He Ren, Zewen Wu, Jingxuan Li, Nan Zhang, Coo Yee Nah, Jiexin Li, Jingyu Zhang, Jonathan F. Lovell, Liyun Zhang, Yumiao Zhang
Rheumatoid arthritis (RA) is a systemic autoimmune disease that leads to the destruction of articular cartilage and bone. RA is characterized by immune cell infiltration and abnormal proliferation of synoviocytes in the joints. Herein, we developed a biomimetic formulation via co‐loading the anti‐inflammatory agent Celastrol (Cel) along with the stabilizer Vitamin K (VK) in antirheumatic methotrexate (MTX)‐conjugated Pluronic F127 (F127) micelles. Micelles were then coated with B cell derived membrane, yielding MTX loaded Cel Micelle (CeViM)‐micelle@B, which were investigated for RA treatment. VK, used at levels well within safety margins, was identified as a carrier compound that could stabilize Cel within micelles, increasing the encapsulation efficiency of Cel. In addition, MTX, a front‐line RA therapeutic, was chemically grafted to F127 via a responsive linker sensitive to the chemically reducing environments. As such, CeViM‐micelle@B released pristine MTX in response to the intracellular reducing environments, which combined with Cel to suppress pro‐inflammatory responses. B cell membrane coating enhanced accumulation of CeViM‐micelle@B in joints, leading to a 75% decrease of inflammatory cytokine secretion in vitro, and significantly ameliorated cartilage and bone structures in the collagen‐induced arthritis murine model. Taken together, this biomimetic nanoparticle holds potential as a next‐generation targeted RA treatment.
类风湿性关节炎（RA）是一种全身性自身免疫性疾病，会导致关节软骨和骨骼的破坏。类风湿性关节炎的特点是免疫细胞浸润和关节滑膜细胞异常增殖。在此，我们通过在抗风湿药物甲氨蝶呤（MTX）共轭聚钚F127（F127）胶束中共同添加抗炎剂塞拉斯托（Celastrol）和稳定剂维生素K（VK），开发了一种生物仿生制剂。然后在胶束上涂覆 B 细胞衍生膜，得到负载 MTX 的 Cel Micelle（CeViM）-micelle@B，并对其进行了 RA 治疗研究。在安全范围内使用的 VK 被确定为一种载体化合物，可将 Cel 稳定在胶束中，从而提高 Cel 的封装效率。此外，通过对化学还原环境敏感的反应性连接体，MTX（一种前线 RA 治疗药物）被化学接枝到 F127 上。因此，CeViM-micelle@B 在细胞内还原环境中释放出原始 MTX，与 Cel 共同抑制促炎反应。B细胞膜涂层增强了CeViM-micelle@B在关节中的积聚，使体外炎性细胞因子分泌减少了75%，并显著改善了胶原诱导的关节炎小鼠模型中的软骨和骨结构。综上所述，这种仿生纳米粒子有望成为下一代的RA靶向治疗药物。
{"title":"A biomimetic, triggered‐release micelle formulation of methotrexate and celastrol controls collagen‐induced arthritis in mice","authors":"He Ren, Zewen Wu, Jingxuan Li, Nan Zhang, Coo Yee Nah, Jiexin Li, Jingyu Zhang, Jonathan F. Lovell, Liyun Zhang, Yumiao Zhang","doi":"10.1002/bmm2.12104","DOIUrl":"https://doi.org/10.1002/bmm2.12104","url":null,"abstract":"Rheumatoid arthritis (RA) is a systemic autoimmune disease that leads to the destruction of articular cartilage and bone. RA is characterized by immune cell infiltration and abnormal proliferation of synoviocytes in the joints. Herein, we developed a biomimetic formulation via co‐loading the anti‐inflammatory agent Celastrol (Cel) along with the stabilizer Vitamin K (VK) in antirheumatic methotrexate (MTX)‐conjugated Pluronic F127 (F127) micelles. Micelles were then coated with B cell derived membrane, yielding MTX loaded Cel Micelle (CeViM)‐micelle@B, which were investigated for RA treatment. VK, used at levels well within safety margins, was identified as a carrier compound that could stabilize Cel within micelles, increasing the encapsulation efficiency of Cel. In addition, MTX, a front‐line RA therapeutic, was chemically grafted to F127 via a responsive linker sensitive to the chemically reducing environments. As such, CeViM‐micelle@B released pristine MTX in response to the intracellular reducing environments, which combined with Cel to suppress pro‐inflammatory responses. B cell membrane coating enhanced accumulation of CeViM‐micelle@B in joints, leading to a 75% decrease of inflammatory cytokine secretion in vitro, and significantly ameliorated cartilage and bone structures in the collagen‐induced arthritis murine model. Taken together, this biomimetic nanoparticle holds potential as a next‐generation targeted RA treatment.","PeriodicalId":503415,"journal":{"name":"BMEMat","volume":"119 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141361977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weilong Tang, Nicholas G. Fischer, Xinzi Kong, Ting Sang, Z. Ye
Dental and orthopedic titanium implants are successfully and widely used but still face challenges due to complications leading to high treatment cost, morbidity, and even mortality. This review focuses on the hybrid coatings designed to prevent and mitigate implant failure by integrating multiple strategies and materials. The forms of manufacturing and synthesizing hybrid coatings were first discussed. We then categorize these coatings based on their biological functions: antibacterial coatings, which are essential for preventing difficult‐to‐treat infection; coatings designed to promote osseointegration, crucial for the mechanical stability of implants; coatings that encourage soft tissue attachment, contributing to the overall success and esthetics of implant. We summarize the state of the art in multifunctional coatings that integrate multiple biological functions as an alternative, holistic approach for reducing implant complications. The review culminates in a discussion on future directions in the field, emphasizing the potential and notable challenges these biofunctional hybrid coatings face toward obtaining commercial success in patients. Together, our article provides a comprehensive overview of current developments and a glimpse into the future of hybrid coatings for potentially revolutionizing dental and orthopedic implants.
{"title":"Hybrid coatings on dental and orthopedic titanium implants: Current advances and challenges","authors":"Weilong Tang, Nicholas G. Fischer, Xinzi Kong, Ting Sang, Z. Ye","doi":"10.1002/bmm2.12105","DOIUrl":"https://doi.org/10.1002/bmm2.12105","url":null,"abstract":"Dental and orthopedic titanium implants are successfully and widely used but still face challenges due to complications leading to high treatment cost, morbidity, and even mortality. This review focuses on the hybrid coatings designed to prevent and mitigate implant failure by integrating multiple strategies and materials. The forms of manufacturing and synthesizing hybrid coatings were first discussed. We then categorize these coatings based on their biological functions: antibacterial coatings, which are essential for preventing difficult‐to‐treat infection; coatings designed to promote osseointegration, crucial for the mechanical stability of implants; coatings that encourage soft tissue attachment, contributing to the overall success and esthetics of implant. We summarize the state of the art in multifunctional coatings that integrate multiple biological functions as an alternative, holistic approach for reducing implant complications. The review culminates in a discussion on future directions in the field, emphasizing the potential and notable challenges these biofunctional hybrid coatings face toward obtaining commercial success in patients. Together, our article provides a comprehensive overview of current developments and a glimpse into the future of hybrid coatings for potentially revolutionizing dental and orthopedic implants.","PeriodicalId":503415,"journal":{"name":"BMEMat","volume":" 865","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141364208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhuo Li, Jiacheng Gong, Shan Lu, Xingjun Li, Xiaobo Gu, Jin Xu, Jawairia Umar Khan, Dayong Jin, Xueyuan Chen
Photothermal lanthanide nanomaterials with unique photophysical properties have been innovatively explored for diagnostics and non‐invasive therapies, and hold great promise for precision theranostics. In this review, we start from the basic principles of excited‐state dynamics and provide a thorough comprehension of the main pathways for photothermal conversion in lanthanide nanocrystals. Aspects influencing the photothermal effect such as lanthanide‐doping concentration, particle size, and crystal structure have been fully discussed. Hybrid strategies for the design of efficient lanthanide‐based photothermal agents, including dye sensitization to break the absorption limit and semiconductor combination to add cross‐relaxation pathways, have also been summarized. Furthermore, we highlight the cutting‐edge applications of photothermal lanthanide nanoplatforms with optical diagnosis and temperature feedback in photothermia‐associated theranostics. Lastly, the current challenges and future efforts for clinical applications are proposed. This review is expected to offer a better understanding of photothermal mechanisms and inspire efforts for designing versatile lanthanide theranostic nanoplatforms.
{"title":"Photothermal lanthanide nanomaterials: From fundamentals to theranostic applications","authors":"Zhuo Li, Jiacheng Gong, Shan Lu, Xingjun Li, Xiaobo Gu, Jin Xu, Jawairia Umar Khan, Dayong Jin, Xueyuan Chen","doi":"10.1002/bmm2.12088","DOIUrl":"https://doi.org/10.1002/bmm2.12088","url":null,"abstract":"Photothermal lanthanide nanomaterials with unique photophysical properties have been innovatively explored for diagnostics and non‐invasive therapies, and hold great promise for precision theranostics. In this review, we start from the basic principles of excited‐state dynamics and provide a thorough comprehension of the main pathways for photothermal conversion in lanthanide nanocrystals. Aspects influencing the photothermal effect such as lanthanide‐doping concentration, particle size, and crystal structure have been fully discussed. Hybrid strategies for the design of efficient lanthanide‐based photothermal agents, including dye sensitization to break the absorption limit and semiconductor combination to add cross‐relaxation pathways, have also been summarized. Furthermore, we highlight the cutting‐edge applications of photothermal lanthanide nanoplatforms with optical diagnosis and temperature feedback in photothermia‐associated theranostics. Lastly, the current challenges and future efforts for clinical applications are proposed. This review is expected to offer a better understanding of photothermal mechanisms and inspire efforts for designing versatile lanthanide theranostic nanoplatforms.","PeriodicalId":503415,"journal":{"name":"BMEMat","volume":"43 46","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140966201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Electrospun scaffolds with aligned fiber orientation are widely used in tissue engineering, such as muscle, heart, nerve, tendon, and cartilage, due to their ability to guide cell morphology and induce cellular functions. However, the dense fibrous structure of the scaffolds poses a critical obstacle to engineering highly cellular and thick 3D tissues, as it prevents cell infiltration. While many techniques have been developed to increase the pore size of electrospun scaffolds and improve cell infiltration/migration, it often leads to a decrease in direct cell‐cell contact, compromising cell differentiation and tissue maturation. This study presents an alternative approach by reducing the thickness of scaffolds to the cellular scale and stacking or rolling the cell‐scaffold complex into 3D constructs. We devise a series of novel tools to fabricate, characterize, and manipulate ultra‐thin electrospun scaffolds, which demonstrate high reproducibility, resolution, and cellularity. Our study provides a solution to the cell infiltration issue in muscle tissue engineering and is highly versatile, and can be applied to various fields that require structures with high‐resolution gradients in a layered pattern or complex spatial distribution in a rolled pattern.
{"title":"Thickening tissue by thinning electrospun scaffolds for skeletal muscle tissue engineering","authors":"Shuo Wang, Xinhuan Wang, Minxuan Jia, Wenli Liu, Qi Gu","doi":"10.1002/bmm2.12084","DOIUrl":"https://doi.org/10.1002/bmm2.12084","url":null,"abstract":"Electrospun scaffolds with aligned fiber orientation are widely used in tissue engineering, such as muscle, heart, nerve, tendon, and cartilage, due to their ability to guide cell morphology and induce cellular functions. However, the dense fibrous structure of the scaffolds poses a critical obstacle to engineering highly cellular and thick 3D tissues, as it prevents cell infiltration. While many techniques have been developed to increase the pore size of electrospun scaffolds and improve cell infiltration/migration, it often leads to a decrease in direct cell‐cell contact, compromising cell differentiation and tissue maturation. This study presents an alternative approach by reducing the thickness of scaffolds to the cellular scale and stacking or rolling the cell‐scaffold complex into 3D constructs. We devise a series of novel tools to fabricate, characterize, and manipulate ultra‐thin electrospun scaffolds, which demonstrate high reproducibility, resolution, and cellularity. Our study provides a solution to the cell infiltration issue in muscle tissue engineering and is highly versatile, and can be applied to various fields that require structures with high‐resolution gradients in a layered pattern or complex spatial distribution in a rolled pattern.","PeriodicalId":503415,"journal":{"name":"BMEMat","volume":"131 35","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140977223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hepatitis and arthritis are prevalent inflammatory diseases, and the utilization of fluorogenic probes incorporating hydrogen sulfide (H2S) as a crucial mediator of inflammation presents significant opportunities for early detection. However, the poor in vivo biodistribution and limited targeted efficacy of molecule probes for inflammation imaging severely impede their ability to differentiate the extent of inflammation and provide real‐time monitoring of inflammatory levels. Therefore, we developed a highly efficient H2S‐activated near‐infrared (NIR) fluorogenic probe (hCy‐DNP) for real‐time tracking and capturing fluctuations in H2S levels within inflammatory lesions. hCy‐DNP demonstrates an exceptionally sensitive fluorescence response to H2S expression, enabling specific differentiation between various levels of lipopolysaccharide (LPS) ‐stimulated early hepatitis models in situ, while also facilitating visual monitoring for diagnosis and efficacy evaluation of arthritis. Therefore, hCy‐DNP offers an innovative tool for exploring early diagnosis and evaluating treatment effectiveness across diverse inflammatory diseases.
{"title":"A simple yet effective H2S‐activated fluorogenic probe for precise imaging of hepatitis and arthritis in situ","authors":"Weier Liang, Yongning Bian, Animesh Samanta, Xueqian Chen, Xiaohe Yu, Yichen Zheng, Xueyun Gao, Dongdong Su","doi":"10.1002/bmm2.12086","DOIUrl":"https://doi.org/10.1002/bmm2.12086","url":null,"abstract":"Hepatitis and arthritis are prevalent inflammatory diseases, and the utilization of fluorogenic probes incorporating hydrogen sulfide (H2S) as a crucial mediator of inflammation presents significant opportunities for early detection. However, the poor in vivo biodistribution and limited targeted efficacy of molecule probes for inflammation imaging severely impede their ability to differentiate the extent of inflammation and provide real‐time monitoring of inflammatory levels. Therefore, we developed a highly efficient H2S‐activated near‐infrared (NIR) fluorogenic probe (hCy‐DNP) for real‐time tracking and capturing fluctuations in H2S levels within inflammatory lesions. hCy‐DNP demonstrates an exceptionally sensitive fluorescence response to H2S expression, enabling specific differentiation between various levels of lipopolysaccharide (LPS) ‐stimulated early hepatitis models in situ, while also facilitating visual monitoring for diagnosis and efficacy evaluation of arthritis. Therefore, hCy‐DNP offers an innovative tool for exploring early diagnosis and evaluating treatment effectiveness across diverse inflammatory diseases.","PeriodicalId":503415,"journal":{"name":"BMEMat","volume":" 22","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140996519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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