highlight the potential of SLNP-SCH/DOX@MS to address the delicate equilibrium between ICD-induced immunity and ADO-mediated immunosuppression for improved HCC treatment. STATEMENT OF SIGNIFICANCE: This study introduces a approach to improve transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC) by addressing the adenosine (ADO) pathway, a known barrier to effective immunogenic cell death (ICD). We developed gelatin microspheres co-loaded with doxorubicin (DOX) and the A2AR antagonist SCH-58,261, which significantly enhance TACE-induced immunity by promoting ICD and counteracting ADO-mediated immunosuppression. In vitro and in vivo results demonstrate robust dendritic cell maturation and amplified tumor-specific immune responses, indicating improved antitumor efficacy. This work provides a promising strategy to optimize TACE for HCC treatment, offering our readership a therapeutic solution that bridges cancer treatment and immunomodulation.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}