Tissue engineering and regenerative medicine最新文献

{"title":"The Porous SilMA Hydrogel Scaffolds Carrying Dual-Sensitive Paclitaxel Nanoparticles Promote Neuronal Differentiation for Spinal Cord Injury Repair.","authors":"Zhixiang Li, Tao Zhou, Zhengqi Bao, Min Wu, Yingji Mao","doi":"10.1007/s13770-024-00659-9","DOIUrl":"10.1007/s13770-024-00659-9","url":null,"abstract":"<p><strong>Background: </strong>In the intricate pathological milieu post-spinal cord injury (SCI), neural stem cells (NSCs) frequently differentiate into astrocytes rather than neurons, significantly limiting nerve repair. Hence, the utilization of biocompatible hydrogel scaffolds in conjunction with exogenous factors to foster the differentiation of NSCs into neurons has the potential for SCI repair.</p><p><strong>Methods: </strong>In this study, we engineered a 3D-printed porous SilMA hydrogel scaffold (SM) supplemented with pH-/temperature-responsive paclitaxel nanoparticles (PTX-NPs). We analyzed the biocompatibility of a specific concentration of PTX-NPs and its effect on NSC differentiation. We also established an SCI model to explore the ability of composite scaffolds for in vivo nerve repair.</p><p><strong>Results: </strong>The physical adsorption of an optimal PTX-NPs dosage can simultaneously achieve pH/temperature-responsive release and commendable biocompatibility, primarily reflected in cell viability, morphology, and proliferation. An appropriate PTX-NPs concentration can steer NSC differentiation towards neurons over astrocytes, a phenomenon that is also efficacious in simulated injury settings. Immunoblotting analysis confirmed that PTX-NPs-induced NSC differentiation occurred via the MAPK/ERK signaling cascade. The repair of hemisected SCI in rats demonstrated that the composite scaffold augmented neuronal regeneration at the injury site, curtailed astrocyte and fibrotic scar production, and enhanced motor function recovery in rat hind limbs.</p><p><strong>Conclusion: </strong>The scaffold's porous architecture serves as a cellular and drug carrier, providing a favorable microenvironment for nerve regeneration. These findings corroborate that this strategy amplifies neuronal expression within the injury milieu, significantly aiding in SCI repair.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"809-827"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Desktop-Stereolithography 3D Printing of a Decellularized Extracellular Matrix/Mesenchymal Stem Cell Exosome Bioink for Vaginal Reconstruction.","authors":"Wenxin Shi, Jiahua Zheng, Jingkun Zhang, Xiaoli Dong, Zhongkang Li, Yanlai Xiao, Qian Li, Xianghua Huang, Yanfang Du","doi":"10.1007/s13770-024-00649-x","DOIUrl":"10.1007/s13770-024-00649-x","url":null,"abstract":"<p><strong>Background: </strong>3D-printing is widely used in regenerative medicine and is expected to achieve vaginal morphological restoration and true functional reconstruction. Mesenchymal stem cells-derived exosomes (MSCs-Exos) were applyed in the regeneration of various tissues. The current study aimed to explore the effctive of MSCs-Exos in vaginal reconstruction.</p><p><strong>Methods: </strong>In this work, hydrogel was designed using decellularized extracellular matrix (dECM) and gelatin methacrylate (GelMA) and silk fibroin (SF). The biological scaffolds were constructed using desktop-stereolithography. The physicochemical properties of the hydrogels were evaluated; Some experiments have been conducted to evaluate exosomes' effect of promotion vaginal reconstruction and to explore the mechanism in this process.</p><p><strong>Results: </strong>It was observed that the sustained release property of exosomes in the hydrogel both in vitro and in vitro.The results revealed that 3D scaffold encapsulating exosomes expressed significant effects on the vascularization and musule regeneration of the regenerative vagina tissue. Also, MSCs-Exos strongly promoted vascularization in the vaginal reconstruction of rats, which may through the PI3K/AKT signaling pathway.</p><p><strong>Conclusion: </strong>The use of exosome-hydrogel composites improved the epithelial regeneration of vaginal tissue, increased angiogenesis, and promoted smooth muscle tissue regeneration. 3D-printed, lumenal scaffold encapsulating exosomes might be used as a cell-free alternative treatment strategy for vaginal reconstruction.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"943-957"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implantation of Culture-Expanded Bone Marrow Derived Mesenchymal Stromal Cells for Treatment of Osteonecrosis of the Femoral Head.","authors":"Seong-Dae Yoon, Bum-Jin Shim, Seung-Hoon Baek, Shin-Yoon Kim","doi":"10.1007/s13770-024-00647-z","DOIUrl":"10.1007/s13770-024-00647-z","url":null,"abstract":"<p><strong>Background: </strong>Although core decompression (CD) with stem cell for the treatment of osteonecrosis of the femoral head (ONFH) showed promising results in many reports, the efficacy remains uncertain. We aimed to evaluate the efficacy of CD with culture-expanded autologous bone marrow-derived mesenchymal stem cell (BM-MSC) implantation in early stage ONFH.</p><p><strong>Methods: </strong>A total of 18 patients (22 hips) with ONFH who underwent CD with culture-expanded BM-MSC implantation from September 2013 to July 2020 were retrospectively reviewed. The median age was 35.0 years [interquartile range (IQR), 28.5-42.0], and the median follow-up period was 4.0 years (IQR, 2.0-5.3). The median number of MSCs was 1.06 × 10⁸. To evaluate radiographic and clinical outcomes, Association Research Circulation Osseous (ARCO) classifications, Japanese Investigation Committee classification, combined necrotic angle (CNA) visual analogue scale (VAS) and Harris Hip Score (HHS) were checked at each follow-up.</p><p><strong>Results: </strong>The preoperative stage of ONFH was ARCO 2 in 14 hips and ARCO 3a in 8 hips. The ARCO staging was maintained in 7 hips in ARCO 2 and 4 hips in ARCO 3a. The radiographic failure rate of ARCO 2 and 3a was 14.3 and 50%, respectively. Furthermore, CNA decreased to more than 20° in 6 hips (four were ARCO 2 and two were ARCO 3a).There was no significant difference in the VAS and HHS (P = 0.052 and P = 0.535, respectively). Total hip arthroplasty was performed in 4 hips.</p><p><strong>Conclusion: </strong>CD with culture-expanded autologous BM-MSCs showed promising results for the treatment of early stage ONFH.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"929-941"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Simplified GBR Treatment and Evaluation of Posterior Seibert Class I Ridge Defects via Bio-collagen and Platelet-Rich Fibrin: A Retrospective Study.","authors":"Zhi Wang, Yafeng Zheng, Jiaqi Xu, Qi Jia, Heng Bo Jiang, Eui-Seok Lee","doi":"10.1007/s13770-024-00654-0","DOIUrl":"10.1007/s13770-024-00654-0","url":null,"abstract":"<p><strong>Background: </strong>Classical guided bone regeneration (GBR) treatments can achieve favorable clinical results for ridge defects. However, extensive bone augmentation in the non-esthetic area in the posterior region for minor ridge defects is unnecessary. Therefore, this study used a collagen and Platelet-rich fibrin (PRF) mixture for bone augmentation on minor posterior ridge defects and evaluated the effects.</p><p><strong>Methods: </strong>22 Seibert Class I ridge defects were treated with BC and covered with a PRF membrane (simplified guided bone regeneration, simplified GBR) and other 22 were treated with Bio-Oss and covered with Bio-Gide (classical GBR). Cone-beam computed tomography imaging was conducted 6 months post-surgery to compare the ridge's horizontal width (HW) and buccal ridge's horizontal width to assess the osteogenic effect. In addition, the buccal ridge contour morphology was studied and classified.</p><p><strong>Results: </strong>The buccal ridge contour of simplified GBR was Type A in 14 cases, Type B in 7 cases, and Type C in 1 case and it of classical GBR was Type A in 11 cases, Type B in 8 cases, and Type C in 3 cases. The mean HW significantly increased by 1.50 mm of simplified GBR treatment, while it increased by 1.83 mm in classical GBR treatment.</p><p><strong>Conclusion: </strong>The combined use of BC and PRF had a significant effect on bone augmentation and this treatment exhibited promising clinical results for correcting posterior Seibert Class I ridge defects. The morphological classification of the reconstructive effect in this study can be utilized in future clinical work.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"959-967"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motion-Accommodating Dual-Layer Hydrogel Dressing to Deliver Adipose-Derived Stem Cells to Wounds.","authors":"Jun Yong Lee, Jie Hyun Kim, Benjamin R Freedman, David J Mooney","doi":"10.1007/s13770-024-00651-3","DOIUrl":"10.1007/s13770-024-00651-3","url":null,"abstract":"<p><strong>Background: </strong>Current dressing materials cannot secure a cell survival-promoting wound environment for stem cell delivery due to insufficient assimilation to skin motion. The authors developed a novel motion-accommodating dual-layer hydrogel dressing for stem cell delivery into such wounds.</p><p><strong>Methods: </strong>Dorsal hand skin movement was evaluated to determine the potential range of deformation for a dressing. The outer hydrogel (OH) was fabricated with an alginate-acrylamide double-network hydrogel with a covalently cross-linked elastomer coat. The tough adhesive consisted of a chitosan-based bridging polymer and coupling reagents. OH material properties and adhesiveness on porcine skin were measured. An oxidized alginate-based inner hydrogel (IH) containing human adipose-derived stem cells (ASCs) was evaluated for cell-supporting and cell-releasing properties. The OH's function as a secondary dressing, and dual-layer hydrogel cell delivery potential in wounds were assessed in a rodent model.</p><p><strong>Results: </strong>The dual-layer hydrogel consisted of OH and IH. The OH target range of deformation was up to 25% strain. The OH adhered to porcine skin, and showed significantly higher adhesion energy than common secondary dressings and endured 900 flexion-extension cycles without detachment. OH showed a similar moisture vapor transmission rate as moisture-retentive dressings. IH maintained embedded cell survival for three days with significant cell release on the contacting surface. OH showed less fibrotic wound healing than other secondary dressings in vivo. The dual-layer hydrogel successfully delivered ASCs into open wounds of nude mice (13 ± 3 cells/HPF).</p><p><strong>Conclusions: </strong>The novel dual-layer hydrogel can accommodate patient movement and deliver ASCs into the wound bed by securing the wound microenvironment.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"843-854"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving Granulosa Cell Function in Premature Ovarian Failure with Umbilical Cord Mesenchymal Stromal Cell Exosome-Derived hsa_circ_0002021.","authors":"Ge Yang, Bo Zhang, Mei Xu, MingJun Wu, Jie Lin, ZiYu Luo, YueHua Chen, Qin Hu, GuoPing Huang, HaiYan Hu","doi":"10.1007/s13770-024-00652-2","DOIUrl":"10.1007/s13770-024-00652-2","url":null,"abstract":"<p><strong>Background: </strong>The therapeutic potential of exosomes from human umbilical cord mesenchymal stem cells (HUMSCs-Exo) for delivering specific circular RNAs (circRNAs) in treating premature ovarian failure (POF) is not well understood. This study aimed to explore the efficacy of HUMSCs-Exo in delivering hsa_circ_0002021 for POF treatment, focusing on its effects on granulosa cell (GC) senescence and ovarian function.</p><p><strong>Methods: </strong>Bioinformatic analysis was conducted on circRNA profiles using the GSE97193 dataset from GEO, targeting granulosa cells from varied age groups. To simulate granulosa cell senescence, KGN cells were treated with cyclophosphamide (CTX). HUMSCs were transfected with pcDNA 3.1 vectors to overexpress hsa_circ_0002021, and the HUMSCs-Exo secreted were isolated. These exosomes were characterized by transmission electron microscopy (TEM) and Western blotting to confirm exosomal markers CD9 and CD63. Co-culture of these exosomes with CTX-treated KGN cells was performed to assess β-galactosidase activity, oxidative stress markers, ROS levels, and apoptosis via flow cytometry. Interaction between hsa_circ_0002021, microRNA-125a-5p (miR-125a-5p), and cyclin-dependent kinase 6 (CDK6) was investigated using dual-luciferase assays and RNA immunoprecipitation (RIP). A POF mouse model was induced with CTX, treated with HUMSCs-Exo, and analyzed histologically and via immunofluorescence staining. Gene expression was quantified using RT-qPCR and Western blot.</p><p><strong>Results: </strong>hsa_circ_0002021 was under expressed in both in vivo and in vitro POF models and was effectively delivered by HUMSCs-Exo to KGN cells, showing a capability to reduce GC senescence. Overexpression of hsa_circ_0002021 in HUMSCs-Exo significantly enhanced these anti-senescence effects. This circRNA acts as a competitive adsorbent of miR-125a-5p, regulating CDK6 expression, which is crucial in modulating cell cycle and apoptosis. Enhanced expression of hsa_circ_0002021 in HUMSCs-Exo ameliorated GC senescence in vitro and improved ovarian function in POF models by modulating oxidative stress and cellular senescence markers.</p><p><strong>Conclusion: </strong>This study confirms that hsa_circ_0002021, when delivered through HUMSCs-Exo, can significantly mitigate GC senescence and restore ovarian function in POF models. These findings provide new insights into the molecular mechanisms of POF and highlight the therapeutic potential of circRNA-enriched exosomes in treating ovarian aging and dysfunction.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"897-914"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose-Derived Mesenchymal Stem Cells and Their Derived Epidermal Progenitor Cells Conditioned Media Ameliorate Skin Aging in Rats.","authors":"Omar I Badr, Aya Anter, Ihab Magdy, Marvellous Chukueggu, Moamen Khorshid, Mohamed Darwish, Mohamed Farrag, Menna Elsayed, Youmna Amr, Yomna Amgad, Tasnim Mahmoud, Mohamed M Kamal","doi":"10.1007/s13770-024-00643-3","DOIUrl":"10.1007/s13770-024-00643-3","url":null,"abstract":"<p><strong>Background: </strong>Skin alterations are among the most prominent signs of aging, and they arise from both intrinsic and extrinsic factors that interact and mutually influence one another. The use of D-galactose as an aging model in animals has been widely employed in anti-aging research. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) are particularly promising for skin anti-aging therapy due to their capacity for effective re-epithelization and secretion of various growth factors essential for skin regeneration. Accordingly, we aimed to examine the potential utility of Ad-MSCs as a therapy for skin anti-aging.</p><p><strong>Methods: </strong>In this study, we isolated and characterized adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of male Sprague Dawley rats. We assessed the in vitro differentiation of Ad-MSCs into epidermal progenitor cells (EPCs) using ascorbic acid and hydrocoritsone. Additionally, we induced skin aging in female Sprague Dawley rats via daily intradermal injection of D-galactose over a period of 8 weeks. Then we evaluated the therapeutic potential of intradermal transplantation of Ad-MSCs and conditioned media (CM) derived from differentiated EPCs in the D-galactose-induced aging rats. Morphological assessments, antioxidant assays, and histopathological examinations were performed to investigate the effects of the treatments.</p><p><strong>Results: </strong>Our findings revealed the significant capability of Ad-MSCs to differentiate into EPCs. Notably, compared to the group that received CM treatment, the Ad-MSCs-treated group exhibited a marked improvement in morphological appearance, antioxidant levels and histological features.</p><p><strong>Conclusions: </strong>These results underscore the effectiveness of Ad-MSCs in restoring skin aging as a potential therapy for skin aging.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"915-927"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Gold-Enhanced Titania: Boosting Cell Proliferation and Combating Bacterial Infestation.","authors":"Touseef Amna, M Shamshi Hassan, Jari S Algethami, Alya Aljuaid, Anas Alfarsi, Rasha Alnefaie, Faheem A Sheikh, Myung-Seob Khil","doi":"10.1007/s13770-024-00630-8","DOIUrl":"10.1007/s13770-024-00630-8","url":null,"abstract":"<p><strong>Background: </strong>In this study an approach was made to efficaciously synthesize gold enhanced titania nanorods by electrospinning. This study aims to address effects of gold enhanced titania nanorods on muscle precursor cells. Additionally, implant related microbial infections are prime cause of various disastrous diseases. So, there is predictable demand for synthesis of novel materials with multifunctional adaptability.</p><p><strong>Methods: </strong>Herein, gold nanoparticles were attached on titania nanorods and described using many sophisticated procedures such as XRD, SEM, EDX and TEM. Antimicrobial studies were probed against Gram-negative Escherichia coli. C2C12 cell lines were exposed to various doses of as-prepared gold enhanced titania nanorods in order to test in vitro cytotoxicity and proliferation. Cell sustainability was assessed through Cell Counting Kit-8 assay at regular intervals. A phase-contrast microscope was used to examine morphology of exposed C2C12 cells and confocal laser scanning microscope was used to quantify cell viability.</p><p><strong>Results: </strong>The findings indicate that titania nanorods enhanced with gold exhibit superior antimicrobial efficacy compared to pure titania. Furthermore, newly synthesized gold-enhanced titania nanorods illustrate that cell viability follows a time and concentration dependent pattern.</p><p><strong>Conclusion: </strong>Consequently, our study provides optimistic findings indicating that titania nanorods adorned with gold hold significant potential as foundational resource for developing forthcoming antimicrobial materials, suitable for applications both in medical and biomedical fields. This work also demonstrates that in addition to being extremely biocompatible, titania nanorods with gold embellishments may be used in a range of tissue engineering applications in very near future.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"711-721"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety Evaluation of Tacrolimus-Eluting Stent in a Porcine Coronary Artery Model.","authors":"Dae Sung Park, Mi Hyang Na, Myung Ho Jeong, Doo Sun Sim, Yu Jeong Jin, Hae Jin Kee, Mun Ki Kim, Jeong Ha Kim, Young Joon Hong, Kyung Hoon Cho, Dae Young Hyun, Seok Oh, Kyung Seob Lim, Dae-Heung Byeon, Jeong Hun Kim","doi":"10.1007/s13770-024-00646-0","DOIUrl":"10.1007/s13770-024-00646-0","url":null,"abstract":"<p><strong>Background: </strong>A drug-eluting stent (DES) is a highly beneficial medical device used to widen or unblock narrowed blood vessels. However, the drugs released by the implantation of DES may hinder the re-endothelialization process, increasing the risk of late thrombosis. We have developed a tacrolimus-eluting stent (TES) that as acts as a potent antiproliferative and immunosuppressive agent, enhancing endothelial regeneration. In addition, we assessed the safety and efficacy of TES through both in vitro and in vivo tests.</p><p><strong>Methods: </strong>Tacrolimus and Poly(lactic-co-glycolic acid) (PLGA) were applied to the metal stent using electrospinning equipment. The surface morphology of the stent was examined before and after coating using a scanning electron microscope (SEM) and energy dispersive X-rays (EDX). The drug release test was conducted through high-performance liquid chromatography (HPLC). Cell proliferation and migration assays were performed using smooth muscle cells (SMC). The stent was then inserted into the porcine coronary artery and monitored for a duration of 4 weeks.</p><p><strong>Results: </strong>SEM analysis confirmed that the coating surface was uniform. Furthermore, EDX analysis showed that the surface was coated with both polymer and drug components. The HPCL analysis of TCL at a wavelength of 215 nm revealed that the drug was continuously released over a period of 4 weeks. Smooth muscle cell migration was significantly decreased in the tacrolimus group (54.1% ± 11.90%) compared to the non-treated group (90.1% ± 4.86%). In animal experiments, the stenosis rate was significantly reduced in the TES group (29.6% ± 7.93%) compared to the bare metal stent group (41.3% ± 10.18%). Additionally, the fibrin score was found to be lower in the TES group compared to the group treated with a sirolimus-eluting stent (SES).</p><p><strong>Conclusion: </strong>Similar to SES, TES reduces neointimal proliferation in a porcine coronary artery model, specifically decreasing the fibrins score. Therefore, tacrolimus could be considered a promising drug for reducing restenosis and thrombosis.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"723-735"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LGR5 Modulates Differentiated Phenotypes of Chondrocytes Through PI3K/AKT Signaling Pathway.","authors":"Xu Wu, Yaoyao Fu, Jing Ma, Chenlong Li, Aijuan He, Tianyu Zhang","doi":"10.1007/s13770-024-00645-1","DOIUrl":"10.1007/s13770-024-00645-1","url":null,"abstract":"<p><strong>Background: </strong>Tissue engineering is increasingly viewed as a promising avenue for functional cartilage reconstruction. However, chondrocyte dedifferentiation during in vitro culture remains an obstacle for clinical translation of tissue engineered cartilage. Re-differentiated induction have been employed to induce dedifferentiated chondrocytes back to their original phenotype. Regrettably, these strategies have been proven to be only moderately effective.</p><p><strong>Methods: </strong>To explore underlying mechanism, RNA transcriptome sequencing was conducted on primary chondrocytes (P0), dedifferentiated chondrocytes (P5), and redifferentiated chondrocytes (redifferentiation-induction of P5, P5.R). Based on multiple bioinformatics analysis, LGR5 was identified as a target gene. Subsequently, stable cell lines with LGR5 knocking-down and overexpression were established using P0 chondrocytes. The phenotypic changes in P1 and P5 chondrocytes with either LGR5 knockdown or overexpression were assessed to ascertain the potential influence of LGR5 dysregulation on chondrocyte phenotypes. Regulatory mechanism was then investigated using bioinformatic analysis, protein-protein docking, immunofluorescence co-localization and immunoprecipitation.</p><p><strong>Results: </strong>The current study found that dysregulation of LGR5 can significantly impact the dedifferentiated phenotypes of chondrocytes (P5). Upregulation of LGR5 appears to activate the PI3K/AKT signal via increasing the phosphorylation levels of AKT (p-AKT1). Moreover, the increase of p-AKT1 may stabilize β-catenin and enhance the intensity of Wnt/β-catenin signal, and help to restore the dedifferentated phenotype of chondrocytes.</p><p><strong>Conclusion: </strong>LGR5 can modulate the phenotypes of chondrocytes in P5 passage through PI3K/AKT signaling pathway.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"791-807"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}