Pub Date : 2024-09-14DOI: 10.1016/j.mtbio.2024.101246
Head and neck squamous cell carcinoma (HNSCC) presents a significant challenge worldwide due to its aggressiveness and high recurrence rates post-treatment, often linked to cancer stem cells (CSCs). Melatonin shows promise as a potent tumor suppressor; however, the effects of melatonin on CSCs remain unclear, and the development of models that closely resemble tumor heterogeneity could help to better understand the effects of this molecule. This study developed a tumor scaffold based on patient fibroblast-derived decellularized extracellular matrix that mimics the HNSCC microenvironment. Our study investigates the antitumoral effects of melatonin within this context. We validated its strong antiproliferative effect on HNSCC CSCs and the reduction of tumor invasion and migration markers, even in a strongly chemoprotective environment, as it is required to increase the minimum doses necessary to impact tumor viability compared to the non-scaffolded tumorspheres culture. Moreover, melatonin exhibited no cytotoxic effects on healthy cells co-cultured in the tumor hydrogel. This scaffold-based platform allows an in vitro study closer to HNSCC tumor reality, including CSCs, stromal component, and a biomimetic matrix, providing a new valuable research tool in precision oncology.
{"title":"A bioengineered tumor matrix-based scaffold for the evaluation of melatonin efficacy on head and neck squamous cancer stem cells","authors":"","doi":"10.1016/j.mtbio.2024.101246","DOIUrl":"10.1016/j.mtbio.2024.101246","url":null,"abstract":"<div><p>Head and neck squamous cell carcinoma (HNSCC) presents a significant challenge worldwide due to its aggressiveness and high recurrence rates post-treatment, often linked to cancer stem cells (CSCs). Melatonin shows promise as a potent tumor suppressor; however, the effects of melatonin on CSCs remain unclear, and the development of models that closely resemble tumor heterogeneity could help to better understand the effects of this molecule. This study developed a tumor scaffold based on patient fibroblast-derived decellularized extracellular matrix that mimics the HNSCC microenvironment. Our study investigates the antitumoral effects of melatonin within this context. We validated its strong antiproliferative effect on HNSCC CSCs and the reduction of tumor invasion and migration markers, even in a strongly chemoprotective environment, as it is required to increase the minimum doses necessary to impact tumor viability compared to the non-scaffolded tumorspheres culture. Moreover, melatonin exhibited no cytotoxic effects on healthy cells co-cultured in the tumor hydrogel. This scaffold-based platform allows an <em>in vitro</em> study closer to HNSCC tumor reality, including CSCs, stromal component, and a biomimetic matrix, providing a new valuable research tool in precision oncology.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424003077/pdfft?md5=db00d5db069bc21eb1ecbc0d8494dabc&pid=1-s2.0-S2590006424003077-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274366","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 : 2024-09-14DOI: 10.1016/j.mtbio.2024.101236
The ever-increasing ageing of the world population is demanding superior orthopedic devices. Issues such as implant infection, poor osseointegration, or chronic inflammation remain problematic to the lifespan and long-term efficacy of implants. Fabrication of materials with bioinspired nanostructures is one emerging antibacterial strategy to prevent implant infection, however their interactions with blood components, and whether they retain their bactericidal properties in an environment displaying a complex protein corona, remains largely unexplored. In the present study, titanium alloy, commercially pure and plasma-sprayed titania were hydrothermally etched, passivated with human native plasma to develop a protein corona, and then incubated with either Staphylococcus aureus, Pseudomonas aeruginosa or human platelets. Surface analysis was first used to characterize the topography, chemical composition or crystallinity of each material. Fluorescence staining and SEM were performed to evaluate the nanostructure bactericidal properties, as well as to study platelet attachment and morphology. Composition of platelet supernatant was studied using ELISA and flow cytometry. Overall, our study showed that the bioinspired nanostructured surfaces displayed both impressive antibacterial properties in a complex environment, and a superior blood biocompatibility profile in terms of platelet activation (particularly for titanium alloy). Additionally, the amount of pro-inflammatory cytokines released by platelets was found to be no different to that found in native plasma (background levels) and, in some cases, presented a more pro-healing profile with an increased secretion of factors such as TGF-β, PDGF-BB or BMP-2. The nanostructured surfaces performed equally, or better, than hydroxyapatite-coated titanium which is one of the current gold standards in orthopedics. Although further in vivo studies are required to validate these results, such bioinspired nanostructured surfaces certainly show promise to be safely applied to medical device surfaces used in orthopedics and other areas.
{"title":"Platelet interaction and performance of antibacterial bioinspired nanostructures passivated with human plasma","authors":"","doi":"10.1016/j.mtbio.2024.101236","DOIUrl":"10.1016/j.mtbio.2024.101236","url":null,"abstract":"<div><div>The ever-increasing ageing of the world population is demanding superior orthopedic devices. Issues such as implant infection, poor osseointegration, or chronic inflammation remain problematic to the lifespan and long-term efficacy of implants. Fabrication of materials with bioinspired nanostructures is one emerging antibacterial strategy to prevent implant infection, however their interactions with blood components, and whether they retain their bactericidal properties in an environment displaying a complex protein corona, remains largely unexplored. In the present study, titanium alloy, commercially pure and plasma-sprayed titania were hydrothermally etched, passivated with human native plasma to develop a protein corona, and then incubated with either <em>Staphylococcus aureus</em>, <em>Pseudomonas aeruginosa</em> or human platelets. Surface analysis was first used to characterize the topography, chemical composition or crystallinity of each material. Fluorescence staining and SEM were performed to evaluate the nanostructure bactericidal properties, as well as to study platelet attachment and morphology. Composition of platelet supernatant was studied using ELISA and flow cytometry. Overall, our study showed that the bioinspired nanostructured surfaces displayed both impressive antibacterial properties in a complex environment, and a superior blood biocompatibility profile in terms of platelet activation (particularly for titanium alloy). Additionally, the amount of pro-inflammatory cytokines released by platelets was found to be no different to that found in native plasma (background levels) and, in some cases, presented a more pro-healing profile with an increased secretion of factors such as TGF-β, PDGF-BB or BMP-2. The nanostructured surfaces performed equally, or better, than hydroxyapatite-coated titanium which is one of the current gold standards in orthopedics. Although further <em>in vivo</em> studies are required to validate these results, such bioinspired nanostructured surfaces certainly show promise to be safely applied to medical device surfaces used in orthopedics and other areas.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323813","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 : 2024-09-14DOI: 10.1016/j.mtbio.2024.101249
Inflammation is a major impediment to the healing of cartilage injuries, yet bioactive scaffolds suitable for cartilage repair in inflammatory environments are extremely rare. Herein, we utilized electrospinning to fabricate a two-dimensional nanofiber scaffold (2DS), which was then subjected to gas foaming to obtain a three-dimensional scaffold (3DS). 3DS was modified with metal phenolic networks (MPNs) composed of epigallocatechin gallate (EGCG) and strontium ions (Sr2+) to afford a MPNs-modified 3D scaffold (3DS-E). Gas-foamed scaffold exhibited multilayered structure conducive to cellular infiltration and proliferation. Compared to other groups, 3DS-E better preserved chondrocytes under interleukin (IL)-1β induced inflammatory environment, showing less apoptosis of chondrocytes and higher expression of cartilage matrix. Additionally, 3DS-E facilitated the regeneration of more mature cartilage in vivo, reduced cell apoptosis, and decreased the expression of pro-inflammatory cytokines.
Taken together, 3DS-E may offer an ideal candidate for cartilage regeneration.
{"title":"Three-dimensional gas-foamed scaffolds decorated with metal phenolic networks for cartilage regeneration","authors":"","doi":"10.1016/j.mtbio.2024.101249","DOIUrl":"10.1016/j.mtbio.2024.101249","url":null,"abstract":"<div><p>Inflammation is a major impediment to the healing of cartilage injuries, yet bioactive scaffolds suitable for cartilage repair in inflammatory environments are extremely rare. Herein, we utilized electrospinning to fabricate a two-dimensional nanofiber scaffold (2DS), which was then subjected to gas foaming to obtain a three-dimensional scaffold (3DS). 3DS was modified with metal phenolic networks (MPNs) composed of epigallocatechin gallate (EGCG) and strontium ions (Sr<sup>2+</sup>) to afford a MPNs-modified 3D scaffold (3DS-E). Gas-foamed scaffold exhibited multilayered structure conducive to cellular infiltration and proliferation. Compared to other groups, 3DS-E better preserved chondrocytes under interleukin (IL)-1β induced inflammatory environment, showing less apoptosis of chondrocytes and higher expression of cartilage matrix. Additionally, 3DS-E facilitated the regeneration of more mature cartilage <em>in vivo</em>, reduced cell apoptosis, and decreased the expression of pro-inflammatory cytokines.</p><p>Taken together, 3DS-E may offer an ideal candidate for cartilage regeneration.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424003107/pdfft?md5=ab4c760f50b36efebb811bc7f1572d90&pid=1-s2.0-S2590006424003107-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274367","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 : 2024-09-14DOI: 10.1016/j.mtbio.2024.101254
Guiding endogenous regeneration of bone defects using biomaterials and regenerative medicine is considered an optimal strategy. One of the effective therapeutic approaches involves using transgene-expressed stem cells to treat tissue destruction and replace damaged parts. Among the various gene editing techniques for cells, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is considered as a promising method owing to the increasing therapeutic potential of cells by targeting specific sites. Herein, a vitamin D-incorporated poly(lactic-co-glycolic acid) (PLGA) scaffold with bone morphogenetic protein 2 (BMP2)/vascular endothelial growth factor (VEGF)-overexpressed tonsil-derived MSCs (ToMSCs) via CRISPR/Cas9 was introduced for bone tissue regeneration. The optimized seeding ratio of engineered ToMSCs on the scaffold demonstrated favorable immunomodulatory function, angiogenesis, and osteogenic activity in vitro. The multifunctional scaffold could potentially support stem cell in vivo and induce the transition from M1 to M2 macrophage with magnesium hydroxide and vitamin D. This study highlights the improved synergistic effect of a vitamin D-incorporated PLGA scaffold and a gene-edited ToMSCs for bone tissue engineering and regenerative medicine.
利用生物材料和再生医学引导骨缺损的内源性再生被认为是一种最佳策略。其中一种有效的治疗方法是利用转基因表达的干细胞来治疗组织破坏和替代受损部位。在各种细胞基因编辑技术中,簇状规则间隔短回文重复序列(CRISPR)/CRISPR相关蛋白9(Cas9)被认为是一种很有前景的方法,因为通过靶向特定位点,细胞的治疗潜力越来越大。在本文中,通过CRISPR/Cas9将维生素D与骨形态发生蛋白2(BMP2)/血管内皮生长因子(VEGF)表达的扁桃体来源间充质干细胞(ToMSCs)结合在一起的聚乳酸(PLGA)支架引入到骨组织再生中。经过优化的工程 ToMSCs 在支架上的播种比例在体外显示出了良好的免疫调节功能、血管生成和成骨活性。该多功能支架有可能在体内支持干细胞,并通过氢氧化镁和维生素 D 诱导巨噬细胞从 M1 向 M2 转变。该研究强调了添加维生素 D 的 PLGA 支架和基因编辑 ToMSCs 在骨组织工程和再生医学中的协同作用。
{"title":"Multifunctional vitamin D-incorporated PLGA scaffold with BMP/VEGF-overexpressed tonsil-derived MSC via CRISPR/Cas9 for bone tissue regeneration","authors":"","doi":"10.1016/j.mtbio.2024.101254","DOIUrl":"10.1016/j.mtbio.2024.101254","url":null,"abstract":"<div><p>Guiding endogenous regeneration of bone defects using biomaterials and regenerative medicine is considered an optimal strategy. One of the effective therapeutic approaches involves using transgene-expressed stem cells to treat tissue destruction and replace damaged parts. Among the various gene editing techniques for cells, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is considered as a promising method owing to the increasing therapeutic potential of cells by targeting specific sites. Herein, a vitamin D-incorporated poly(lactic-co-glycolic acid) (PLGA) scaffold with bone morphogenetic protein 2 (BMP2)/vascular endothelial growth factor (VEGF)-overexpressed tonsil-derived MSCs (ToMSCs) via CRISPR/Cas9 was introduced for bone tissue regeneration. The optimized seeding ratio of engineered ToMSCs on the scaffold demonstrated favorable immunomodulatory function, angiogenesis, and osteogenic activity <em>in vitro</em>. The multifunctional scaffold could potentially support stem cell <em>in vivo</em> and induce the transition from M1 to M2 macrophage with magnesium hydroxide and vitamin D. This study highlights the improved synergistic effect of a vitamin D-incorporated PLGA scaffold and a gene-edited ToMSCs for bone tissue engineering and regenerative medicine.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424003156/pdfft?md5=bf243ccb3a040b857f200eee3764c7ba&pid=1-s2.0-S2590006424003156-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242375","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 : 2024-09-14DOI: 10.1016/j.mtbio.2024.101239
Immune checkpoint blockade (ICB) therapy, particularly PD1/PDL1 inhibition, has demonstrated success in bolstering durable responses in patients. However, the response rate remains below 30 %. In this study, we developed a polymeric bispecific antibody (BsAb) targeting PD1/PDL1 to enhance ICB therapy. Specifically, poly(L-glutamic acid) (PGLU) was conjugated with a double cyclic Fc binding peptide, Fc-III-4C, through condensation reactions between the -COOH group of PGLU and the -NH2 group of Fc-III-4C. This conjugate was then mixed with αPD1 and αPDL1 monoclonal antibodies (mAbs) in an aqueous solution. Mechanistically, the PD1/PDL1 BsAb (BsAbαPD1+αPDL1) acts as a bridge between tumor cells and CD8+ T cells, continuously activating CD8+ T cells to a greater extent. This leads to significantly suppressed tumor growth and prolonged survival in a mouse model of colon cancer compared to treatment with either a single mAb or a mixture of free mAbs. The tumor suppression rate achieved by the BsAbαPD1+αPDL1 was 90.1 %, with a corresponding survival rate of 83.3 % after 48 days. Thus, this study underscores the effectiveness of the BsAbαPD1+αPDL1 as a synchronizing T cell engager and dual ICBs, offering theoretical guidance for clinical ICB therapy.
免疫检查点阻断(ICB)疗法,尤其是 PD1/PDL1 抑制疗法,在增强患者的持久应答方面取得了成功。然而,应答率仍低于30%。在这项研究中,我们开发了一种靶向 PD1/PDL1 的聚合物双特异性抗体 (BsAb),以增强 ICB 疗法。具体来说,通过 PGLU 的 -COOH 基团和 Fc-III-4C 的 -NH2 基团之间的缩合反应,聚(L-谷氨酸)(PGLU)与双环 Fc 结合肽 Fc-III-4C 共轭。然后将这种共轭物与水溶液中的αPD1和αPDL1单克隆抗体(mAbs)混合。从机理上讲,PD1/PDL1 BsAb(BsAbαPD1+αPDL1)可作为肿瘤细胞和 CD8+ T 细胞之间的桥梁,持续激活 CD8+ T 细胞。与使用单一 mAb 或游离 mAb 混合物治疗相比,这种方法能明显抑制肿瘤生长,延长小鼠结肠癌模型的存活时间。BsAbαPD1+αPDL1 的肿瘤抑制率为 90.1%,48 天后的相应存活率为 83.3%。因此,本研究强调了 BsAbαPD1+αPDL1 作为同步 T 细胞吞噬剂和双重 ICB 的有效性,为临床 ICB 治疗提供了理论指导。
{"title":"Polymeric PD1/PDL1 bispecific antibody enhances immune checkpoint blockade therapy","authors":"","doi":"10.1016/j.mtbio.2024.101239","DOIUrl":"10.1016/j.mtbio.2024.101239","url":null,"abstract":"<div><p>Immune checkpoint blockade (ICB) therapy, particularly PD1/PDL1 inhibition, has demonstrated success in bolstering durable responses in patients. However, the response rate remains below 30 %. In this study, we developed a polymeric bispecific antibody (BsAb) targeting PD1/PDL1 to enhance ICB therapy. Specifically, poly(<sub>L</sub>-glutamic acid) (PGLU) was conjugated with a double cyclic Fc binding peptide, Fc-III-4C, through condensation reactions between the -COOH group of PGLU and the -NH<sub>2</sub> group of Fc-III-4C. This conjugate was then mixed with αPD1 and αPDL1 monoclonal antibodies (mAbs) in an aqueous solution. Mechanistically, the PD1/PDL1 BsAb (BsAb<sub>αPD1+αPDL1</sub>) acts as a bridge between tumor cells and CD8<sup>+</sup> T cells, continuously activating CD8<sup>+</sup> T cells to a greater extent. This leads to significantly suppressed tumor growth and prolonged survival in a mouse model of colon cancer compared to treatment with either a single mAb or a mixture of free mAbs. The tumor suppression rate achieved by the BsAb<sub>αPD1+αPDL1</sub> was 90.1 %, with a corresponding survival rate of 83.3 % after 48 days. Thus, this study underscores the effectiveness of the BsAb<sub>αPD1+αPDL1</sub> as a synchronizing T cell engager and dual ICBs, offering theoretical guidance for clinical ICB therapy.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424003004/pdfft?md5=9b006b2ebddadc48b0fc7609aa138200&pid=1-s2.0-S2590006424003004-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242372","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 : 2024-09-14DOI: 10.1016/j.mtbio.2024.101251
Hydrogels are widely used to explore emerging minimally invasive strategies for intervertebral disc degeneration (IVDD) due to their suitability as drug and cell delivery vehicles. There has been no review of the latest research trends and strategies of hydrogel delivery systems in IVDD for the last decade. In this study, we identify the application trends and strategies in this field through bibliometric analysis, including aspects such as publication years, countries and institutions, authors and publications, and co-occurrence of keywords. The results reveal that the literature in this field has been receiving increasing attention with a trend of growth annually. Subsequently, the hotspots of hydrogels in this field were described and discussed in detail, and we proposed the “four core factors”, hydrogels, cells, cell stimulators, and microenvironmental regulation, required for a multifunctional hydrogel for IVDD. Finally, we discuss the popular and emerging mechanistic strategies of hydrogel therapy for IVDD in terms of five aspects: fundamental pathologic changes in IVDD, counteracting cellular senescence, counteracting cell death, improving organelle function, and replenishing exogenous cells. This study provides a reference and a new perspective for future research in this urgently needed field.
{"title":"Application trends and strategies of hydrogel delivery systems in intervertebral disc degeneration: A bibliometric review","authors":"","doi":"10.1016/j.mtbio.2024.101251","DOIUrl":"10.1016/j.mtbio.2024.101251","url":null,"abstract":"<div><p>Hydrogels are widely used to explore emerging minimally invasive strategies for intervertebral disc degeneration (IVDD) due to their suitability as drug and cell delivery vehicles. There has been no review of the latest research trends and strategies of hydrogel delivery systems in IVDD for the last decade. In this study, we identify the application trends and strategies in this field through bibliometric analysis, including aspects such as publication years, countries and institutions, authors and publications, and co-occurrence of keywords. The results reveal that the literature in this field has been receiving increasing attention with a trend of growth annually. Subsequently, the hotspots of hydrogels in this field were described and discussed in detail, and we proposed the “four core factors”, hydrogels, cells, cell stimulators, and microenvironmental regulation, required for a multifunctional hydrogel for IVDD. Finally, we discuss the popular and emerging mechanistic strategies of hydrogel therapy for IVDD in terms of five aspects: fundamental pathologic changes in IVDD, counteracting cellular senescence, counteracting cell death, improving organelle function, and replenishing exogenous cells. This study provides a reference and a new perspective for future research in this urgently needed field.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424003120/pdfft?md5=7395ca53b698dbf60b5359e9757ac6ec&pid=1-s2.0-S2590006424003120-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242378","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 : 2024-09-14DOI: 10.1016/j.mtbio.2024.101238
This study introduces the time-gated analysis of room-temperature phosphorescence (RTP) for the in-situ analysis of the visible and spectral information of photons. Time-gated analysis is performed using a microscopic system consisting of a spectrometer, which is advantageous for in-situ analysis since it facilitates the real-time measurement of luminescence signal changes. An RTP material hybridized with a DNA aptamer that targets a specific protein enhances the intensity and lifetime of phosphorescence after selective recognition with the target protein. In addition, time-gated analysis allows for the millisecond-scale imaging of phosphorescence signals, excluding autofluorescence, and improves the signal-to-background ratio (SBR) through the accumulation of signals. While collecting the time-gated images and spectra of RTP and autofluorescent materials simultaneously, we develop a method for obtaining phosphorescence signals by means of selective exclusion of autofluorescence signals in simulated or real cell conditions. It is confirmed that the accumulated time-gated analysis can provide ample information about luminescence signals for bioimaging and biosensing applications.
本研究介绍了室温磷光(RTP)的时间门控分析,用于原位分析光子的可见光和光谱信息。时间门控分析是利用光谱仪组成的显微系统进行的,这对于原位分析非常有利,因为它有助于实时测量发光信号的变化。与针对特定蛋白质的 DNA 类似物杂交的 RTP 材料在与目标蛋白质进行选择性识别后,会增强磷光的强度和寿命。此外,时间门控分析可对磷光信号进行毫秒级成像,排除自发荧光,并通过信号积累提高信噪比(SBR)。在同时收集 RTP 和自发荧光材料的时间门控图像和光谱的同时,我们开发了一种在模拟或真实细胞条件下通过选择性排除自发荧光信号来获取磷光信号的方法。经证实,累积的时间门控分析可为生物成像和生物传感应用提供有关发光信号的充足信息。
{"title":"Accumulated in-situ spectral information analysis of room-temperature phosphorescence with time-gated bioimaging","authors":"","doi":"10.1016/j.mtbio.2024.101238","DOIUrl":"10.1016/j.mtbio.2024.101238","url":null,"abstract":"<div><p>This study introduces the time-gated analysis of room-temperature phosphorescence (RTP) for the in-situ analysis of the visible and spectral information of photons. Time-gated analysis is performed using a microscopic system consisting of a spectrometer, which is advantageous for in-situ analysis since it facilitates the real-time measurement of luminescence signal changes. An RTP material hybridized with a DNA aptamer that targets a specific protein enhances the intensity and lifetime of phosphorescence after selective recognition with the target protein. In addition, time-gated analysis allows for the millisecond-scale imaging of phosphorescence signals, excluding autofluorescence, and improves the signal-to-background ratio (SBR) through the accumulation of signals. While collecting the time-gated images and spectra of RTP and autofluorescent materials simultaneously, we develop a method for obtaining phosphorescence signals by means of selective exclusion of autofluorescence signals in simulated or real cell conditions. It is confirmed that the accumulated time-gated analysis can provide ample information about luminescence signals for bioimaging and biosensing applications.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424002990/pdfft?md5=d4a8408d3840fab5ae74eaeefdb58eb1&pid=1-s2.0-S2590006424002990-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243129","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 : 2024-09-13DOI: 10.1016/j.mtbio.2024.101233
Lower urinary tract dysfunction (LUTD) is a prevalent condition characterized by symptoms such as urinary frequency, urgency, incontinence, and difficulty in urination, which can significantly impair patient's quality of life and lead to severe physiological complications. Despite the availability of diverse treatment options, including pharmaceutical and behavioral therapies, these approaches are not without challenges. The objective of this study was to enhance treatment options for LUTD by developing a wireless, battery-free device for managing bladder contractions. We designed and validated a compact, fully implantable, battery-free pulse generator using the magnetic induction coupling mechanism of wireless power transmission. Weighing less than 0.2 g and with a volume of less than 0.1 cubic centimeters, this device enables precise stimulation of muscles or neurons at voltages ranging from 0 to 10 V. Wireless technology allows real-time adjustment of key stimulation parameters such as voltage, duration, frequency, pulse width, and pulse interval. Our findings demonstrate that the device effectively controlled bladder contractions in mice when used to stimulate the Major Pelvic Ganglion (MPG). Additionally, the device successfully managed micturition in mice with bilateral transection of the pudendal nerve. In conclusion, the development of this innovative wireless pulse generator provides a safer and more cost-effective alternative to conventional battery-powered neurostimulators for bladder control, addressing the limitations of such devices. We anticipate that this novel technology will play a pivotal role in the future of electrical stimulation therapies for voiding dysfunctions.
{"title":"A wireless, battery-free device for electrical neuromodulation of bladder contractions","authors":"","doi":"10.1016/j.mtbio.2024.101233","DOIUrl":"10.1016/j.mtbio.2024.101233","url":null,"abstract":"<div><p>Lower urinary tract dysfunction (LUTD) is a prevalent condition characterized by symptoms such as urinary frequency, urgency, incontinence, and difficulty in urination, which can significantly impair patient's quality of life and lead to severe physiological complications. Despite the availability of diverse treatment options, including pharmaceutical and behavioral therapies, these approaches are not without challenges. The objective of this study was to enhance treatment options for LUTD by developing a wireless, battery-free device for managing bladder contractions. We designed and validated a compact, fully implantable, battery-free pulse generator using the magnetic induction coupling mechanism of wireless power transmission. Weighing less than 0.2 g and with a volume of less than 0.1 cubic centimeters, this device enables precise stimulation of muscles or neurons at voltages ranging from 0 to 10 V. Wireless technology allows real-time adjustment of key stimulation parameters such as voltage, duration, frequency, pulse width, and pulse interval. Our findings demonstrate that the device effectively controlled bladder contractions in mice when used to stimulate the Major Pelvic Ganglion (MPG). Additionally, the device successfully managed micturition in mice with bilateral transection of the pudendal nerve. In conclusion, the development of this innovative wireless pulse generator provides a safer and more cost-effective alternative to conventional battery-powered neurostimulators for bladder control, addressing the limitations of such devices. We anticipate that this novel technology will play a pivotal role in the future of electrical stimulation therapies for voiding dysfunctions.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424002941/pdfft?md5=17547b73f6791b80aff2b083d1120774&pid=1-s2.0-S2590006424002941-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242379","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 : 2024-09-13DOI: 10.1016/j.mtbio.2024.101241
Corneal opacity and deformation, which often require corneal transplantation for treatment, are among the leading causes of monocular blindness. To restore corneal clarity and integrity, there is a need for an artificial stroma that not only matches the transparency of donated human cornea but also effectively integrates to the corneal tissue. In this study, a transparent decellularized cornea was successfully developed using the high hydrostatic pressure method with processing conditions optimized for corneal decellularization. Biochemical analyses demonstrated the effective removal of cellular components from the transparent decellularized corneas, while preserving collagen and glycosaminoglycans. Proteome analysis also revealed that core matrisome and matrisome-associated proteins remained following decellularization, similar to the composition observed in untreated corneas. The light transmittance of the transparent decellularized corneas was 86.4 ± 1.5 % in the visible region, comparable to that of donated human corneas. No complications, such as angiogenesis, were observed following interlamellar corneal transplantation in rabbits. The grafts were almost imperceptible immediately following surgery and achieved complete transparency within a few days, becoming indistinguishable even under a microscope. The transparent decellularized cornea presented here has promising potential as a material for application in lamellar keratoplasty.
{"title":"Preparation, physico-biochemical characterization, and proteomic analysis of highly transparent corneal extracellular matrices for lamellar keratoplasty and tissue-engineered cornea construction","authors":"","doi":"10.1016/j.mtbio.2024.101241","DOIUrl":"10.1016/j.mtbio.2024.101241","url":null,"abstract":"<div><p>Corneal opacity and deformation, which often require corneal transplantation for treatment, are among the leading causes of monocular blindness. To restore corneal clarity and integrity, there is a need for an artificial stroma that not only matches the transparency of donated human cornea but also effectively integrates to the corneal tissue. In this study, a transparent decellularized cornea was successfully developed using the high hydrostatic pressure method with processing conditions optimized for corneal decellularization. Biochemical analyses demonstrated the effective removal of cellular components from the transparent decellularized corneas, while preserving collagen and glycosaminoglycans. Proteome analysis also revealed that core matrisome and matrisome-associated proteins remained following decellularization, similar to the composition observed in untreated corneas. The light transmittance of the transparent decellularized corneas was 86.4 ± 1.5 % in the visible region, comparable to that of donated human corneas. No complications, such as angiogenesis, were observed following interlamellar corneal transplantation in rabbits. The grafts were almost imperceptible immediately following surgery and achieved complete transparency within a few days, becoming indistinguishable even under a microscope. The transparent decellularized cornea presented here has promising potential as a material for application in lamellar keratoplasty.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424003028/pdfft?md5=d265a3c226bcf533ac4f851c0091fdd3&pid=1-s2.0-S2590006424003028-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242376","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}