Bioengineering & Translational Medicine最新文献

{"title":"Assessing the impact of airborne particulate pollution on human skin utilizing a novel human skin equivalent containing MUTZ-3-derived Langerhans cells","authors":"Amy Simpson,&nbsp;Teresa DiColandrea,&nbsp;Stefan Przyborski","doi":"10.1002/btm2.10738","DOIUrl":"10.1002/btm2.10738","url":null,"abstract":"<p>Air pollution is an exogenous stressor known to have a detrimental impact on skin health through the induction of inflammation; however, the direct effect of topical pollution exposure is still being elucidated. Human skin equivalents (HSE) aim to reproduce in vitro the structure and function of the native skin tissue. However, HSEs typically lack skin-resident immune cells, which could play a key role in the inflammatory response induced by pollution exposure. We outline the development of a HSE-containing MUTZ-3-derived Langerhans cells (MUTZ-3-LCs), which show dendritic morphology and Langerhans cell marker expression. We demonstrated that HSE-containing MUTZ-3-LC have lower basal levels of proinflammatory cytokines, but topical stimulation with allergens and irritant compounds induced a greater inflammatory response in these models compared to HSE without immune cells. To study the effect of pollution, we created a technique to apply diesel particulate matter (DPM) to HSEs. Though our microscopic analysis demonstrated that DPM does not penetrate the stratum corneum, we showed that DPM did induce production of proinflammatory cytokines, but notably only in HSEs containing MUTZ-3-LCs. These data suggest that topical exposure to air pollution can induce cutaneous inflammation and that skin-resident immune cells contribute to this response. This highlights the significance of immune-competent HSEs to the study of exogenous stressors in vitro.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 2","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10738","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced glutathione enhances adipose tissue-derived mesenchymal stem cell engraftment efficiency for liver fibrosis by targeting TGFβ1/SMAD3/NOX4 pathway","authors":"Shaoxiong Yu,&nbsp;Yingchao Wang,&nbsp;Yingjun Shi,&nbsp;Saihua Yu,&nbsp;Bixing Zhao,&nbsp;Naishun Liao,&nbsp;Xiaolong Liu","doi":"10.1002/btm2.10735","DOIUrl":"10.1002/btm2.10735","url":null,"abstract":"<p>Reduced glutathione (GSH) could reduce oxidative stress to improve adipose tissue-derived mesenchymal stem cell (ADSC) engraftment efficiency in vivo. However, the underlying mechanisms remain unclear. Our goal is to investigate whether GSH enhances ADSC engraftment through targeting the TGFβ/SMAD3/NOX4 pathway. Liver fibrotic male mice were administrated GSH, setanaxib (STX), and SIS3 during ADSC transplantation. ADSC engraftment efficiency and reactive oxygen species (ROS) level were detected both in vivo and ex vivo. Biochemical analysis was used to analyze the content of superoxide and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) in liver tissues. Immunohistochemistry and western blotting were used to examine the protein level of NOX1, NOX2, NOX4, transforming growth factor-β1 (TGFβ1), SMAD3, and p-SMAD3 in liver tissues. Additionally, the therapeutic efficacy of the ADSC transplantation was further investigated. We found that GSH significantly improved ADSC engraftment efficiency, which was closely related to the reduced ROS generation in liver tissues. However, the enhanced cell engraftment was abolished after the combined treatment with STX or SIS3. GSH could effectively reduce superoxide and NOXs content, and selectively inhibit NOX4 expression in liver tissues. The co-localization results showed that GSH could reduce NOX4 expressed in activated hepatic stellate cells. Mechanistically, GSH down-regulated TGFβ/SMAD3 signaling. More importantly, GSH enhanced the therapeutic efficacy of ADSC therapy in liver fibrotic mice. Taken together, GSH could improve the engraftment efficiency of ADSCs in liver fibrosis by targeting TGFβ1/SMAD3/NOX4 signaling pathway, which provides a new theoretical basis for GSH enhancing ADSC engraftment efficiency in liver diseases.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 2","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10735","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green/red fluorescent protein disrupting drugs for real-time permeability tracking in three-dimensional tumor spheroids","authors":"Maytal Avrashami,&nbsp;Danna Niezni,&nbsp;Dana Meron Azagury,&nbsp;Hagit Sason,&nbsp;Yosi Shamay","doi":"10.1002/btm2.10731","DOIUrl":"10.1002/btm2.10731","url":null,"abstract":"<p>Three-dimensional (3D) spheroid models offer a more physiologically relevant and complex environment compared to traditional two-dimensional cultures, making them a promising tool for studying tumor biology and drug response. However, these models often face challenges in real-time monitoring of drug diffusion, penetration, and target engagement, limiting their predictive power for in vivo and clinical outcomes. This study introduces a novel approach for real-time tracking of drug permeability using small molecule drugs with GFP/RFP-disrupting properties that correlate with their efficacy. We developed a reproducible 3D spheroid model with various cancer cell lines expressing GFP/RFP for efficient drug screening. Through screening over 20 FDA-approved enzyme inhibitors, we identified three covalent kinase inhibitors—osimertinib, afatinib, and neratinib—that irreversibly disrupt GFP and RFP fluorescence. Our results reveal distinct drug diffusion and penetration profiles within GFP/RFP-expressing spheroids, varying with drug concentration and formulation, and correlating with clinical volume of distribution (Vd) values. Additionally, we demonstrate that our approach is useful for evaluating different drug formulations as well as screening penetration enhancers for solid tumors. These findings offer a valuable 3D model for studying kinetics of drug permeability and efficacy in tumor-like environments, with potential implications for drug delivery research and formulation development.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10731","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoluminal photodynamic therapy with a photoreactive stent-based catheter system to treat malignant colorectal obstruction","authors":"Seung Jin Eo,&nbsp;Dae Sung Ryu,&nbsp;Hyeonseung Lee,&nbsp;Ji Won Kim,&nbsp;Song Hee Kim,&nbsp;Jin Hee Noh,&nbsp;Yuri Kim,&nbsp;Seokin Kang,&nbsp;Kun Na,&nbsp;Jung-Hoon Park,&nbsp;Do Hoon Kim","doi":"10.1002/btm2.10732","DOIUrl":"10.1002/btm2.10732","url":null,"abstract":"<p>Photodynamic therapy (PDT) using photosensitizer (PS)-embedded silicone membrane-covered self-expandable metallic stents (SEMSs) can function in palliative therapeutic option for malignant gastrointestinal tract obstruction. However, stent-related complications should be considered, and accurate delivery of light sources is technically difficult. Here, a Chlorin e6 (Ce6)-an embedded stent-based catheter is developed to improve its therapeutic efficacy and safety. PDT using Ce6-embedded stent successfully induced cell death of colorectal cancer cell line. PDT-treated liver tissues showed an increase in ablation depth in proportion to irradiation energy, and 600 J/cm² demonstrates an even and sufficient ablation depth. Endoluminal PDT using the Ce6-embedded stent-based catheter was technically successful in a rat colon model without procedure-related complications such as colonic perforation or stricture formation. The results in colonoscopy, colonography, and histological examination, along with statistical analysis, suggest that a novel PDT modality using a Ce6-embedded stent-based catheter was safely conducted and demonstrated apoptotic cell death at 12 h after PDT, and it gradually recovered from 2 to 4 weeks. Thus, the PDT using the Ce6-embedded stent-based catheter may represent a promising new approach for the treatment of malignant colorectal obstruction.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 2","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10732","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fecal microbiota transplantation for the treatment of intestinal and extra-intestinal diseases: Mechanism basis, clinical application, and potential prospect","authors":"Dongxin Yi,&nbsp;Tao Li,&nbsp;Yuji Xiao,&nbsp;Xue Zhang,&nbsp;Qiangqiang Hao,&nbsp;Feng Zhang,&nbsp;Tianming Qiu,&nbsp;Guang Yang,&nbsp;Xiance Sun,&nbsp;Ying Dong,&nbsp;Ningning Wang","doi":"10.1002/btm2.10728","DOIUrl":"10.1002/btm2.10728","url":null,"abstract":"<p>To review the theoretical basis and therapeutic effects of fecal microbiota transplantation (FMT) in various diseases in animal experiments and clinical studies, as well as the limitations and current standards of FMT application. PubMed and Web of Science databases were searched for articles published only in English between 1975 and 2023 on reliable results of animal experiments and clinical treatment of FMT. The properties of the gut microbiota and its interactions with the host metabolism are critical to human health, and microbiome disturbance is closely associated with human intestinal and extra-intestinal diseases. Therefore, therapeutic tools targeting on the modulation of gut microbiota have attracted increasing attention, among which FMT represents the most widely studied intervention strategy. This review gathered and summarized application of FMT in intestinal diseases, metabolic diseases, hypertension, cancer, nervous system diseases and arthritis, and elaborated the beneficial effects that can be achieved by altering the microbiota with FMT and the mechanisms of action. In addition, the potential risks and side effects of FMT approach are discussed, as well as current efforts to standardize the development of FMT. Through a systemic review of the outcome and mechanism of FMT in the treatment of intestinal diseases and extra-intestinal diseases, we aimed to provide a theoretical basis for the construction of an optimized FMT framework, so as to better exert its application prospects.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 2","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10728","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ColMA-based bioprinted 3D scaffold allowed to study tenogenic events in human tendon stem cells","authors":"Giacomo Cortella,&nbsp;Erwin Pavel Lamparelli,&nbsp;Maria Camilla Ciardulli,&nbsp;Joseph Lovecchio,&nbsp;Emanuele Giordano,&nbsp;Nicola Maffulli,&nbsp;Giovanna Della Porta","doi":"10.1002/btm2.10723","DOIUrl":"10.1002/btm2.10723","url":null,"abstract":"<p>The advent of bioprinting has enabled the creation of precise three-dimensional (3D) cell cultures suitable for biomimetic in vitro models. In this study, we developed a novel protocol for 3D printing methacrylated collagen (ColMa, or PhotoCol®) combined with tendon stem/progenitor cells (hTSPCs) derived from human tendon explants. Although pure ColMa has not previously been proposed as a printable hydrogel, this paper outlines a robust and highly reproducible pipeline for bioprinting this material. Indeed, we successfully fabricated a 3D bioengineered scaffold and cultured it for 21 days under perfusion conditions with medium supplemented with growth/differentiation factor-5 (GDF-5). This bioprinting pipeline and the culture conditions created an exceptionally favorable 3D environment, enabling the cells to proliferate, exhibit tenogenic behaviors, and produce a new collagen type I matrix, thereby remodeling the surrounding environment. Indeed, over the 21-day culture period under perfusion condition, tenomodulin expression showed a significant upregulation on day 7, with a 2.3-fold increase, compared to days 14 and 21. Collagen type I gene expression was upregulated nearly 10-fold by day 14. This trend was further confirmed by western blot analysis, which revealed a statistically significant difference in tenomodulin expression between day 21 and both day 7 and day 14. For type I collagen, significant differences were observed between day 0 and day 21, as well as between day 0 and day 14, with a <i>p</i>-value of 0.01. These results indicate a progressive over-expression of type I collagen, reflecting cell differentiation towards a proper tenogenic phenotype. Cytokines, such as IL-8 and IL-6, levels peaked at 8566 and 7636 pg/mL, respectively, on day 7, before decreasing to 54 and 46 pg/mL by day 21. Overall, the data suggest that the novel ColMa bioprinting protocol effectively provided a conducive environment for the growth and proper differentiation of hTSPCs, showcasing its potential for studying cell behavior and tenogenic differentiation.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10723","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease","authors":"Huimin Li,&nbsp;Xueyu Wen,&nbsp;Xinyi Gong,&nbsp;Yange Wu,&nbsp;Puxuan Zhao,&nbsp;Yun Zhang,&nbsp;Zhuomin Sha,&nbsp;Hao Chang,&nbsp;Xuepeng Chen","doi":"10.1002/btm2.10730","DOIUrl":"10.1002/btm2.10730","url":null,"abstract":"<p>Minocycline is a commonly used drug for adjunctive therapy in periodontal disease. However, the current mainstream local medications primarily rely on intra-pocket administration, which, while avoiding the side effects of traditional systemic drugs, presents challenges such as inconvenience, discomfort, and the need for professional assistance, thus affecting patient compliance. Herein, we introduce a minocycline-loaded dissolvable microneedle (Mino-DMN) patch that allows for local and efficient delivery of minocycline to gingiva for the treatment of periodontitis. A two-step casting micro-molding process involving vacuum drying and freeze drying is employed to concentrate minocycline in the microneedle part and limit its diffusion into the patch backing. The resulting Mino-DMN patch features an array of minocycline-enriched gelatin MNs with a porous HA patch backing. The microneedles can penetrate into gingiva with enough mechanical strength and quickly release minocycline into the gingival tissue, ensuring prolonged local residence of the drug and minimizing its loss to saliva. In vivo experiments show Mino-DMN inhibits pro-inflammatory factors, promotes anti-inflammatory factors, and stimulates bone formation, surpassing topical application and comparable to the inconvenient and discomfort administration of Periocline®. This proposed Mino-DMN offers a simple, efficient, user-friendly strategy for the adjunctive treatment of periodontal disease.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 2","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10730","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature-sensitive sodium beta-glycerophosphate/chitosan hydrogel loaded with all-trans retinoic acid regulates Pin1 to inhibit the formation of spinal cord injury-induced rat glial scar","authors":"Rongmou Zhang,&nbsp;Ting Tang,&nbsp;Huafeng Zhuang,&nbsp;Peiwen Wang,&nbsp;Haiming Yu,&nbsp;Hao Xu,&nbsp;Xuedong Yao","doi":"10.1002/btm2.10729","DOIUrl":"10.1002/btm2.10729","url":null,"abstract":"<p>Glial scar formation is a major obstacle to nerve regeneration following spinal cord injury (SCI). Pin1 and the PI3K/AKT/CDK2 signaling pathway play crucial roles in neuronal regulation, but research on their involvement in glial scarring remains limited. In this study, we have for the first time observed that Pin1, PI3K, AKT, and CDK2 are upregulated and interact with each other following SCI. Further experiments revealed that Pin1 contributes to the development of glial scars by promoting astrocyte proliferation, inhibiting apoptosis, and activating the PI3K/AKT/CDK2 pathway. Additionally, all-trans retinoic acid (ATRA), a specific chemical inhibitor of Pin1, effectively suppresses Pin1 expression. However, its clinical application is limited by its short half-life and susceptibility to inactivation. To address these issues, we have developed a thermosensitive sodium beta-glycerophosphate (β-GP)/chitosan (CS) hydrogel loaded with ATRA (β-GP/CS@ATRA). This hydrogel exhibits favorable morphology and biocompatibility. Compared to free ATRA, the β-GP/CS@ATRA hydrogel significantly enhances functional motor recovery after SCI and protects spinal cord tissue, thereby inhibiting glial scar formation. Mechanistically, ATRA administration blocks the development of glial scars and the activation of the PI3K/AKT/CDK2 pathway by inhibiting Pin1 expression. This study suggests that combining ATRA with a hydrogel to target Pin1 expression may be a promising strategy for treating glial scar formation following SCI.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10729","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent regulatory developments in EU Medical Device Regulation and their impact on biomaterials translation","authors":"Klaudia M. Jurczak,&nbsp;Torben A. B. van der Boon,&nbsp;Raul Devia-Rodriguez,&nbsp;Richte C. L. Schuurmann,&nbsp;Jelmer Sjollema,&nbsp;Lidia van Huizen,&nbsp;Jean-Paul P. M. De Vries,&nbsp;Patrick van Rijn","doi":"10.1002/btm2.10721","DOIUrl":"10.1002/btm2.10721","url":null,"abstract":"<p>We envision this work to assist researchers and medical device developers (beside other stakeholders) to better understand biomaterial-based medical device development and its approval process proposed by the new MDR and IVDR in the European Union, as more complex biomaterials emerge, with the MDR reflecting the progress in biomaterial discoveries. Additionally, insufficient international harmonization in regulatory laws and poor-quality data reporting contribute to the problem. This review describes the possible reasons for a slowing biomaterials translational trend observed over the past decades, focusing on the European Market, and suggests a feasible approach for biomaterials-based medical device translation into the clinic. Suitable solutions to upgrade biomaterial translation to the clinic have not yet been provided by the field: no additional hurdles should be imposed for researchers, clinicians, the medical device industry, and insurance companies, which all should collaborate on bringing innovative solutions to patients. The new MDR and IVDR represent a substantial advancement in ensuring patient safety and reflect a major step forward in healthcare. However, they should not constrain innovation in biomaterials-based medical device development. Incorporating reverse engineering from patient safety and a ‘safe by design’ (SbD) strategy early into medical device development might lead to a smoother and successful approval process. A solid R&amp;D phase, with an emphasis on device safety and performance assessment, is fundamental to ensure an effective transition into the clinic. We offer an overview of the recently implemented regulations on medical devices and in vitro diagnostics across the EU, describing a shifting paradigm in the field of biomaterials discovery. As more complex biomaterials emerge, suitable regulations will be necessary to keep bringing safe and well-performing medical solutions to patients.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 2","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10721","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photobiomodulation improves functional recovery after mild traumatic brain injury","authors":"Andrew R. Stevens,&nbsp;Mohammed Hadis,&nbsp;Abhinav Thareja,&nbsp;Freya G. Anderson,&nbsp;Michael R. Milward,&nbsp;Valentina Di Pietro,&nbsp;Antonio Belli,&nbsp;William Palin,&nbsp;David J. Davies,&nbsp;Zubair Ahmed","doi":"10.1002/btm2.10727","DOIUrl":"10.1002/btm2.10727","url":null,"abstract":"<p>Mild traumatic brain injury (mTBI) is a common consequence of head injury but there are no recognized interventions to promote recovery of the brain. We previously showed that photobiomodulation (PBM) significantly reduced the number of apoptotic cells in adult rat hippocampal organotypic slice cultures. In this study, we first optimized PBM delivery parameters for use in mTBI, conducting cadaveric studies to calibrate 660 and 810 nm lasers for transcutaneous delivery of PBM to the cortical surface. We then used an in vivo weight drop mTBI model in adult rats and delivered daily optimized doses of 660, 810 nm, or combined 660/810 nm PBM. Functional recovery was assessed using novel object recognition (NOR) and beam balance tests, whilst histology and immunohistochemistry were used to assess the mTBI neuropathology. We found that PBM at 810, 660 nm, or 810/660 nm all significantly improved both NOR and beam balance performance, with 810 nm PBM having the greatest effects. Histology demonstrated no overt structural damage in the brain after mTBI, however, immunohistochemistry using brain sections showed significantly reduced activation of both CD11b⁺ microglia and glial fibrillary acidic protein (GFAP)⁺ astrocytes at 3 days post-injury. Significantly reduced cortical localization of the apoptosis marker, cleaved caspase-3, and modest reductions in extracellular matrix deposition after PBM treatment, limited to choroid plexus and periventricular areas were also observed. Our results demonstrate that 810 nm PBM optimally improved functional outcomes after mTBI, reduced markers associated with apoptosis and astrocyte/microglial activation, and thus may be useful as a potential regenerative therapy.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 2","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10727","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142415629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}