Bioactive MaterialsPub Date : 2025-04-12DOI: 10.1016/j.bioactmat.2025.03.022
Chuwei Zhang , Shuai Fan , Jing Zhang , Ganghua Yang , Chao Cai , Shixuan Chen , Yongjin Fang , Wenbing Wan
{"title":"A multifunctional trap-capture-kill antibacterial system for enhanced wound healing via modified decellularized mushroom aerogels","authors":"Chuwei Zhang , Shuai Fan , Jing Zhang , Ganghua Yang , Chao Cai , Shixuan Chen , Yongjin Fang , Wenbing Wan","doi":"10.1016/j.bioactmat.2025.03.022","DOIUrl":"10.1016/j.bioactmat.2025.03.022","url":null,"abstract":"<div><div>Wound infections are prevalent and can result in prolonged healing times. In this study, we referred to the “trap-capture-kill” antibacterial strategy to create a wound dressing (DS/PDA@GO-L) by coupling graphene oxide (GO) with lysine and coating it onto the decellularized mushroom stem (DS) using polydopamine (PDA). The mechanism of action of the bacteria-killing process involves lysine chemotaxis and the siphoning effect of DS aerogel, with the process of killing the bacteria being initiated via near-infrared photothermal treatment. In vitro studies demonstrated that DS/PDA@GO-L exhibited excellent blood and cell compatibility, while in vivo experiments revealed its remarkable efficacy in combating bacterial infections. Specifically, the combination of DS/PDA@GO-L with photothermal therapy led to the elimination of over 95 % of <em>S. aureus</em>, <em>E. coli</em>, and <em>Pseudomonas aeruginosa</em>. Furthermore, the aerogel, when used in conjunction with photothermal therapy, significantly reduced bacterial infection at the wound site and accelerated wound healing. During the wound's proliferative phase, it notably enhanced vascularization and extracellular matrix deposition. Furthermore, immunohistochemical staining revealed that bacterial clearance led to a reduction in pro-inflammatory responses and a decrease in the expression of pro-inflammatory cytokines, thereby restoring the wound's inflammatory environment to a pro-regenerative state. Taken together, the developed DS/PDA@GO-L holds great potential in the field of infected skin wound healing.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 232-245"},"PeriodicalIF":18.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-11DOI: 10.1016/j.bioactmat.2025.04.005
Chen-Yu Zou , Chen Han , Ming Xiong , Juan-Juan Hu , Yan-Lin Jiang , Xiu-Zhen Zhang , Ya-Xing Li , Long-Mei Zhao , Yu-Ting Song , Qing-Yi Zhang , Qian-Jin Li , Rong Nie , Yue-Qi Zhang , Jesse Li-Ling , Hui-Qi Xie
{"title":"All-in-one extracellular matrix-based powders with instant self-assembly and multiple bioactivities integrate hemostasis and in-situ tissue functional repair","authors":"Chen-Yu Zou , Chen Han , Ming Xiong , Juan-Juan Hu , Yan-Lin Jiang , Xiu-Zhen Zhang , Ya-Xing Li , Long-Mei Zhao , Yu-Ting Song , Qing-Yi Zhang , Qian-Jin Li , Rong Nie , Yue-Qi Zhang , Jesse Li-Ling , Hui-Qi Xie","doi":"10.1016/j.bioactmat.2025.04.005","DOIUrl":"10.1016/j.bioactmat.2025.04.005","url":null,"abstract":"<div><div>Non-compressible hemorrhage poses a severe threat to life globally, yet achieving effective hemostasis and facilitating tissue repair remain a significant challenge and desired requirement. Herein, the all-in-one extracellular matrix (ECM)-based powder, composed of modified small intestinal submucosa (SIS) and sodium alginate, was ingeniously designed to realize one-stop management for non-compressible hemorrhage. Specifically, upon contact bleeding site, the powder's extreme liquid absorption allows for the rapid removal of interfacial blood. Simultaneously, based on the instant self-assembly strategy of covalent/non-covalent interaction, the powder can transform to wet bio-adhesive hydrogel within 5 s, effectively sealing the wound. Using the inherent bioactivities, the ECM-based powder exhibits satisfactory biocompatibility, enhanced cell recruitment, angiogenesis and endothelial cell functions. Ulteriorly, excellent hemostasis performance have verified in rabbit liver non-compressible hemorrhage and heart/artery massive hemorrhage models, significantly reducing the blood loss. More importantly, after hemostasis, the impaired liver demonstrates functional restoration that the more vessels and bile ducts formation, facilitated by the biodegradation of ECM-derived powders <em>in vivo</em> and the multi-biological cues response. Collectively, leveraging the merits of powder and hydrogel, this novel powder fulfills the all-in-one need for both non-compressible hemorrhage control and subsequent tissue repair, signifying it a valuable material in first aid.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 215-231"},"PeriodicalIF":18.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-10DOI: 10.1016/j.bioactmat.2025.04.001
Yunan Lu , Ting Zhang , Kai Chen , Federico Canavese , Chenyang Huang , Hongtao Yang , Jiahui Shi , Wubing He , Yufeng Zheng , Shunyou Chen
{"title":"Application of biodegradable implants in pediatric orthopedics: shifting from absorbable polymers to biodegradable metals","authors":"Yunan Lu , Ting Zhang , Kai Chen , Federico Canavese , Chenyang Huang , Hongtao Yang , Jiahui Shi , Wubing He , Yufeng Zheng , Shunyou Chen","doi":"10.1016/j.bioactmat.2025.04.001","DOIUrl":"10.1016/j.bioactmat.2025.04.001","url":null,"abstract":"<div><div>Over the past two decades, advances in pediatric orthopedics and closed reduction combined with percutaneous internal fixation techniques have led to significant growth in pediatric orthopedics surgery. Implants such as Kirschner-wires, cannulated screws and elastic stabilization intramedullary nails are commonly used in these procedures. However, traditional implants made of metal or inert materials are not absorbable, leading to complications that affect treatment outcomes. To address this issue, absorbable materials with excellent mechanical properties, good biocompatibility, and controlled degradation rates have been developed and applied in clinical practice. These materials include absorbable polymers and biodegradable metals. This article provides a comprehensive summary of these resorbable materials from a clinician's perspective. In addition, an in-depth discussion of the feasibility of their clinical applications and related research in pediatric orthopedics is included. We found that the applications of absorbable implants in pediatric orthopedics are shifting from absorbable polymers to biodegradable metals and emphasize that the functional characteristics of resorbable materials must be coordinated and complementary to the treatment in pediatric orthopedics.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 189-214"},"PeriodicalIF":18.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143807344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-08DOI: 10.1016/j.bioactmat.2025.04.006
Tianliang Ma , Qimeng Liu , Zheyu Zhang, Jiangyu Nan, Guanzhi Liu, Yute Yang, Yihe Hu, Jie Xie
{"title":"Fused exosomal targeted therapy in periprosthetic osteolysis through regulation of bone metabolic homeostasis","authors":"Tianliang Ma , Qimeng Liu , Zheyu Zhang, Jiangyu Nan, Guanzhi Liu, Yute Yang, Yihe Hu, Jie Xie","doi":"10.1016/j.bioactmat.2025.04.006","DOIUrl":"10.1016/j.bioactmat.2025.04.006","url":null,"abstract":"<div><div>The onset of periprosthetic osteolysis is mediated by wear particles following artificial arthroplasty. This manifests as a disturbed bone metabolism microenvironment, characterized by insufficient osteogenesis and angiogenesis, and enhanced osteoclastic activity. To target and remodel the homeostatic environment of bone metabolism in the sterile region around the prosthesis, we successfully pioneered the proposal and construction of a fused exosome (f-exo) system with M2 macrophage-derived exosomes (M2-exo) and urine-derived stem cell exosomes (USC-exo). The results demonstrate that f-exo effectively combines the osteolysis region-targeting capabilities of M2-exo with the bone metabolic homeostasis modulation effects of two exosomes (M2-exo and USC-exo), thereby achieving a significantly enhanced bone metabolic homeostasis targeting effect in the periprosthetic osteolysis region. The proteomic analysis of M2-exo, USC-exo, and f-exo revealed the potential mechanism of f-exo in targeting-regulation of bone metabolic homeostasis. Our study employs an innovative approach utilizing the fused exosome system for exosome targeted delivery, which offers a novel intervention strategy for the clinical management of periprosthetic osteolysis. Furthermore, it provides a novel conceptual framework for the development of exosome-based drug-targeting delivery systems.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 171-188"},"PeriodicalIF":18.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791395","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}
Bioactive MaterialsPub Date : 2025-04-08DOI: 10.1016/j.bioactmat.2025.03.020
Shengming Zhang , Weixian Hu , Yanzhi Zhao , Yuheng Liao , Kangkang Zha , Wenqian Zhang , Chenyan Yu , Jiewen Liao , Hui Li , Wu Zhou , Faqi Cao , Bobin Mi , Guohui Liu
{"title":"Bidirectional modulation of glycolysis using a multifunctional nanocomposite hydrogel promotes bone fracture healing in type 2 diabetes mellitus","authors":"Shengming Zhang , Weixian Hu , Yanzhi Zhao , Yuheng Liao , Kangkang Zha , Wenqian Zhang , Chenyan Yu , Jiewen Liao , Hui Li , Wu Zhou , Faqi Cao , Bobin Mi , Guohui Liu","doi":"10.1016/j.bioactmat.2025.03.020","DOIUrl":"10.1016/j.bioactmat.2025.03.020","url":null,"abstract":"<div><div>Fracture healing in patients with type 2 diabetes mellitus (T2D) is markedly impaired, characterized by a prolonged inflammation phase and defective osteoblast differentiation at the fracture site. In this study, we identified aberrant cellular glycolysis at T2D fracture sites, with bone marrow mesenchymal stem cells (BMSCs) exhibiting suppressed glycolysis and macrophages displaying enhanced glycolysis, mediated by the dysregulation of hypoxia-inducible factor-1α (HIF-1α). To rectify these metabolic imbalances, we developed a multifunctional nanocomposite PN@MHV hydrogel. Myricitrin, a flavonoid glycoside, forms the MHV hydrogel by cross-linking with HA-PBA and PVA via hydrogen bonds, and upregulates glycolysis through HIF-1α, thus promoting osteoblast differentiation under high glucose environment. To further regulate the inflammatory microenvironment, we incorporated nanoparticles loaded with PX-478, a HIF-1α specific inhibitor, into the hydrogel, with folic acid covalently modified to target proinflammatory M1 macrophages. This PN@MHV hydrogel bidirectionally regulated glycolysis via HIF-1α, enhancing osteoblast differentiation while attenuating macrophage-mediated inflammation. Comprehensive in vitro and in vivo experiments in a T2D fracture mouse model confirmed the hydrogel's ability to improve the inflammatory microenvironment and accelerate bone healing. Our findings underscore the therapeutic potential of targeting cellular glycolysis as a promising approach for enhancing fracture healing in diabetic patients.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 152-170"},"PeriodicalIF":18.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791394","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}
Bioactive MaterialsPub Date : 2025-04-05DOI: 10.1016/j.bioactmat.2025.03.027
Zhuohao Wen , Shuyi Li , Yi Liu , Xueyan Liu , Huiguo Qiu , Yuejuan Che , Liming Bian , Miao Zhou
{"title":"An engineered M2 macrophage-derived exosomes-loaded electrospun biomimetic periosteum promotes cell recruitment, immunoregulation, and angiogenesis in bone regeneration","authors":"Zhuohao Wen , Shuyi Li , Yi Liu , Xueyan Liu , Huiguo Qiu , Yuejuan Che , Liming Bian , Miao Zhou","doi":"10.1016/j.bioactmat.2025.03.027","DOIUrl":"10.1016/j.bioactmat.2025.03.027","url":null,"abstract":"<div><div>The periosteum, a fibrous tissue membrane covering bone surfaces, is critical to osteogenesis and angiogenesis in bone reconstruction. Artificial periostea have been widely developed for bone defect repair, but most of these are lacking of periosteal bioactivity. Herein, a biomimetic periosteum (termed PEC-Apt-NP-Exo) is prepared based on an electrospun membrane combined with engineered exosomes (Exos). The electrospun membrane is fabricated using poly(ε-caprolactone) (core)-periosteal decellularized extracellular matrix (shell) fibers via coaxial electrospinning, to mimic the fibrous structure, mechanical property, and tissue microenvironment of natural periosteum. The engineered Exos derived from M2 macrophages are functionalized by surface modification of bone marrow mesenchymal stem cell (BMSC)-specific aptamers to further enhance cell recruitment, immunoregulation, and angiogenesis in bone healing. The engineered Exos are covalently bonded to the electrospun membrane, to achieve rich loading and long-term effects of Exos. <em>In vitro</em> experiments demonstrate that the biomimetic periosteum promotes BMSC migration and osteogenic differentiation via Rap1/PI3K/AKT signaling pathway, and enhances vascular endothelial growth factor secretion from BMSCs to facilitate angiogenesis. <em>In vivo</em> studies reveal that the biomimetic periosteum promotes new bone formation in large bone defect repair by inducing M2 macrophage polarization, endogenous BMSC recruitment, osteogenic differentiation, and vascularization. This research provides valuable insights into the development of a multifunctional biomimetic periosteum for bone regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 95-115"},"PeriodicalIF":18.0,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777355","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}
Bioactive MaterialsPub Date : 2025-04-04DOI: 10.1016/j.bioactmat.2025.03.028
Shuyi Wu , Yingyue Sun , Qihong Zhang , Wen Si , Peng Gao , Lei Lu , Zhennan Deng , Lihua Xu , Xinkun Shen , Jinsong Liu
{"title":"Elytra-inspired zirconium phosphate nanonetwork: Toward high-quality osseointegration and physical-chemical-mechanical bond at the interface for zirconia-based dental materials","authors":"Shuyi Wu , Yingyue Sun , Qihong Zhang , Wen Si , Peng Gao , Lei Lu , Zhennan Deng , Lihua Xu , Xinkun Shen , Jinsong Liu","doi":"10.1016/j.bioactmat.2025.03.028","DOIUrl":"10.1016/j.bioactmat.2025.03.028","url":null,"abstract":"<div><div>Yttria-stabilized zirconia (YSZ) is widely used in dental implants and prostheses due to its excellent aesthetic and restorative properties. However, its bio-inert surface limits early osseointegration and weakens bonding strengths with porcelain veneer/resin cement. Inspired by the structure of beetle elytra, this work proposes a novel strategy involving a self-assembled trabecular-honeycomb biomimetic zirconium phosphate (ZrP) nanonetwork to modify YSZ surfaces. This approach simultaneously enhances energy dissipation, interfacial bonding, and osseointegration. The pore size of ZrP nanonetwork was precisely controlled by adjusting reaction temperatures (120 °C and 160 °C) and phosphoric acid concentrations (1.0 wt% and 2.5 wt%). Compared to conventional YSZ, the ZrP nanonetworks achieved remarkable improvements in bond strength, showing increases of 111 % with porcelain veneer and 336 % with resin cement. These enhancements are attributed to multiscale physical-chemical-mechanical interactions, including micromechanical anchoring, chemical bonding via phosphate groups, and energy dissipation through topological optimization. <em>In vitro</em> studies demonstrated that large-pore-size nanonetworks promote osteogenic differentiation of osteoblasts and modulate macrophage polarization toward the M2 phenotype, fostering an immune environment conducive to bone regeneration. <em>In vivo</em> experiments further validated the superior osseointegration and bone regeneration capacities of the large-pore-size ZrP nanonetwork. Collectively, this biomimetic ZrP nanonetwork-modified YSZ, with its exceptional physical-chemical-mechanical bonding properties, osseointegration potential, and immune-modulating capabilities, represents a groundbreaking advancement in zirconia-based material for dental implants and prostheses.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 116-133"},"PeriodicalIF":18.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768889","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}
Bioactive MaterialsPub Date : 2025-04-04DOI: 10.1016/j.bioactmat.2025.03.029
Moran Huang , Wan Li , Yaying Sun , Jize Dong , Chaojing Li , Henjie Jia , Yongjie Jiao , Lu Wang , Shanxing Zhang , Fujun Wang , Jiwu Chen
{"title":"Janus piezoelectric adhesives regulate macrophage TRPV1/Ca2+/cAMP axis to stimulate tendon-to-bone healing by multi-omics analysis","authors":"Moran Huang , Wan Li , Yaying Sun , Jize Dong , Chaojing Li , Henjie Jia , Yongjie Jiao , Lu Wang , Shanxing Zhang , Fujun Wang , Jiwu Chen","doi":"10.1016/j.bioactmat.2025.03.029","DOIUrl":"10.1016/j.bioactmat.2025.03.029","url":null,"abstract":"<div><div>Piezoelectric stimulation has garnered substantial interest as a promising strategy for tissue regeneration. However, studies investigating its impact on tendon-to-bone healing characterized by fibrocartilage remain scarce. Moreover, there are considerable technical challenges in achieving minimally invasive application of piezoelectric stimulation on the irregular tendon-to-bone interface. Herein, we developed Janus asymmetric piezoelectric adhesives by assembling adhesive hydrogel (GAN) and non-adhesive hydrogel (GM) on each side of piezoelectric poly (L-lactic acid) nanofiber. Piezoelectric adhesives exhibited superior anti-inflammatory effects both <em>in vitro</em> and <em>ex vivo</em>. Notably, the transient receptor potential (TRP) ion channels, a class of versatile signaling molecules, are closely associated with the regulation of inflammation. This study demonstrated that piezoelectric stimulation promoted Ca<sup>2+</sup> influx through the activation of transient receptor potential vanilloid 1 (TRPV1), further enhancing cAMP signaling pathway in macrophages by RNA sequencing. Additionally, <em>in vivo</em> proteomic analysis revealed Arachidonic acid metabolism and TNF-α signaling pathway downregulation and VEGF signaling pathway upregulation in a rat rotator cuff repair model. Piezoelectric adhesives ultimately achieved inflammation alleviation, angiogenesis enhancement, and fibrocartilage regeneration promotion, improving the biomechanical strength of the enthesis. This study elucidated the mechanism by which piezoelectric stimulation regulated tendon-to-bone healing through multi-omics analysis. The piezoelectric adhesives hold promise as a convenient and effective strategy for enhancing tendon-to-bone healing in clinical practice.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 134-151"},"PeriodicalIF":18.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768890","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}
Bioactive MaterialsPub Date : 2025-04-03DOI: 10.1016/j.bioactmat.2025.03.025
Zetao Wang , Zhipeng Sun , Shuangli Zhu , Zhihao Qin , Xiaohong Yin , Yilin Ding , Huichang Gao , Xiaodong Cao
{"title":"A multifunctional hydrogel loaded with magnesium-doped bioactive glass-induced vesicle clusters enhances diabetic wound healing by promoting intracellular delivery of extracellular vesicles","authors":"Zetao Wang , Zhipeng Sun , Shuangli Zhu , Zhihao Qin , Xiaohong Yin , Yilin Ding , Huichang Gao , Xiaodong Cao","doi":"10.1016/j.bioactmat.2025.03.025","DOIUrl":"10.1016/j.bioactmat.2025.03.025","url":null,"abstract":"<div><div>The treatment of diabetic wounds (DWs) poses a significant medical challenge. Mesenchymal stem cell-derived small extracellular vesicles (sEVs) have demonstrated potential in accelerating healing by delivering growth factors and microRNAs. However, the rapid clearance by the circulatory system limits their concentration and bioavailability within cells. This study employed magnesium-doped bioactive glass (MgBG) to autonomously program sEVs into a vesicle cluster (EPPM), which was subsequently incorporated into a hydrogel to create a comprehensive repair system that enhanced the delivery of both sEVs and MgBG, thereby promoting rapid healing of diabetic wounds. This hydrogel exhibited excellent injectable, self-healing and bioadhesive properties, making it an ideal physical barrier for DWs. In addition, the hydrogels also possessed photoresponsive properties that facilitated their bactericidal activity. The released EPPM significantly increased the intracellular uptake and accumulation of sEVs, with approximately 8.2-fold enhancement in macrophages and 16.7-fold in endothelial cells. The EPPM clusters efficiently induce macrophage M2 polarization, reduce inflammatory responses at the wound site, and recruit cells, thereby promoting angiogenesis and collagen deposition. This integrated repair system provided a new platform for the comprehensive treatment of diabetic wounds.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 30-46"},"PeriodicalIF":18.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759294","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}
Bioactive MaterialsPub Date : 2025-04-03DOI: 10.1016/j.bioactmat.2025.03.026
Zhanyu Chang , Xinyue Ran , Yaru Chu , Bohui Li , Zhenlin Fan , Genke Li , Dan Li , Wenjie Ren , Yujie Hua , Guangdong Zhou
{"title":"Dynamic-covalent hybrid hydrogels with cartilaginous immune microenvironment temporally regulating meniscus regeneration","authors":"Zhanyu Chang , Xinyue Ran , Yaru Chu , Bohui Li , Zhenlin Fan , Genke Li , Dan Li , Wenjie Ren , Yujie Hua , Guangdong Zhou","doi":"10.1016/j.bioactmat.2025.03.026","DOIUrl":"10.1016/j.bioactmat.2025.03.026","url":null,"abstract":"<div><div>Meniscus is a crescent-shaped fibrocartilage tissue for providing structural congruence and absorbing mechanical forces. Currently, the development of material-guided regeneration medicine strategy has emerged as a promising alternative for meniscus treatment. However, it often presents more complex pathological conditions of immune-inflammatory responses, and thus inevitably causes a harsh microenvironment that extremely hinders fibrocartilage regeneration. Therefore, there is an urgent need to develop bioactive materials to achieve cartilaginous immunomodulatory throughout the whole regenerative periods. In this study, we develop a novel dynamic-covalent hybrid (<strong>DCH</strong>) hydrogel with cartilaginous immune microenvironment (<strong>CIME</strong>) to temporally regulate meniscus regeneration. By combining dynamic boronic ester crosslinking and covalent photopolymerization reactions, <strong>DCH</strong> hydrogels exhibit favorable injectability, self-healing, and tissue adhesion properties for practical operation. Furthermore, <strong>CIME</strong> is successfully created by the introduction of a temporally on-demand regulatory system: naproxen anti-inflammatory drugs are preferentially released to regulate M1/M2 macrophage polarization through PI3K/Akt/mTOR signaling pathway at early stage, while TGFβ3/CTGF growth factors are on-demand released to promote fibrochondrogenic differentiation of stem cells in the post-regulatory microenvironment at later stage. Finally, <em>in vivo</em> experiments demonstrate the satisfactory repair of meniscus cartilage defects in rabbits by activating the endogenous repair of stem cells homing based on our established cartilaginous immunomodulatory strategy.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 14-29"},"PeriodicalIF":18.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759293","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}