Pub Date : 2025-11-27DOI: 10.1016/j.actbio.2025.11.054
Huiqi Zhang , Zhengmao Lu , Wenshang Liu , Dong Luo , Manman Hu , Xiaohui Pu , Zhen Fan , Zhengyu Shen , Meng Li
Persistent fibrotic scarring after cutaneous wound closure remains a major clinical burden that current prophylactic and therapeutic strategies fail to resolve, leading to marked compromise of both aesthetic and functional outcomes. Mechanotransduction cascades, and in particular Hippo-YAP signalling, are now recognised as pivotal drivers of fibrogenesis. In this study, we engineered an in situ mechanoresponsive hydrogel dressing that enables spatiotemporal control of wound-edge tension while simultaneously delivering a rationally designed peptide that antagonises YAP–TEAD association. C-terminal extension of the peptide with a cationic glycine-rich segment endowed broad-spectrum antibacterial activity and promoted self-assembly into monodisperse nanoparticles. These nanoparticles were homogeneously entrapped within a gelatin–sodium alginate network that was further functionalised with poly(N-isopropylacrylamide) to impart thermally reversible contraction. The resultant GAPNP hydrogel underwent pronounced radial shrinkage of 63.83 % at 45 °C, thereby validating its robust mechanoadaptability. In murine full-thickness excisional wounds, the dressing accelerated re-epithelialisation to 60.35 % within 48 h. Histopathological and immunohistochemical analyses revealed pronounced downregulation of YAP and alpha smooth-muscle actin, and a rabbit ear hypertrophic scar model ultimately achieved scarless regeneration. Collectively, this work establishes a previously unreported paradigm that integrates mechanomodulation with peptide-based molecular intervention and provides a clinically translatable strategy for fibrosis-free cutaneous repair.
Statement of significance
Hypertrophic scars develop in 40–70 % of wounds, particularly in high-tension anatomical sites such as joints, and inflict persistent pain, contractures, and substantial socioeconomic costs. Existing hydrogels cannot modulate the dynamic mechanical environment of healing tissue, whereas pharmacological YAP–TEAD blockade is hindered by suboptimal release profiles, unpredictable kinetics, and inadequate targeting. To overcome these limitations, we engineered a self-contractile peptide hydrogel that couples a PNIPAAm-reinforced gelatin–sodium alginate matrix with Peptide8, a YAP–TEAD antagonist rationally modified to self-assemble into antibacterial nanoparticles and to be released in a sustained manner. This concomitant mechanomodulatory and molecular intervention offers a comprehensive, clinically translatable strategy for scar-free cutaneous repair.
{"title":"Mechanically responsive yes-associated protein-inhibiting peptide hydrogel for scarless wound healing","authors":"Huiqi Zhang , Zhengmao Lu , Wenshang Liu , Dong Luo , Manman Hu , Xiaohui Pu , Zhen Fan , Zhengyu Shen , Meng Li","doi":"10.1016/j.actbio.2025.11.054","DOIUrl":"10.1016/j.actbio.2025.11.054","url":null,"abstract":"<div><div>Persistent fibrotic scarring after cutaneous wound closure remains a major clinical burden that current prophylactic and therapeutic strategies fail to resolve, leading to marked compromise of both aesthetic and functional outcomes. Mechanotransduction cascades, and in particular Hippo-YAP signalling, are now recognised as pivotal drivers of fibrogenesis. In this study, we engineered an in situ mechanoresponsive hydrogel dressing that enables spatiotemporal control of wound-edge tension while simultaneously delivering a rationally designed peptide that antagonises YAP–TEAD association. C-terminal extension of the peptide with a cationic glycine-rich segment endowed broad-spectrum antibacterial activity and promoted self-assembly into monodisperse nanoparticles. These nanoparticles were homogeneously entrapped within a gelatin–sodium alginate network that was further functionalised with poly(N-isopropylacrylamide) to impart thermally reversible contraction. The resultant GAPNP hydrogel underwent pronounced radial shrinkage of 63.83 % at 45 °C, thereby validating its robust mechanoadaptability. In murine full-thickness excisional wounds, the dressing accelerated re-epithelialisation to 60.35 % within 48 h. Histopathological and immunohistochemical analyses revealed pronounced downregulation of YAP and alpha smooth-muscle actin, and a rabbit ear hypertrophic scar model ultimately achieved scarless regeneration. Collectively, this work establishes a previously unreported paradigm that integrates mechanomodulation with peptide-based molecular intervention and provides a clinically translatable strategy for fibrosis-free cutaneous repair.</div></div><div><h3>Statement of significance</h3><div>Hypertrophic scars develop in 40–70 % of wounds, particularly in high-tension anatomical sites such as joints, and inflict persistent pain, contractures, and substantial socioeconomic costs. Existing hydrogels cannot modulate the dynamic mechanical environment of healing tissue, whereas pharmacological YAP–TEAD blockade is hindered by suboptimal release profiles, unpredictable kinetics, and inadequate targeting. To overcome these limitations, we engineered a self-contractile peptide hydrogel that couples a PNIPAAm-reinforced gelatin–sodium alginate matrix with Peptide8, a YAP–TEAD antagonist rationally modified to self-assemble into antibacterial nanoparticles and to be released in a sustained manner. This concomitant mechanomodulatory and molecular intervention offers a comprehensive, clinically translatable strategy for scar-free cutaneous repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 306-321"},"PeriodicalIF":9.6,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-27DOI: 10.1016/j.actbio.2025.11.057
Emily R. Briggs , Alexandre Xavier Mendes , Adriana Texixeira do Nascimento , Simon E. Moulton , Jonny J. Blaker , Sarah H. Cartmell
Conductive hydrogels offer an exciting opportunity to combine the hydrophilicity, biocompatibility, and tuneable viscoelastic properties of hydrogels with the conductive properties of electroactive species and conducting polymers. Reported applications of conductive hydrogels include but are not limited to electroactive wound dressings, wearable electronics, stimuli-responsive drug delivery systems, and tissue-engineered implants. With the rise of electroactive materials in biomaterials research, the electrical and electrochemical measurement techniques used to characterise their conductive properties have also emerged. The vast range of novel materials and the wide scope for application-specific requirements may leave researchers unable to discern the appropriate techniques, measurement conditions, and analysis to apply within their research. This review concisely summarises the techniques utilised to characterise the electrical properties of conductive hydrogels, including four-point probe conductivity measurements, cyclic voltammetry, and electrochemical impedance spectroscopy. Furthermore, the limitations and practical considerations of each technique are detailed. Recommendations for optimal sample preparation and experimental parameters are made, referencing current literature where conductive hydrogels have been successfully characterised. The fundamental principles of conductivity, electrical percolation, and indirect electrical stimulation are also discussed, to provide researchers with a comprehensive resource to develop and translate conductive hydrogels within biomedical research.
Statement of Significance
Electrically conductive hydrogels have gained increasing attention in wearable electronics, drug-delivery systems, and tissue engineering research. In existing literature there is a lack of standardisation in the electrical and electrochemical characterisation of these materials, as well as a variation in reported experimental conditions and data interpretation. This review is significant in providing a concise and practical resource to guide researchers in conducting accurate and impactful characterisation of the electrical properties of conductive hydrogels. It will contribute to research as a unique guide for best practise, promoting the advancement and translation of conductive hydrogels and their ever-expanding applications.
{"title":"Electrical characterisation of conductive hydrogels for biomedical applications","authors":"Emily R. Briggs , Alexandre Xavier Mendes , Adriana Texixeira do Nascimento , Simon E. Moulton , Jonny J. Blaker , Sarah H. Cartmell","doi":"10.1016/j.actbio.2025.11.057","DOIUrl":"10.1016/j.actbio.2025.11.057","url":null,"abstract":"<div><div>Conductive hydrogels offer an exciting opportunity to combine the hydrophilicity, biocompatibility, and tuneable viscoelastic properties of hydrogels with the conductive properties of electroactive species and conducting polymers. Reported applications of conductive hydrogels include but are not limited to electroactive wound dressings, wearable electronics, stimuli-responsive drug delivery systems, and tissue-engineered implants. With the rise of electroactive materials in biomaterials research, the electrical and electrochemical measurement techniques used to characterise their conductive properties have also emerged. The vast range of novel materials and the wide scope for application-specific requirements may leave researchers unable to discern the appropriate techniques, measurement conditions, and analysis to apply within their research. This review concisely summarises the techniques utilised to characterise the electrical properties of conductive hydrogels, including four-point probe conductivity measurements, cyclic voltammetry, and electrochemical impedance spectroscopy. Furthermore, the limitations and practical considerations of each technique are detailed. Recommendations for optimal sample preparation and experimental parameters are made, referencing current literature where conductive hydrogels have been successfully characterised. The fundamental principles of conductivity, electrical percolation, and indirect electrical stimulation are also discussed, to provide researchers with a comprehensive resource to develop and translate conductive hydrogels within biomedical research.</div></div><div><h3>Statement of Significance</h3><div>Electrically conductive hydrogels have gained increasing attention in wearable electronics, drug-delivery systems, and tissue engineering research. In existing literature there is a lack of standardisation in the electrical and electrochemical characterisation of these materials, as well as a variation in reported experimental conditions and data interpretation. This review is significant in providing a concise and practical resource to guide researchers in conducting accurate and impactful characterisation of the electrical properties of conductive hydrogels. It will contribute to research as a unique guide for best practise, promoting the advancement and translation of conductive hydrogels and their ever-expanding applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 23-37"},"PeriodicalIF":9.6,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-27DOI: 10.1016/j.actbio.2025.11.059
Qiuyi Yu , Huihui Zhang , Lianglong Chen , Xuerong Wei , Erlian Xie , Xinxi Zhu , Jun Ma , Lei Huang , Yanbin Gao , Zijun Zheng , Lei Yang
Platelet-rich plasma (PRP) demonstrates therapeutic potential for wound healing but is limited by its burst-release kinetics and short biological half-life. We developed snADM@PPRP, a composite biomaterial that integrates sulfonated hyaluronic acid into an acellular dermal matrix. This material employs bioorthogonal click chemistry to covalently immobilize PRP, while sulfonate groups (-SO3⁻) electrostatically sequester cationic growth factors, thereby establishing a dual-mechanism sustained-release system. In vitro, snADM@PPRP exhibited high water absorption, enhanced mechanical properties, and prolonged growth factor release, significantly promoting fibroblast adhesion, proliferation, migration, and endothelial tube formation. In a murine full-thickness wound model, snADM@PPRP accelerated healing by alleviating inflammation, enhancing neovascularization, and increasing collagen deposition, achieving near-complete closure by day 21. This bioorthogonal click chemistry-based approach provides an effective strategy for tissue regeneration with broad therapeutic potential.
Statement of significance
Platelet-rich plasma (PRP) therapy for wounds is limited due to the rapid leakage of growth factors. We developed a biomaterial scaffold that solves this problem using a unique click chemistry method to securely lock PRP in place. Furthermore, negative charges on the scaffold surface hold the positively charged growth factors, creating a dual mechanism for sustained release. In animal tests, this system significantly accelerated wound healing by promoting new blood vessel formation and tissue regeneration. Our work provides a more effective and reliable strategy for treating chronic wounds, offering a promising new tool for regenerative medicine.
{"title":"A bioorthogonal click reaction-based platelet-rich plasma delivery system for accelerating wound healing","authors":"Qiuyi Yu , Huihui Zhang , Lianglong Chen , Xuerong Wei , Erlian Xie , Xinxi Zhu , Jun Ma , Lei Huang , Yanbin Gao , Zijun Zheng , Lei Yang","doi":"10.1016/j.actbio.2025.11.059","DOIUrl":"10.1016/j.actbio.2025.11.059","url":null,"abstract":"<div><div>Platelet-rich plasma (PRP) demonstrates therapeutic potential for wound healing but is limited by its burst-release kinetics and short biological half-life. We developed snADM@PPRP, a composite biomaterial that integrates sulfonated hyaluronic acid into an acellular dermal matrix. This material employs bioorthogonal click chemistry to covalently immobilize PRP, while sulfonate groups (-SO<sub>3</sub>⁻) electrostatically sequester cationic growth factors, thereby establishing a dual-mechanism sustained-release system. <em>In vitro</em>, snADM@PPRP exhibited high water absorption, enhanced mechanical properties, and prolonged growth factor release, significantly promoting fibroblast adhesion, proliferation, migration, and endothelial tube formation. In a murine full-thickness wound model, snADM@PPRP accelerated healing by alleviating inflammation, enhancing neovascularization, and increasing collagen deposition, achieving near-complete closure by day 21. This bioorthogonal click chemistry-based approach provides an effective strategy for tissue regeneration with broad therapeutic potential.</div></div><div><h3>Statement of significance</h3><div>Platelet-rich plasma (PRP) therapy for wounds is limited due to the rapid leakage of growth factors. We developed a biomaterial scaffold that solves this problem using a unique click chemistry method to securely lock PRP in place. Furthermore, negative charges on the scaffold surface hold the positively charged growth factors, creating a dual mechanism for sustained release. In animal tests, this system significantly accelerated wound healing by promoting new blood vessel formation and tissue regeneration. Our work provides a more effective and reliable strategy for treating chronic wounds, offering a promising new tool for regenerative medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 322-338"},"PeriodicalIF":9.6,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-27DOI: 10.1016/j.actbio.2025.11.055
Bing Wu , Ye Yang , Xiancheng Huang , Yuanchao Shi , Chongzhou Fang , Fei Liu , Yang-Chi-Dung Lin , Jiaxin Wang , Jianjing Lin , Jing Mu , Xintao Zhang
Osteoarthritis (OA) is a progressive degenerative joint disease characterized by synovial inflammation and cartilage degradation, and its progression is closely related to excessive production of reactive oxygen species (ROS) and upregulation of catabolic enzymes such as matrix metalloproteinases. Here, we developed a self-assembled multifunctional polymeric nanoparticle (NP) system for the co-delivery the ROS scavenger 2,2,6,6-Tetramethylpiperidoxyl (TEMPO) and small interfering RNA (siRNA) against MMP-13 (siMMP-13). The nanoplatform is constructed from antioxidant TEMPO-PEG-PLGA and cationic PEG-PLGA-OA9 to enable efficient siRNA encapsulation and intra-articular delivery. TEMPO mimics superoxide dismutase to neutralize ROS, while siMMP-13 silences catabolic gene expression to suppress cartilage degradation. This redox- and gene-regulatory NP system demonstrated potent anti-inflammatory and cartilage-protective effects in vitro and in vivo, effectively attenuating cartilage damage and inflammation in Osteoarthritis. This work presents a promising and translational approach to Osteoarthritis treatment via integrated redox and gene regulation strategies.
Statement of significance
Osteoarthritis (OA) remains a major clinical challenge due to its complex and multifactorial pathogenesis, which current palliative therapies fail to adequately address. This study presents a novel, multifunctional therapeutic strategy that concurrently targets two critical pathological features of OA—oxidative stress and extracellular matrix degradation—through the co-delivery of a reactive oxygen species (ROS) scavenger (TEMPO) and MMP-13–targeting siRNA via a self-assembled polymeric nanoparticle system. By integrating redox modulation and gene silencing within a single nanoplatform, this approach enables precise regulation of inflammatory and catabolic pathways, thereby enhancing therapeutic efficacy and cartilage preservation. The findings offer a promising foundation for the development of next-generation disease-modifying OA therapies with strong potential for clinical translation.
{"title":"Self-assembled polymeric nanoparticles for redox- and gene-regulated Osteoarthritis therapy","authors":"Bing Wu , Ye Yang , Xiancheng Huang , Yuanchao Shi , Chongzhou Fang , Fei Liu , Yang-Chi-Dung Lin , Jiaxin Wang , Jianjing Lin , Jing Mu , Xintao Zhang","doi":"10.1016/j.actbio.2025.11.055","DOIUrl":"10.1016/j.actbio.2025.11.055","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a progressive degenerative joint disease characterized by synovial inflammation and cartilage degradation, and its progression is closely related to excessive production of reactive oxygen species (ROS) and upregulation of catabolic enzymes such as matrix metalloproteinases. Here, we developed a self-assembled multifunctional polymeric nanoparticle (NP) system for the co-delivery the ROS scavenger 2,2,6,6-Tetramethylpiperidoxyl (TEMPO) and small interfering RNA (siRNA) against MMP-13 (siMMP-13). The nanoplatform is constructed from antioxidant TEMPO-PEG-PLGA and cationic PEG-PLGA-OA9 to enable efficient siRNA encapsulation and intra-articular delivery. TEMPO mimics superoxide dismutase to neutralize ROS, while siMMP-13 silences catabolic gene expression to suppress cartilage degradation. This redox- and gene-regulatory NP system demonstrated potent anti-inflammatory and cartilage-protective effects <em>in vitro</em> and <em>in vivo</em>, effectively attenuating cartilage damage and inflammation in Osteoarthritis. This work presents a promising and translational approach to Osteoarthritis treatment via integrated redox and gene regulation strategies.</div></div><div><h3>Statement of significance</h3><div>Osteoarthritis (OA) remains a major clinical challenge due to its complex and multifactorial pathogenesis, which current palliative therapies fail to adequately address. This study presents a novel, multifunctional therapeutic strategy that concurrently targets two critical pathological features of OA—oxidative stress and extracellular matrix degradation—through the co-delivery of a reactive oxygen species (ROS) scavenger (TEMPO) and MMP-13–targeting siRNA via a self-assembled polymeric nanoparticle system. By integrating redox modulation and gene silencing within a single nanoplatform, this approach enables precise regulation of inflammatory and catabolic pathways, thereby enhancing therapeutic efficacy and cartilage preservation. The findings offer a promising foundation for the development of next-generation disease-modifying OA therapies with strong potential for clinical translation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 583-593"},"PeriodicalIF":9.6,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.actbio.2025.11.051
Ramin Shahbad , Sivapriya Kuniyil , Alexey Kamenskiy , Elizabeth Zermeno , Kaspars Maleckis , Jason MacTaggart , Anastasia Desyatova
<div><div><strong>Background:</strong> Compliance mismatch is a key contributor to adverse vascular remodeling and long-term hemodynamic complications following endovascular aortic repair. However, few in vivo studies have systematically compared the biomechanical and hemodynamic impacts of compliant versus conventional stent-grafts. <strong>Objectives:</strong> In this study, we evaluated an elastomeric nanofibrillar stent-graft (NF-SG) against a commercially available stiff stent-graft (CS-SG) in a swine model, focusing on the effect of stent-graft type on the hemodynamic indices. <strong>Methods:</strong> Twenty Yucatan minipigs were divided into three groups: Control, CS-SG, and NF-SG. The latter two underwent endovascular implantation of the stent-grafts. Hemodynamic assessments were conducted at baseline, immediately post-implantation, and at 18-week follow-up. Local PWV, pressure, pulsatility, distensibility, and harmonic waveform analyses were performed at the ascending and descending thoracic aorta. <strong>Results:</strong> CS-SG implantation led to a significant increase in PWV (from 4.72 to 7.66 m/s), marked reductions in aortic pulsatility at the stented site (from 6.4% to 1.7%), as well as suppressed harmonic contribution (from 39.3% to 29.3%) and distortion (from 0.12 to 0.05), indicating impaired distal impedance regulation. In contrast, the NF-SG preserved baseline PWV (4.69 to 5.37 m/s) and maintained physiological waveform profiles, with minimal changes in harmonic contribution and distortion. NF-SG also showed a smaller reduction in pulsatility at the stented site (from 6.1% to 3.1%). <strong>Conclusions:</strong> These findings demonstrate that NF-SG exhibits superior biomechanical compatibility by preserving aortic compliance and normal hemodynamic function. Compliant stent-grafts may offer a promising strategy to reduce the long-term cardiovascular burden associated with conventional endovascular repairs.</div></div><div><h3>Statement of Significance</h3><div>Compliance mismatch is a significant challenge in endovascular aortic repair, contributing to adverse remodeling and long-term hemodynamic complications. Despite its clinical importance, few in vivo studies have systematically compared the biomechanical and hemodynamic impacts of compliant versus conventional stent-grafts. To address this gap, we performed a longitudinal study in a porcine model, comparing the performance of an innovative elastomeric nanofibrillar stent-graft with that of a commercially available stiff stent-graft. We demonstrate that implantation of the stiff stent-graft led to significant and sustained increases in pulse wave velocity, reduced aortic pulsatility, and impaired distal impedance regulation. In contrast, our elastomeric stent-graft preserved physiological aortic compliance and hemodynamic function, with minimal disruption to harmonic waveform profiles and distal pulsatility. These findings suggest that compliant stent-grafts may offer a
{"title":"Effect of stent-graft compliance on hemodynamics and aortic stiffening in an in vivo porcine study","authors":"Ramin Shahbad , Sivapriya Kuniyil , Alexey Kamenskiy , Elizabeth Zermeno , Kaspars Maleckis , Jason MacTaggart , Anastasia Desyatova","doi":"10.1016/j.actbio.2025.11.051","DOIUrl":"10.1016/j.actbio.2025.11.051","url":null,"abstract":"<div><div><strong>Background:</strong> Compliance mismatch is a key contributor to adverse vascular remodeling and long-term hemodynamic complications following endovascular aortic repair. However, few in vivo studies have systematically compared the biomechanical and hemodynamic impacts of compliant versus conventional stent-grafts. <strong>Objectives:</strong> In this study, we evaluated an elastomeric nanofibrillar stent-graft (NF-SG) against a commercially available stiff stent-graft (CS-SG) in a swine model, focusing on the effect of stent-graft type on the hemodynamic indices. <strong>Methods:</strong> Twenty Yucatan minipigs were divided into three groups: Control, CS-SG, and NF-SG. The latter two underwent endovascular implantation of the stent-grafts. Hemodynamic assessments were conducted at baseline, immediately post-implantation, and at 18-week follow-up. Local PWV, pressure, pulsatility, distensibility, and harmonic waveform analyses were performed at the ascending and descending thoracic aorta. <strong>Results:</strong> CS-SG implantation led to a significant increase in PWV (from 4.72 to 7.66 m/s), marked reductions in aortic pulsatility at the stented site (from 6.4% to 1.7%), as well as suppressed harmonic contribution (from 39.3% to 29.3%) and distortion (from 0.12 to 0.05), indicating impaired distal impedance regulation. In contrast, the NF-SG preserved baseline PWV (4.69 to 5.37 m/s) and maintained physiological waveform profiles, with minimal changes in harmonic contribution and distortion. NF-SG also showed a smaller reduction in pulsatility at the stented site (from 6.1% to 3.1%). <strong>Conclusions:</strong> These findings demonstrate that NF-SG exhibits superior biomechanical compatibility by preserving aortic compliance and normal hemodynamic function. Compliant stent-grafts may offer a promising strategy to reduce the long-term cardiovascular burden associated with conventional endovascular repairs.</div></div><div><h3>Statement of Significance</h3><div>Compliance mismatch is a significant challenge in endovascular aortic repair, contributing to adverse remodeling and long-term hemodynamic complications. Despite its clinical importance, few in vivo studies have systematically compared the biomechanical and hemodynamic impacts of compliant versus conventional stent-grafts. To address this gap, we performed a longitudinal study in a porcine model, comparing the performance of an innovative elastomeric nanofibrillar stent-graft with that of a commercially available stiff stent-graft. We demonstrate that implantation of the stiff stent-graft led to significant and sustained increases in pulse wave velocity, reduced aortic pulsatility, and impaired distal impedance regulation. In contrast, our elastomeric stent-graft preserved physiological aortic compliance and hemodynamic function, with minimal disruption to harmonic waveform profiles and distal pulsatility. These findings suggest that compliant stent-grafts may offer a ","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 408-425"},"PeriodicalIF":9.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.actbio.2025.11.050
Yi-Jhen Lai , Po-Ju Ting , Shu-Jyuan Yang , Grace Chen , Chieh-Ming Tsai , Chih-Hao Chang , Yi-Cheun Yeh
Injectable second near-infrared (NIR-II)-responsive nanocomposite hydrogels have emerged as promising biomaterials for tumor therapy due to their ability to achieve spatiotemporal control over drug release at the targeted site. Nevertheless, the clinical translation of these hydrogels is often hindered by the poor distribution and photothermal conversion effect of the photosensitizer within the hydrogel matrix. To address these challenges, an advanced NIR-II-responsive nanocomposite hydrogel is developed by functionalizing carbon nanotubes (CNTs) with gold nanoparticles (AuNPs) and hydrophilic surfaces, positioning them as effective photosensitizers and crosslinkers. The hydrophilic AuNP-decorated CNTs and polyethyleneimine (PEI) react with alginate dialdehyde (ADA) via dynamic imine and boronate ester bonds to construct the hydrogel network. The AuNPs also form coordination and electrostatic interactions with the polymeric network. Additionally, poly(N-isopropylacrylamide) (PNIPAM) is incorporated to impart thermal-responsiveness to the hydrogel matrix. Comprehensive investigations of the microstructures, properties, and controlled drug release behavior of the nanocomposite hydrogels are conducted. Notably, the nanocomposite hydrogel enables controlled release of hydrophilic drugs under NIR-II light exposure. In vivo studies further demonstrate their synergistic chemo-photothermal effectiveness in tumor treatment. Taken together, this work introduces a promising injectable NIR-II-responsive AuNP-decorated CNT-containing nanocomposite hydrogel as a versatile platform for precise drug delivery and effective tumor therapy.
Statement of significance
This study presents an innovative injectable NIR-II-responsive nanocomposite hydrogel platform designed for precision tumor therapy through synergistic chemo-photothermal treatment. By engineering gold nanoparticle-functionalized carbon nanotubes with hydrophilic surfaces, the hydrogel addresses key limitations of conventional systems, including poor photosensitizer distribution and insufficient photothermal conversion efficiency. The unique incorporation of dynamic imine and boronate ester linkages, combined with thermal-responsive PNIPAM, enhances mechanical integrity, thermal sensitivity, and drug delivery control. Importantly, this work demonstrates that this hydrogel can spatiotemporally release 5-fluorouracil under NIR-II irradiation and achieve effective tumor ablation both in vitro and in vivo. This contribution significantly impacts the field of stimuli-responsive biomaterials and cancer theranostics by offering a robust, multifunctional, and translationally promising hydrogel platform.
{"title":"Injectable NIR-II-responsive nanocomposite hydrogels containing gold nanoparticle-decorated carbon nanotubes for controllable drug delivery and tumor therapy","authors":"Yi-Jhen Lai , Po-Ju Ting , Shu-Jyuan Yang , Grace Chen , Chieh-Ming Tsai , Chih-Hao Chang , Yi-Cheun Yeh","doi":"10.1016/j.actbio.2025.11.050","DOIUrl":"10.1016/j.actbio.2025.11.050","url":null,"abstract":"<div><div>Injectable second near-infrared (NIR-II)-responsive nanocomposite hydrogels have emerged as promising biomaterials for tumor therapy due to their ability to achieve spatiotemporal control over drug release at the targeted site. Nevertheless, the clinical translation of these hydrogels is often hindered by the poor distribution and photothermal conversion effect of the photosensitizer within the hydrogel matrix. To address these challenges, an advanced NIR-II-responsive nanocomposite hydrogel is developed by functionalizing carbon nanotubes (CNTs) with gold nanoparticles (AuNPs) and hydrophilic surfaces, positioning them as effective photosensitizers and crosslinkers. The hydrophilic AuNP-decorated CNTs and polyethyleneimine (PEI) react with alginate dialdehyde (ADA) via dynamic imine and boronate ester bonds to construct the hydrogel network. The AuNPs also form coordination and electrostatic interactions with the polymeric network. Additionally, poly(N-isopropylacrylamide) (PNIPAM) is incorporated to impart thermal-responsiveness to the hydrogel matrix. Comprehensive investigations of the microstructures, properties, and controlled drug release behavior of the nanocomposite hydrogels are conducted. Notably, the nanocomposite hydrogel enables controlled release of hydrophilic drugs under NIR-II light exposure. <em>In vivo</em> studies further demonstrate their synergistic chemo-photothermal effectiveness in tumor treatment. Taken together, this work introduces a promising injectable NIR-II-responsive AuNP-decorated CNT-containing nanocomposite hydrogel as a versatile platform for precise drug delivery and effective tumor therapy.</div></div><div><h3>Statement of significance</h3><div>This study presents an innovative injectable NIR-II-responsive nanocomposite hydrogel platform designed for precision tumor therapy through synergistic chemo-photothermal treatment. By engineering gold nanoparticle-functionalized carbon nanotubes with hydrophilic surfaces, the hydrogel addresses key limitations of conventional systems, including poor photosensitizer distribution and insufficient photothermal conversion efficiency. The unique incorporation of dynamic imine and boronate ester linkages, combined with thermal-responsive PNIPAM, enhances mechanical integrity, thermal sensitivity, and drug delivery control. Importantly, this work demonstrates that this hydrogel can spatiotemporally release 5-fluorouracil under NIR-II irradiation and achieve effective tumor ablation both <em>in vitro</em> and <em>in vivo</em>. This contribution significantly impacts the field of stimuli-responsive biomaterials and cancer theranostics by offering a robust, multifunctional, and translationally promising hydrogel platform.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 225-240"},"PeriodicalIF":9.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.actbio.2025.11.048
Huijing Chen , Liangxiao Huang , XianXi Li , Jiawei Du , Zishu Wang , lu Chen , Pengwu Zheng , Cunpeng Nie , Minuo Yin , Wufu Zhu , Dan Qiao , Qingshan Pan
Bio-heterojunctions, as an emerging class of functional materials, have demonstrated significant potential in antibacterial applications owing to their unique interfacial effects. The heterojunction interface plays a critical role in generating synergistic behaviors and enhancing antibacterial efficacy. In this review, we systematically summarize recent advances in the rational design and construction of bio-heterojunctions, with particular focus on structural engineering strategies aimed at improving their antibacterial performance. Furthermore, we provide an in-depth exploration of the underlying bactericidal mechanisms, including bacterial membrane disruption, modulation of microbial electron transfer processes, and promotion of bactericidal substance formation under external stimuli. We also discuss and summarize the applications of bio-heterojunctions in advanced antibacterial treatment modalities, along with the latest research progress in addressing common bacterial infectious diseases. Finally, this review offers perspectives on the future development of bio-heterojunction-based antibacterial therapy. We propose that a multidisciplinary approach combined with machine learning can be leveraged to predict structure–activity relationships, thereby facilitating high-throughput screening and the discovery of highly efficient and stable catalytic systems. These research efforts are expected to accelerate the development of next-generation bio-heterojunctions and advance the field of antibacterial nanomedicine.
Statement of significance
Bio-heterojunctions signify a transformative advancement in antibacterial therapy by introducing an innovative platform to address the challenges of multidrug-resistant bacteria. Through the strategic integration of distinct nanomaterials, these heterostructures exploit synergistic effects-such as enhanced charge separation, robust reactive oxygen species (ROS) generation, and effective bacterial membrane disruption-to significantly improve antibacterial performance. Their multifunctional nature enables the combination of photothermal, photodynamic, and chemodynamic therapeutic modalities, allowing for highly targeted and efficient bacterial eradication while presenting a compelling alternative to conventional antibiotics. As a result, bio-heterojunctions possess substantial potential to reshape antibacterial strategies, particularly in managing recalcitrant infections and mitigating the development of further antimicrobial resistance.
{"title":"Interfacial Engineering Strategies in Bio-heterojunctions for Antibacterial Therapeutics and Biomedical Applications","authors":"Huijing Chen , Liangxiao Huang , XianXi Li , Jiawei Du , Zishu Wang , lu Chen , Pengwu Zheng , Cunpeng Nie , Minuo Yin , Wufu Zhu , Dan Qiao , Qingshan Pan","doi":"10.1016/j.actbio.2025.11.048","DOIUrl":"10.1016/j.actbio.2025.11.048","url":null,"abstract":"<div><div>Bio-heterojunctions, as an emerging class of functional materials, have demonstrated significant potential in antibacterial applications owing to their unique interfacial effects. The heterojunction interface plays a critical role in generating synergistic behaviors and enhancing antibacterial efficacy. In this review, we systematically summarize recent advances in the rational design and construction of bio-heterojunctions, with particular focus on structural engineering strategies aimed at improving their antibacterial performance. Furthermore, we provide an in-depth exploration of the underlying bactericidal mechanisms, including bacterial membrane disruption, modulation of microbial electron transfer processes, and promotion of bactericidal substance formation under external stimuli. We also discuss and summarize the applications of bio-heterojunctions in advanced antibacterial treatment modalities, along with the latest research progress in addressing common bacterial infectious diseases. Finally, this review offers perspectives on the future development of bio-heterojunction-based antibacterial therapy. We propose that a multidisciplinary approach combined with machine learning can be leveraged to predict structure–activity relationships, thereby facilitating high-throughput screening and the discovery of highly efficient and stable catalytic systems. These research efforts are expected to accelerate the development of next-generation bio-heterojunctions and advance the field of antibacterial nanomedicine.</div></div><div><h3>Statement of significance</h3><div>Bio-heterojunctions signify a transformative advancement in antibacterial therapy by introducing an innovative platform to address the challenges of multidrug-resistant bacteria. Through the strategic integration of distinct nanomaterials, these heterostructures exploit synergistic effects-such as enhanced charge separation, robust reactive oxygen species (ROS) generation, and effective bacterial membrane disruption-to significantly improve antibacterial performance. Their multifunctional nature enables the combination of photothermal, photodynamic, and chemodynamic therapeutic modalities, allowing for highly targeted and efficient bacterial eradication while presenting a compelling alternative to conventional antibiotics. As a result, bio-heterojunctions possess substantial potential to reshape antibacterial strategies, particularly in managing recalcitrant infections and mitigating the development of further antimicrobial resistance.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 120-147"},"PeriodicalIF":9.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.actbio.2025.11.038
Maurizio Gulino , Donghoon Kim , Qiao Tang , Semih Sevim , Elric Zhang , Hao Ye , Xiang-Zhong Chen , Miguel Rafael Gonçalves Morais , Sofia Duque Santos , Salvador Pané , Ana Paula Pêgo
This work presents functional multiferroic cobalt ferrite-based nanoparticles (CFO NPs) coated with calcium/zirconium‐doped barium titanate (CFO-BCZT) that demonstrate notable magnetoelectric coupling and biocompatibility for neural applications. The core-shell structure was synthesized through hydrothermal and sol-gel processes. Uncoated CFO NPs and CFO NPs coated with bismuth ferrite (CFO-BFO) were used for comparison. X-ray diffraction revealed cubic CFO core and tetragonal BCZT shell without any secondary phase, nor impurities. Magnetoelectric coupling effect of CFO-BCZT MENPs was revealed through piezoresponse force microscopy. Biological cellular responses to CFO-BCZT MENPs were evaluated through cytotoxicity assays, microscopy analysis, and cellular uptake on primary neurons, astrocytes or microglia cultures. Long-term effects were studied in rodent 3D organotypic hippocampal cultures. Moreover, the magnetoelectric performance of CFO-BCZT and CFO-BFO MENPs was assessed in vitro with SH-SY5Y human neuronal cell lines under magnetic stimulation. The results showed CFO-BCZT MENPs superior biocompatibility both in vitro and ex vivo in organotypic brain slices, while CFO-BFO MENPs reduced microglial viability and induced inflammatory changes. Additionally, tissue penetration of CFO-BCZT MENPs through magnetic attraction was successfully achieved on organotypic hippocampal cultures, without causing either cell damage or disruption of neural connections. Finally, SH-SY5Y neuronal cell line showed good neurite outgrowth with the tested magnetic stimulation parameters. In conclusion, CFO-BCZT MENPs not only exhibited a magnetoelectric coupling effect but also greater biocompatibility compared to CFO-BFO and uncoated CFO NPs, positioning them as promising composite materials for brain stimulation therapies.
Statement of significance
Magnetoelectric nanoparticles are emerging as promising tools for non-invasive brain stimulation therapies. Our work introduces biocompatible multiferroic cobalt ferrite- based nanoparticles (CFO NPs) coated with calcium/zirconium-doped barium titanate (CFO-BCZT) as candidate materials for neural applications, representing a combination of cobalt ferrite cores with calcium/zirconium-doped barium titanate shells. These core-shell nanostructures exhibit strong magnetoelectric coupling and significantly improved biocompatibility compared to conventional alternatives, such as bismuth ferrite coatings. Their ability to penetrate brain tissue through magnetic attraction without inducing cellular toxicity or inflammation on ex vivo organotypic hippocampal slices, while promoting neurite outgrowth on in vitro neuronal cell cultures, positions them as promising tools for non-invasive neural modulation. This study paves the way for safe, wireless brain stimulation platforms using multifunctional nanomaterials.
{"title":"Magnetoelectric core-shell nanoparticles for nervous tissue electrostimulation: Performance in In vitro and ex vivo organotypic cultures","authors":"Maurizio Gulino , Donghoon Kim , Qiao Tang , Semih Sevim , Elric Zhang , Hao Ye , Xiang-Zhong Chen , Miguel Rafael Gonçalves Morais , Sofia Duque Santos , Salvador Pané , Ana Paula Pêgo","doi":"10.1016/j.actbio.2025.11.038","DOIUrl":"10.1016/j.actbio.2025.11.038","url":null,"abstract":"<div><div>This work presents functional multiferroic cobalt ferrite-based nanoparticles (CFO NPs) coated with calciu<em>m/z</em>irconium‐doped barium titanate (CFO-BCZT) that demonstrate notable magnetoelectric coupling and biocompatibility for neural applications. The core-shell structure was synthesized through hydrothermal and sol-gel processes. Uncoated CFO NPs and CFO NPs coated with bismuth ferrite (CFO-BFO) were used for comparison. X-ray diffraction revealed cubic CFO core and tetragonal BCZT shell without any secondary phase, nor impurities. Magnetoelectric coupling effect of CFO-BCZT MENPs was revealed through piezoresponse force microscopy. Biological cellular responses to CFO-BCZT MENPs were evaluated through cytotoxicity assays, microscopy analysis, and cellular uptake on primary neurons, astrocytes or microglia cultures. Long-term effects were studied in rodent 3D organotypic hippocampal cultures. Moreover, the magnetoelectric performance of CFO-BCZT and CFO-BFO MENPs was assessed in vitro with SH-SY5Y human neuronal cell lines under magnetic stimulation. The results showed CFO-BCZT MENPs superior biocompatibility both in vitro and ex vivo in organotypic brain slices, while CFO-BFO MENPs reduced microglial viability and induced inflammatory changes. Additionally, tissue penetration of CFO-BCZT MENPs through magnetic attraction was successfully achieved on organotypic hippocampal cultures, without causing either cell damage or disruption of neural connections. Finally, SH-SY5Y neuronal cell line showed good neurite outgrowth with the tested magnetic stimulation parameters. In conclusion, CFO-BCZT MENPs not only exhibited a magnetoelectric coupling effect but also greater biocompatibility compared to CFO-BFO and uncoated CFO NPs, positioning them as promising composite materials for brain stimulation therapies.</div></div><div><h3>Statement of significance</h3><div>Magnetoelectric nanoparticles are emerging as promising tools for non-invasive brain stimulation therapies. Our work introduces biocompatible multiferroic cobalt ferrite- based nanoparticles (CFO NPs) coated with calcium/zirconium-doped barium titanate (CFO-BCZT) as candidate materials for neural applications, representing a combination of cobalt ferrite cores with calcium/zirconium-doped barium titanate shells. These core-shell nanostructures exhibit strong magnetoelectric coupling and significantly improved biocompatibility compared to conventional alternatives, such as bismuth ferrite coatings. Their ability to penetrate brain tissue through magnetic attraction without inducing cellular toxicity or inflammation on ex vivo organotypic hippocampal slices, while promoting neurite outgrowth on in vitro neuronal cell cultures, positions them as promising tools for non-invasive neural modulation. This study paves the way for safe, wireless brain stimulation platforms using multifunctional nanomaterials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 504-520"},"PeriodicalIF":9.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25DOI: 10.1016/j.actbio.2025.11.035
Linzhuo Huang , Rui Xu , Weirong Li , Li Lv , Chunhao Lin , Xianzhu Yang , Yandan Yao , Phei Er Saw , Xiaoding Xu
{"title":"Corrigendum to “Repolarization of macrophages to improve sorafenib sensitivity for combination cancer therapy” [Acta Biomaterialia 162 (2023) 98–109]","authors":"Linzhuo Huang , Rui Xu , Weirong Li , Li Lv , Chunhao Lin , Xianzhu Yang , Yandan Yao , Phei Er Saw , Xiaoding Xu","doi":"10.1016/j.actbio.2025.11.035","DOIUrl":"10.1016/j.actbio.2025.11.035","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 638-639"},"PeriodicalIF":9.6,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25DOI: 10.1016/j.actbio.2025.11.042
Mingzhu Liu , Jiashu Chen , Jun Sun , Xiaoqian Liu , Meijiu Zhang , Shuwei Huang , Qinyao Zhang , Yifan Cui , Yiting Zhang , Jiaxing Yang , Lei Lei , Wei Liu , Fang Lv , Hemin Nie
Pancreatic fibrosis represents a progressive and pathological hallmark of chronic pancreatitis and serves as a valuable diagnostic marker for pancreatic diseases, including pancreatic cancer. However, early detection and accurate staging of pancreatic fibrosis remain significant clinical challenges. Extracellular matrix molecules, particularly fibronectin, have emerged as promising biomarkers for advanced diagnostic imaging. In this study, we introduce a novel approach utilizing DNA aptamer ZY-1-based fluorescent probes, specifically designed to target cellular fibronectin, as an innovative tool for the early detection and precise staging of pancreatic fibrosis. We first demonstrated the exceptional specificity and sensitivity of ZY-1 in binding cellular fibronectin on activated mouse pancreatic stellate cells. Building on this, we conducted comprehensive evaluations of the real-time imaging capabilities of ZY-1 fluorescent probes in mouse models, successfully distinguishing pancreatic fibrosis across different developmental stages. Furthermore, we rigorously validated the diagnostic potential of these probes using biopsy samples from patients with varying degrees of pancreatic fibrosis. This study represents the first systematic application of ZY-1 fluorescent probes for identifying and discriminating mild, intermediate, and severe pancreatic fibrosis in both experimental animal models and human clinical specimens. Our findings provide a critical foundation for advancing clinical diagnosis and personalized treatment strategies for pancreatic fibrosis-related pathologies.
Statement of significance
Pancreatic fibrosis marks chronic pancreatitis and helps diagnose diseases such as pancreatic cancer, yet early detection and staging remain clinical challenges. Building on our prior work with the DNA aptamer ZY-1 targeting cellular fibronectin (cFN) for early liver fibrosis, we extend ZY-1 to pancreatic fibrosis, an underexplored disease. We demonstrate strong binding specificity and sensitivity of ZY-1 to activated pancreatic stellate cells and validate detection across Caerulein-induced mouse models and human biopsy samples at multiple stages. This work delivers a novel, noninvasive molecular imaging tool with stage-specific detection, broadening ZY-1′s translational potential and addressing the urgent need for improved pancreatic fibrosis diagnostics.
{"title":"Precise diagnosis of pancreatic fibrosis using fluorescent aptamer probes targeting cellular fibronectin","authors":"Mingzhu Liu , Jiashu Chen , Jun Sun , Xiaoqian Liu , Meijiu Zhang , Shuwei Huang , Qinyao Zhang , Yifan Cui , Yiting Zhang , Jiaxing Yang , Lei Lei , Wei Liu , Fang Lv , Hemin Nie","doi":"10.1016/j.actbio.2025.11.042","DOIUrl":"10.1016/j.actbio.2025.11.042","url":null,"abstract":"<div><div>Pancreatic fibrosis represents a progressive and pathological hallmark of chronic pancreatitis and serves as a valuable diagnostic marker for pancreatic diseases, including pancreatic cancer. However, early detection and accurate staging of pancreatic fibrosis remain significant clinical challenges. Extracellular matrix molecules, particularly fibronectin, have emerged as promising biomarkers for advanced diagnostic imaging. In this study, we introduce a novel approach utilizing DNA aptamer ZY-1-based fluorescent probes, specifically designed to target cellular fibronectin, as an innovative tool for the early detection and precise staging of pancreatic fibrosis. We first demonstrated the exceptional specificity and sensitivity of ZY-1 in binding cellular fibronectin on activated mouse pancreatic stellate cells. Building on this, we conducted comprehensive evaluations of the real-time imaging capabilities of ZY-1 fluorescent probes in mouse models, successfully distinguishing pancreatic fibrosis across different developmental stages. Furthermore, we rigorously validated the diagnostic potential of these probes using biopsy samples from patients with varying degrees of pancreatic fibrosis. This study represents the first systematic application of ZY-1 fluorescent probes for identifying and discriminating mild, intermediate, and severe pancreatic fibrosis in both experimental animal models and human clinical specimens. Our findings provide a critical foundation for advancing clinical diagnosis and personalized treatment strategies for pancreatic fibrosis-related pathologies.</div></div><div><h3>Statement of significance</h3><div>Pancreatic fibrosis marks chronic pancreatitis and helps diagnose diseases such as pancreatic cancer, yet early detection and staging remain clinical challenges. Building on our prior work with the DNA aptamer ZY-1 targeting cellular fibronectin (cFN) for early liver fibrosis, we extend ZY-1 to pancreatic fibrosis, an underexplored disease. We demonstrate strong binding specificity and sensitivity of ZY-1 to activated pancreatic stellate cells and validate detection across Caerulein-induced mouse models and human biopsy samples at multiple stages. This work delivers a novel, noninvasive molecular imaging tool with stage-specific detection, broadening ZY-1′s translational potential and addressing the urgent need for improved pancreatic fibrosis diagnostics.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 594-608"},"PeriodicalIF":9.6,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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