Pub Date : 2025-01-25DOI: 10.1016/j.bioactmat.2025.01.024
Zhiqing Liu , Tianlong Wang , Jinhui Zhao , Lei Zhang , Yiping Luo , Yixing Chen , Xinhui Wu , Yaqi Liu , Aihemaitijiang Aierken , Dilixiati Duolikun , Hui Jiang , Xinyu Zhao , Chang Li , Yingchuan Li , Wentao Cao , Jianzhong Du , Longpo Zheng
The pathological microenvironment in diabetic wounds is delineated by heightened inflammatory responses and persistent proinflammatory macrophage activity, which significantly hinders the wound healing process. Exogenous electrical stimulation (ES), by modulating the electric field distribution in wounds, has shown significant potential in treating inflammatory wounds. However, this approach relies on additional power sources and complex circuit designs. Here, a bionic neuro-immuno-regulatory (BNIR) system was proposed for reshaping the endogenous electric fields (EFs) through collecting ion flow. The BNIR system comprises microporous structure scaffolds and nanosheets, enabling swift biofluid collection and electrical signal transmission, with the ability to promote cell proliferation and migration and exhibit antioxidant properties. More importantly, the BNIR system induced the transition of M1 macrophages to M2 macrophages through neuro-immuno-regulatory. In diabetic rat skin wounds, the BNIR system significantly enhanced healing by simultaneously neuro-immuno-regulatory, promoting angiogenesis, scavenging ROS, and facilitating tissue remodeling. This work aims to advance the development of a bionic system for electrosensitive tissue repair.
{"title":"Endogenous electric field-driven neuro-immuno-regulatory scaffold for effective diabetic wound healing","authors":"Zhiqing Liu , Tianlong Wang , Jinhui Zhao , Lei Zhang , Yiping Luo , Yixing Chen , Xinhui Wu , Yaqi Liu , Aihemaitijiang Aierken , Dilixiati Duolikun , Hui Jiang , Xinyu Zhao , Chang Li , Yingchuan Li , Wentao Cao , Jianzhong Du , Longpo Zheng","doi":"10.1016/j.bioactmat.2025.01.024","DOIUrl":"10.1016/j.bioactmat.2025.01.024","url":null,"abstract":"<div><div>The pathological microenvironment in diabetic wounds is delineated by heightened inflammatory responses and persistent proinflammatory macrophage activity, which significantly hinders the wound healing process. Exogenous electrical stimulation (ES), by modulating the electric field distribution in wounds, has shown significant potential in treating inflammatory wounds. However, this approach relies on additional power sources and complex circuit designs. Here, a bionic neuro-immuno-regulatory (BNIR) system was proposed for reshaping the endogenous electric fields (EFs) through collecting ion flow. The BNIR system comprises microporous structure scaffolds and nanosheets, enabling swift biofluid collection and electrical signal transmission, with the ability to promote cell proliferation and migration and exhibit antioxidant properties. More importantly, the BNIR system induced the transition of M1 macrophages to M2 macrophages through neuro-immuno-regulatory. In diabetic rat skin wounds, the BNIR system significantly enhanced healing by simultaneously neuro-immuno-regulatory, promoting angiogenesis, scavenging ROS, and facilitating tissue remodeling. This work aims to advance the development of a bionic system for electrosensitive tissue repair.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 266-282"},"PeriodicalIF":18.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135288","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 : 2025-01-24DOI: 10.1016/j.bioactmat.2025.01.019
Sunyoung Park , Yeo-Jun Yoon , Yongpyo Hong , Jianning Yu , Jae-Min Cho , Ye Jin Jeong , Haeun Yu , Hyorim Jeong , Hyunjin Lee , Seungyeon Hwang , Won-Gun Koh , Ji Yeong Yang , Kyung-A Hyun , Hyo-Il Jung , Jae-Yol Lim
Extracellular vesicles (EVs) derived from stem cells offer promising potential for cell-free therapy. However, refining their cargo for precise disease targeting and delivery remains challenging. This study employed chemical reprogramming via dual inhibition of transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) to expand salivary gland basal progenitor cells (sgBPCs). CD9-enriched (CD9+) EVs were then isolated from the sgBPC secretome concentrate using a dual microfluidic chip. Notably, CD9+ EVs demonstrated superior uptake by salivary epithelial cells compared to CD9-depleted (CD9−) EVs and total EVs. In vivo studies using a salivary gland (SG) obstruction mouse model and ex vivo studies in SG fibrosis organoids revealed that CD9+ EVs significantly enhanced anti-fibrotic effects over CD9− EVs and control treatments. The presence of miR-3162 and miR-1290 in CD9+ EVs supported their anti-fibrotic properties by downregulating ACVR1 expression. The chemical reprogramming culture method effectively expanded sgBPCs, enabling consistent and scalable EV production. Utilizing microfluidic chip-isolated CD9+ EVs and ductal delivery presents a targeted and efficient approach for anti-fibrotic SG regeneration.
{"title":"CD9-enriched extracellular vesicles from chemically reprogrammed basal progenitors of salivary glands mitigate salivary gland fibrosis","authors":"Sunyoung Park , Yeo-Jun Yoon , Yongpyo Hong , Jianning Yu , Jae-Min Cho , Ye Jin Jeong , Haeun Yu , Hyorim Jeong , Hyunjin Lee , Seungyeon Hwang , Won-Gun Koh , Ji Yeong Yang , Kyung-A Hyun , Hyo-Il Jung , Jae-Yol Lim","doi":"10.1016/j.bioactmat.2025.01.019","DOIUrl":"10.1016/j.bioactmat.2025.01.019","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) derived from stem cells offer promising potential for cell-free therapy. However, refining their cargo for precise disease targeting and delivery remains challenging. This study employed chemical reprogramming via dual inhibition of transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) to expand salivary gland basal progenitor cells (sgBPCs). CD9-enriched (CD9<sup>+</sup>) EVs were then isolated from the sgBPC secretome concentrate using a dual microfluidic chip. Notably, CD9<sup>+</sup> EVs demonstrated superior uptake by salivary epithelial cells compared to CD9-depleted (CD9<sup>−</sup>) EVs and total EVs. <em>In vivo</em> studies using a salivary gland (SG) obstruction mouse model and <em>ex vivo</em> studies in SG fibrosis organoids revealed that CD9<sup>+</sup> EVs significantly enhanced anti-fibrotic effects over CD9<sup>−</sup> EVs and control treatments. The presence of miR-3162 and miR-1290 in CD9<sup>+</sup> EVs supported their anti-fibrotic properties by downregulating ACVR1 expression. The chemical reprogramming culture method effectively expanded sgBPCs, enabling consistent and scalable EV production. Utilizing microfluidic chip-isolated CD9<sup>+</sup> EVs and ductal delivery presents a targeted and efficient approach for anti-fibrotic SG regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 229-247"},"PeriodicalIF":18.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135289","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 : 2025-01-24DOI: 10.1016/j.bioactmat.2025.01.012
Xiongfa Ji , Xin Qian , Guowen Luo , Wenjie Yang , Wenhan Huang , Zehua Lei , Jiaqi Zhou , Guoqing Zhong , Jielong Zhou , Nan Liu , Limin Ma , Mei Li , Xiangmei Liu , Shuilin Wu , Yu Zhang
Osteosarcoma (OS) is a lethal bone tumor that primarily affects adolescents. OS is characterized by a high incidence of recurrence following surgical intervention, which is attributed to the presence of residual microscopic disease. Tumor-associated macrophages, which dominate the tumor microenvironment, often suppress immune responses and facilitate tumor progression and recurrence. This study developed an innovative nanotherapeutic approach by utilizing genetically engineered macrophage membranes with M1 polarization, stably overexpressing signal regulatory protein alpha (SIRPα), to encapsulate microwave-responsive nano-Prussian blue (SIRPα-M@nanoPB) nanoparticles. These nanoparticles induce tumor cell death selectively through hyperthermia and microwave dynamic effects upon targeted microwave irradiation. It is of critical importance to note that the enhancement of SIRPα on the nanoparticle surface actively targets and binds CD47 of tumor cells, thereby disrupting the "don't-eat-me" signal and effectively countering the immunosuppressive tumor environment. This action restores macrophage phagocytosis with M1 polarization, triggering potent immune responses. Our strategy holds considerable promise when it comes to improving the efficacy of microwave ablation through immune modulation, while reducing thermal damage to adjacent normal tissue and minimizing the risk of tumor recurrence. Thus, it offers a significant advancement in microwave therapies for patients with OS.
{"title":"Engineered macrophage nanoparticles enhance microwave ablation efficacy in osteosarcoma via targeting the CD47-SIRPα Axis: A novel Biomimetic immunotherapeutic approach","authors":"Xiongfa Ji , Xin Qian , Guowen Luo , Wenjie Yang , Wenhan Huang , Zehua Lei , Jiaqi Zhou , Guoqing Zhong , Jielong Zhou , Nan Liu , Limin Ma , Mei Li , Xiangmei Liu , Shuilin Wu , Yu Zhang","doi":"10.1016/j.bioactmat.2025.01.012","DOIUrl":"10.1016/j.bioactmat.2025.01.012","url":null,"abstract":"<div><div>Osteosarcoma (OS) is a lethal bone tumor that primarily affects adolescents. OS is characterized by a high incidence of recurrence following surgical intervention, which is attributed to the presence of residual microscopic disease. Tumor-associated macrophages, which dominate the tumor microenvironment, often suppress immune responses and facilitate tumor progression and recurrence. This study developed an innovative nanotherapeutic approach by utilizing genetically engineered macrophage membranes with M1 polarization, stably overexpressing signal regulatory protein alpha (SIRPα), to encapsulate microwave-responsive nano-Prussian blue (SIRPα-M@nanoPB) nanoparticles. These nanoparticles induce tumor cell death selectively through hyperthermia and microwave dynamic effects upon targeted microwave irradiation. It is of critical importance to note that the enhancement of SIRPα on the nanoparticle surface actively targets and binds CD47 of tumor cells, thereby disrupting the \"don't-eat-me\" signal and effectively countering the immunosuppressive tumor environment. This action restores macrophage phagocytosis with M1 polarization, triggering potent immune responses. Our strategy holds considerable promise when it comes to improving the efficacy of microwave ablation through immune modulation, while reducing thermal damage to adjacent normal tissue and minimizing the risk of tumor recurrence. Thus, it offers a significant advancement in microwave therapies for patients with OS.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 248-265"},"PeriodicalIF":18.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135290","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 : 2025-01-23DOI: 10.1016/j.bioactmat.2025.01.008
Jiayi Shi , Xuekai Qi , Ying Ran , Qiang Zhou , Yiqin Ding , Lujian Li , Youyun Zeng , Dongchao Qiu , Zhibin Cai , Xiaojun Cai , Yihuai Pan
Dental caries is primarily caused by cariogenic bacteria metabolizing carbohydrates to produce acidic substances that erode the dental hard tissues. Traditional remineralization treatments often have limited efficacy due to their lack of antibacterial activity. According to the Interrupting Dental Caries (IDC) theory, ideal caries-preventive materials should possess both antibacterial and remineralizing properties. Furthermore, effective adhesion to dental surfaces is crucial. Inspired by the wet adhesion properties of the salivary acquired pellicle, we developed a multifunctional gargle named Ce6@PDN-SAP (CP-SAP). This formulation employed peptide dendrimer nanogels (PDN) as a carrier for the photosensitizer Ce6, further functionalized with saliva-acquired peptide (SAP) to confer wet adhesion properties. CP-SAP rapidly adhered to the dental surface and remained effective for extended periods. Upon laser irradiation, Ce6 generated reactive oxygen species (ROS), disrupting bacterial outer membrane integrity, causing protein leakage, and reducing ATP levels, thereby achieving potent antibacterial effects. Following this, PDN and SAP acted as nucleation templates to promote in situ remineralization of demineralized dental hard tissues. In vivo studies using rat models demonstrated that CP-SAP provided significantly superior caries-preventive effects compared to chlorhexidine gargle. In conclusion, CP-SAP, as an innovative approach grounded in the IDC theory, holds great promise for the prevention and treatment of dental caries.
{"title":"Saliva-acquired pellicle inspired multifunctional gargle with wet adhesion, photodynamic antimicrobial, and In situ remineralization properties for dental caries prevention","authors":"Jiayi Shi , Xuekai Qi , Ying Ran , Qiang Zhou , Yiqin Ding , Lujian Li , Youyun Zeng , Dongchao Qiu , Zhibin Cai , Xiaojun Cai , Yihuai Pan","doi":"10.1016/j.bioactmat.2025.01.008","DOIUrl":"10.1016/j.bioactmat.2025.01.008","url":null,"abstract":"<div><div>Dental caries is primarily caused by cariogenic bacteria metabolizing carbohydrates to produce acidic substances that erode the dental hard tissues. Traditional remineralization treatments often have limited efficacy due to their lack of antibacterial activity. According to the Interrupting Dental Caries (IDC) theory, ideal caries-preventive materials should possess both antibacterial and remineralizing properties. Furthermore, effective adhesion to dental surfaces is crucial. Inspired by the wet adhesion properties of the salivary acquired pellicle, we developed a multifunctional gargle named Ce6@PDN-SAP (CP-SAP). This formulation employed peptide dendrimer nanogels (PDN) as a carrier for the photosensitizer Ce6, further functionalized with saliva-acquired peptide (SAP) to confer wet adhesion properties. CP-SAP rapidly adhered to the dental surface and remained effective for extended periods. Upon laser irradiation, Ce6 generated reactive oxygen species (ROS), disrupting bacterial outer membrane integrity, causing protein leakage, and reducing ATP levels, thereby achieving potent antibacterial effects. Following this, PDN and SAP acted as nucleation templates to promote in situ remineralization of demineralized dental hard tissues. In vivo studies using rat models demonstrated that CP-SAP provided significantly superior caries-preventive effects compared to chlorhexidine gargle. In conclusion, CP-SAP, as an innovative approach grounded in the IDC theory, holds great promise for the prevention and treatment of dental caries.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 212-228"},"PeriodicalIF":18.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135335","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 : 2025-01-22DOI: 10.1016/j.bioactmat.2025.01.015
Yaqian Li , Weijie Tian , Jianbin Guo , Yang Ye , Qianqian Gao , Yiwei Zhang , Xiaoyue Zhao , Jianwu Dai , Lan Zhu
Congenital deficiency or extensive cervical injury leads to female genital tract obstruction and cervical laxity, resulting in infertility or miscarriage. Current clinical approaches could be conducted to restore the continuity of cervix. However, full-thickness and large-scale cervical regeneration with complete structural and functional restoration have not been reported. In this study, we fabricated a double-layered collagen membrane (CM) scaffold based on decellularized extracellular matrix. Each layer was adapted to support the growth of epithelial cells and stromal cells, respectively. Further, the thickness and folded “sandwich” structure were tailored to match the cervical structure. When transplanted into rabbit full-thickness and total ectocervix excision models, only CM scaffold groups enabled the regeneration of neo-ectocervix tissue, including epithelium, stroma and muscular layers after 3 and 6 months. The neo-ectocervix regenerated by CM scaffolds exhibited significantly higher expression of secretory glands and estrogen receptors, more secretion of neutral and acidic mucins, showing functional maturity of regenerated epithelium. Notably, CM scaffolds supported the regeneration of stroma and muscular layers. The mechanical strength of neo ectocervix was comparable to that of normal ectocervix. CM scaffolds demonstrate good biocompatibility, support different cell growth, and enhance superior regeneration of epithelium, stromal and muscular tissue, confirming its construction capacity as new strategies for addressing cervical deficiency and damage.
{"title":"Full-thickness cervix reconstruction via collagen scaffolds in rabbits","authors":"Yaqian Li , Weijie Tian , Jianbin Guo , Yang Ye , Qianqian Gao , Yiwei Zhang , Xiaoyue Zhao , Jianwu Dai , Lan Zhu","doi":"10.1016/j.bioactmat.2025.01.015","DOIUrl":"10.1016/j.bioactmat.2025.01.015","url":null,"abstract":"<div><div>Congenital deficiency or extensive cervical injury leads to female genital tract obstruction and cervical laxity, resulting in infertility or miscarriage. Current clinical approaches could be conducted to restore the continuity of cervix. However, full-thickness and large-scale cervical regeneration with complete structural and functional restoration have not been reported. In this study, we fabricated a double-layered collagen membrane (CM) scaffold based on decellularized extracellular matrix. Each layer was adapted to support the growth of epithelial cells and stromal cells, respectively. Further, the thickness and folded “sandwich” structure were tailored to match the cervical structure. When transplanted into rabbit full-thickness and total ectocervix excision models, only CM scaffold groups enabled the regeneration of neo-ectocervix tissue, including epithelium, stroma and muscular layers after 3 and 6 months. The neo-ectocervix regenerated by CM scaffolds exhibited significantly higher expression of secretory glands and estrogen receptors, more secretion of neutral and acidic mucins, showing functional maturity of regenerated epithelium. Notably, CM scaffolds supported the regeneration of stroma and muscular layers. The mechanical strength of neo ectocervix was comparable to that of normal ectocervix. CM scaffolds demonstrate good biocompatibility, support different cell growth, and enhance superior regeneration of epithelium, stromal and muscular tissue, confirming its construction capacity as new strategies for addressing cervical deficiency and damage.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 170-180"},"PeriodicalIF":18.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135334","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 : 2025-01-22DOI: 10.1016/j.bioactmat.2025.01.010
Yu Zhang , Haiyan Liu , Weiqi Zhang , Yinghao Ding , Shengyi Zhang , Xiaowan Huang , Jiali Chen , Zhimou Yang , Feng Lin
Iodine is widely acknowledged for its potent antimicrobial properties. However, its clinical utility is often hampered by its unsatisfactory stability, uncontrolled release of active iodine and toxicity in moist environments. In this study, we report a novel iodine-containing hydrogel (I2@Nap-FFGP) designed for sustained iodine delivery under humid physiological and pathological conditions. I2@Nap-FFGP was fabricated using a self-assembling peptide-based hydrogel containing a proline motif to form a stable iodine complex. The resulting hydrogel exhibited excellent biocompatibility and robust antibacterial effect, it significantly inhibited bacteria-associated endometrial infections in mice and effectively alleviated inflammation. Moreover, the hydrogel successfully restored endometrial architecture and function. Notably, I2@Nap-FFGP remarkably improved pregnancy rates in mice with endometritis owing to its therapeutic effects. Our findings highlight the potential of this innovative hydrogel system for stable iodine application under humid and aqueous physiological conditions, offering a promising platform for future antibacterial therapies in clinical settings.
{"title":"Injectable iodine-containing peptide hydrogel for treatment of MRSA infection","authors":"Yu Zhang , Haiyan Liu , Weiqi Zhang , Yinghao Ding , Shengyi Zhang , Xiaowan Huang , Jiali Chen , Zhimou Yang , Feng Lin","doi":"10.1016/j.bioactmat.2025.01.010","DOIUrl":"10.1016/j.bioactmat.2025.01.010","url":null,"abstract":"<div><div>Iodine is widely acknowledged for its potent antimicrobial properties. However, its clinical utility is often hampered by its unsatisfactory stability, uncontrolled release of active iodine and toxicity in moist environments. In this study, we report a novel iodine-containing hydrogel (I<sub>2</sub>@Nap-FFGP) designed for sustained iodine delivery under humid physiological and pathological conditions. I<sub>2</sub>@Nap-FFGP was fabricated using a self-assembling peptide-based hydrogel containing a proline motif to form a stable iodine complex. The resulting hydrogel exhibited excellent biocompatibility and robust antibacterial effect, it significantly inhibited bacteria-associated endometrial infections in mice and effectively alleviated inflammation. Moreover, the hydrogel successfully restored endometrial architecture and function. Notably, I<sub>2</sub>@Nap-FFGP remarkably improved pregnancy rates in mice with endometritis owing to its therapeutic effects. Our findings highlight the potential of this innovative hydrogel system for stable iodine application under humid and aqueous physiological conditions, offering a promising platform for future antibacterial therapies in clinical settings.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 198-208"},"PeriodicalIF":18.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135379","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 : 2025-01-22DOI: 10.1016/j.bioactmat.2025.01.016
Danmei Li , Shuai Li , Shukun He , Hongpu He , Guangxun Yuan , Binbin Ma , Yijun Zhang , Chengjie Yuan , Zhiqin Liu , Zhenhan Deng , Jian Xu
Tendinopathy is a common musculoskeletal disorder in which a significant number of patients do not attain effective therapeutic outcomes. The extent of the inflammatory response and the dynamics of collagen synthesis metabolism are critical factors that influence the intrinsic self-repair capacity of tendons. However, the poor microenvironment within the tendon significantly impedes the self-repair process in tendinopathy. In this study, an injectable tendon-derived decellularized extracellular matrix (tdECM) hydrogel was utilized to treat tendinopathy. This hydrogel provides a more cytocompatible microenvironment while retaining certain bioactive factors of native tendon extracellular matrix (ECM), compared to collagen hydrogel. Notably, it was discovered for the first time that the tdECM hydrogel promotes M2 macrophage polarization, thereby exerting an anti-inflammatory effect in vivo. Furthermore, utilizing tdECM as a carrier for the sustained release of tendon-derived stem cells exosomes (TDSCs-Exos), our findings from both in vitro and in vivo studies indicate that the tdECM hydrogel, in conjunction with exosomes, demonstrated a pronounced synergistic enhancement in modulating inflammation, promoting M2 macrophage polarization, and facilitating tendon regeneration and repair efficacy. These results suggest its potential as a promising therapeutic strategy for tendon disorders.
{"title":"Restoring tendon microenvironment in tendinopathy: Macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon-derived stem cells exosomes","authors":"Danmei Li , Shuai Li , Shukun He , Hongpu He , Guangxun Yuan , Binbin Ma , Yijun Zhang , Chengjie Yuan , Zhiqin Liu , Zhenhan Deng , Jian Xu","doi":"10.1016/j.bioactmat.2025.01.016","DOIUrl":"10.1016/j.bioactmat.2025.01.016","url":null,"abstract":"<div><div>Tendinopathy is a common musculoskeletal disorder in which a significant number of patients do not attain effective therapeutic outcomes. The extent of the inflammatory response and the dynamics of collagen synthesis metabolism are critical factors that influence the intrinsic self-repair capacity of tendons. However, the poor microenvironment within the tendon significantly impedes the self-repair process in tendinopathy. In this study, an injectable tendon-derived decellularized extracellular matrix (tdECM) hydrogel was utilized to treat tendinopathy. This hydrogel provides a more cytocompatible microenvironment while retaining certain bioactive factors of native tendon extracellular matrix (ECM), compared to collagen hydrogel. Notably, it was discovered for the first time that the tdECM hydrogel promotes M2 macrophage polarization, thereby exerting an anti-inflammatory effect in vivo. Furthermore, utilizing tdECM as a carrier for the sustained release of tendon-derived stem cells exosomes (TDSCs-Exos), our findings from both in vitro and in vivo studies indicate that the tdECM hydrogel, in conjunction with exosomes, demonstrated a pronounced synergistic enhancement in modulating inflammation, promoting M2 macrophage polarization, and facilitating tendon regeneration and repair efficacy. These results suggest its potential as a promising therapeutic strategy for tendon disorders.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 152-169"},"PeriodicalIF":18.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135378","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 : 2025-01-22DOI: 10.1016/j.bioactmat.2025.01.017
Kaichao Hu , Junrui Ye , Pinglong Fan , Ruifang Zheng , Shasha Wang , Ye Peng , Yuan Ruan , Xu Yan , Zhao Zhang , Shifeng Chu , Naihong Chen
Stroke remains one of the leading causes of adult disability worldwide, with neovascularization is crucial for brain repair after stroke. However, neutrophil infiltration hinders effective neovascularization, necessitating timely clearance by microglia through phagocytosis. Unfortunately, microglial phagocytic function is often impaired by metabolic defects, hindering post-stroke recovery. Ginsenoside Rg1, derived from Panax ginseng, exhibits neuroprotective properties and regulates cellular metabolism in vitro but its therapeutic application is limited by poor brain penetration. Here, we present a targeted delivery system utilizing neutrophil-like cell membrane vesicles (NCM), prepared via nitrogen cavitation, to enhance Rg1 delivery to the brain. These biomimetic vesicles exploit the inherent targeting ability of neutrophil membranes to reach brain injury sites and are subsequently taken up by microglia. Our findings demonstrate that Rg1-loaded vesicles enhance microglial clearance of neutrophils, reduce neutrophil extracellular traps release, and mitigate tissue damage. These effects improve the post-stroke microenvironment, promote vascular remodeling, and ultimately contribute to functional recovery. This strategy highlights the potential of targeted reprogramming microglial cells to enhance their endogenous repair capabilities, offering a promising therapeutic avenue for ischemic stroke management.
{"title":"Targeting and reprogramming microglial phagocytosis of neutrophils by ginsenoside Rg1 nanovesicles promotes stroke recovery","authors":"Kaichao Hu , Junrui Ye , Pinglong Fan , Ruifang Zheng , Shasha Wang , Ye Peng , Yuan Ruan , Xu Yan , Zhao Zhang , Shifeng Chu , Naihong Chen","doi":"10.1016/j.bioactmat.2025.01.017","DOIUrl":"10.1016/j.bioactmat.2025.01.017","url":null,"abstract":"<div><div>Stroke remains one of the leading causes of adult disability worldwide, with neovascularization is crucial for brain repair after stroke. However, neutrophil infiltration hinders effective neovascularization, necessitating timely clearance by microglia through phagocytosis. Unfortunately, microglial phagocytic function is often impaired by metabolic defects, hindering post-stroke recovery. Ginsenoside Rg1, derived from Panax ginseng, exhibits neuroprotective properties and regulates cellular metabolism <em>in vitro</em> but its therapeutic application is limited by poor brain penetration. Here, we present a targeted delivery system utilizing neutrophil-like cell membrane vesicles (NCM), prepared via nitrogen cavitation, to enhance Rg1 delivery to the brain. These biomimetic vesicles exploit the inherent targeting ability of neutrophil membranes to reach brain injury sites and are subsequently taken up by microglia. Our findings demonstrate that Rg1-loaded vesicles enhance microglial clearance of neutrophils, reduce neutrophil extracellular traps release, and mitigate tissue damage. These effects improve the post-stroke microenvironment, promote vascular remodeling, and ultimately contribute to functional recovery. This strategy highlights the potential of targeted reprogramming microglial cells to enhance their endogenous repair capabilities, offering a promising therapeutic avenue for ischemic stroke management.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 181-197"},"PeriodicalIF":18.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135333","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 : 2025-01-20DOI: 10.1016/j.bioactmat.2025.01.007
Yaqiang Li , Xiaowei Xun , Liang Duan , Erji Gao , Jiaxin Li , Lei Lin , Xinping Li , Aijuan He , Haiyong Ao , Yong Xu , Huitang Xia
Tissue engineering strategies hold promise for constructing biomimetic tracheal substitutes to repair circumferential tracheal defects. However, current strategies for constructing off-the-shelf cartilage analogs for artificial trachea grafts face challenges of chondrocyte scarcity and inadequate culture strategies, which require extensive cell expansion and prolonged in vitro culture to generate robust neo-cartilage. To address these issues, we developed a nanofiber-hydrogel composite with superior mechanical performance by incorporating fragment oxidized bacterial cellulose (BC) nanofibers into a gelatin methacryloyl (GelMA) hydrogel network. Additionally, a biomaterial system was developed based on this composite, featuring dual-release functionality of fibroblast growth factor (FGF) and transforming growth factor beta (TGF-β) to facilitate step-wise maturation of neo-cartilage tissue. This process includes early-stage proliferation followed by second-stage extracellular matrix (ECM) deposition, driving the transition from proliferation to chondrogenesis. By encapsulating chondrocytes within the biomaterial system, mature neo-cartilage tissues with typical cartilage lacunae structures and abundant homogeneous cartilage-specific ECM deposition were successfully regenerated in vitro and in vivo. Furthermore, with a tailor-made growth factor-releasing strategy, the biomaterial system with low cell seeding density achieved biochemically and biomechanically functional neo-cartilage tissue regeneration, comparable to that achieved with high cell seeding density in the nanofiber-hydrogel composite. Based on the current biomaterial system, mature and functional cartilage-ring analogs were successfully constructed and applied to repair tracheal defects. Overall, the biomaterial system developed in this study provides a promising strategy for engineering transplantable, high-quality cartilage substitutes, with translational potential for artificial trachea construction.
{"title":"Cartilage structure-inspired nanofiber-hydrogel composite with robust proliferation and stable chondral lineage-specific differentiation function to orchestrate cartilage regeneration for artificial tracheal construction","authors":"Yaqiang Li , Xiaowei Xun , Liang Duan , Erji Gao , Jiaxin Li , Lei Lin , Xinping Li , Aijuan He , Haiyong Ao , Yong Xu , Huitang Xia","doi":"10.1016/j.bioactmat.2025.01.007","DOIUrl":"10.1016/j.bioactmat.2025.01.007","url":null,"abstract":"<div><div>Tissue engineering strategies hold promise for constructing biomimetic tracheal substitutes to repair circumferential tracheal defects. However, current strategies for constructing off-the-shelf cartilage analogs for artificial trachea grafts face challenges of chondrocyte scarcity and inadequate culture strategies, which require extensive cell expansion and prolonged <em>in vitro</em> culture to generate robust neo-cartilage. To address these issues, we developed a nanofiber-hydrogel composite with superior mechanical performance by incorporating fragment oxidized bacterial cellulose (BC) nanofibers into a gelatin methacryloyl (GelMA) hydrogel network. Additionally, a biomaterial system was developed based on this composite, featuring dual-release functionality of fibroblast growth factor (FGF) and transforming growth factor beta (TGF-β) to facilitate step-wise maturation of neo-cartilage tissue. This process includes early-stage proliferation followed by second-stage extracellular matrix (ECM) deposition, driving the transition from proliferation to chondrogenesis. By encapsulating chondrocytes within the biomaterial system, mature neo-cartilage tissues with typical cartilage lacunae structures and abundant homogeneous cartilage-specific ECM deposition were successfully regenerated <em>in vitro</em> and <em>in vivo</em>. Furthermore, with a tailor-made growth factor-releasing strategy, the biomaterial system with low cell seeding density achieved biochemically and biomechanically functional neo-cartilage tissue regeneration, comparable to that achieved with high cell seeding density in the nanofiber-hydrogel composite. Based on the current biomaterial system, mature and functional cartilage-ring analogs were successfully constructed and applied to repair tracheal defects. Overall, the biomaterial system developed in this study provides a promising strategy for engineering transplantable, high-quality cartilage substitutes, with translational potential for artificial trachea construction.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 136-151"},"PeriodicalIF":18.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078449","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}