Bioactive MaterialsPub Date : 2024-12-27DOI: 10.1016/j.bioactmat.2024.12.023
Kishwor Poudel , Zhenyu Ji , Ching-Ni Njauw , Anpuchchelvi Rajadurai , Brijesh Bhayana , Ryan J. Sullivan , Jong Oh Kim , Hensin Tsao
{"title":"Fabrication and functional validation of a hybrid biomimetic nanovaccine (HBNV) against KitK641E-mutant melanoma","authors":"Kishwor Poudel , Zhenyu Ji , Ching-Ni Njauw , Anpuchchelvi Rajadurai , Brijesh Bhayana , Ryan J. Sullivan , Jong Oh Kim , Hensin Tsao","doi":"10.1016/j.bioactmat.2024.12.023","DOIUrl":"10.1016/j.bioactmat.2024.12.023","url":null,"abstract":"<div><div>Cancer nanovaccines hold the promise for personalization, precision, and pliability by integrating all the elements essential for effective immune stimulation. An effective immune response requires communication and interplay between antigen-presenting cells (APCs), tumor cells, and immune cells to stimulate, extend, and differentiate antigen-specific and non-specific anti-tumor immune cells. The versatility of nanomedicine can be adapted to deliver both immunoadjuvant payloads and antigens from the key players in immunity (i.e., APCs and tumor cells). The imperative for novel cancer medicine is particularly pressing for less common but more devastating KIT-mutated acral and mucosal melanomas that are resistant to small molecule c-kit and immune checkpoint inhibitors. To overcome this challenge, we successfully engineered nanotechnology-enabled hybrid biomimetic nanovaccine (HBNV) comprised of membrane proteins (antigens to activate immunity and homing/targeting ligand to tumor microenvironment (TME) and lymphoid organs) from fused cells (of APCs and tumor cells) and immunoadjuvant. These HBNVs are efficiently internalized to the target cells, assisted in the maturation of APCs via antigens and adjuvant, activated the release of anti-tumor cytokines/inhibited the release of immunosuppressive cytokine, showed a homotypic effect on TME and lymph nodes, activated the anti-tumor immune cells/downregulated the immunosuppressive immune cells, reprogram the tumor microenvironment, and showed successful anti-tumor therapeutic and prophylactic effects.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 347-364"},"PeriodicalIF":18.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999287","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}
{"title":"Degradation products of magnesium implant synergistically enhance bone regeneration: Unraveling the roles of hydrogen gas and alkaline environment","authors":"Yuanming An , Haozhi Zhang , Shi'an Zhang , Yuantao Zhang , Lizhen Zheng , Xin Chen , Wenxue Tong , Jiankun Xu , Ling Qin","doi":"10.1016/j.bioactmat.2024.12.020","DOIUrl":"10.1016/j.bioactmat.2024.12.020","url":null,"abstract":"<div><div>Biodegradable magnesium (Mg) implant generally provides temporary fracture fixation and facilitates bone regeneration. However, the exact effects of generated Mg ions (Mg<sup>2+</sup>), hydrogen gas (H<sub>2</sub>), and hydroxide ions (OH<sup>-</sup>) by Mg degradation on enhancing fracture healing are not fully understood. Here we investigate the <em>in vivo</em> degradation of Mg intramedullary nail (Mg-IMN), revealing the generation of these degradation products around the fracture site during early stages. Bulk-RNA seq indicates that H<sub>2</sub> and alkaline pH increase periosteal cell proliferation, while Mg<sup>2+</sup> may mainly enhance extracellular matrix formation and cell adhesion in the femur <em>ex vivo</em>. <em>In vivo</em> studies further reveal that H<sub>2</sub>, Mg<sup>2+</sup> and alkaline pH individually generate comparable effects to the enhanced bone regeneration in the Mg-IMN group. Mechanistically, the degradation products elevate sensory calcitonin gene-related peptide (CGRP) and simultaneously suppress adrenergic factors in newly formed bone. H<sub>2</sub> and Mg<sup>2+</sup>, instead of alkaline pH, increase CGRP synthesis and inhibit adrenergic receptors. Our findings, for the first time, elucidate that Mg<sup>2+</sup>, H<sub>2</sub>, and alkaline pH environment generated by Mg-IMN act distinctly and synergistically mediated by the skeletal interoceptive regulation to accelerate bone regeneration. These findings may advance the understanding on biological functions of Mg-IMN in fracture repair and even other bone disorders.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 331-346"},"PeriodicalIF":18.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999278","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 : 2024-12-25DOI: 10.1016/j.bioactmat.2024.11.036
Wenhan Tian , Yuzeng Liu , Bo Han , Fengqi Cheng , Kang Yang , Weiyuan Hu , Dongdong Ye , Sujun Wu , Jiping Yang , Qi Chen , Yong Hai , Robert O. Ritchie , Guanping He , Juan Guan
{"title":"Mechanically robust surface-degradable implant from fiber silk composites demonstrates regenerative potential","authors":"Wenhan Tian , Yuzeng Liu , Bo Han , Fengqi Cheng , Kang Yang , Weiyuan Hu , Dongdong Ye , Sujun Wu , Jiping Yang , Qi Chen , Yong Hai , Robert O. Ritchie , Guanping He , Juan Guan","doi":"10.1016/j.bioactmat.2024.11.036","DOIUrl":"10.1016/j.bioactmat.2024.11.036","url":null,"abstract":"<div><div>Through millions of years of evolution, bones have developed a complex and elegant hierarchical structure, utilizing tropocollagen and hydroxyapatite to attain an intricate balance between modulus, strength, and toughness. In this study, continuous fiber silk composites (CFSCs) of large size are prepared to mimic the hierarchical structure of natural bones, through the inheritance of the hierarchical structure of fiber silk and the integration with a polyester matrix. Due to the robust interface between the matrix and fiber silk, CFSCs show maintained stable long-term mechanical performance under wet conditions. During <em>in vivo</em> degradation, this material primarily undergoes host cell-mediated surface degradation, rather than bulk hydrolysis. We demonstrate significant capabilities of CFSCs in promoting vascularization and macrophage differentiation toward repair. A bone defect model further indicates the potential of CFSC for bone graft applications. Our belief is that the material family of CFSCs may promise a novel biomaterial strategy for yet to be achieved excellent regenerative implants.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 584-598"},"PeriodicalIF":18.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982579","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 : 2024-12-25DOI: 10.1016/j.bioactmat.2024.12.019
Sara Freitas-Ribeiro , Andreia F. Carvalho , Daniel B. Rodrigues , Luís Martins , Ricardo A. Pires , Vera M. Mendes , Bruno Manadas , Mariana Jarnalo , Ricardo Horta , Rui L. Reis , Rogério P. Pirraco
{"title":"Cryogenic, but not hypothermic, preservation disrupts the extracellular matrix of cell sheets","authors":"Sara Freitas-Ribeiro , Andreia F. Carvalho , Daniel B. Rodrigues , Luís Martins , Ricardo A. Pires , Vera M. Mendes , Bruno Manadas , Mariana Jarnalo , Ricardo Horta , Rui L. Reis , Rogério P. Pirraco","doi":"10.1016/j.bioactmat.2024.12.019","DOIUrl":"10.1016/j.bioactmat.2024.12.019","url":null,"abstract":"<div><div>Cell sheet (CS)-based approaches hold significant potential for tissue regeneration, relying on the extracellular matrix (ECM) for success. Like in native tissues, the ECM provides structural and biochemical support for cellular homeostasis and function. Effective preservation strategies that maintain ECM integrity are critical to enhance the therapeutic potential of CS-based approaches. While cryogenic and hypothermic preservation methods offer potential solutions, their impact on CS ECM structure is not fully understood. Therefore, a comprehensive analysis of the ECM of hASCs CS following cryogenic and hypothermic preservation for 3 and 7 days, was conducted. Although proteomic analysis indicated that cryopreservation had no significant effect on the overall composition of the ECM, it induced significant ECM structural alterations, particularly disrupting collagen organization, which was not observed following hypothermic preservation. These structural changes were accompanied by alterations in mechanical properties, including a reduction in elastic modulus. In contrast, hypothermic preservation maintained ECM integrity and mechanical properties similar to the control. The notable ECM structural changes following cryogenic preservation can potentially impact cellular behavior, including adhesion, proliferation, and differentiation, thereby affecting the efficacy of CS therapies in vivo. This suggests that hypothermia may offer a promising alternative to cryopreservation for preserving CS integrity and functionality.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 301-310"},"PeriodicalIF":18.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982214","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 : 2024-12-25DOI: 10.1016/j.bioactmat.2024.12.018
Tian Zhang , Dongsheng Tang , Pengfei Wu , Shaoping Jiang , Yuquan Zhang , Abid Naeem , Yong Li , Chunhui Li , Bo Hu , Shuai Guo , Caixia Sun , Haihua Xiao , Ran Yan , Yuhua Weng , Yuanyu Huang
{"title":"NIR-II photo-accelerated polymer nanoparticles boost tumor immunotherapy via PD-L1 silencing and immunogenic cell death","authors":"Tian Zhang , Dongsheng Tang , Pengfei Wu , Shaoping Jiang , Yuquan Zhang , Abid Naeem , Yong Li , Chunhui Li , Bo Hu , Shuai Guo , Caixia Sun , Haihua Xiao , Ran Yan , Yuhua Weng , Yuanyu Huang","doi":"10.1016/j.bioactmat.2024.12.018","DOIUrl":"10.1016/j.bioactmat.2024.12.018","url":null,"abstract":"<div><div>Immune checkpoint blockade (ICB) therapy is a widely favored anti-tumor treatment, but it shows limited response to non-immunogenic “cold” tumors and suffers from drug resistance. Photodynamic therapy (PDT), as a powerful localized treatment approach, can convert a “cold tumor” into a “hot tumor” by inducing immunogenic cell death (ICD) in tumor cells, thereby enhancing tumor immunogenicity and promoting tumor immunotherapy. However, the effectiveness of PDT is largely hindered by the limited penetration depth into tumor tissues. To address these issues, we proposed an all-in-one drug system with NIR-II photo-accelerated PDT effects, efficient immune checkpoint gene silencing, and a facile manufacturing process. The so-called all-in-one drug system comprises a multi-modal designed polymer PPNP and siRNA. PPNP is an amphipathic polymer that includes the near infrared-II (NIR-II) photosensitizer Aza-boron-dipyrromethene (Aza-BODIPY), a glutathione (GSH)-cleavable linker, and a cationic monomer derived from cholesterol. PPNP can self-assemble and efficiently load siRNA. Under laser irradiation, PPNP triggers a potent ICD cascade, causing the on-demand release of siPD-L1, reshaping the tumor's immunosuppressive microenvironment, effectively inhibiting the growth of various tumors, and stimulating the immune memory. This study represents a generalized platform for PDT and gene silencing, designed to modulate immune-related signaling pathways for improved anticancer therapy.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 285-300"},"PeriodicalIF":18.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982396","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 : 2024-12-25DOI: 10.1016/j.bioactmat.2024.12.016
Xiong-Xin Lei , Meng-Long Liu , Chao-Feng Lu , Li-Li Han , Jie-Zhi Jia , Zheng Li , Na Xu , Jiang-Feng Li , Xuan-Jian Fu , Ya-Bin Jin , Ri-Kuan Tong , Yun-Long Yu , Gao-Xing Luo , Yang Chen
{"title":"A self-hygroscopic, rapidly self-gelling polysaccharide-based sponge with robust wet adhesion for non-compressible hemorrhage control and infected wounds healing","authors":"Xiong-Xin Lei , Meng-Long Liu , Chao-Feng Lu , Li-Li Han , Jie-Zhi Jia , Zheng Li , Na Xu , Jiang-Feng Li , Xuan-Jian Fu , Ya-Bin Jin , Ri-Kuan Tong , Yun-Long Yu , Gao-Xing Luo , Yang Chen","doi":"10.1016/j.bioactmat.2024.12.016","DOIUrl":"10.1016/j.bioactmat.2024.12.016","url":null,"abstract":"<div><div>Uncontrollable non-compressible hemorrhage and traumatic infection have been major causes of mortality and disability in both civilian and military populations. A dressing designed for point-of-care control of non-compressible hemorrhage and prevention of traumatic infections represents an urgent medical need. Here, a novel self-gelling sponge OHN@ε-pL is developed, integrating N-succinimidyl ester oxidized hyaluronic acid (OHN) and ε-poly-L-lysine (ε-pL). Upon application to the wound site, the sponge can rapidly absorb interfacial fluids and undergo a phase transition from sponge to gel. The transformed gel facilitates robust tissue adhesion and achieves synergistic hemostasis by enriching coagulation factors within the sponge phase and providing a barrier effect in the gel phase. The in vitro and in vivo studies revealed that the optimized OHN@ε-pL<sub>3</sub> sponge possesses self-gelling capability, tissue adhesion, enhanced coagulation ability, and exhibits excellent biocompatibility and antibacterial efficacy. In hemostasis, OHN@ε-pL<sub>3</sub> sponges exhibited reduced blood loss and decreased hemostatic time compared to commercial hemostatic agents, as demonstrated in rat liver, femoral vein, and tail truncation bleeding models. Furthermore, the OHN@ε-pL<sub>3</sub> sponge exhibited superior performance in accelerating wound closure and healing of <em>S. aureus</em>-infected wounds. Collectively, OHN@ε-pL sponges represent a promising candidate for medical dressings, specifically for managing uncontrollable non-compressible hemorrhage and traumatic infections.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 311-330"},"PeriodicalIF":18.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982582","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 : 2024-12-24DOI: 10.1016/j.bioactmat.2024.12.013
Lu Wang , Changjiang Yu , Ting You , Xinkui Zhang , Haotao Su , Bihui Cao , Sainiwaer Anwaier , Hongmo Xiang , Chengming Dai , Xiang Long , Linjiang Han , Dengfeng Zhang , Junwei Wang , Peng Zhu , Xinjian Yan , Jialiang Liang , Zerui Chen , Huanlei Huang , Shuoji Zhu , Tucheng Sun , Ping Zhu
{"title":"Injection of ROS-Responsive Hydrogel Loaded with IL-1β-targeted nanobody for ameliorating myocardial infarction","authors":"Lu Wang , Changjiang Yu , Ting You , Xinkui Zhang , Haotao Su , Bihui Cao , Sainiwaer Anwaier , Hongmo Xiang , Chengming Dai , Xiang Long , Linjiang Han , Dengfeng Zhang , Junwei Wang , Peng Zhu , Xinjian Yan , Jialiang Liang , Zerui Chen , Huanlei Huang , Shuoji Zhu , Tucheng Sun , Ping Zhu","doi":"10.1016/j.bioactmat.2024.12.013","DOIUrl":"10.1016/j.bioactmat.2024.12.013","url":null,"abstract":"<div><div>The cardiac microenvironment profoundly restricts the efficacy of myocardial regeneration tactics for the treatment of myocardial infarction (MI). A prospective approach for MI therapeutics encompasses the combined strategy of scavenging reactive oxygen species (ROS) to alleviate oxidative stress injury and facilitating macrophage polarization towards the regenerative M2 phenotype. In this investigation, we fabricated a ROS-sensitive hydrogel engineered to deliver our previously engineered IL-1β-VHH for myocardial restoration. In mouse and rat models of myocardial infarction, the therapeutic gel was injected into the pericardial cavity, effectively disseminated over the heart surface, forming an in situ epicardial patch. The IL-1β-VHH released from the hydrogel exhibited penetrative potential into the myocardium. Our results imply that this infarct-targeting gel can adhere to the damaged cardiac tissue and augment the quantity of anti-IL-1β antibodies. Moreover, the anti-IL-1β hydrogel safeguards cardiomyocytes from apoptosis by neutralizing IL-1β and inducing M2-type polarization within the myocardial infarction regions, thereby facilitating therapeutic cardiac repair. Our results emphasize the effectiveness of this synergistic comprehensive treatment modality in the management of MI and showcase its considerable potential for promoting recovery in infarcted hearts.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 273-284"},"PeriodicalIF":18.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982390","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}
{"title":"Compensatory effect-based oxidative stress management microneedle for psoriasis treatment","authors":"Chaoxiong Wu, Xinyu Yang, Kaiyue Yang, Qingyu Yu, Chenlu Huang, Fangzhou Li, Linhua Zhang, Dunwan Zhu","doi":"10.1016/j.bioactmat.2024.12.015","DOIUrl":"10.1016/j.bioactmat.2024.12.015","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) at elevated levels trigger oxidative DNA damage, which is a significant factor in psoriasis exacerbation. However, normal ROS levels are essential for cell signaling, cell growth regulation, differentiation, and immune responses. To address this, we developed ROS control strategies inspired by compensatory effects. DNA nanostructures with the advantage of being more stable than linear nucleic acid molecules in physiological environments were exquisitely fabricated and incorporated into microneedles (MN). These nanostructures regulate ROS levels and facilitate the delivery of IL-17A siRNA to psoriatic lesions. Our findings demonstrate that this transdermal drug delivery system effectively manages ROS levels in the psoriatic microenvironment, inhibiting pyroptosis and abnormal immune activation. Moreover, modulating ROS levels enhances the therapeutic impact of IL-17A siRNA, offering a promising <em>in situ</em> treatment approach for psoriasis.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 229-241"},"PeriodicalIF":18.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982122","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 : 2024-12-16DOI: 10.1016/j.bioactmat.2024.12.012
Changjiang Liu , Kun Liu , Dong Zhang , Yuting Liu , Yifeng Yu , Haifei Kang , Xianzhen Dong , Honglian Dai , Aixi Yu
{"title":"Dual-layer microneedles with NO/O2 releasing for diabetic wound healing via neurogenesis, angiogenesis, and immune modulation","authors":"Changjiang Liu , Kun Liu , Dong Zhang , Yuting Liu , Yifeng Yu , Haifei Kang , Xianzhen Dong , Honglian Dai , Aixi Yu","doi":"10.1016/j.bioactmat.2024.12.012","DOIUrl":"10.1016/j.bioactmat.2024.12.012","url":null,"abstract":"<div><div>Diabetic wounds present multiple functional impairments, including neurovascular dysregulation, oxidative imbalance, and immune dysfunction, making wound healing particularly challenging, while traditional therapeutical strategies fail to address these complex issues effectively. Herein, we propose a strategy utilizing dual-layer microneedles to deliver therapeutic gases by modulating neurovascular coupling and immune functions for diabetic wound treatment. The microneedle can respond to reactive oxygen species (ROS) in the diabetic microenvironment and subsequently generate oxygen (O<sub>2</sub>) and nitric oxide (NO). These gases comprehensively promote neuro-vascular regeneration, reduce oxidative stress levels, and attenuate inflammation. <em>In vivo</em> studies demonstrate that the microneedle can accelerate diabetic wound healing by modulating neurovascular regeneration and inflammatory processes. Transcriptomic analyses further validate the involvement of related advantageous signaling pathways. The potential mechanism involves the activation of the PI3K-AKT-mTOR pathway to facilitate autophagy, ultimately accelerating the healing process. Thus, our multifunctional dual-layer microneedles provide an effective strategy for treating diabetic wounds.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 213-228"},"PeriodicalIF":18.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969536","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 : 2024-12-14DOI: 10.1016/j.bioactmat.2024.12.010
Ziji Ling , Xiao Ge , Chengyu Jin , Zesheng Song , Hang Zhang , Yu Fu , Kai Zheng , Rongyao Xu , Hongbing Jiang
{"title":"Copper doped bioactive glass promotes matrix vesicles-mediated biomineralization via osteoblast mitophagy and mitochondrial dynamics during bone regeneration","authors":"Ziji Ling , Xiao Ge , Chengyu Jin , Zesheng Song , Hang Zhang , Yu Fu , Kai Zheng , Rongyao Xu , Hongbing Jiang","doi":"10.1016/j.bioactmat.2024.12.010","DOIUrl":"10.1016/j.bioactmat.2024.12.010","url":null,"abstract":"<div><div>Bone defect repair remains a great challenge in the field of orthopedics. Human body essential trace element such as copper is essential for bone regeneration, but how to use it in bone defects and the underlying its mechanisms of promoting bone formation need to be further explored. In this study, by doping copper into mesoporous bioactive glass nanoparticles (Cu-MBGNs), we unveil a previously unidentified role of copper in facilitating osteoblast mitophagy and mitochondrial dynamics, which enhance amorphous calcium phosphate (ACP) release and subsequent biomineralization, ultimately accelerating the process of bone regeneration. Specifically, by constructing conditional knockout mice lacking the autophagy gene <em>Atg5</em> in osteogenic lineage cells, we first confirmed the role of Cu-MBGNs-promoted bone formation via mediating osteoblast autophagy pathway. Then, the <em>in vitro</em> studies revealed that Cu-MBGNs strengthened mitophagy by inducing ROS production and recruiting PINK1/Parkin, thereby facilitating the efficient release of ACP from mitochondria into matrix vesicles for biomineralization during bone regeneration. Moreover, we found that Cu-MBGNs promoted mitochondrion fission via activating dynamin related protein 1 (Drp1) to reinforce mitophagy pathway. Together, this study highlights the potential of Cu-MBGNs‐mediated mitophagy and biomineralization for augmenting bone regeneration, offering a promising avenue for the development of advanced bioactive materials in orthopedic applications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 195-212"},"PeriodicalIF":18.0,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930647","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}