Pub Date : 2025-02-01DOI: 10.1016/j.mtbio.2024.101378
Zhiyi Fan , Guofu Zhang , Wanda Zhan , Juehan Wang , Chaoyong Wang , QianYing Yue , Zhangheng Huang , Yongxiang Wang
Spinal cord injury (SCI) is a neurological condition that causes significant loss of sensory, motor, and autonomic functions below the level of injury. Current clinical treatment strategies often fail to meet expectations. Hyaluronidase is typically associated with tumor progression and bacterial infections. Analysis showed that hyaluronidase also persistently increased in a rat total excision model. In this study, we designed a highly biocompatible dual-responsive hydrogel. Hyaluronic acid (HA)-Gelatin (Gel) served as the base for the hydrogel, crosslinked via an amide reaction to form the hydrogel. The hydrogel was further combined with Neurotrophic growth factor (NGF) and Fe3O4 nanoparticles, exhibiting low toxicity, good mechanical properties, self-healing ability, and sustained drug release. In cellular experiments, the novel hydrogel significantly promoted neural axon growth and development under an external magnetic field. Therapeutic results were confirmed in a rat spinal cord resection model, where inflammation was reduced, chondroitin sulfate proteoglycans decreased and a favorable environment for nerve regeneration was provided; neural regeneration improved hind limb motor function in SCI rats. These results underscore the therapeutic potential of hydrogel.
{"title":"Hyaluronidase-responsive hydrogel loaded with magnetic nanoparticles combined with external magnetic stimulation for spinal cord injury repair","authors":"Zhiyi Fan , Guofu Zhang , Wanda Zhan , Juehan Wang , Chaoyong Wang , QianYing Yue , Zhangheng Huang , Yongxiang Wang","doi":"10.1016/j.mtbio.2024.101378","DOIUrl":"10.1016/j.mtbio.2024.101378","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a neurological condition that causes significant loss of sensory, motor, and autonomic functions below the level of injury. Current clinical treatment strategies often fail to meet expectations. Hyaluronidase is typically associated with tumor progression and bacterial infections. Analysis showed that hyaluronidase also persistently increased in a rat total excision model. In this study, we designed a highly biocompatible dual-responsive hydrogel. Hyaluronic acid (HA)-Gelatin (Gel) served as the base for the hydrogel, crosslinked via an amide reaction to form the hydrogel. The hydrogel was further combined with Neurotrophic growth factor (NGF) and Fe<sub>3</sub>O<sub>4</sub> nanoparticles, exhibiting low toxicity, good mechanical properties, self-healing ability, and sustained drug release. In cellular experiments, the novel hydrogel significantly promoted neural axon growth and development under an external magnetic field. Therapeutic results were confirmed in a rat spinal cord resection model, where inflammation was reduced, chondroitin sulfate proteoglycans decreased and a favorable environment for nerve regeneration was provided; neural regeneration improved hind limb motor function in SCI rats. These results underscore the therapeutic potential of hydrogel.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101378"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.mtbio.2024.101395
Xin Wang , Yixue Huang , Yilin Yang , Xin Tian , Yesheng Jin , Weimin Jiang , Hanliang He , Yong Xu , Yijie Liu
Intervertebral disc (IVD) degeneration represents a significant cause of chronic back pain and disability, with a substantial impact on the quality of life. Conventional therapeutic modalities frequently address the symptoms rather than the underlying etiology, underscoring the necessity for regenerative therapies that restore disc function. Polysaccharide-based materials, such as hyaluronic acid, alginate, chitosan, and chondroitin sulfate, have emerged as promising candidates for intervertebral disc degeneration (IVDD) therapy due to their biocompatibility, biodegradability, and ability to mimic the native extracellular matrix (ECM) of the nucleus pulposus (NP). These materials have demonstrated the capacity to support cell viability, facilitate matrix production, and alleviate inflammation in vitro and in vivo, thus supporting tissue regeneration and restoring disc function in comparison to conventional treatment. Furthermore, polysaccharide-based hydrogels have demonstrated the potential to deliver bioactive molecules, including growth factors, cytokines and anti-inflammatory drugs, directly to the degenerated disc environment, thereby enhancing therapeutic outcomes. Therefore, polysaccharide-based materials provide structural support and facilitate the regeneration of native tissue, representing a versatile and effective approach for the treatment of IVDD. Despite their promise, challenges such as limited long-term stability, potential immunogenicity, and the difficulty in scaling up production for clinical use remain. This review delineates the potential of various polysaccharides during the fabrication of hydrogels and scaffolds for disc regeneration, guiding and inspiring future research to focus on optimizing these materials for clinical translation for IVDD repair and regeneration.
{"title":"Polysaccharide-based biomaterials for regenerative therapy in intervertebral disc degeneration","authors":"Xin Wang , Yixue Huang , Yilin Yang , Xin Tian , Yesheng Jin , Weimin Jiang , Hanliang He , Yong Xu , Yijie Liu","doi":"10.1016/j.mtbio.2024.101395","DOIUrl":"10.1016/j.mtbio.2024.101395","url":null,"abstract":"<div><div>Intervertebral disc (IVD) degeneration represents a significant cause of chronic back pain and disability, with a substantial impact on the quality of life. Conventional therapeutic modalities frequently address the symptoms rather than the underlying etiology, underscoring the necessity for regenerative therapies that restore disc function. Polysaccharide-based materials, such as hyaluronic acid, alginate, chitosan, and chondroitin sulfate, have emerged as promising candidates for intervertebral disc degeneration (IVDD) therapy due to their biocompatibility, biodegradability, and ability to mimic the native extracellular matrix (ECM) of the nucleus pulposus (NP). These materials have demonstrated the capacity to support cell viability, facilitate matrix production, and alleviate inflammation in vitro and in vivo, thus supporting tissue regeneration and restoring disc function in comparison to conventional treatment. Furthermore, polysaccharide-based hydrogels have demonstrated the potential to deliver bioactive molecules, including growth factors, cytokines and anti-inflammatory drugs, directly to the degenerated disc environment, thereby enhancing therapeutic outcomes. Therefore, polysaccharide-based materials provide structural support and facilitate the regeneration of native tissue, representing a versatile and effective approach for the treatment of IVDD. Despite their promise, challenges such as limited long-term stability, potential immunogenicity, and the difficulty in scaling up production for clinical use remain. This review delineates the potential of various polysaccharides during the fabrication of hydrogels and scaffolds for disc regeneration, guiding and inspiring future research to focus on optimizing these materials for clinical translation for IVDD repair and regeneration.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101395"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.mtbio.2024.101407
Jian Chen , Qiyu Zhan , Lie Li , Simin Xi , Longmei Cai , Ruiyuan Liu , Lujia Chen
Cell membrane targeting sonodynamic therapy could induce the accumulation of lipid peroxidation (LPO), drive ferroptosis, and further enhances immunogenic cell death (ICD) effects. However, ferroptosis is restrained by the ferroptosis suppressor protein 1 (FSP1) at the plasma membrane, which can catalyze the regeneration of ubiquinone (CoQ10) by using NAD(P)H to suppress the LPO accumulation. This work describes the construction of US-active nanoparticles (TiF NPs), which combinate cell-membrane targeting sonosensitizer TBT-CQi with FSP1 inhibitor (iFSP1), facilitating cell-membrane targeting sonodynamic-triggered ferroptosis. TiF NPs could induce a sonodynamic effect, which promotes lipid peroxidation and drives apoptosis. Furthermore, TiF NPs could suppress FSP1, induce CoQ10 depletion, down-regulate the NADH, enhance LPO accumulation, and finally induce ferroptosis. In vitro results demonstrated that synergetic cell membrane targeting SDT/FSP1 inhibition triggered immunogenic cell death (ICD). Moreover, the as-synthesized TiF NPs-mediated cell membrane targeting SDT/FSP1 inhibition thoroughly inhibited the tumor growth and simultaneously activated antitumor immunity to suppress lung metastasis. This work represents a promising tumor therapeutic strategy combining cell membrane targeting SDT and FSP1 inhibition, potentially inspiring further research in developing logical and effective cancer therapies based on synergistic SDT/ferroptosis.
{"title":"Cell-membrane targeting sonodynamic therapy combination with FSP1 inhibition for ferroptosis-boosted immunotherapy","authors":"Jian Chen , Qiyu Zhan , Lie Li , Simin Xi , Longmei Cai , Ruiyuan Liu , Lujia Chen","doi":"10.1016/j.mtbio.2024.101407","DOIUrl":"10.1016/j.mtbio.2024.101407","url":null,"abstract":"<div><div>Cell membrane targeting sonodynamic therapy could induce the accumulation of lipid peroxidation (LPO), drive ferroptosis, and further enhances immunogenic cell death (ICD) effects. However, ferroptosis is restrained by the ferroptosis suppressor protein 1 (FSP1) at the plasma membrane, which can catalyze the regeneration of ubiquinone (CoQ10) by using NAD(P)H to suppress the LPO accumulation. This work describes the construction of US-active nanoparticles (TiF NPs), which combinate cell-membrane targeting sonosensitizer TBT-CQi with FSP1 inhibitor (iFSP1), facilitating cell-membrane targeting sonodynamic-triggered ferroptosis. TiF NPs could induce a sonodynamic effect, which promotes lipid peroxidation and drives apoptosis. Furthermore, TiF NPs could suppress FSP1, induce CoQ10 depletion, down-regulate the NADH, enhance LPO accumulation, and finally induce ferroptosis. <em>In vitro</em> results demonstrated that synergetic cell membrane targeting SDT/FSP1 inhibition triggered immunogenic cell death (ICD). Moreover, the as-synthesized TiF NPs-mediated cell membrane targeting SDT/FSP1 inhibition thoroughly inhibited the tumor growth and simultaneously activated antitumor immunity to suppress lung metastasis. This work represents a promising tumor therapeutic strategy combining cell membrane targeting SDT and FSP1 inhibition, potentially inspiring further research in developing logical and effective cancer therapies based on synergistic SDT/ferroptosis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101407"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.mtbio.2025.101453
Tongtong Tian , Wenjing Yang , Xiaohuan Wang , Te Liu , Baishen Pan , Wei Guo , Beili Wang
The rise of antibiotic resistance poses a significant and ongoing challenge to public health, with pathogenic bacteria remaining a persistent threat. Traditional culture methods, while considered the gold standard for bacterial detection and viability assessment, are time-consuming and labor-intensive. To address this limitation, we developed a novel point-of-care (POC) detection method leveraging citrate- and alkyne-modified gold nanorods (AuNRs) synthesized with click chemistry properties. These AuNRs exhibit superior biocompatibility and enhanced quantitative performance compared to conventional surfactant-modified AuNRs. Our method, termed AuNRs–bacteria-initiated click chemistry (AuNRs–BICC), detects CuII-reducing bacteria by quantifying AuNRs bound to a biosensing interface via bacteria-mediated CuII reduction to CuI and subsequent click chemistry with biosensing interface of azide modifications. Using dark-field microscopy (DFM), we demonstrated a strong linear correlation between AuNR counts and the logarithm of bacterial concentration for both Gram-negative Escherichia coli (including KPC-2-expressing antibiotic-resistant strains) and Gram-positive Staphylococcus aureus across a range of 101 to 107 cells, achieving a remarkable detection limit of 101 cells. The AuNRs–BICC biosensor exhibits high selectivity for target bacterial strains and provides rapid detection within 3 h. Furthermore, it can assess bacterial viability in the presence of various antibiotics, including meropenem, ceftriaxone and tetracycline, suggesting its potential for rapid antibiotic susceptibility testing and facilitating timely clinical intervention for infectious diseases.
{"title":"Click chemistry-enabled gold nanorods for sensitive detection and viability evaluation of copper(II)-reducing bacteria","authors":"Tongtong Tian , Wenjing Yang , Xiaohuan Wang , Te Liu , Baishen Pan , Wei Guo , Beili Wang","doi":"10.1016/j.mtbio.2025.101453","DOIUrl":"10.1016/j.mtbio.2025.101453","url":null,"abstract":"<div><div>The rise of antibiotic resistance poses a significant and ongoing challenge to public health, with pathogenic bacteria remaining a persistent threat. Traditional culture methods, while considered the gold standard for bacterial detection and viability assessment, are time-consuming and labor-intensive. To address this limitation, we developed a novel point-of-care (POC) detection method leveraging citrate- and alkyne-modified gold nanorods (AuNRs) synthesized with click chemistry properties. These AuNRs exhibit superior biocompatibility and enhanced quantitative performance compared to conventional surfactant-modified AuNRs. Our method, termed AuNRs–bacteria-initiated click chemistry (AuNRs–BICC), detects Cu<sup>II</sup>-reducing bacteria by quantifying AuNRs bound to a biosensing interface via bacteria-mediated Cu<sup>II</sup> reduction to Cu<sup>I</sup> and subsequent click chemistry with biosensing interface of azide modifications. Using dark-field microscopy (DFM), we demonstrated a strong linear correlation between AuNR counts and the logarithm of bacterial concentration for both Gram-negative <em>Escherichia coli</em> (including KPC-2-expressing antibiotic-resistant strains) and Gram-positive <em>Staphylococcus aureus</em> across a range of 10<sup>1</sup> to 10<sup>7</sup> cells, achieving a remarkable detection limit of 10<sup>1</sup> cells. The AuNRs–BICC biosensor exhibits high selectivity for target bacterial strains and provides rapid detection within 3 h. Furthermore, it can assess bacterial viability in the presence of various antibiotics, including meropenem, ceftriaxone and tetracycline, suggesting its potential for rapid antibiotic susceptibility testing and facilitating timely clinical intervention for infectious diseases.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101453"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.mtbio.2025.101448
Haolin Bian , Fangfang Song , Shilei Wang , Wei Sun , Bo Hu , Xichao Liang , Hongye Yang , Cui Huang
Inspired by the initial mineralization process with bone matrix vesicles (MVs), this study innovatively developed a delivery system to mediate mineralization during bone regeneration. The system comprises nanofibrous chitosan microspheres (NCM) and poly (allylamine hydrochloride)-stabilized amorphous calcium phosphate (PAH-ACP), which is thereafter referred to as NCMP. NCM is synthesized through the thermal induction of chitosan molecular chains, serving as the carrier, while PAH-ACP functions as the mineralization precursor. Additionally, the nanofibrous network of NCMP mimics the architecture of natural extracellular matrix (ECM), creating an optimal niche for the active adhesion of stem cells to its surface, exhibiting good biocompatibility, immunoregulation, and osteogenic performance. In vivo, NCMP effectively recruits cells and mineralizes collagen, modulates cell behavior and differentiation, and promotes in situ biomineralization in rat calvarial defects. These results underscore the dual efficacy of NCMP not only as an effective delivery system for mineralization precursors but also as ECM-mimicking bio-blocks, offering a promising avenue for enhancing the repair and regeneration of bone defects.
{"title":"Matrix vesicle-inspired delivery system based on nanofibrous chitosan microspheres for enhanced bone regeneration","authors":"Haolin Bian , Fangfang Song , Shilei Wang , Wei Sun , Bo Hu , Xichao Liang , Hongye Yang , Cui Huang","doi":"10.1016/j.mtbio.2025.101448","DOIUrl":"10.1016/j.mtbio.2025.101448","url":null,"abstract":"<div><div>Inspired by the initial mineralization process with bone matrix vesicles (MVs), this study innovatively developed a delivery system to mediate mineralization during bone regeneration. The system comprises nanofibrous chitosan microspheres (NCM) and poly (allylamine hydrochloride)-stabilized amorphous calcium phosphate (PAH-ACP), which is thereafter referred to as NCMP. NCM is synthesized through the thermal induction of chitosan molecular chains, serving as the carrier, while PAH-ACP functions as the mineralization precursor. Additionally, the nanofibrous network of NCMP mimics the architecture of natural extracellular matrix (ECM), creating an optimal niche for the active adhesion of stem cells to its surface, exhibiting good biocompatibility, immunoregulation, and osteogenic performance. <em>In vivo</em>, NCMP effectively recruits cells and mineralizes collagen, modulates cell behavior and differentiation, and promotes <em>in situ</em> biomineralization in rat calvarial defects. These results underscore the dual efficacy of NCMP not only as an effective delivery system for mineralization precursors but also as ECM-mimicking bio-blocks, offering a promising avenue for enhancing the repair and regeneration of bone defects.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101448"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.mtbio.2024.101402
Tun Wang , Sheng Liao , Peng Lu , Zhenyu He , Siyuan Cheng , Tianjian Wang , Zibo Cheng , Yangyang An , Mo Wang , Chang Shu
Decellularized tissue-engineered vascular grafts (dTEVGs) exhibit superior biocompatibility, anti-infection properties and repair potential, contributing to better patency and making them a more ideal choice for arteriovenous grafts (AVGs) in hemodialysis compared to chemically synthesized grafts. However, the unsatisfactory reendothelialization and smooth muscle remodeling of current dTEVGs limit their advantages. In this study, we investigated the use of elastase to improve the porosity of elastic fiber layers in dTEVGs, aiming to promote cell infiltration and achieve superior reendothelialization and smooth muscle remodeling. Our findings revealed that elastase treatment induced scattered cracks and holes in the elastic fiber layers of dTEVGs. Porous dTEVGs demonstrated increased cell infiltration in rat subcutaneous tissue. In the rat AVG models, mildly elastase-treated dTEVGs significantly improved cell infiltration and graft remodeling, including adequate smooth muscle cell (SMC) repopulation, impressive reendothelization and regeneration of the extracellular matrix, without stenosis, dilation or disintegration of the grafts. This study demonstrates that porous dTEVGs promote reendothelization, smooth muscle remodeling and extracellular matrix regeneration while retaining a stable graft structure, enhancing durability and puncture resistance in hemodialysis.
{"title":"Improved porosity promotes reendothelialization and smooth muscle remodeling in decellularized tissue-engineered vascular grafts","authors":"Tun Wang , Sheng Liao , Peng Lu , Zhenyu He , Siyuan Cheng , Tianjian Wang , Zibo Cheng , Yangyang An , Mo Wang , Chang Shu","doi":"10.1016/j.mtbio.2024.101402","DOIUrl":"10.1016/j.mtbio.2024.101402","url":null,"abstract":"<div><div>Decellularized tissue-engineered vascular grafts (dTEVGs) exhibit superior biocompatibility, anti-infection properties and repair potential, contributing to better patency and making them a more ideal choice for arteriovenous grafts (AVGs) in hemodialysis compared to chemically synthesized grafts. However, the unsatisfactory reendothelialization and smooth muscle remodeling of current dTEVGs limit their advantages. In this study, we investigated the use of elastase to improve the porosity of elastic fiber layers in dTEVGs, aiming to promote cell infiltration and achieve superior reendothelialization and smooth muscle remodeling. Our findings revealed that elastase treatment induced scattered cracks and holes in the elastic fiber layers of dTEVGs. Porous dTEVGs demonstrated increased cell infiltration in rat subcutaneous tissue. In the rat AVG models, mildly elastase-treated dTEVGs significantly improved cell infiltration and graft remodeling, including adequate smooth muscle cell (SMC) repopulation, impressive reendothelization and regeneration of the extracellular matrix, without stenosis, dilation or disintegration of the grafts. This study demonstrates that porous dTEVGs promote reendothelization, smooth muscle remodeling and extracellular matrix regeneration while retaining a stable graft structure, enhancing durability and puncture resistance in hemodialysis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101402"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11714392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.mtbio.2024.101409
Zekai Cui , Xiaoxue Li , Yiwen Ou , Xihao Sun , Jianing Gu , Chengcheng Ding , Zhexiong Yu , Yonglong Guo , Yuqin Liang , Shengru Mao , Jacey Hongjie Ma , Hon Fai Chan , Shibo Tang , Jiansu Chen
Diabetic keratopathy (DK), a significant complication of diabetes, often leads to corneal damage and vision impairment. Effective models are essential for studying DK pathogenesis and evaluating potential therapeutic interventions. This study developed a novel biomimetic full-thickness corneal model for the first time, incorporating corneal epithelial cells, stromal cells, endothelial cells, and nerves to simulate DK conditions in vitro. By exposing the model to a high-glucose (HG) environment, the pathological characteristics of DK, including nerve bundle disintegration, compromised barrier integrity, increased inflammation, and oxidative stress, were successfully replicated. Transcriptomic analysis revealed that HG downregulated genes associated with axon and synapse formation while upregulating immune response and oxidative stress pathways, with C-C Motif Chemokine Ligand 5 (CCL5) identified as a key hub gene in DK pathogenesis. The therapeutic effects of Lycium barbarum glycopeptide (LBGP) were evaluated using this model and validated in db/db diabetic mice. LBGP promoted nerve regeneration, alleviated inflammation and oxidative stress in both in vitro and in vivo models. Notably, LBGP suppressed the expression of CCL5, highlighting its potential mechanism of action. This study establishes a robust biomimetic platform for investigating DK and other corneal diseases, and identifies LBGP as a promising therapeutic candidate for DK. These findings provide valuable insights into corneal disease mechanisms and pave the way for future translational research and clinical applications.
{"title":"Novel full-thickness biomimetic corneal model for studying pathogenesis and treatment of diabetic keratopathy","authors":"Zekai Cui , Xiaoxue Li , Yiwen Ou , Xihao Sun , Jianing Gu , Chengcheng Ding , Zhexiong Yu , Yonglong Guo , Yuqin Liang , Shengru Mao , Jacey Hongjie Ma , Hon Fai Chan , Shibo Tang , Jiansu Chen","doi":"10.1016/j.mtbio.2024.101409","DOIUrl":"10.1016/j.mtbio.2024.101409","url":null,"abstract":"<div><div>Diabetic keratopathy (DK), a significant complication of diabetes, often leads to corneal damage and vision impairment. Effective models are essential for studying DK pathogenesis and evaluating potential therapeutic interventions. This study developed a novel biomimetic full-thickness corneal model for the first time, incorporating corneal epithelial cells, stromal cells, endothelial cells, and nerves to simulate DK conditions <em>in vitro</em>. By exposing the model to a high-glucose (HG) environment, the pathological characteristics of DK, including nerve bundle disintegration, compromised barrier integrity, increased inflammation, and oxidative stress, were successfully replicated. Transcriptomic analysis revealed that HG downregulated genes associated with axon and synapse formation while upregulating immune response and oxidative stress pathways, with C-C Motif Chemokine Ligand 5 (CCL5) identified as a key hub gene in DK pathogenesis. The therapeutic effects of Lycium barbarum glycopeptide (LBGP) were evaluated using this model and validated in db/db diabetic mice. LBGP promoted nerve regeneration, alleviated inflammation and oxidative stress in both <em>in vitro</em> and <em>in vivo</em> models. Notably, LBGP suppressed the expression of CCL5, highlighting its potential mechanism of action. This study establishes a robust biomimetic platform for investigating DK and other corneal diseases, and identifies LBGP as a promising therapeutic candidate for DK. These findings provide valuable insights into corneal disease mechanisms and pave the way for future translational research and clinical applications.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101409"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.mtbio.2024.101416
Gergely Stankovits , Kata Szayly , Dorián László Galata , János Móczó , András Szilágyi , Benjámin Gyarmati
Mucosal membranes with strong variability in their viscoelastic properties line numerous organs and are often targeted by mucoadhesive formulations, e.g., highly swellable hydroxypropylmethylcellulose (HPMC) and slightly cross-linked poly(acrylic acid) (PAA) tablets. Although the factors determining the strength of mucoadhesion are hierarchical and affected by both reversible and irreversible processes, the currently available strategies generally view mucoadhesion as the individual performance of the mucoadhesive excipient. We propose an integrated concept that considers the viscoelasticity and tensile properties of both the adhesive interphase and the bulk phases. To reduce the complexity of the mucosal membrane and eliminate the effect of specific macromolecular interactions, we studied the adhesion on mucosa-mimetic freeze/thawed (FT) poly(vinyl alcohol) (PVA) hydrogels. Their viscoelastic properties were controlled by the number of FT cycles and the polymer concentration. The adhesive strength of HPMC tablets displayed a pronounced dependence on the viscoelasticity of PVA gels, explained by the limited chain flexibility and interpenetration of HPMC, resulting in the formation of a thin the adhesive interphase compared to PAA. We recognized scaling laws between toughness and strength for tensile and adhesive properties as well as general correlations between viscoelastic and adhesive properties, which can aid the more rational design of both mucoadhesive formulations and mucosa-mimetic materials.
{"title":"The adhesion mechanism of mucoadhesive tablets with dissimilar chain flexibility on viscoelastic hydrogels","authors":"Gergely Stankovits , Kata Szayly , Dorián László Galata , János Móczó , András Szilágyi , Benjámin Gyarmati","doi":"10.1016/j.mtbio.2024.101416","DOIUrl":"10.1016/j.mtbio.2024.101416","url":null,"abstract":"<div><div>Mucosal membranes with strong variability in their viscoelastic properties line numerous organs and are often targeted by mucoadhesive formulations, e.g., highly swellable hydroxypropylmethylcellulose (HPMC) and slightly cross-linked poly(acrylic acid) (PAA) tablets. Although the factors determining the strength of mucoadhesion are hierarchical and affected by both reversible and irreversible processes, the currently available strategies generally view mucoadhesion as the individual performance of the mucoadhesive excipient. We propose an integrated concept that considers the viscoelasticity and tensile properties of both the adhesive interphase and the bulk phases. To reduce the complexity of the mucosal membrane and eliminate the effect of specific macromolecular interactions, we studied the adhesion on mucosa-mimetic freeze/thawed (FT) poly(vinyl alcohol) (PVA) hydrogels. Their viscoelastic properties were controlled by the number of FT cycles and the polymer concentration. The adhesive strength of HPMC tablets displayed a pronounced dependence on the viscoelasticity of PVA gels, explained by the limited chain flexibility and interpenetration of HPMC, resulting in the formation of a thin the adhesive interphase compared to PAA. We recognized scaling laws between toughness and strength for tensile and adhesive properties as well as general correlations between viscoelastic and adhesive properties, which can aid the more rational design of both mucoadhesive formulations and mucosa-mimetic materials.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101416"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.mtbio.2024.101415
Rajiv Borah , Daniel Diez Clarke , Jnanendra Upadhyay , Michael G. Monaghan
Peripheral nerve repair (PNR) is a major healthcare challenge due to the limited regenerative capacity of the nervous system, often leading to severe functional impairments. While nerve autografts are the gold standard, their implications are constrained by issues such as donor site morbidity and limited availability, necessitating innovative alternatives like nerve guidance conduits (NGCs). However, the inherently slow nerve growth rate (∼1 mm/day) and prolonged neuroinflammation, delay recovery even with the use of passive (no-conductive) NGCs, resulting in muscle atrophy and loss of locomotor function. Electrical stimulation (ES) has the ability to enhance nerve regeneration rate by modulating the innate bioelectrical microenvironment of nerve tissue while simultaneously fostering a reparative environment through immunoregulation. In this context, electrically conductive polymer (ECP)-based biomaterials offer unique advantages for nerve repair combining their flexibility, akin to traditional plastics, and mixed ionic-electronic conductivity, similar to ionically conductive nerve tissue, as well as their biocompatibility and ease of fabrication. This review focuses on the progress, challenges, and emerging techniques for integrating ECP based NGCs with ES for functional nerve regeneration. It critically evaluates the various approaches using ECP based scaffolds, identifying gaps that have hindered clinical translation. Key challenges discussed include designing effective 3D NGCs with high electroactivity, optimizing ES modules, and better understanding of immunoregulation during nerve repair. The review also explores innovative strategies in material development and wireless, self-powered ES methods. Furthermore, it emphasizes the need for non-invasive ES delivery methods combined with hybrid ECP based neural scaffolds, highlighting future directions for advancing preclinical and clinical translation. Together, ECP based NGCs combined with ES represent a promising avenue for advancing PNR and improving patient outcomes.
{"title":"From innovation to clinic: Emerging strategies harnessing electrically conductive polymers to enhance electrically stimulated peripheral nerve repair","authors":"Rajiv Borah , Daniel Diez Clarke , Jnanendra Upadhyay , Michael G. Monaghan","doi":"10.1016/j.mtbio.2024.101415","DOIUrl":"10.1016/j.mtbio.2024.101415","url":null,"abstract":"<div><div>Peripheral nerve repair (PNR) is a major healthcare challenge due to the limited regenerative capacity of the nervous system, often leading to severe functional impairments. While nerve autografts are the gold standard, their implications are constrained by issues such as donor site morbidity and limited availability, necessitating innovative alternatives like nerve guidance conduits (NGCs). However, the inherently slow nerve growth rate (∼1 mm/day) and prolonged neuroinflammation, delay recovery even with the use of passive (no-conductive) NGCs, resulting in muscle atrophy and loss of locomotor function. Electrical stimulation (ES) has the ability to enhance nerve regeneration rate by modulating the innate bioelectrical microenvironment of nerve tissue while simultaneously fostering a reparative environment through immunoregulation. In this context, electrically conductive polymer (ECP)-based biomaterials offer unique advantages for nerve repair combining their flexibility, akin to traditional plastics, and mixed ionic-electronic conductivity, similar to ionically conductive nerve tissue, as well as their biocompatibility and ease of fabrication. This review focuses on the progress, challenges, and emerging techniques for integrating ECP based NGCs with ES for functional nerve regeneration. It critically evaluates the various approaches using ECP based scaffolds, identifying gaps that have hindered clinical translation. Key challenges discussed include designing effective 3D NGCs with high electroactivity, optimizing ES modules, and better understanding of immunoregulation during nerve repair. The review also explores innovative strategies in material development and wireless, self-powered ES methods. Furthermore, it emphasizes the need for non-invasive ES delivery methods combined with hybrid ECP based neural scaffolds, highlighting future directions for advancing preclinical and clinical translation. Together, ECP based NGCs combined with ES represent a promising avenue for advancing PNR and improving patient outcomes.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101415"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.mtbio.2024.101420
Li Wen , Chengxue He , Yanhui Guo , Nina Zhou , Xiangxi Meng , Yuwen Chen , Cheng Ma , Hua Zhu , Zhi Yang , Lei Xia
Fibroblast activating protein (FAP) is up-regulated in cancer-associated fibroblasts (CAFs) of more than 90 % of tumor microenvironment and also highly expressed on the surface of multiple tumor cells like glioblastoma, which can be used as a specific target for tumor diagnosis and treatment. At present, small-molecule radiotracer targeting FAP with high specificity exhibit limited functionality, which hinders the integration of theranostics as well as multifunctionality. In this work, we have engineered a multifunctional nanoplatform utilizing organic melanin nanoparticles that specifically targets FAP, facilitating both multimodal imaging and synergistic therapeutic applications. This nanoplatform can perform positron emission tomography (PET), magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) with strong near infrared absorption and metal chelating ability, achieving efficiently targeting accumulation and display long retention in the tumor region. Meanwhile, 131I-labeled nanoplatform for targeted radioisotope therapy (TRT) and photothermal therapy (PTT) were significantly suppressed tumor growth in glioblastoma xenograft models without obvious side effects. These results demonstrated that this novel nanoparticles-based theranostics nanoplatform can effectively enhance multimodal imaging and targeted radionuclide-photothermal synergistic therapy for solid tumors with FAP expression.
{"title":"Strategies for specific multimodal imaging of cancer-associated fibroblasts and applications in theranostics of cancer","authors":"Li Wen , Chengxue He , Yanhui Guo , Nina Zhou , Xiangxi Meng , Yuwen Chen , Cheng Ma , Hua Zhu , Zhi Yang , Lei Xia","doi":"10.1016/j.mtbio.2024.101420","DOIUrl":"10.1016/j.mtbio.2024.101420","url":null,"abstract":"<div><div>Fibroblast activating protein (FAP) is up-regulated in cancer-associated fibroblasts (CAFs) of more than 90 % of tumor microenvironment and also highly expressed on the surface of multiple tumor cells like glioblastoma, which can be used as a specific target for tumor diagnosis and treatment. At present, small-molecule radiotracer targeting FAP with high specificity exhibit limited functionality, which hinders the integration of theranostics as well as multifunctionality. In this work, we have engineered a multifunctional nanoplatform utilizing organic melanin nanoparticles that specifically targets FAP, facilitating both multimodal imaging and synergistic therapeutic applications. This nanoplatform can perform positron emission tomography (PET), magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) with strong near infrared absorption and metal chelating ability, achieving efficiently targeting accumulation and display long retention in the tumor region. Meanwhile, <sup>131</sup>I-labeled nanoplatform for targeted radioisotope therapy (TRT) and photothermal therapy (PTT) were significantly suppressed tumor growth in glioblastoma xenograft models without obvious side effects. These results demonstrated that this novel nanoparticles-based theranostics nanoplatform can effectively enhance multimodal imaging and targeted radionuclide-photothermal synergistic therapy for solid tumors with FAP expression.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101420"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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