{"title":"Exosomes-Shuttled lncRNA SNHG7 by Bone Marrow Mesenchymal Stem Cells Alleviates Osteoarthritis Through Targeting miR-485-5p/FSP1 Axis-Mediated Chondrocytes Ferroptosis and Inflammation.","authors":"Yue Wang, Kaili Hu, Changdi Liao, Ting Han, Fenglin Jiang, Zixin Gao, Jinhua Yan","doi":"10.1007/s13770-024-00668-8","DOIUrl":"10.1007/s13770-024-00668-8","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown.</p><p><strong>Methods: </strong>OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1β to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-α and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p.</p><p><strong>Results: </strong>The expressions of SNHG7 and FSP1 were both reduced in IL-1β-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCs-derived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCs-Exos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1β-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7.</p><p><strong>Conclusions: </strong>Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1β-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1203-1216"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372946","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}
Lu Fan, Ying Zhang, Xiankun Yin, Silu Chen, Pin Wu, Tianru Huyan, Ziyang Wang, Qun Ma, Hua Zhang, Wenhui Wang, Chunyan Gu, Lu Tie, Long Zhang
{"title":"The Effect of Platelet Fibrin Plasma (PFP) on Postoperative Refractory Wounds: Physiologically Concentrated Platelet Plasma in Wound Repair.","authors":"Lu Fan, Ying Zhang, Xiankun Yin, Silu Chen, Pin Wu, Tianru Huyan, Ziyang Wang, Qun Ma, Hua Zhang, Wenhui Wang, Chunyan Gu, Lu Tie, Long Zhang","doi":"10.1007/s13770-024-00665-x","DOIUrl":"10.1007/s13770-024-00665-x","url":null,"abstract":"<p><strong>Objective: </strong>Surgical wounds that can't complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing.</p><p><strong>Approach: </strong>The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function.</p><p><strong>Results: </strong>PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate > 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells.</p><p><strong>Innovation: </strong>Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds.</p><p><strong>Conclusion: </strong>Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1255-1267"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475492","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}
Delger Bayarsaikhan, Govigerel Bayarsaikhan, Hyun A Kang, Su Bin Lee, So Hee Han, Teruo Okano, Kyungsook Kim, Bonghee Lee
{"title":"A Study on iPSC-Associated Factors in the Generation of Hepatocytes.","authors":"Delger Bayarsaikhan, Govigerel Bayarsaikhan, Hyun A Kang, Su Bin Lee, So Hee Han, Teruo Okano, Kyungsook Kim, Bonghee Lee","doi":"10.1007/s13770-024-00674-w","DOIUrl":"10.1007/s13770-024-00674-w","url":null,"abstract":"<p><strong>Background: </strong>Hepatocytes are an attractive cell source in hepatic tissue engineering because they are the primary cells of the liver, maintaining liver homeostasis through their intrinsic function. Due to the increasing demand for liver donors, a wide range of methods are being studied to obtain functionally active hepatocytes. iPSCs are one of the alternative cell sources, which shows great promise as a tool for generating hepatocytes.</p><p><strong>Methods: </strong>This study determined whether factors associated with iPSCs contributed to variation in hepatocyte-like cells derived from iPSCs. The factors of concern for the iPSCs included the culture system, the source of iPSCs, and cell seeding density for initiating the differentiation.</p><p><strong>Results: </strong>Our results found iPSC-dependent variances among differentiated hepatocyte-like cells. The matrix used in culturing iPSCs significantly impacts cell morphologies, characteristics, and the expression of pluripotent genes, such as OCT4 and SOX2, varied in iPSCs derived from different sources. These characteristics, in turn, play a consequential role in determining the functional activity of the iPSC-derived hepatocyte-like cells. In addition, cell seeding density was observed to be an essential factor for the efficient generation of iPSC-derived hepatocyte-like cells, with 2- 4 × 10 cells/cm of seeding density resulting in good morphology and functionality.</p><p><strong>Conclusion: </strong>This study provides the baseline of effective differentiation protocols for iPSC-derived hepatocyte-like cells with the appropriate conditions, including cell culture media, iPSC source, and the seeding density of iPSCs.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1245-1254"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567926","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}
James R Henstock, Joshua C F A Price, Alicia J El Haj
{"title":"Determining Which Hydrostatic Pressure Regimes Promote Osteogenesis in Human Mesenchymal Stem Cells.","authors":"James R Henstock, Joshua C F A Price, Alicia J El Haj","doi":"10.1007/s13770-024-00666-w","DOIUrl":"10.1007/s13770-024-00666-w","url":null,"abstract":"<p><strong>Background: </strong>Compressive loading of bone causes hydrostatic pressure changes which have been proposed as an osteogenic differentiation stimulus for mesenchymal stem cells (hMSCs). We hypothesised that hMSCs are adapted to differentiate only in response to cyclic hydrostatic pressures above critical thresholds of magnitude and frequency which correspond to physiological levels of anabolic bone loading.</p><p><strong>Methods: </strong>Using a pneumatic-hydrostatic bioreactor, we applied hydrostatic pressure regimes to human hMSCs in 3D collagen hydrogel cultures for 1 h/day over 28 days to determine which levels of pressure and frequency stimulated osteogenesis in vitro.</p><p><strong>Results: </strong>Stimulation of the 3D cultures with 0-280 kPa cyclic hydrostatic pressure at 1 Hz resulted in up to 75% mineralisation in the hydrogel (without exogenous growth factors), whilst static culture or variations of the regime with either constant high pressure (280 kPa, 0 Hz), low-frequency (0.05 Hz, 280 kPa) or low-magnitude (70 kPa, 1 Hz) stimulation had no osteogenic effects (< 2% mineralisation). Nuclear translocation of YAP was observed following cyclic hydrostatic pressure in mature MLO-A5 osteoblasts but not in hMSCs, suggesting that cyclic hydrostatic pressure activates different mechanotransduction pathways in undifferentiated stem cells and committed osteoblasts.</p><p><strong>Conclusions: </strong>Hydrostatic pressure is a potent stimulus for differentiating MSC into highly active osteoblasts and may therefore be a versatile tool for translational cell engineering. We have demonstrated that there are minimum levels of force and frequency needed to trigger osteogenesis, i.e. a pressure 'switch', which corresponds to the physiological forces experienced by cells in their native mesenchymal niche. The mechanotransduction mechanisms underpinning these effects are the subject of further study.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1141-1151"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073933","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":"Macrophage Polarization: A Novel Target and Strategy for Pathological Scarring.","authors":"Xinyi Wang, Dewu Liu","doi":"10.1007/s13770-024-00669-7","DOIUrl":"10.1007/s13770-024-00669-7","url":null,"abstract":"<p><strong>Background: </strong>Abnormal scarring imposes considerable challenges and burdens on the lives of patients and healthcare system. Macrophages at the wound site are found to be of great concern to overall wound healing. There have been many studies indicating an inextricably link between dysfunctional macrophages and fibrotic scars. Macrophages are not only related to pathogen destruction and phagocytosis of apoptotic cells, but also involved in angiogenesis, keratinization and collagen deposition. These abundant cell functions are attributed to specific heterogeneity and plasticity of macrophages, which also add an extra layer of complexity to correlational researches.</p><p><strong>Methods: </strong>This article summarizes current understanding of macrophage polarization in scar formation and several prevention and treatment strategies on pathological scarring related to regulation of macrophage behaviors by utilizing databases such as PubMed, Google Scholar and so on.</p><p><strong>Results: </strong>There are many studies proving that macrophages participate in the course of wound healing by converting their predominant phenotype. The potential of macrophages in managing hypertrophic scars and keloid lesions have been underscored.</p><p><strong>Conclusion: </strong>Macrophage polarization offers new prevention strategies for pathological scarring. Learning about and targeting at macrophages may be helpful in achieving optimum wound healing.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1109-1124"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354415","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":"Potential Use of Organoids in Regenerative Medicine.","authors":"Wahyunia L Septiana, Jeanne A Pawitan","doi":"10.1007/s13770-024-00672-y","DOIUrl":"10.1007/s13770-024-00672-y","url":null,"abstract":"<p><strong>Background: </strong>In vitro cell culture is crucial for studying human diseases and development. Compared to traditional monolayer cultures, 3D culturing with organoids offers significant advantages by more accurately replicating natural tissues' structural and functional features. This advancement enhances disease modeling, drug testing, and regenerative medicine applications. Organoids, derived from stem cells, mimic tissue physiology in a more relevant manner. Despite their promise, the clinical use of regenerative medicine currently needs to be improved by reproducibility, scalability, and maturation issues.</p><p><strong>Methods: </strong>This article overviews recent organoid research, focusing on their types, sources, 3D culturing methods, and applications in regenerative medicine. A literature review of \"organoid\" and \"regenerative medicine\" in PubMed/MEDLINE highlighted relevant studies published over the past decade, emphasizing human-sourced organoids and their regenerative benefits, as well as the availability of free full-text articles. The review uses descriptive data, including tables and text, to illustrate the challenges and potential of organoids in regenerative medicine.</p><p><strong>Results: </strong>The transition from 2D to 3D models, particularly organoids, has significantly advanced in vitro research. This review covers a decade of progress in various organoid types-such as liver, cholangiocyte, intestinal, pancreatic, cardiac, brain, thymus, and mammary organoids-and their 3D culture methods and applications. It addresses critical issues of maturity, scalability, and reproducibility and underscores the need for standardization and improved production techniques to facilitate broader clinical applications in regenerative medicine.</p><p><strong>Conclusions: </strong>Successful therapy requires increased scalability and standardization. Organoids have enormous potential in biological research, notwithstanding obstacles.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1125-1139"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475491","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":"Preparation and Evaluation of Poloxamer/Carbopol In-Situ Gel Loaded with Quercetin: In-Vitro Drug Release and Cell Viability Study.","authors":"Pinxuan Zheng, Xueying Liu, Yanqing Jiao, Xuran Mao, Zhaorong Zong, Qi Jia, Heng Bo Jiang, Eui-Seok Lee, Qi Chen","doi":"10.1007/s13770-024-00671-z","DOIUrl":"10.1007/s13770-024-00671-z","url":null,"abstract":"<p><strong>Background: </strong>Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system.</p><p><strong>Methods: </strong>In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 μmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X<sub>1</sub>: poloxamer 407 and X<sub>2</sub>: carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables.</p><p><strong>Results: </strong>These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect.</p><p><strong>Conclusions: </strong>The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1153-1171"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565231","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}
Nicole Gorbenko, John C Vaccaro, Ryan Fagan, Robert A Cerro, Jonah M Khorrami, Lucia Galindo, Nick Merna
{"title":"Perfusion Bioreactor Conditioning of Small-diameter Plant-based Vascular Grafts.","authors":"Nicole Gorbenko, John C Vaccaro, Ryan Fagan, Robert A Cerro, Jonah M Khorrami, Lucia Galindo, Nick Merna","doi":"10.1007/s13770-024-00670-0","DOIUrl":"10.1007/s13770-024-00670-0","url":null,"abstract":"<p><strong>Background: </strong>Vascular grafts are mainly composed of synthetic materials, but are prone to thrombosis and intimal hyperplasia at small diameters. Decellularized plant scaffolds have emerged that provide promising alternatives for tissue engineering. We previously developed robust, endothelialized small-diameter vessels from decellularized leatherleaf viburnum. This is the first study to precondition and analyze plant-based vessels under physiological fluid flow and pressure waveforms. Using decellularized leatherleaf viburnum as tissue-engineered grafts for implantation can have profound impacts on healthcare due to their biocompatibility and cost-effective production.</p><p><strong>Methods: </strong>A novel perfusion bioreactor was designed, capable of accurately controlling fluid flow rate and pressure waveforms for preconditioning of small-diameter vascular grafts. A closed-loop system controlled pressure waveforms, mimicking physiological values of 50-120 mmHg at a frequency of 8.75 Hz for fluid flow reaching 5 mL/min. Plant-based vascular grafts were recellularized with endothelial and vascular smooth muscle cells and cultured for up to 3 weeks in this bioreactor. Cell density, scaffold structure and mechanics, thrombogenicity, and immunogenicity of grafts were evaluated.</p><p><strong>Results: </strong>Bioreactor treatment with fluid flow significantly increased luminal endothelial cell density, while pressure waveforms reduced thrombus formation and maintained viable vascular smooth muscle cells within inner layers of grafts compared to static controls. Suture retention of grafts met transplantation standards and white cell viability was suitable for vascular remodeling.</p><p><strong>Conclusion: </strong>Low thrombogenicity of endothelialized leatherleaf viburnum holds great potential for vascular repair. This study provides insight into benefits of conditioning plant-based materials with hemodynamic forces at higher frequencies that have not previously been investigated.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1189-1201"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362136","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}
Travis Nguyen, Gokhan Gundogdu, Christina Bottini, Ambika K Chaudhuri, Joshua R Mauney
{"title":"Evaluation of Bi-layer Silk Fibroin Grafts for Inlay Vaginoplasty in a Rat Model.","authors":"Travis Nguyen, Gokhan Gundogdu, Christina Bottini, Ambika K Chaudhuri, Joshua R Mauney","doi":"10.1007/s13770-024-00653-1","DOIUrl":"10.1007/s13770-024-00653-1","url":null,"abstract":"<p><strong>Background: </strong>Autologous tissues derived from bowel, buccal mucosa and skin are primarily used to repair or replace diseased vaginal segments as well as create neovaginas for male-to-female transgenders. These grafts are often limited by scarce tissue supply, donor site morbidity and post-operative complications. Bi-layer silk fibroin (BLSF) biomaterials represent potential alternatives for vaginoplasty given their structural strength and elasticity, low immunogenicity, and processing flexibility. The goals of the current study were to assess the potential of acellular BLSF scaffolds for vaginal tissue regeneration in respect to conventional small intestinal submucosal (SIS) matrices in a rat model of vaginoplasty.</p><p><strong>Methods: </strong>Inlay vaginoplasty was performed with BLSF and SIS scaffolds (N = 21 per graft) in adult female rats for up to 2 months of implantation. Nonsurgical controls (N = 4) were investigated in parallel. Outcome analyses included histologic, immunohistochemical and histomorphometric evaluations of wound healing patterns; µ-computed tomography (CT) of vaginal continuity; and breeding assessments.</p><p><strong>Results: </strong>Animals in both scaffold cohorts exhibited 100% survival rates with no severe post-operative complications. At 2 months post-op, µ-CT analysis revealed normal vaginal anatomy and continuity in both graft groups similar to controls. In parallel, BLSF and SIS grafts also induced comparable constructive remodeling patterns and were histologically equivalent in their ability to support formation of vascularized vaginal neotissues with native tissue architecture, however with significantly less smooth muscle content. Vaginal tissues reconstructed with both implants were capable of supporting copulation, pregnancy and similar amounts of live births.</p><p><strong>Conclusions: </strong>BLSF biomaterials represent potential \"off-the-shelf\" candidates for vaginoplasty.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"985-994"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184646","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}
Shin Hyun Kim, Jung Min Oh, Hyun Roh, Kee-Won Lee, Ju Hee Lee, Won Jai Lee
{"title":"Zinc-Alpha-2-Glycoprotein Peptide Downregulates Type I and III Collagen Expression via Suppression of TGF-β and p-Smad 2/3 Pathway in Keloid Fibroblasts and Rat Incisional Model.","authors":"Shin Hyun Kim, Jung Min Oh, Hyun Roh, Kee-Won Lee, Ju Hee Lee, Won Jai Lee","doi":"10.1007/s13770-024-00664-y","DOIUrl":"10.1007/s13770-024-00664-y","url":null,"abstract":"<p><strong>Background: </strong>Keloids and hypertrophic scars result from abnormal collagen accumulation and the inhibition of its degradation. Although the pathogenesis remains unclear, excessive accumulation of the extracellular matrix (ECM) is believed to be associated with the TGF-β/SMAD pathway. Zinc-alpha-2-glycoprotein (ZAG) inhibits TGF-β-mediated epithelial-to-mesenchymal transdifferentiation and impacts skin barrier functions. In this study, we investigated the potential of a small ZAG-derived peptide against hypertrophic scars and keloids.</p><p><strong>Methods: </strong>The study examined cell proliferation and mRNA expression of collagen types I and III in human dermal fibroblast (HDF) cell lines and keloid-derived fibroblasts (KF) following ZAG peptide treatment. A rat incisional wound model was used to evaluate the effect of ZAG peptide in scar tissue.</p><p><strong>Results: </strong>Significantly lower mRNA levels of collagen types I and III were observed in ZAG-treated fibroblasts, whereas matrix metalloproteinase (MMP)-1 and MMP-3 mRNA levels were significantly increased in HDFs and KFs. Furthermore, ZAG peptide significantly reduced protein expression of collagen type I and III, TGF-β1, and p-Smad2/3 complex in KFs. Rat incisional scar models treated with ZAG peptide presented narrower scar areas and reduced immature collagen deposition, along with decreased expression of collagen type I, α-SMA, and p-Smad2/3.</p><p><strong>Conclusion: </strong>ZAG peptide effectively suppresses the TGF-β and p-Smad2/3 pathway and inhibits excessive cell proliferation during scar formation, suggesting its potential therapeutic implications against keloids and hypertrophic scars.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1079-1092"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894375","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}