Pub Date : 2024-09-28DOI: 10.1016/j.bioactmat.2024.08.041
Sen Li , Han Gao , Haoji Wang , Xiaolin Zhao , Da Pan , Idaira Pacheco-Fernández , Ming Ma , Jianjun Liu , Jouni Hirvonen , Zehua Liu , Hélder A. Santos
Metal-organic frameworks (MOFs) hold promise as theranostic carriers for atherosclerosis. However, to further advance their therapeutic effects with higher complexity and functionality, integrating multiple components with complex synthesis procedures are usually involved. Here, we reported a facile and general strategy to prepare multifunctional anti-atherosclerosis theranostic platform in a single-step manner. A custom-designed multifunctional polymer, poly(butyl methacrylate-co-methacrylic acid) branched phosphorylated β-glucan (PBMMA-PG), can effectively entrap different MOFs via coordination, simultaneously endow the MOF with enhanced stability, lesional macrophages selectivity and enhanced endosome escape. Sequential ex situ characterization and computational studies elaborated the potential mechanism. This facile post-synthetic modification granted the administered nanoparticles atherosclerotic tropism by targeting Dectin-1+ macrophages, enhancing in situ MR signal intensity by 72 %. Delivery of siNLRP3 effectively mitigated NLRP3 inflammasomes activation, resulting a 43 % reduction of plaque area. Overall, the current study highlights a simple and general approach for fabricating a MOF-based theranostic platform towards atherosclerosis conditioning, which may also expand to other indications targeting the lesional macrophages.
{"title":"Tailored polysaccharide entrapping metal-organic framework for RNAi therapeutics and diagnostics in atherosclerosis","authors":"Sen Li , Han Gao , Haoji Wang , Xiaolin Zhao , Da Pan , Idaira Pacheco-Fernández , Ming Ma , Jianjun Liu , Jouni Hirvonen , Zehua Liu , Hélder A. Santos","doi":"10.1016/j.bioactmat.2024.08.041","DOIUrl":"10.1016/j.bioactmat.2024.08.041","url":null,"abstract":"<div><div>Metal-organic frameworks (MOFs) hold promise as theranostic carriers for atherosclerosis. However, to further advance their therapeutic effects with higher complexity and functionality, integrating multiple components with complex synthesis procedures are usually involved. Here, we reported a facile and general strategy to prepare multifunctional anti-atherosclerosis theranostic platform in a single-step manner. A custom-designed multifunctional polymer, poly(butyl methacrylate-co-methacrylic acid) branched phosphorylated β-glucan (PBMMA-PG), can effectively entrap different MOFs via coordination, simultaneously endow the MOF with enhanced stability, lesional macrophages selectivity and enhanced endosome escape. Sequential ex situ characterization and computational studies elaborated the potential mechanism. This facile post-synthetic modification granted the administered nanoparticles atherosclerotic tropism by targeting Dectin-1<sup>+</sup> macrophages, enhancing in situ MR signal intensity by 72 %. Delivery of siNLRP3 effectively mitigated NLRP3 inflammasomes activation, resulting a 43 % reduction of plaque area. Overall, the current study highlights a simple and general approach for fabricating a MOF-based theranostic platform towards atherosclerosis conditioning, which may also expand to other indications targeting the lesional macrophages.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 376-391"},"PeriodicalIF":18.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-28DOI: 10.1016/j.bioactmat.2024.08.025
Yifan Cheng , Yuan Lu
Many chronic diseases have become severe public health problems with the development of society. A safe and efficient healthcare method is to utilize physical stimulus-responsive polymer patches, which may respond to physical stimuli, including light, electric current, temperature, magnetic field, mechanical force, and ultrasound. Under certain physical stimuli, these patches have been widely used in therapy for diabetes, cancer, wounds, hair loss, obesity, and heart diseases since they could realize controllable treatment and reduce the risks of side effects. This review sketches the design principles of polymer patches, including composition, properties, and performances. Besides, control methods of using different kinds of physical stimuli were introduced. Then, the fabrication methods and characterization of patches were explored. Furthermore, recent applications of these patches in the biomedical field were demonstrated. Finally, we discussed the challenges and prospects for its clinical translation. We anticipate that physical stimulus-responsive polymer patches will open up new avenues for healthcare by acting as a platform with multiple functions.
{"title":"Physical stimuli-responsive polymeric patches for healthcare","authors":"Yifan Cheng , Yuan Lu","doi":"10.1016/j.bioactmat.2024.08.025","DOIUrl":"10.1016/j.bioactmat.2024.08.025","url":null,"abstract":"<div><div>Many chronic diseases have become severe public health problems with the development of society. A safe and efficient healthcare method is to utilize physical stimulus-responsive polymer patches, which may respond to physical stimuli, including light, electric current, temperature, magnetic field, mechanical force, and ultrasound. Under certain physical stimuli, these patches have been widely used in therapy for diabetes, cancer, wounds, hair loss, obesity, and heart diseases since they could realize controllable treatment and reduce the risks of side effects. This review sketches the design principles of polymer patches, including composition, properties, and performances. Besides, control methods of using different kinds of physical stimuli were introduced. Then, the fabrication methods and characterization of patches were explored. Furthermore, recent applications of these patches in the biomedical field were demonstrated. Finally, we discussed the challenges and prospects for its clinical translation. We anticipate that physical stimulus-responsive polymer patches will open up new avenues for healthcare by acting as a platform with multiple functions.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 342-375"},"PeriodicalIF":18.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1016/j.bioactmat.2024.09.011
Wenxuan Wang , Qing Ma , Da Li , Wentai Zhang , Zhilu Yang , Wenjie Tian , Nan Huang
Thrombosis associated with implants can severely impact therapeutic outcomes and lead to increased morbidity and mortality. Thus, developing blood-contacting materials with superior anticoagulant properties is essential to prevent and mitigate device-related thrombosis. Herein, we propose a novel single-molecule multi-functional strategy for creating blood-compatible surfaces. The synthesized azide-modified Cu-DOTA-(Lys)3 molecule, which possesses both NO release and fibrinolysis functions, was immobilized on material surfaces via click chemistry. Due to the specificity, rapidity, and completeness of click chemistry, the firmly grafted Cu-DOTA-(Lys)3 endows the modified material with excellent antithrombotic properties of vascular endothelium and thrombolytic properties of fibrinolytic system. This surface effectively prevented thrombus formation in both in vitro and in vivo experiments, owing to the synergistic effect of anticoagulation and thrombolysis. Moreover, the modified material maintained its functional efficacy after one month of PBS immersion, demonstrating excellent stability. Overall, this single-molecule multifunctional strategy may become a promising surface engineering technique for blood-contacting materials.
{"title":"Engineered endothelium-mimicking antithrombotic surfaces via combination of nitric oxide-generation with fibrinolysis strategies","authors":"Wenxuan Wang , Qing Ma , Da Li , Wentai Zhang , Zhilu Yang , Wenjie Tian , Nan Huang","doi":"10.1016/j.bioactmat.2024.09.011","DOIUrl":"10.1016/j.bioactmat.2024.09.011","url":null,"abstract":"<div><div>Thrombosis associated with implants can severely impact therapeutic outcomes and lead to increased morbidity and mortality. Thus, developing blood-contacting materials with superior anticoagulant properties is essential to prevent and mitigate device-related thrombosis. Herein, we propose a novel single-molecule multi-functional strategy for creating blood-compatible surfaces. The synthesized azide-modified Cu-DOTA-(Lys)<sub>3</sub> molecule, which possesses both NO release and fibrinolysis functions, was immobilized on material surfaces via click chemistry. Due to the specificity, rapidity, and completeness of click chemistry, the firmly grafted Cu-DOTA-(Lys)<sub>3</sub> endows the modified material with excellent antithrombotic properties of vascular endothelium and thrombolytic properties of fibrinolytic system. This surface effectively prevented thrombus formation in both <em>in vitro</em> and <em>in vivo</em> experiments, owing to the synergistic effect of anticoagulation and thrombolysis. Moreover, the modified material maintained its functional efficacy after one month of PBS immersion, demonstrating excellent stability. Overall, this single-molecule multifunctional strategy may become a promising surface engineering technique for blood-contacting materials.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 319-329"},"PeriodicalIF":18.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.bioactmat.2024.09.023
Le Wang , Zhou Gong , Ming Wang , Yi-Zhong Liang , Jing Zhao , Qi Xie , Xiao-Wei Wu , Qin-Ying Li , Cong Zhang , Li-Yun Ma , Si-Yang Zheng , Ming Jiang , Xu Yu , Li Xu
Extracellular vesicles (EVs) have garnered significant attention in biomedical applications. However, the rapid, efficient, and unbiased separation of EVs from complex biological fluids remains a challenge due to their heterogeneity and low abundance in biofluids. Herein, we report a novel approach to reconfigure and modify an artificial insertion peptide for the unbiased and rapid isolation of EVs in 20 min with ∼80% recovery in neutral conditions. Moreover, the approach demonstrates exceptional anti-interference capability and achieves a high purity of EVs comparable to standard ultracentrifugation and other methods. Importantly, the isolated EVs could be directly applied for downstream protein and nucleic acid analyses, including proteomics analysis, exome sequencing analysis, as well as the detection of both epidermal growth factor receptor (EGFR) and V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) gene mutation in clinical plasma samples. Our approach offers great possibilities for utilizing EVs in liquid biopsy, as well as in various other biomedical applications.
{"title":"Rapid and unbiased enrichment of extracellular vesicles via a meticulously engineered peptide","authors":"Le Wang , Zhou Gong , Ming Wang , Yi-Zhong Liang , Jing Zhao , Qi Xie , Xiao-Wei Wu , Qin-Ying Li , Cong Zhang , Li-Yun Ma , Si-Yang Zheng , Ming Jiang , Xu Yu , Li Xu","doi":"10.1016/j.bioactmat.2024.09.023","DOIUrl":"10.1016/j.bioactmat.2024.09.023","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) have garnered significant attention in biomedical applications. However, the rapid, efficient, and unbiased separation of EVs from complex biological fluids remains a challenge due to their heterogeneity and low abundance in biofluids. Herein, we report a novel approach to reconfigure and modify an artificial insertion peptide for the unbiased and rapid isolation of EVs in 20 min with ∼80% recovery in neutral conditions. Moreover, the approach demonstrates exceptional anti-interference capability and achieves a high purity of EVs comparable to standard ultracentrifugation and other methods. Importantly, the isolated EVs could be directly applied for downstream protein and nucleic acid analyses, including proteomics analysis, exome sequencing analysis, as well as the detection of both epidermal growth factor receptor (EGFR) and V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) gene mutation in clinical plasma samples. Our approach offers great possibilities for utilizing EVs in liquid biopsy, as well as in various other biomedical applications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 292-304"},"PeriodicalIF":18.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.bioactmat.2024.09.021
Min Ju Lim , Hyeryeon Oh , Jimin Jeon , Chanmi Cho , Jin Sil Lee , Yiseul Hwang , Seok Jung Kim , Jung-Soon Mo , Panmo Son , Ho Chul Kang , Won Il Choi , Siyoung Yang
Mitochondrial dysfunction increases ROS production and is closely related to many degenerative cellular organelle diseases. The NOX4-p22phox axis is a major contributor to ROS production and its dysregulation is expected to disrupt mitochondrial function. However, the field lacks a competitive inhibitor of the NOX4-p22phox interaction. Here, we created a povidone micelle-based Prussian blue nanozyme that we named “Mitocelle” to target the NOX4-p22phox axis, and characterized its impact on the major degenerative cellular organelle disease, osteoarthritis (OA). Mitocelle is composed of FDA-approved and biocompatible materials, has a regular spherical shape, and is approximately 88 nm in diameter. Mitocelle competitively inhibits the NOX4-p22phox interaction, and its uptake by chondrocytes can protect against mitochondrial malfunction. Upon intra-articular injection to an OA mouse model, Mitocelle shows long-term stability, effective uptake into the cartilage matrix, and the ability to attenuate joint degradation. Collectively, our findings suggest that Mitocelle, which functions as a competitive inhibitor of NOX4-p22phox, may be suitable for translational research as a therapeutic for OA and cellular organelle diseases related to dysfunctional mitochondria.
{"title":"An intra articular injectable Mitocelle recovers dysfunctional mitochondria in cellular organelle disorders","authors":"Min Ju Lim , Hyeryeon Oh , Jimin Jeon , Chanmi Cho , Jin Sil Lee , Yiseul Hwang , Seok Jung Kim , Jung-Soon Mo , Panmo Son , Ho Chul Kang , Won Il Choi , Siyoung Yang","doi":"10.1016/j.bioactmat.2024.09.021","DOIUrl":"10.1016/j.bioactmat.2024.09.021","url":null,"abstract":"<div><div>Mitochondrial dysfunction increases ROS production and is closely related to many degenerative cellular organelle diseases. The NOX4-p22phox axis is a major contributor to ROS production and its dysregulation is expected to disrupt mitochondrial function. However, the field lacks a competitive inhibitor of the NOX4-p22phox interaction. Here, we created a povidone micelle-based Prussian blue nanozyme that we named “Mitocelle” to target the NOX4-p22phox axis, and characterized its impact on the major degenerative cellular organelle disease, osteoarthritis (OA). Mitocelle is composed of FDA-approved and biocompatible materials, has a regular spherical shape, and is approximately 88 nm in diameter. Mitocelle competitively inhibits the NOX4-p22phox interaction, and its uptake by chondrocytes can protect against mitochondrial malfunction. Upon intra-articular injection to an OA mouse model, Mitocelle shows long-term stability, effective uptake into the cartilage matrix, and the ability to attenuate joint degradation. Collectively, our findings suggest that Mitocelle, which functions as a competitive inhibitor of NOX4-p22phox, may be suitable for translational research as a therapeutic for OA and cellular organelle diseases related to dysfunctional mitochondria.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 305-318"},"PeriodicalIF":18.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25DOI: 10.1016/j.bioactmat.2024.09.022
Xinchen Lu , Jinmei Jin , Ye Wu , Jiayi Lin , Xiaokun Zhang , Shengxin Lu , Jiyuan Zhang , Chunling Zhang , Maomao Ren , Hongzhuan Chen , Weidong Zhang , Xin Luan
Both β-catenin and STAT3 drive colorectal cancer (CRC) growth, progression, and immune evasion, and their co-overexpression is strongly associated with a poor prognosis. However, current small molecule inhibitors have limited efficacy due to the reciprocal feedback activation between STAT3 and β-catenin. Inspired by the PROteolysis TArgeting Chimera (PROTAC), a promising pharmacological modality for the selective degradation of proteins, we developed a strategy of nanoengineered peptide PROTACs (NP-PROTACs) to degrade both β-catenin and STAT3 effectively. The NP-PROTACs were engineered by coupling the peptide PROTACs with DSPE-PEG via disulfide bonds and self-assembled into nanoparticles. Notably, the dual degradation of β-catenin and STAT3 mediated by NP-PROTACs led to a synergistic antitumor effect compared to single-target treatment. Moreover, NP-PROTACs treatment enhanced CD103+ dendritic cell infiltration and T-cell cytotoxicity, alleviating the immunosuppressive microenvironment induced by β-catenin/STAT3 in CRC. These results highlight the potential of NP-PROTACs in facilitating the simultaneous degradation of two pathogenic proteins, thereby providing a novel avenue for cancer therapy.
{"title":"Self-assembled PROTACs enable protein degradation to reprogram the tumor microenvironment for synergistically enhanced colorectal cancer immunotherapy","authors":"Xinchen Lu , Jinmei Jin , Ye Wu , Jiayi Lin , Xiaokun Zhang , Shengxin Lu , Jiyuan Zhang , Chunling Zhang , Maomao Ren , Hongzhuan Chen , Weidong Zhang , Xin Luan","doi":"10.1016/j.bioactmat.2024.09.022","DOIUrl":"10.1016/j.bioactmat.2024.09.022","url":null,"abstract":"<div><div>Both β-catenin and STAT3 drive colorectal cancer (CRC) growth, progression, and immune evasion, and their co-overexpression is strongly associated with a poor prognosis. However, current small molecule inhibitors have limited efficacy due to the reciprocal feedback activation between STAT3 and β-catenin. Inspired by the PROteolysis TArgeting Chimera (PROTAC), a promising pharmacological modality for the selective degradation of proteins, we developed a strategy of nanoengineered peptide PROTACs (NP-PROTACs) to degrade both β-catenin and STAT3 effectively. The NP-PROTACs were engineered by coupling the peptide PROTACs with DSPE-PEG via disulfide bonds and self-assembled into nanoparticles. Notably, the dual degradation of β-catenin and STAT3 mediated by NP-PROTACs led to a synergistic antitumor effect compared to single-target treatment. Moreover, NP-PROTACs treatment enhanced CD103<sup>+</sup> dendritic cell infiltration and T-cell cytotoxicity, alleviating the immunosuppressive microenvironment induced by β-catenin/STAT3 in CRC. These results highlight the potential of NP-PROTACs in facilitating the simultaneous degradation of two pathogenic proteins, thereby providing a novel avenue for cancer therapy.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 255-272"},"PeriodicalIF":18.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25DOI: 10.1016/j.bioactmat.2024.09.017
Miao Chen , Yusen Qiao , Lei Yu , Wei Wang , Wentao Wang , Haifu Sun , Yaozeng Xu , Jiaxiang Bai , Jun Zhou , Dechun Geng
Failure of intraosseous prostheses is primarily attributed to implant loosening and infections. Current primary therapeutic modalities, such as antibiotics and local debridement, not only face challenges in thoroughly eliminating obstinate adhered bacteria but also encounter difficulties in ameliorating undue inflammatory reactions and regenerating impaired peri-implant bone tissues. Polyetheretherketone (PEEK) has excellent mechanical and physicochemical characteristics and has been used extensively as a medical biomaterial. However, the limited bactericidal and osseointegrative activities of bioinert PEEK restrict its clinical application. Herein, a microenvironment responsive coating with immobilised immunomodulatory magnesium ions (Mg2+) and disinfectant cerium oxide nanoparticles (CNPs) is designed via ion coordination mediated by polydopamine (PDA) and electrospinning based on collagen structure-bionic silk fibroin (SF). By utilising the pH responsiveness of SF, CNPs exhibit potent antibacterial effects in an acidic environment (pH 5.0) caused by local bacterial infection. Due to the chelation interaction with PDA and the constraint of SF, Mg2+ is slowly released, ameliorating the local immune microenvironment and boosting osteogenesis by upregulating M2 phenotype macrophages. Bioinformatics analysis indicates that the inflammation is suppressed via the NF-κB signaling pathway. Overall, this SF-based coating maximizes the synergistic effect of CNPs and Mg2+, offering enhanced antibacterial and osteoimmunomodulatory bioactivity for successful implantation.
骨内修复失败的主要原因是种植体松动和感染。目前的主要治疗方法，如抗生素和局部清创，不仅在彻底清除顽固的附着细菌方面面临挑战，而且在改善不当的炎症反应和再生受损的种植体周围骨组织方面也遇到困难。聚醚醚酮（PEEK）具有优良的机械和物理化学特性，已被广泛用作医用生物材料。然而，生物惰性 PEEK 的杀菌和骨结合活性有限，限制了其临床应用。在此，通过聚多巴胺（PDA）介导的离子配位和基于胶原结构-仿生蚕丝纤维蛋白（SF）的电纺丝，设计了一种具有固定免疫调节镁离子（Mg2+）和消毒剂氧化铈纳米颗粒（CNPs）的微环境响应涂层。通过利用 SF 的 pH 响应性，CNPs 在局部细菌感染引起的酸性环境（pH 值为 5.0）中表现出强大的抗菌效果。由于与 PDA 的螯合作用和 SF 的约束，Mg2+ 被缓慢释放，从而改善了局部免疫微环境，并通过上调 M2 表型巨噬细胞促进成骨。生物信息学分析表明，炎症是通过 NF-κB 信号通路被抑制的。总之，这种基于 SF 的涂层最大限度地发挥了 CNPs 和 Mg2+ 的协同作用，增强了抗菌和骨免疫调节生物活性，有助于成功植入。
{"title":"A microenvironment responsive polyetheretherketone implant with antibacterial and osteoimmunomodulatory properties facilitates osseointegration","authors":"Miao Chen , Yusen Qiao , Lei Yu , Wei Wang , Wentao Wang , Haifu Sun , Yaozeng Xu , Jiaxiang Bai , Jun Zhou , Dechun Geng","doi":"10.1016/j.bioactmat.2024.09.017","DOIUrl":"10.1016/j.bioactmat.2024.09.017","url":null,"abstract":"<div><div>Failure of intraosseous prostheses is primarily attributed to implant loosening and infections. Current primary therapeutic modalities, such as antibiotics and local debridement, not only face challenges in thoroughly eliminating obstinate adhered bacteria but also encounter difficulties in ameliorating undue inflammatory reactions and regenerating impaired peri-implant bone tissues. Polyetheretherketone (PEEK) has excellent mechanical and physicochemical characteristics and has been used extensively as a medical biomaterial. However, the limited bactericidal and osseointegrative activities of bioinert PEEK restrict its clinical application. Herein, a microenvironment responsive coating with immobilised immunomodulatory magnesium ions (Mg<sup>2+</sup>) and disinfectant cerium oxide nanoparticles (CNPs) is designed via ion coordination mediated by polydopamine (PDA) and electrospinning based on collagen structure-bionic silk fibroin (SF). By utilising the pH responsiveness of SF, CNPs exhibit potent antibacterial effects in an acidic environment (pH 5.0) caused by local bacterial infection. Due to the chelation interaction with PDA and the constraint of SF, Mg<sup>2+</sup> is slowly released, ameliorating the local immune microenvironment and boosting osteogenesis by upregulating M2 phenotype macrophages. Bioinformatics analysis indicates that the inflammation is suppressed via the NF-κB signaling pathway. Overall, this SF-based coating maximizes the synergistic effect of CNPs and Mg<sup>2+</sup>, offering enhanced antibacterial and osteoimmunomodulatory bioactivity for successful implantation.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 273-291"},"PeriodicalIF":18.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/j.bioactmat.2024.09.025
Irem Deniz Derman , Joseph Christakiran Moses , Taino Rivera , Ibrahim T. Ozbolat
The epithelium is one of the important tissues in the body as it plays a crucial barrier role serving as a gateway into and out of the body. Most organs in the body contain an epithelial tissue component, where the tightly connected, organ-specific epithelial cells organize into cysts, invaginations, or tubules, thereby performing distinct to endocrine or exocrine secretory functions. Despite the significance of epithelium, engineering functional epithelium in vitro has remained a challenge due to it is special architecture, heterotypic composition of epithelial tissues, and most importantly, difficulty in attaining the apico-basal and planar polarity of epithelial cells. Bioprinting has brought a paradigm shift in fabricating such apico-basal polarized tissues. In this review, we provide an overview of epithelial tissues and provide insights on recapitulating their cellular arrangement and polarization to achieve epithelial function. We describe the different bioprinting techniques that have been successful in engineering polarized epithelium, which can serve as in vitro models for understanding homeostasis and studying diseased conditions. We also discuss the different attempts that have been investigated to study these 3D bioprinted engineered epithelium for preclinical use. Finally, we highlight the challenges and the opportunities that need to be addressed for translation of 3D bioprinted epithelial tissues towards paving way for personalized healthcare in the future.
{"title":"Understanding the cellular dynamics, engineering perspectives and translation prospects in bioprinting epithelial tissues","authors":"Irem Deniz Derman , Joseph Christakiran Moses , Taino Rivera , Ibrahim T. Ozbolat","doi":"10.1016/j.bioactmat.2024.09.025","DOIUrl":"10.1016/j.bioactmat.2024.09.025","url":null,"abstract":"<div><div>The epithelium is one of the important tissues in the body as it plays a crucial barrier role serving as a gateway into and out of the body. Most organs in the body contain an epithelial tissue component, where the tightly connected, organ-specific epithelial cells organize into cysts, invaginations, or tubules, thereby performing distinct to endocrine or exocrine secretory functions. Despite the significance of epithelium, engineering functional epithelium <em>in vitro</em> has remained a challenge due to it is special architecture, heterotypic composition of epithelial tissues, and most importantly, difficulty in attaining the apico-basal and planar polarity of epithelial cells. Bioprinting has brought a paradigm shift in fabricating such apico-basal polarized tissues. In this review, we provide an overview of epithelial tissues and provide insights on recapitulating their cellular arrangement and polarization to achieve epithelial function. We describe the different bioprinting techniques that have been successful in engineering polarized epithelium, which can serve as <em>in vitro</em> models for understanding homeostasis and studying diseased conditions. We also discuss the different attempts that have been investigated to study these 3D bioprinted engineered epithelium for preclinical use. Finally, we highlight the challenges and the opportunities that need to be addressed for translation of 3D bioprinted epithelial tissues towards paving way for personalized healthcare in the future.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 195-224"},"PeriodicalIF":18.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24004201/pdfft?md5=e6f562713d2942a130faf3ac8594bdb7&pid=1-s2.0-S2452199X24004201-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/j.bioactmat.2024.09.006
Chuanlu Lin , Yiqiang Hu , Ze Lin , Longyu Du , Yixin Hu , Lizhi Ouyang , Xudong Xie , Peng Cheng , Jiewen Liao , Li Lu , Ruiyin Zeng , Ping Xia , Zhiyong Hou , Guohui Liu , Hankun Hu
Ferroptosis plays a crucial role in the progression of diabetic wounds, suggesting potential therapeutic strategies to target ferroptosis. Transient receptor potential ankyrin 1 (TRPA1) is a non-selective calcium channel that acts as a receptor for a variety of physical or chemical stimuli. Cinnamaldehyde (CA) is a specific TRPA1 agonist. In in vitro experiments, we observed that high glucose (HG) treatment induced endothelial cell ferroptosis, impairing cell function. CA successfully inhibited endothelial cell ferroptosis, improving migration, proliferation, and tube formation. Further mechanistic studies showed that CA-activated TRPA1-induced Ca2+ influx promoted the phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and nuclear factor-E 2-related factor 2 (Nrf2) translocation, which contributed to the elevation of glutathione peroxidase 4 (GPX4), leading to the inhibition of endothelial cell ferroptosis. In addition, CA was incorporated into an MMP-9-responsive injectable duplex hybrid hydrogel (CA@HA-Gel), allowing its efficient sustained release into diabetic wounds in an inflammation-responsive manner. The results showed that CA@HA-Gel inhibited wound endothelial cell ferroptosis and significantly promoted diabetic wound healing. In summary, the results presented in this study emphasize the potential therapeutic application of CA@HA-Gel in the treatment of diseases associated with ferroptosis.
{"title":"MMP-9 responsive hydrogel promotes diabetic wound healing by suppressing ferroptosis of endothelial cells","authors":"Chuanlu Lin , Yiqiang Hu , Ze Lin , Longyu Du , Yixin Hu , Lizhi Ouyang , Xudong Xie , Peng Cheng , Jiewen Liao , Li Lu , Ruiyin Zeng , Ping Xia , Zhiyong Hou , Guohui Liu , Hankun Hu","doi":"10.1016/j.bioactmat.2024.09.006","DOIUrl":"10.1016/j.bioactmat.2024.09.006","url":null,"abstract":"<div><div>Ferroptosis plays a crucial role in the progression of diabetic wounds, suggesting potential therapeutic strategies to target ferroptosis. Transient receptor potential ankyrin 1 (TRPA1) is a non-selective calcium channel that acts as a receptor for a variety of physical or chemical stimuli. Cinnamaldehyde (CA) is a specific TRPA1 agonist. In in vitro experiments, we observed that high glucose (HG) treatment induced endothelial cell ferroptosis, impairing cell function. CA successfully inhibited endothelial cell ferroptosis, improving migration, proliferation, and tube formation. Further mechanistic studies showed that CA-activated TRPA1-induced Ca<sup>2+</sup> influx promoted the phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and nuclear factor-E 2-related factor 2 (Nrf2) translocation, which contributed to the elevation of glutathione peroxidase 4 (GPX4), leading to the inhibition of endothelial cell ferroptosis. In addition, CA was incorporated into an MMP-9-responsive injectable duplex hybrid hydrogel (CA@HA-Gel), allowing its efficient sustained release into diabetic wounds in an inflammation-responsive manner. The results showed that CA@HA-Gel inhibited wound endothelial cell ferroptosis and significantly promoted diabetic wound healing. In summary, the results presented in this study emphasize the potential therapeutic application of CA@HA-Gel in the treatment of diseases associated with ferroptosis.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 240-254"},"PeriodicalIF":18.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003931/pdfft?md5=5bf0ac6e1742022c12ab6bd9c2b1a02c&pid=1-s2.0-S2452199X24003931-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/j.bioactmat.2024.07.023
Weilue He , Keith W. MacRenaris , Adam Griebel , Maria P. Kwesiga , Erico Freitas , Amani Gillette , Jeremy Schaffer , Thomas V. O'Halloran , Roger J. Guillory II
While metal materials historically have served as permanent implants and were designed to avoid degradation, next generation bioabsorbable metals for medical devices such as vascular stents are under development, which would elute metal ions and corrosion byproducts into tissues. The fate of these eluted products and their local distribution in vascular tissue largely under studied. In this study, we employ a high spatial resolution spectrometric imaging modality, laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOF-MS) to map the metal distribution, (herein refered to as laser ablation mapping, or LAM) from Mg alloys within the mouse vascular system and approximate their local concentrations. We used a novel rare earth element bearing Mg alloy (WE22) wire implanted within the abdominal aorta of transgenic hypercholesterolemic mice (APOE−/−) to simulate a bioabsorbable vascular prosthesis for up to 30 days. We describe qualitatively and semi-quantitatively implant-derived corrosion product presence throughout the tissue cross sections, and their approximate concentrations within the various vessel structures. Additionally, we report the spatial changes of corrosion products, which we postulate are mediated by phagocytic inflammatory cells such as macrophages (MΦ’s).
{"title":"Semi-quantitative elemental imaging of corrosion products from bioabsorbable Mg vascular implants in vivo","authors":"Weilue He , Keith W. MacRenaris , Adam Griebel , Maria P. Kwesiga , Erico Freitas , Amani Gillette , Jeremy Schaffer , Thomas V. O'Halloran , Roger J. Guillory II","doi":"10.1016/j.bioactmat.2024.07.023","DOIUrl":"10.1016/j.bioactmat.2024.07.023","url":null,"abstract":"<div><div>While metal materials historically have served as permanent implants and were designed to avoid degradation, next generation bioabsorbable metals for medical devices such as vascular stents are under development, which would elute metal ions and corrosion byproducts into tissues. The fate of these eluted products and their local distribution in vascular tissue largely under studied. In this study, we employ a high spatial resolution spectrometric imaging modality, laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOF-MS) to map the metal distribution, (herein refered to as laser ablation mapping, or LAM) from Mg alloys within the mouse vascular system and approximate their local concentrations. We used a novel rare earth element bearing Mg alloy (WE22) wire implanted within the abdominal aorta of transgenic hypercholesterolemic mice (APOE−/−) to simulate a bioabsorbable vascular prosthesis for up to 30 days. We describe qualitatively and semi-quantitatively implant-derived corrosion product presence throughout the tissue cross sections, and their approximate concentrations within the various vessel structures. Additionally, we report the spatial changes of corrosion products, which we postulate are mediated by phagocytic inflammatory cells such as macrophages (MΦ’s).</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 225-239"},"PeriodicalIF":18.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24002949/pdfft?md5=2af21a7d2947fe0912264e01326f0d88&pid=1-s2.0-S2452199X24002949-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314768","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}
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