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Selenide-linked polydopamine-reinforced hybrid hydrogels with on-demand degradation and light-triggered nanozyme release for diabetic wound healing. 具有随需降解和光触发纳米酶释放的硒联聚多巴胺增强杂化水凝胶用于糖尿病伤口愈合。
IF 11.3 1区 医学
Biomaterials Research Pub Date : 2023-05-18 DOI: 10.1186/s40824-023-00367-w
Wenjing Li, Ying Bei, Xiangqiang Pan, Jian Zhu, Zhengbiao Zhang, Tinglin Zhang, Jieting Liu, Dan Wu, Meng Li, Yan Wu, Jie Gao
{"title":"Selenide-linked polydopamine-reinforced hybrid hydrogels with on-demand degradation and light-triggered nanozyme release for diabetic wound healing.","authors":"Wenjing Li,&nbsp;Ying Bei,&nbsp;Xiangqiang Pan,&nbsp;Jian Zhu,&nbsp;Zhengbiao Zhang,&nbsp;Tinglin Zhang,&nbsp;Jieting Liu,&nbsp;Dan Wu,&nbsp;Meng Li,&nbsp;Yan Wu,&nbsp;Jie Gao","doi":"10.1186/s40824-023-00367-w","DOIUrl":"https://doi.org/10.1186/s40824-023-00367-w","url":null,"abstract":"<p><strong>Background: </strong>Multifunctional hydrogels with controllable degradation and drug release have attracted extensive attention in diabetic wound healing. This study focused on the acceleration of diabetic wound healing with selenide-linked polydopamine-reinforced hybrid hydrogels with on-demand degradation and light-triggered nanozyme release.</p><p><strong>Methods: </strong>Herein, selenium-containing hybrid hydrogels, defined as DSeP@PB, were fabricated via the reinforcement of selenol-end capping polyethylene glycol (PEG) hydrogels by polydopamine nanoparticles (PDANPs) and Prussian blue nanozymes in a one-pot approach in the absence of any other chemical additive or organic solvent based on diselenide and selenide bonding-guided crosslinking, making them accessible for large-scale mass production.</p><p><strong>Results: </strong>Reinforcement by PDANPs greatly increases the mechanical properties of the hydrogels, realizing excellent injectability and flexible mechanical properties for DSeP@PB. Dynamic diselenide introduction endowed the hydrogels with on-demand degradation under reducing or oxidizing conditions and light-triggered nanozyme release. The bioactivity of Prussian blue nanozymes afforded the hydrogels with efficient antibacterial, ROS-scavenging and immunomodulatory effects, which protected cells from oxidative damage and reduced inflammation. Further animal studies indicated that DSeP@PB under red light irradiation showed the most efficient wound healing activity by stimulating angiogenesis and collagen deposition and inhibiting inflammation.</p><p><strong>Conclusion: </strong>The combined merits of DSeP@PB (on-demand degradation, light-triggered release, flexible mechanical robustness, antibacterial, ROS-scavenging and immunomodulatory capacities) enable its high potential as a new hydrogel dressing that can be harnessed for safe and efficient therapeutics for diabetic wound healing.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851294","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: 4
Emerging biomaterials for tumor immunotherapy. 用于肿瘤免疫治疗的新兴生物材料。
IF 11.3 1区 医学
Biomaterials Research Pub Date : 2023-05-16 DOI: 10.1186/s40824-023-00369-8
Minna Xiao, Qinglai Tang, Shiying Zeng, Qian Yang, Xinming Yang, Xinying Tong, Gangcai Zhu, Lanjie Lei, Shisheng Li
{"title":"Emerging biomaterials for tumor immunotherapy.","authors":"Minna Xiao,&nbsp;Qinglai Tang,&nbsp;Shiying Zeng,&nbsp;Qian Yang,&nbsp;Xinming Yang,&nbsp;Xinying Tong,&nbsp;Gangcai Zhu,&nbsp;Lanjie Lei,&nbsp;Shisheng Li","doi":"10.1186/s40824-023-00369-8","DOIUrl":"https://doi.org/10.1186/s40824-023-00369-8","url":null,"abstract":"<p><strong>Background: </strong>The immune system interacts with cancer cells in various intricate ways that can protect the individual from overproliferation of cancer cells; however, these interactions can also lead to malignancy. There has been a dramatic increase in the application of cancer immunotherapy in the last decade. However, low immunogenicity, poor specificity, weak presentation efficiency, and off-target side effects still limit its widespread application. Fortunately, advanced biomaterials effectively contribute immunotherapy and play an important role in cancer treatment, making it a research hotspot in the biomedical field.</p><p><strong>Main body: </strong>This review discusses immunotherapies and the development of related biomaterials for application in the field. The review first summarizes the various types of tumor immunotherapy applicable in clinical practice as well as their underlying mechanisms. Further, it focuses on the types of biomaterials applied in immunotherapy and related research on metal nanomaterials, silicon nanoparticles, carbon nanotubes, polymer nanoparticles, and cell membrane nanocarriers. Moreover, we introduce the preparation and processing technologies of these biomaterials (liposomes, microspheres, microneedles, and hydrogels) and summarize their mechanisms when applied to tumor immunotherapy. Finally, we discuss future advancements and shortcomings related to the application of biomaterials in tumor immunotherapy.</p><p><strong>Conclusion: </strong>Research on biomaterial-based tumor immunotherapy is booming; however, several challenges remain to be overcome to transition from experimental research to clinical application. Biomaterials have been optimized continuously and nanotechnology has achieved continuous progression, ensuring the development of more efficient biomaterials, thereby providing a platform and opportunity for breakthroughs in tumor immunotherapy.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9857890","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: 8
CRISPR/Cas9 assisted stem cell therapy in Parkinson's disease. CRISPR/Cas9辅助干细胞治疗帕金森病
IF 11.3 1区 医学
Biomaterials Research Pub Date : 2023-05-16 DOI: 10.1186/s40824-023-00381-y
Poojitha Pinjala, Kamatham Pushpa Tryphena, Renuka Prasad, Dharmendra Kumar Khatri, Woong Sun, Shashi Bala Singh, Dalapathi Gugulothu, Saurabh Srivastava, Lalitkumar Vora
{"title":"CRISPR/Cas9 assisted stem cell therapy in Parkinson's disease.","authors":"Poojitha Pinjala,&nbsp;Kamatham Pushpa Tryphena,&nbsp;Renuka Prasad,&nbsp;Dharmendra Kumar Khatri,&nbsp;Woong Sun,&nbsp;Shashi Bala Singh,&nbsp;Dalapathi Gugulothu,&nbsp;Saurabh Srivastava,&nbsp;Lalitkumar Vora","doi":"10.1186/s40824-023-00381-y","DOIUrl":"https://doi.org/10.1186/s40824-023-00381-y","url":null,"abstract":"<p><p>Since its discovery in 2012, CRISPR Cas9 has been tried as a direct treatment approach to correct the causative gene mutation and establish animal models in neurodegenerative disorders. Since no strategy developed until now could completely cure Parkinson's disease (PD), neuroscientists aspire to use gene editing technology, especially CRISPR/Cas9, to induce a permanent correction in genetic PD patients expressing mutated genes. Over the years, our understanding of stem cell biology has improved. Scientists have developed personalized cell therapy using CRISPR/Cas9 to edit embryonic and patient-derived stem cells ex-vivo. This review details the importance of CRISPR/Cas9-based stem cell therapy in Parkinson's disease in developing PD disease models and developing therapeutic strategies after elucidating the possible pathophysiological mechanisms.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10190035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9488281","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: 7
Molecularly imprinted polymers (MIPs): emerging biomaterials for cancer theragnostic applications. 分子印迹聚合物(MIPs):癌症治疗应用的新兴生物材料。
IF 11.3 1区 医学
Biomaterials Research Pub Date : 2023-05-13 DOI: 10.1186/s40824-023-00388-5
Min Seok Kang, Euni Cho, Hye Eun Choi, Chaima Amri, Jin-Ho Lee, Ki Su Kim
{"title":"Molecularly imprinted polymers (MIPs): emerging biomaterials for cancer theragnostic applications.","authors":"Min Seok Kang,&nbsp;Euni Cho,&nbsp;Hye Eun Choi,&nbsp;Chaima Amri,&nbsp;Jin-Ho Lee,&nbsp;Ki Su Kim","doi":"10.1186/s40824-023-00388-5","DOIUrl":"10.1186/s40824-023-00388-5","url":null,"abstract":"<p><p>Cancer is a disease caused by abnormal cell growth that spreads through other parts of the body and threatens life by destroying healthy tissues. Therefore, numerous techniques have been employed not only to diagnose and monitor the progress of cancer in a precise manner but also to develop appropriate therapeutic agents with enhanced efficacy and safety profiles. In this regard, molecularly imprinted polymers (MIPs), synthetic receptors that recognize targeted molecules with high affinity and selectivity, have been intensively investigated as one of the most attractive biomaterials for theragnostic approaches. This review describes diverse synthesis strategies to provide the rationale behind these synthetic antibodies and provides a selective overview of the recent progress in the in vitro and in vivo targeting of cancer biomarkers for diagnosis and therapeutic applications. Taken together, the topics discussed in this review provide concise guidelines for the development of novel MIP-based systems to diagnose cancer more precisely and promote successful treatment. Molecularly imprinted polymers (MIPs), synthetic receptors that recognize targeted molecules with high affinity and selectivity, have been intensively investigated as one of the most attractive biomaterials for cancer theragnostic approaches. This review describes diverse synthesis strategies to provide the rationale behind these synthetic antibodies and provides a selective overview of the recent progress in the in vitro and in vivo targeting of cancer biomarkers for diagnosis and therapeutic applications. The topics discussed in this review aim to provide concise guidelines for the development of novel MIP-based systems to diagnose cancer more precisely and promote successful treatment.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9458920","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: 1
Copper-induced injectable hydrogel with nitric oxide for enhanced immunotherapy by amplifying immunogenic cell death and regulating cancer associated fibroblasts. 铜诱导的含一氧化氮的可注射水凝胶通过放大免疫原性细胞死亡和调节癌症相关成纤维细胞来增强免疫治疗。
IF 11.3 1区 医学
Biomaterials Research Pub Date : 2023-05-10 DOI: 10.1186/s40824-023-00389-4
Shuilin Shen, Zimeng Zhang, Haixiao Huang, Jing Yang, Xinyue Tao, Zhengjie Meng, Hao Ren, Xueming Li
{"title":"Copper-induced injectable hydrogel with nitric oxide for enhanced immunotherapy by amplifying immunogenic cell death and regulating cancer associated fibroblasts.","authors":"Shuilin Shen,&nbsp;Zimeng Zhang,&nbsp;Haixiao Huang,&nbsp;Jing Yang,&nbsp;Xinyue Tao,&nbsp;Zhengjie Meng,&nbsp;Hao Ren,&nbsp;Xueming Li","doi":"10.1186/s40824-023-00389-4","DOIUrl":"https://doi.org/10.1186/s40824-023-00389-4","url":null,"abstract":"<p><strong>Background: </strong>Immunogenic cell death (ICD) induced by different cancer treatments has been widely evaluated to recruit immune cells and trigger the specific antitumor immunity. However, cancer associated fibroblasts (CAFs) can hinder the invasion of immune cells and polarize the recruited monocytes to M2-type macrophages, which greatly restrict the efficacy of immunotherapy (IT).</p><p><strong>Methods: </strong>In this study, an injectable hydrogel induced by copper (Cu) has been designed to contain antibody of PD-L1 and nitric oxide (NO) donor. The therapeutic efficacy of hydrogel was studied in 4T1 cells and CAFs in vitro and 4T1 tumor-bearing mice in vivo. The immune effects on cytotoxic T lymphocytes, dendritic cells (DCs) and macrophages were analyzed by flow cytometry. Enzyme-linked immunosorbent assay, immunofluorescence and transcriptome analyses were also performed to evaluate the underlying mechanism.</p><p><strong>Results: </strong>Due to the absorbance of Cu with the near-infrared laser irradiation, the injectable hydrogel exhibits persistent photothermal effect to kill cancer cells. In addition, the Cu of hydrogel shows the Fenton-like reaction to produce reactive oxygen species as chemodynamic therapy, thereby enhancing cancer treatment and amplifying ICD. More interestingly, we have found that the released NO can significantly increase depletion of CAFs and reduce the proportion of M2-type macrophages in vitro. Furthermore, due to the amplify of ICD, injectable hydrogel can effectively increase the infiltration of immune cells and reverse the immunosuppressive tumor microenvironment (TME) by regulating CAFs to enhance the therapeutic efficacy of anti-PD-L1 in vivo.</p><p><strong>Conclusions: </strong>The ion induced self-assembled hydrogel with NO could enhance immunotherapy via amplifying ICD and regulating CAFs. It provides a novel strategy to provoke a robust antitumor immune response for clinical cancer immunotherapy.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9505628","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: 1
Bionic natural small molecule co-assemblies towards targeted and synergistic Chemo/PDT/CDT. 面向靶向和协同化疗/PDT/CDT的仿生天然小分子共组装。
IF 11.3 1区 医学
Biomaterials Research Pub Date : 2023-05-09 DOI: 10.1186/s40824-023-00380-z
Shiyao Fu, Mingao Wang, Bin Li, Xu Li, Jianjun Cheng, Haitian Zhao, Hua Zhang, Aijun Dong, Weihong Lu, Xin Yang
{"title":"Bionic natural small molecule co-assemblies towards targeted and synergistic Chemo/PDT/CDT.","authors":"Shiyao Fu,&nbsp;Mingao Wang,&nbsp;Bin Li,&nbsp;Xu Li,&nbsp;Jianjun Cheng,&nbsp;Haitian Zhao,&nbsp;Hua Zhang,&nbsp;Aijun Dong,&nbsp;Weihong Lu,&nbsp;Xin Yang","doi":"10.1186/s40824-023-00380-z","DOIUrl":"https://doi.org/10.1186/s40824-023-00380-z","url":null,"abstract":"<p><strong>Background: </strong>Multi-component nano-delivery systems based on chemotherapy (chemo)- photodynamic therapy (PDT)- chemodynamic therapy (CDT) have gained increased attention as a promising strategy to improve clinical outcomes in cancer treatment. However, there remains a challenge in developing biodegradable, biocompatible, less toxic, yet highly efficient multicomponent nanobased drug delivery systems (DDS). Here, our study presents the screening and development of a novel DDS based on co-assemblies natural small molecule (NSMs). These molecules (oleanolic acid, and betulinic acid) are combined with photosensitizers Chlorine6 (Ce6) and Cu<sup>2+</sup> that are encapsulated by tumor cell membranes. This nanocarrier encapsulated in tumor cell membranes achieved good tumor targeting and a significant improvement in tumor accumulation.</p><p><strong>Methods: </strong>A reprecipitation method was used to prepare the co-assembled nanocarrier, followed by the introduction of Cu<sup>2 +</sup> into the DDS (OABACe6 NPs). Then, by wrapping the surface of NPs with the cell membranes of 4T1 which is a kind of mouse breast cancer cells (CM@OABACe6/Cu NPs). and analysis of its structure and size distribution with UV-Vis, XPS, FT-IR, SEM, TEM, and DLS. The synergistic effects of in vitro chemotherapy, CDT and PDT and targeting were also validated by cellular and animal studies.</p><p><strong>Results: </strong>It was shown that CM@OABACe6/Cu NPs achieved good tumor targeting and a significant improvement in tumor accumulation. In the composite nano-assembly, the NSMs work together with the Ce6 to provide effective and safe chemo and PDT. Moreover, the effect of reduced PDT due to the depletion of reactive oxygen species (ROS) by excess glutathione (GSH) in the tumor can be counteracted when Cu<sup>2 +</sup> is introduced. More importantly, it also confers CDT through a Fenton-like catalytic reaction with H<sub>2</sub>O overexpressed at the tumor site.</p><p><strong>Conclusions: </strong>By constructing CM@OABACe6/Cu NPs with homologous targeting, we create a triple synergistic platform for cancer therapy using PDT, chemo, and CDT. We propose here a novel combinatorial strategy for designing more naturally co-assembled small molecules, especially for the development of multifunctional synergistic therapies that utilize NSMs.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10169343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9450713","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
Advanced cancer targeting using aptamer functionalized nanocarriers for site-specific cargo delivery. 利用适体功能化纳米载体进行部位特异性货物递送的晚期癌症靶向。
IF 11.3 1区 医学
Biomaterials Research Pub Date : 2023-05-06 DOI: 10.1186/s40824-023-00365-y
Mahavir Narwade, Aazam Shaikh, Kavita R Gajbhiye, Prashant Kesharwani, Virendra Gajbhiye
{"title":"Advanced cancer targeting using aptamer functionalized nanocarriers for site-specific cargo delivery.","authors":"Mahavir Narwade,&nbsp;Aazam Shaikh,&nbsp;Kavita R Gajbhiye,&nbsp;Prashant Kesharwani,&nbsp;Virendra Gajbhiye","doi":"10.1186/s40824-023-00365-y","DOIUrl":"https://doi.org/10.1186/s40824-023-00365-y","url":null,"abstract":"<p><p>The non-specificity of standard anticancer therapies has profound detrimental consequences in clinical treatment. Therapeutic specificity can be precisely achieved using cutting-edge ligands. Small synthetic oligonucleotide-ligands chosen through Systematic evolution of ligands by exponential enrichment (SELEX) would be an unceasing innovation in using nucleic acids as aptamers, frequently referred to as \"chemical antibodies.\" Aptamers act as externally controlled switching materials that can attach to various substrates, for example, membrane proteins or nucleic acid structures. Aptamers pose excellent specificity and affinity for target molecules and can be used as medicines to suppress tumor cell growth directly. The creation of aptamer-conjugated nanoconstructs has recently opened up innovative options in cancer therapy that are more effective and target tumor cells with minor toxicity to healthy tissues. This review focuses on a comprehensive description of the most capable classes of aptamer-tethered nanocarriers for precise recognition of cancer cells with significant development in proficiency, selectivity, and targetability for cancer therapy. Existing theranostic applications with the problems and future directions are also highlighted.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9422007","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: 4
Cardiac-targeted delivery of nuclear receptor RORα via ultrasound targeted microbubble destruction optimizes the benefits of regular dose of melatonin on sepsis-induced cardiomyopathy. 通过超声靶向微泡破坏核受体RORα的心脏靶向递送优化了常规剂量褪黑素对败血症性心肌病的益处。
IF 11.3 1区 医学
Biomaterials Research Pub Date : 2023-05-05 DOI: 10.1186/s40824-023-00377-8
Shanjie Wang, Kegong Chen, Ye Wang, Zeng Wang, Zhaoying Li, JunChen Guo, Jianfeng Chen, Wenhua Liu, Xiaohui Guo, Guangcan Yan, Chenchen Liang, Huai Yu, Shaohong Fang, Bo Yu
{"title":"Cardiac-targeted delivery of nuclear receptor RORα via ultrasound targeted microbubble destruction optimizes the benefits of regular dose of melatonin on sepsis-induced cardiomyopathy.","authors":"Shanjie Wang,&nbsp;Kegong Chen,&nbsp;Ye Wang,&nbsp;Zeng Wang,&nbsp;Zhaoying Li,&nbsp;JunChen Guo,&nbsp;Jianfeng Chen,&nbsp;Wenhua Liu,&nbsp;Xiaohui Guo,&nbsp;Guangcan Yan,&nbsp;Chenchen Liang,&nbsp;Huai Yu,&nbsp;Shaohong Fang,&nbsp;Bo Yu","doi":"10.1186/s40824-023-00377-8","DOIUrl":"https://doi.org/10.1186/s40824-023-00377-8","url":null,"abstract":"<p><strong>Background: </strong>Large-dose melatonin treatment in animal experiments was hardly translated into humans, which may explain the dilemma that the protective effects against myocardial injury in animal have been challenged by clinical trials. Ultrasound-targeted microbubble destruction (UTMD) has been considered a promising drug and gene delivery system to the target tissue. We aim to investigate whether cardiac gene delivery of melatonin receptor mediated by UTMD technology optimizes the efficacy of clinically equivalent dose of melatonin in sepsis-induced cardiomyopathy.</p><p><strong>Methods: </strong>Melatonin and cardiac melatonin receptors in patients and rat models with lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-induced sepsis were assessed. Rats received UTMD-mediated cardiac delivery of RORα/cationic microbubbles (CMBs) at 1, 3 and 5 days before CLP surgery. Echocardiography, histopathology and oxylipin metabolomics were assessed at 16-20 h after inducing fatal sepsis.</p><p><strong>Results: </strong>We observed that patients with sepsis have lower serum melatonin than healthy controls, which was observed in the blood and hearts of Sprague-Dawley rat models with LPS- or CLP-induced sepsis. Notably, a mild dose (2.5 mg/kg) of intravenous melatonin did not substantially improve septic cardiomyopathy. We found decreased nuclear receptors RORα, not melatonin receptors MT1/2, under lethal sepsis that may weaken the potential benefits of a mild dose of melatonin treatment. In vivo, repeated UTMD-mediated cardiac delivery of RORα/CMBs exhibited favorable biosafety, efficiency and specificity, significantly strengthening the effects of a safe dose of melatonin on heart dysfunction and myocardial injury in septic rats. The cardiac delivery of RORα by UTMD technology and melatonin treatment improved mitochondrial dysfunction and oxylipin profiles, although there was no significant influence on systemic inflammation.</p><p><strong>Conclusions: </strong>These findings provide new insights to explain the suboptimal effect of melatonin use in clinic and potential solutions to overcome the challenges. UTMD technology may be a promisingly interdisciplinary pattern against sepsis-induced cardiomyopathy.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9424657","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: 2
Self-assembled peptide-substance P hydrogels alleviate inflammation and ameliorate the cartilage regeneration in knee osteoarthritis. 自组装肽- P物质水凝胶减轻膝关节骨性关节炎的炎症和改善软骨再生。
IF 11.3 1区 医学
Biomaterials Research Pub Date : 2023-05-04 DOI: 10.1186/s40824-023-00387-6
Sang Jun Kim, Ji Eun Kim, Goeun Choe, Da Hyun Song, Sun Jeong Kim, Tae Hee Kim, Jin Yoo, Soo Hyun Kim, Youngmee Jung
{"title":"Self-assembled peptide-substance P hydrogels alleviate inflammation and ameliorate the cartilage regeneration in knee osteoarthritis.","authors":"Sang Jun Kim,&nbsp;Ji Eun Kim,&nbsp;Goeun Choe,&nbsp;Da Hyun Song,&nbsp;Sun Jeong Kim,&nbsp;Tae Hee Kim,&nbsp;Jin Yoo,&nbsp;Soo Hyun Kim,&nbsp;Youngmee Jung","doi":"10.1186/s40824-023-00387-6","DOIUrl":"https://doi.org/10.1186/s40824-023-00387-6","url":null,"abstract":"<p><strong>Background: </strong>Self-assembled peptide (SAP)-substance P (SP) hydrogels can be retained in the joint cavity longer than SP alone, and they can alleviate inflammation and ameliorate cartilage regeneration in knee osteoarthritis (OA). We conducted a preclinical study using diverse animal models of OA and an in vitro study using human synoviocytes and patient-derived synovial fluids to demonstrate the effect of SAP-SP complex on the inflammation and cartilage regeneration.</p><p><strong>Methods: </strong>Surgical induction OA model was prepared with New Zealand white female rabbits and chemical induction, and naturally occurring OA models were prepared using Dunkin Hartely female guinea pigs. The SAP-SP complex or control (SAP, SP, or saline) was injected into the joint cavities in each model. We performed micro-computed tomography (Micro-CT) analysis, histological evaluation, immunofluorescent analysis, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling (TUNEL) assay and analyzed the recruitment of intrinsic mesenchymal stem cells (MSCs), macrophage activity, and inflammatory cytokine in each OA model. Human synoviocytes were cultured in synovial fluid extracted from human OA knee joints injected with SAP-SP complexes or other controls. Proliferative capacity and inflammatory cytokine levels were analyzed.</p><p><strong>Results: </strong>Alleviation of inflammation, inhibition of apoptosis, and enhancement of intrinsic MSCs have been established in the SAP-SP group in diverse animal models. Furthermore, the inflammatory effects on human samples were examined in synoviocytes and synovial fluid from patients with OA. In this study, we observed that SAP-SP showed anti-inflammatory action in OA conditions and increased cartilage regeneration by recruiting intrinsic MSCs, inhibiting progression of OA.</p><p><strong>Conclusions: </strong>These therapeutic effects have been validated in diverse OA models, including rabbits, Dunkin Hartley guinea pigs, and human synoviocytes. Therefore, we propose that SAP-SP may be an effective injectable therapeutic agent for treating OA. In this manuscript, we report a preclinical study of novel self-assembled peptide (SAP)-substance P (SP) hydrogels with diverse animal models and human synoviocytes and it displays anti-inflammatory effects, apoptosis inhibition, intrinsic mesenchymal stem cells recruitments and cartilage regeneration.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10161637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9429592","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: 1
Application of molecular dynamics simulation in self-assembled cancer nanomedicine. 分子动力学模拟在自组装肿瘤纳米药物中的应用。
IF 11.3 1区 医学
Biomaterials Research Pub Date : 2023-05-04 DOI: 10.1186/s40824-023-00386-7
Xueli Xu, Ao Liu, Shuangqing Liu, Yanling Ma, Xinyu Zhang, Meng Zhang, Jinhua Zhao, Shuo Sun, Xiao Sun
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引用次数: 6
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