Bioactive Materials最新文献

英文中文

Integrated biomimetic bioprinting of perichondrium with cartilage for auricle reconstruction

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-14 DOI: 10.1016/j.bioactmat.2025.02.011

Litao Jia, Siyu Liu, Luosha Gu, Xiaomin Liu, Kexin Sun, Feiyang Chu, Jinshi Zeng, Wenshuai Liu, Haiyue Jiang, Xia Liu

The construction and regeneration of tissue-engineered auricles are pacesetters in tissue engineering and have realized their first international clinical application. However, the unstable regeneration quality and insufficient mechanical strength have become significant obstacles impeding its clinical promotion. The perichondrium is indispensable for the nutritional and vascular supply of the underlying cartilage tissue, as well as for proper anatomical functioning and mechanical performance. This study presents a novel strategy for integrated construction of bioengineered perichondrium with bioprinted cartilage to enhance the regeneration quality and mechanical properties of tissue-engineered auricles. Simulating the anatomical structure of the native auricle designs a sandwich construction model containing bilateral perichondrium and intermediate cartilage, employing a photocrosslinkable acellular cartilage matrix and gelatin bionics matrix microenvironment, applying co-cultured auricular chondrocytes and adipose-derived stem cells creates functional cell populations, designing hatch patterns imitates microscopic arrangement structures, utilizing sacrificial materials forms interlaminar network traffic to enhance the tight connection between layers, and finally, assessing the regenerative quality of the constructs explores their feasibility and stability. The multi-level and multi-scale biomimetic construction strategy overcomes the technical limitation of the integrated construction of perichondrium-wrapped auricles and realizes biomimicry in morphology, structure, and biomechanics. Altogether, this study provides a technical reference for the hierarchical construction of complex tissues and promotes the clinical translation and application of engineered tissues or organs.

{"title":"Integrated biomimetic bioprinting of perichondrium with cartilage for auricle reconstruction","authors":"Litao Jia, Siyu Liu, Luosha Gu, Xiaomin Liu, Kexin Sun, Feiyang Chu, Jinshi Zeng, Wenshuai Liu, Haiyue Jiang, Xia Liu","doi":"10.1016/j.bioactmat.2025.02.011","DOIUrl":"10.1016/j.bioactmat.2025.02.011","url":null,"abstract":"<div><div>The construction and regeneration of tissue-engineered auricles are pacesetters in tissue engineering and have realized their first international clinical application. However, the unstable regeneration quality and insufficient mechanical strength have become significant obstacles impeding its clinical promotion. The perichondrium is indispensable for the nutritional and vascular supply of the underlying cartilage tissue, as well as for proper anatomical functioning and mechanical performance. This study presents a novel strategy for integrated construction of bioengineered perichondrium with bioprinted cartilage to enhance the regeneration quality and mechanical properties of tissue-engineered auricles. Simulating the anatomical structure of the native auricle designs a sandwich construction model containing bilateral perichondrium and intermediate cartilage, employing a photocrosslinkable acellular cartilage matrix and gelatin bionics matrix microenvironment, applying co-cultured auricular chondrocytes and adipose-derived stem cells creates functional cell populations, designing hatch patterns imitates microscopic arrangement structures, utilizing sacrificial materials forms interlaminar network traffic to enhance the tight connection between layers, and finally, assessing the regenerative quality of the constructs explores their feasibility and stability. The multi-level and multi-scale biomimetic construction strategy overcomes the technical limitation of the integrated construction of perichondrium-wrapped auricles and realizes biomimicry in morphology, structure, and biomechanics. Altogether, this study provides a technical reference for the hierarchical construction of complex tissues and promotes the clinical translation and application of engineered tissues or organs.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 100-117"},"PeriodicalIF":18.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403173","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}

引用次数: 0

A self-sacrificing anti-inflammatory coating promotes simultaneous cardiovascular repair and reendothelialization of implanted devices

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-13 DOI: 10.1016/j.bioactmat.2025.01.037

Pai Peng , Shili Ding , Min Liang , Weiwei Zheng , Yongyuan Kang , Wenxing Liu , Haifei Shi , Changyou Gao

During interventional surgeries of implantable cardiovascular devices in addressing cardiovascular diseases (CVD), the inevitable tissue damage will trigger host inflammation and vascular lumen injury, leading to delayed re-endothelization and intimal hyperplasia. Endowing cardiovascular implants with anti-inflammatory and endothelialization functions is conducive to the target site, offering significant tissue repair and regeneration benefits. Herein, inspired by the snake's molting process, a ShedWise device was developed by using the poly(propylene fumarate) polyurethane (PPFU) as the foundational material, which was clicked with hyperbranched polylysine (HBPL) and followed by conjugation with pro-endothelial functional Arg-Glu-Asp-Val peptide (REDV), and finally coated with a “self-sacrificing” layer having reactive oxygen species (ROS)-scavenging ability and degradability. During the acute inflammation in the initial stage of implantation, the ROS-responsive hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol (HBPAK) coating effectively modulated the level of environmental inflammation and resisted initial protein adsorption, showcasing robust tissue protection. As the coating gradually “sacrificed”, the exposed hyperbranched HBPL-REDV layer recruited specifically endothelial cells and promoted surface endothelialization. In a rat vascular injury model, the ShedWise demonstrated remarkable efficiency in reducing vascular restenosis, protecting the injured tissue, and fostering re-endothelization of the target site. This innovative design will introduce a novel strategy for surface engineering of cardiovascular implants and other medical devices.

{"title":"A self-sacrificing anti-inflammatory coating promotes simultaneous cardiovascular repair and reendothelialization of implanted devices","authors":"Pai Peng , Shili Ding , Min Liang , Weiwei Zheng , Yongyuan Kang , Wenxing Liu , Haifei Shi , Changyou Gao","doi":"10.1016/j.bioactmat.2025.01.037","DOIUrl":"10.1016/j.bioactmat.2025.01.037","url":null,"abstract":"<div><div>During interventional surgeries of implantable cardiovascular devices in addressing cardiovascular diseases (CVD), the inevitable tissue damage will trigger host inflammation and vascular lumen injury, leading to delayed re-endothelization and intimal hyperplasia. Endowing cardiovascular implants with anti-inflammatory and endothelialization functions is conducive to the target site, offering significant tissue repair and regeneration benefits. Herein, inspired by the snake's molting process, a ShedWise device was developed by using the poly(propylene fumarate) polyurethane (PPFU) as the foundational material, which was clicked with hyperbranched polylysine (HBPL) and followed by conjugation with pro-endothelial functional Arg-Glu-Asp-Val peptide (REDV), and finally coated with a “self-sacrificing” layer having reactive oxygen species (ROS)-scavenging ability and degradability. During the acute inflammation in the initial stage of implantation, the ROS-responsive hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol (HBPAK) coating effectively modulated the level of environmental inflammation and resisted initial protein adsorption, showcasing robust tissue protection. As the coating gradually “sacrificed”, the exposed hyperbranched HBPL-REDV layer recruited specifically endothelial cells and promoted surface endothelialization. In a rat vascular injury model, the ShedWise demonstrated remarkable efficiency in reducing vascular restenosis, protecting the injured tissue, and fostering re-endothelization of the target site. This innovative design will introduce a novel strategy for surface engineering of cardiovascular implants and other medical devices.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 502-512"},"PeriodicalIF":18.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395988","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}

引用次数: 0

Red blood cells-derived components as biomimetic functional materials: Matching versatile delivery strategies based on structure and function

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-13 DOI: 10.1016/j.bioactmat.2025.01.021

Hangbing Liu , Yi Li , Yuli Wang , Liying Zhang , Xiaoqing Liang , Chunsheng Gao , Yang Yang

Red blood cells (RBCs), often referred to as "intelligent delivery systems", can serve as biological or hybrid drug carriers due to their inherent advantages and characteristics. This innovative approach has the potential to enhance biocompatibility, pharmacokinetics, and provide targeting properties for drugs. By leveraging the unique structure and contents of RBCs, drug-loading pathways can be meticulously designed to align with these distinctive features. This review article primarily discusses the drug delivery strategies and their applications that are informed by the structural and functional properties of the main components of RBCs, including living RBCs, membranes, hollow RBCs, and hemoglobin. Overall, this review article would assist efforts to make better decisions on optimization and rational utilization of RBCs derivatives-based drug delivery strategies for the future direction in clinical translation.

引用次数: 0

Targeted codelivery of nitric oxide and hydrogen sulfide for enhanced antithrombosis efficacy

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-13 DOI: 10.1016/j.bioactmat.2025.02.012

Weiliang Deng , Zhixin Xu , Tong Hua , Guangbo Ji , Zihang Wang , Pei Liu , Yupeng Zhang , Shuo Li , Yuqiu Chao , Meng Qian , Qiang Zhao , Jinwei Tian

Thrombosis is a leading cause of mortality worldwide. As important gaseous signaling molecules, both nitric oxide (NO) and hydrogen sulfide (H₂S) demonstrate antiplatelet and anticoagulant functions, but little attention has been given to their synergistic effect and the underlying mechanism. In the present study, we developed an NO/H₂S codelivery system based on enzyme prodrug therapy (EPT) strategy in which the prodrugs are specifically recognized by the engineered β-galactosidase. Targeted codelivery of NO and H₂S in vivo was demonstrated by near-infrared fluorescence imaging and confirmed by measuring plasma and tissue levels; as a result, the side effects caused by systemic delivery, such as bleeding time, were reduced. Delivery of an optimized combination of NO and H₂S with a low combination index (CI) results in a synergistic effect on the inhibition of platelet adhesion and activation. Mechanistically, NO and H₂S cooperatively enhance the cGMP level through redox-based posttranslational modifications of phosphodiesterase 5A (PDE5A), which leads to activation of the cGMP/PKG signaling pathway. Furthermore, targeted codelivery of NO and H₂S demonstrates enhanced therapeutic efficacy for thrombosis in two mouse models of FeCl₃-induced arterial thrombosis and deep vein thrombosis. Collectively, these results confirm the synergistic efficacy of NO and H₂S for antithrombotic therapy, and the codelivery system developed in this study represents a promising candidate for clinical translation.

{"title":"Targeted codelivery of nitric oxide and hydrogen sulfide for enhanced antithrombosis efficacy","authors":"Weiliang Deng , Zhixin Xu , Tong Hua , Guangbo Ji , Zihang Wang , Pei Liu , Yupeng Zhang , Shuo Li , Yuqiu Chao , Meng Qian , Qiang Zhao , Jinwei Tian","doi":"10.1016/j.bioactmat.2025.02.012","DOIUrl":"10.1016/j.bioactmat.2025.02.012","url":null,"abstract":"<div><div>Thrombosis is a leading cause of mortality worldwide. As important gaseous signaling molecules, both nitric oxide (NO) and hydrogen sulfide (H<sub>2</sub>S) demonstrate antiplatelet and anticoagulant functions, but little attention has been given to their synergistic effect and the underlying mechanism. In the present study, we developed an NO/H<sub>2</sub>S codelivery system based on enzyme prodrug therapy (EPT) strategy in which the prodrugs are specifically recognized by the engineered β-galactosidase. Targeted codelivery of NO and H<sub>2</sub>S <em>in vivo</em> was demonstrated by near-infrared fluorescence imaging and confirmed by measuring plasma and tissue levels; as a result, the side effects caused by systemic delivery, such as bleeding time, were reduced. Delivery of an optimized combination of NO and H<sub>2</sub>S with a low combination index (CI) results in a synergistic effect on the inhibition of platelet adhesion and activation. Mechanistically, NO and H<sub>2</sub>S cooperatively enhance the cGMP level through redox-based posttranslational modifications of phosphodiesterase 5A (PDE5A), which leads to activation of the cGMP/PKG signaling pathway. Furthermore, targeted codelivery of NO and H<sub>2</sub>S demonstrates enhanced therapeutic efficacy for thrombosis in two mouse models of FeCl<sub>3</sub>-induced arterial thrombosis and deep vein thrombosis. Collectively, these results confirm the synergistic efficacy of NO and H<sub>2</sub>S for antithrombotic therapy, and the codelivery system developed in this study represents a promising candidate for clinical translation.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 29-42"},"PeriodicalIF":18.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394599","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}

引用次数: 0

A natural biological adhesive from slug mucus for wound repair

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-13 DOI: 10.1016/j.bioactmat.2025.01.030

Zhengchao Yuan , Siyuan Wu , Liwen Fu , Xinyi Wang , Zewen Wang , Muhammad Shafiq , Hao Feng , Lu Han , Jiahui Song , Mohamed EL-Newehy , Meera Moydeen Abdulhameed , Yuan Xu , Xiumei Mo , Shichao Jiang

Slugs could secrete mucus with multifunctional characteristics, such as reversible gelation, mucoadhesiveness, and viscoelasticity, which can be harnessed for multifaceted biotechnological and healthcare applications. The dried mucus (DM) was prepared using slug, which can be adhered to the tissue surface through different types of interactions (lap-shear force, 1.1 N for DM-3 group). The DM-3 further exhibited the highest hemostatic ability as discerned in a liver trauma injury model (hemostasis time, <15 s), biocompatibility and biodegradability (an insignificant residue at 4 weeks) in vivo, and considerably improved skin repair in full-thickness excisional wounds (wound closure, 96.2 % at day 14). Taken together, slug's mucus can be easily prepared with an economic and an eco-friendly method, which may have broad biotechnological and healthcare implications and potential utility in other related disciplines. This transition from natural components to the biomaterial may provide an invaluable platform for different types of applications.

{"title":"A natural biological adhesive from slug mucus for wound repair","authors":"Zhengchao Yuan , Siyuan Wu , Liwen Fu , Xinyi Wang , Zewen Wang , Muhammad Shafiq , Hao Feng , Lu Han , Jiahui Song , Mohamed EL-Newehy , Meera Moydeen Abdulhameed , Yuan Xu , Xiumei Mo , Shichao Jiang","doi":"10.1016/j.bioactmat.2025.01.030","DOIUrl":"10.1016/j.bioactmat.2025.01.030","url":null,"abstract":"<div><div>Slugs could secrete mucus with multifunctional characteristics, such as reversible gelation, mucoadhesiveness, and viscoelasticity, which can be harnessed for multifaceted biotechnological and healthcare applications. The dried mucus (DM) was prepared using slug, which can be adhered to the tissue surface through different types of interactions (lap-shear force, 1.1 N for DM-3 group). The DM-3 further exhibited the highest hemostatic ability as discerned in a liver trauma injury model (hemostasis time, <15 s), biocompatibility and biodegradability (an insignificant residue at 4 weeks) <em>in vivo</em>, and considerably improved skin repair in full-thickness excisional wounds (wound closure, 96.2 % at day 14). Taken together, slug's mucus can be easily prepared with an economic and an eco-friendly method, which may have broad biotechnological and healthcare implications and potential utility in other related disciplines. This transition from natural components to the biomaterial may provide an invaluable platform for different types of applications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 513-527"},"PeriodicalIF":18.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395407","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}

引用次数: 0

Corrigendum to “Construction of nanofibrous scaffolds with interconnected perfusable microchannel networks for engineering of vascularized bone tissue” [Bioact. Mater. 6 (2021),3254–3268]

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-13 DOI: 10.1016/j.bioactmat.2025.01.040

Jiani Gu, Qiangian Zhang, Mengru Geng, Weizhong Wang, Jin Yang, Atta ur Rehman Khan, Haibo Du, Zhou Sha, Xiaojun Zhou, Chuanglong He

引用次数: 0

Polylactic acid electrospun membranes coated with chiral hierarchical-structured hydroxyapatite nanoplates promote tendon healing based on a macrophage-homeostatic modulation strategy

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-13 DOI: 10.1016/j.bioactmat.2025.01.027

Gang Luo , Juehong Li , Shuai Chen , Zhengqiang Yuan , Ziyang Sun , Tengfei Lou , Zhenyu Chen , Hang Liu , Chao Zhou , Cunyi Fan , Hongjiang Ruan

Tendon injury is a common and challenging problem in the motor system that lacks an effective treatment, affecting daily activities and lowering the quality of life. Limited tendon regenerative capability and immune microenvironment dyshomeostasis are considered the leading causes hindering tendon repair. The chirality of biomaterials was proved to dictate immune microenvironment and dramatically affect tissue repair. Herein, chiral hierarchical structure hydroxylapatite (CHAP) nanoplates are innovatively synthesized for immunomodulatory purposes and further coated onto polylactic acid electrospinning membranes to achieve long-term release for tendon regeneration adaption. Notably, levorotatory-chiral HAP (L-CHAP) nanoplates rather than dextral-chiral or racemic-chiral exhibit good biocompatibility and bioactivity. In vitro experiments demonstrate that L-CHAP induces macrophage M2 polarization by enhancing macrophage efferocytosis, which alleviates inflammatory damage to tendon stem cells (TDSCs) through downregulated IL-17-NF-κB signaling. Meanwhile, L-CHAP-mediated macrophage efferocytosis also promotes TDSCs proliferation and tenogenic differentiation. By establishing a rat model of Achilles tendon injury, L-CHAP was demonstrated to comprehensively promoting tendon repair by enhancing macrophage efferocytosis and M2 polarization in vivo, finally leading to improvement of tendon ultrastructural and mechanical properties and motor function. This novel strategy highlights the role of L-CHAP in tendon repair and thus provides a promising therapeutic strategy for tendon injury.

{"title":"Polylactic acid electrospun membranes coated with chiral hierarchical-structured hydroxyapatite nanoplates promote tendon healing based on a macrophage-homeostatic modulation strategy","authors":"Gang Luo , Juehong Li , Shuai Chen , Zhengqiang Yuan , Ziyang Sun , Tengfei Lou , Zhenyu Chen , Hang Liu , Chao Zhou , Cunyi Fan , Hongjiang Ruan","doi":"10.1016/j.bioactmat.2025.01.027","DOIUrl":"10.1016/j.bioactmat.2025.01.027","url":null,"abstract":"<div><div>Tendon injury is a common and challenging problem in the motor system that lacks an effective treatment, affecting daily activities and lowering the quality of life. Limited tendon regenerative capability and immune microenvironment dyshomeostasis are considered the leading causes hindering tendon repair. The chirality of biomaterials was proved to dictate immune microenvironment and dramatically affect tissue repair. Herein, chiral hierarchical structure hydroxylapatite (CHAP) nanoplates are innovatively synthesized for immunomodulatory purposes and further coated onto polylactic acid electrospinning membranes to achieve long-term release for tendon regeneration adaption. Notably, levorotatory-chiral HAP (L-CHAP) nanoplates rather than dextral-chiral or racemic-chiral exhibit good biocompatibility and bioactivity. In vitro experiments demonstrate that L-CHAP induces macrophage M2 polarization by enhancing macrophage efferocytosis, which alleviates inflammatory damage to tendon stem cells (TDSCs) through downregulated IL-17-NF-<em>κ</em>B signaling. Meanwhile, L-CHAP-mediated macrophage efferocytosis also promotes TDSCs proliferation and tenogenic differentiation. By establishing a rat model of Achilles tendon injury, L-CHAP was demonstrated to comprehensively promoting tendon repair by enhancing macrophage efferocytosis and M2 polarization in vivo, finally leading to improvement of tendon ultrastructural and mechanical properties and motor function. This novel strategy highlights the role of L-CHAP in tendon repair and thus provides a promising therapeutic strategy for tendon injury.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 460-480"},"PeriodicalIF":18.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395409","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}

引用次数: 0

cGAMP-targeting injectable hydrogel system promotes periodontal restoration by alleviating cGAS-STING pathway activation

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-13 DOI: 10.1016/j.bioactmat.2025.02.010

Xiang Liu , Hua Zhang , Lei Xu , Huayu Ye , Jinghuan Huang , Jing Xiang , Yunying He , Huan Zhou , Lingli Fang , Yunyan Zhang , Xuerong Xiang , Richard D. Cannon , Ping Ji , Qiming Zhai

The impaired function of periodontal ligament stem cells (PDLSCs) impedes restoration of periodontal tissues. The cGAS-cGAMP-STING pathway is an innate immune pathway that sensing cytosolic double-stranded DNA (dsDNA), but its role in regulating the function of PDLSCs is still unclear. In this study, we found that mitochondrial DNA (mtDNA) was released into the cytoplasm through the mitochondrial permeability transition pore (mPTP) in PDLSCs upon inflammation, which binds to cGAS and activated the STING pathway by promoting the production of cGAMP, and ultimately impaired the osteogenic differentiation of PDLSCs. Additionally, it is first found that inflammation can down-regulate the level of the ATP-binding cassette membrane subfamily member C1 (ABCC1, a cGAMP exocellular transporter) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, a cGAMP hydrolase), which further aggravated the accumulation of intracellular cGAMP, leading to the persistent activation of the cGAS-STING pathway and thus the impaired the differentiation capacity of PDLSCs. Furthermore, we designed a hydrogel system loaded with a mPTP blocker, an ABCC1 agonist and ENPP1 to promote periodontal tissue regeneration by modulating the production, exocytosis, and clearance of cGAMP. In conclusion, our results highlight the profound effects, and specific mechanisms, of the cGAS-STING pathway on the function of stem cells and propose a new strategy to promote periodontal tissue restoration based on the reestablishment of cGAMP homeostasis.

{"title":"cGAMP-targeting injectable hydrogel system promotes periodontal restoration by alleviating cGAS-STING pathway activation","authors":"Xiang Liu , Hua Zhang , Lei Xu , Huayu Ye , Jinghuan Huang , Jing Xiang , Yunying He , Huan Zhou , Lingli Fang , Yunyan Zhang , Xuerong Xiang , Richard D. Cannon , Ping Ji , Qiming Zhai","doi":"10.1016/j.bioactmat.2025.02.010","DOIUrl":"10.1016/j.bioactmat.2025.02.010","url":null,"abstract":"<div><div>The impaired function of periodontal ligament stem cells (PDLSCs) impedes restoration of periodontal tissues. The cGAS-cGAMP-STING pathway is an innate immune pathway that sensing cytosolic double-stranded DNA (dsDNA), but its role in regulating the function of PDLSCs is still unclear. In this study, we found that mitochondrial DNA (mtDNA) was released into the cytoplasm through the mitochondrial permeability transition pore (mPTP) in PDLSCs upon inflammation, which binds to cGAS and activated the STING pathway by promoting the production of cGAMP, and ultimately impaired the osteogenic differentiation of PDLSCs. Additionally, it is first found that inflammation can down-regulate the level of the ATP-binding cassette membrane subfamily member C1 (ABCC1, a cGAMP exocellular transporter) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, a cGAMP hydrolase), which further aggravated the accumulation of intracellular cGAMP, leading to the persistent activation of the cGAS-STING pathway and thus the impaired the differentiation capacity of PDLSCs. Furthermore, we designed a hydrogel system loaded with a mPTP blocker, an ABCC1 agonist and ENPP1 to promote periodontal tissue regeneration by modulating the production, exocytosis, and clearance of cGAMP. In conclusion, our results highlight the profound effects, and specific mechanisms, of the cGAS-STING pathway on the function of stem cells and propose a new strategy to promote periodontal tissue restoration based on the reestablishment of cGAMP homeostasis.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 55-70"},"PeriodicalIF":18.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394605","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}

引用次数: 0

Investigation into recent advanced strategies of reactive oxygen species-mediated therapy based on Prussian blue: Conceptualization and prospect

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-13 DOI: 10.1016/j.bioactmat.2025.01.023

Hee-Young Kwon , Yuna Jung , Hojeong Jeon , Hyung-Seop Han

Prussian blue (PB) has garnered considerable scholarly interest in the field of biomedical research owing to its notably high biocompatibility, formidable multi-enzyme mimetic capabilities, and established clinical safety profile. These properties in combination with its reactive oxygen species (ROS) scavenging activity have facilitated significant progress in disease diagnosis and therapy for various ROS-mediated pathologies, where overproduced ROS exacerbates disease symptoms. Additionally, the underlying ROS-associated mechanisms are disease-specific. Hence, we systematically examined the role of ROS and its basic underlying mechanisms in representative disease categories and comprehensively reviewed the effect of PB-based materials in effectively alleviating pathological states. Furthermore, we present a thorough synthesis of disease-specific design methodologies and prospective directions for PB as a potent ROS-scavenging biotherapeutic material with emphasis on its applications in neurological, cardiovascular, inflammatory, and other pathological states. Through this review, we aim to accelerate the progress of research on disease treatment using PB-based integrated therapeutic system.

{"title":"Investigation into recent advanced strategies of reactive oxygen species-mediated therapy based on Prussian blue: Conceptualization and prospect","authors":"Hee-Young Kwon , Yuna Jung , Hojeong Jeon , Hyung-Seop Han","doi":"10.1016/j.bioactmat.2025.01.023","DOIUrl":"10.1016/j.bioactmat.2025.01.023","url":null,"abstract":"<div><div>Prussian blue (PB) has garnered considerable scholarly interest in the field of biomedical research owing to its notably high biocompatibility, formidable multi-enzyme mimetic capabilities, and established clinical safety profile. These properties in combination with its reactive oxygen species (ROS) scavenging activity have facilitated significant progress in disease diagnosis and therapy for various ROS-mediated pathologies, where overproduced ROS exacerbates disease symptoms. Additionally, the underlying ROS-associated mechanisms are disease-specific. Hence, we systematically examined the role of ROS and its basic underlying mechanisms in representative disease categories and comprehensively reviewed the effect of PB-based materials in effectively alleviating pathological states. Furthermore, we present a thorough synthesis of disease-specific design methodologies and prospective directions for PB as a potent ROS-scavenging biotherapeutic material with emphasis on its applications in neurological, cardiovascular, inflammatory, and other pathological states. Through this review, we aim to accelerate the progress of research on disease treatment using PB-based integrated therapeutic system.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 71-99"},"PeriodicalIF":18.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403172","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}

引用次数: 0

MiR-19-loaded oxidative stress-relief microgels with immunomodulatory and regeneration functions to reduce cardiac remodeling after myocardial infarction

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-13 DOI: 10.1016/j.bioactmat.2025.02.004

Kai Wang , Jun Wen , Wen-Yao Wang , Kefei Zhao , Tong Zhou , Shunqin Wang , Qiaoxuan Wang , Liyin Shen , Yanxin Xiang , Tanchen Ren , Jinghai Chen , Yi-Da Tang , Yang Zhu , Changyou Gao

Regeneration therapeutic strategy by microRNAs for boosting cardiomyocyte proliferation in treating myocardial infarction (MI) has the challenges of efficient delivery, and toxicity and risk of sudden death. Herein, oxidative stress-relief microgels were developed for miR-19a/b delivery, modulation of inflammatory tissue microenvironment, promotion of cardiomyocyte proliferation, and maintenance of heart function post MI. The cholesterol-modified miR-19a/b was encapsulated into the cavity of β-cyclodextrin in selenoketal-containing microgels. The microgels could effectively scavenge typical reactive oxygen species (ROS), and down-regulate the intracellular ROS level and the levels of typical inflammatory factors. The microgels could improve the acute inflammatory microenvironment for better cardiomyocyte survival and cellular uptake of miR-19a/b, leading to significant promotion of cardiomyocyte proliferation in vivo. In the rat and minipig models of MI, the microgels most effectively inhibited the acute inflammatory response and reduced the cardiomyocytes apoptosis, resulting in a significant improvement of cardiac function and restriction of pathological remodeling post MI, and thereby best heart function revealed by echocardiography and histological analysis.

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