Tissue engineering and regenerative medicine最新文献

{"title":"Exosomes Secreted During Myogenic Differentiation of Human Fetal Cartilage-Derived Progenitor Cells Promote Skeletal Muscle Regeneration through miR-145-5p.","authors":"Dong Il Shin, Yong Jun Jin, Sujin Noh, Hee-Woong Yun, Do Young Park, Byoung-Hyun Min","doi":"10.1007/s13770-023-00618-w","DOIUrl":"10.1007/s13770-023-00618-w","url":null,"abstract":"<p><strong>Background: </strong>Currently, there is no apparent treatment for sarcopenia, which is characterized by diminished myoblast function. We aimed to manufacture exosomes that retain the myogenic differentiation capacity of human fetal cartilage-derived progenitor cells (hFCPCs) and investigate their muscle regenerative efficacy in myoblasts and a sarcopenia rat model.</p><p><strong>Methods: </strong>The muscle regeneration potential of exosomes (F-Exo) secreted during myogenic differentiation of hFCPCs was compared to human bone marrow mesenchymal stem cells-derived (hBMSCs) exosomes (B-Exo) in myoblasts and sarcopenia rat model. The effect of F-Exo was analyzed through known microRNAs (miRNAs) analysis. The mechanism of action of F-Exo was confirmed by measuring the expression of proteins involved in the Wnt signaling pathway.</p><p><strong>Results: </strong>F-Exo and B-Exo showed similar exosome characteristics. However, F-Exo induced the expression of muscle markers (MyoD, MyoG, and MyHC) and myotube formation in myoblasts more effectively than B-Exo. Moreover, F-Exo induced greater increases in muscle fiber cross-sectional area and muscle mass compared to B-Exo in a sarcopenia rat. The miR-145-5p, relevant to muscle regeneration, was found in high concentrations in the F-Exo, and RNase pretreatment reduced the efficacy of exosomes. The effects of F-Exo on the expression of myogenic markers in myoblasts were paralleled by the miR-145-5p mimics, while the inhibitor partially negated this effect. F-Exo was involved in the Wnt signaling pathway by enhancing the expression of Wnt5a and β-catenin.</p><p><strong>Conclusion: </strong>F-Exo improved muscle regeneration by activating the Wnt signaling pathway via abundant miR-145-5p, mimicking the remarkable myogenic differentiation potential of hFCPCs.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"487-497"},"PeriodicalIF":4.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642996","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":"Effect of Gelatin Content on Degradation Behavior of PLLA/Gelatin Hybrid Membranes","authors":"Yunyoung Jang, Juwoong Jang, Bae-Yeon Kim, Yo-Seung Song, Deuk Yong Lee","doi":"10.1007/s13770-024-00626-4","DOIUrl":"https://doi.org/10.1007/s13770-024-00626-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background:</h3><p>Poly(L-lactic acid) (PLLA) is a biodegradable polymer (BP) that replaces conventional petroleum-based polymers. The hydrophobicity of biodegradable PLLA periodontal barrier membrane in wet state can be solved by alloying it with natural polymers. Alloying PLLA with gelatin imparts wet mechanical properties, hydrophilicity, shrinkage, degradability and biocompatibility to the polymeric matrix.</p><h3 data-test=\"abstract-sub-heading\">Methods:</h3><p>To investigate membrane performance in the wet state, PLLA/gelatin membranes were synthesized by varying the gelatin concentration from 0 to 80 wt%. The membrane was prepared by electrospinning.</p><h3 data-test=\"abstract-sub-heading\">Results:</h3><p>At the macroscopic scale, PLLA containing gelatin can tune the wet mechanical properties, hydrophilicity, water uptake capacity (WUC), degradability and biocompatibility of PLLA/gelatin membranes. As the gelatin content increased from 0 to 80 wt%, the dry tensile strength of the membranes increased from 6.4 to 38.9 MPa and the dry strain at break decreased from 1.7 to 0.19. PLLA/gelatin membranes with a gelatin content exceeding 40% showed excellent biocompatibility and hydrophilicity. However, dimensional change (37.5% after 7 days of soaking), poor tensile stress in wet state (3.48 MPa) and rapid degradation rate (73.7%) were observed. The highest WUC, hydrophilicity, porosity, suitable mechanical properties and biocompatibility were observed for the PLLA/40% gelatin membrane.</p><h3 data-test=\"abstract-sub-heading\">Conclusion:</h3><p>PLLA/gelatin membranes with gelatin content less than 40% are suitable as barrier membranes for absorbable periodontal tissue regeneration due to their tunable wet mechanical properties, degradability, biocompatibility and lack of dimensional changes.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":"110 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140125800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signal Transducer and Activator of Transcription 4-Induced Up-Regulated LINC01278 Enhances Proliferation and Invasion of Non-Small Cell Lung Cancer Cells via the MicroRNA-877-5p/Activating Transcription Factor 4 Axis","authors":"LinZhu Yang, Yi Xiao, ShouJun Deng, DaiLing Yan, ZhenHua Li, Ying Wang, ChangCheng Lei","doi":"10.1007/s13770-024-00625-5","DOIUrl":"https://doi.org/10.1007/s13770-024-00625-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background:</h3><p>The purpose of this study was to investigate the specific effects of signal transducer and activator of transcription 4 (STAT4)-induced long intergenic nonprotein coding RNA 1278 (LINC01278) on the growth of non-small cell lung cancer (NSCLC) cells involved in the microRNA (miR)-877-5p/activated transcription factor 4 (ATF4) axis.</p><h3 data-test=\"abstract-sub-heading\">Methods:</h3><p>NSCLC tumor tissue and adjacent normal tissue were collected. Human normal lung epithelial cell BEAS-2B and human NSCLC cell lines (H1299, H1975, A549, H2228) were collected. The expression levels of STAT4, LINC01278, miR-877-5p, and ATF4 were detected. A549 cells were screened for subsequent experiments. The proliferation ability of cells was detected by colony formation experiment. Cell apoptosis was tested by flow cytometry. Scratch test and transwell assay were used to detect the migration and invasion ability of cells. Biological function of LINC01278 in NSCLC was confirmed by xenograft experiments.</p><h3 data-test=\"abstract-sub-heading\">Results:</h3><p>Low expression miR-877-5p and high expression of STAT4, LINC01278 and ATF4 were detected in NSCLC. Silenced LINC01278 in A549 cell depressed cell proliferation, migration and invasion, but facilitated cell apoptosis. LINC01278 was positively correlated with STAT4 and could directly bind to miR-877-5p. Upregulating miR-877-5p suppressed NSCLC cell progression, while downregulating miR-877-5p had the opposite effect. Upregulating miR-877-5p abrogated the effects of silenced LINC01278 on NSCLC cell progression. MiR-877-5p targeted ATF4. ATF4 upregulation could partly restore the carcinogenic effect of LINC01278 <i>in vitro</i> and <i>in vivo</i>.</p><h3 data-test=\"abstract-sub-heading\">Conclusion:</h3><p>Our data supports that STAT4-induced upregulation of LINC01278 promotes NSCLC progression by modulating the miR-877-5p/ATF4 axis, suggesting a novel direction for NSCLC treatment.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":"27 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140098695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Cocktail Factor Approach to Generate Salivary Gland Progenitors through Co-Culture Techniques","authors":"Yifei Zhang, Shuang Yan, Zi Mei, He Zhang, Chong Ding, Siqi Zhang, Shicheng Wei","doi":"10.1007/s13770-024-00632-6","DOIUrl":"https://doi.org/10.1007/s13770-024-00632-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background:</h3><p>The derivation of salivary gland (SG) progenitors from pluripotent stem cells (PSCs) presents significant potential for developmental biology and regenerative medicine. However, the existing protocols for inducing SG include limited factors, making it challenging to mimic the <i>in vivo</i> microenvironment of embryonic SGs.</p><h3 data-test=\"abstract-sub-heading\">Methods:</h3><p>We reported a cocktail factor approach to promote the differentiation of mouse embryonic stem cell (mESC)-derived oral epithelium (OE) into SG progenitors through a three-dimensional co-culture method. Upon confirming that the embryonic SG can promote the differentiation of mESC-derived OE, we performed RNA sequence analysis to identify factors involved in the differentiation of SG progenitors.</p><h3 data-test=\"abstract-sub-heading\">Results:</h3><p>Our findings highlight several efficient pathways related to SG development, with frequent appearances of four factors: IFN-γ, TGF-β2, EGF, and IGF-1. The combined treatment using these cocktail factors increased the expression of key SG progenitor markers, including Sox9, Sox10, Krt5, and Krt14. However, absence of any one of these cocktail factors did not facilitate differentiation. Notably, aggregates treated with the cocktail factor formed SG epithelial-like structures and pre-bud-like structures on the surface.</p><h3 data-test=\"abstract-sub-heading\">Conclusion:</h3><p>In conclusion, this study offers a novel approach to developing a differentiation protocol that closely mimics the <i>in vivo</i> microenvironment of embryonic SGs. This provides a foundation for generating PSC-derived organoids with near-physiological cell behaviors and structures.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":"42 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140098585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Gal Nanoparticles in CNS Trauma: II. Immunomodulation Following Spinal Cord Injury (SCI) Improves Functional Outcomes","authors":"Bhavani Gopalakrishnan, Uri Galili, Megan Saenger, Noah J. Burket, Wendy Koss, Manjari S. Lokender, Kaitlyn M. Wolfe, Samantha J. Husak, Collin J. Stark, Luis Solorio, Abigail Cox, August Dunbar, Riyi Shi, Jianming Li","doi":"10.1007/s13770-023-00616-y","DOIUrl":"https://doi.org/10.1007/s13770-023-00616-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">BACKGROUND:</h3><p>Previous investigations have shown that local application of nanoparticles presenting the carbohydrate moiety galactose-α-1,3-galactose (α-gal epitopes) enhance wound healing by activating the complement system and recruiting pro-healing macrophages to the injury site. Our companion <i>in vitro</i> paper suggest α-gal epitopes can similarly recruit and polarize human microglia toward a pro-healing phenotype. In this continuation study, we investigate the <i>in vivo</i> implications of α-gal nanoparticle administration directly to the injured spinal cord.</p><h3 data-test=\"abstract-sub-heading\">METHODS:</h3><p>α-Gal knock-out (KO) mice subjected to spinal cord crush were injected either with saline (control) or with α-gal nanoparticles immediately following injury. Animals were assessed longitudinally with neurobehavioral and histological endpoints.</p><h3 data-test=\"abstract-sub-heading\">RESULTS:</h3><p>Mice injected with α-gal nanoparticles showed increased recruitment of anti-inflammatory macrophages to the injection site in conjunction with increased production of anti-inflammatory markers and a reduction in apoptosis. Further, the treated group showed increased axonal infiltration into the lesion, a reduction in reactive astrocyte populations and increased angiogenesis. These results translated into improved sensorimotor metrics versus the control group.</p><h3 data-test=\"abstract-sub-heading\">CONCLUSIONS:</h3><p>Application of α-gal nanoparticles after spinal cord injury (SCI) induces a pro-healing inflammatory response resulting in neuroprotection, improved axonal ingrowth into the lesion and enhanced sensorimotor recovery. The data shows α-gal nanoparticles may be a promising avenue for further study in CNS trauma.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3><p>Putative mechanism of therapeutic action by α-gal nanoparticles. <b>A.</b> Nanoparticles injected into the injured cord bind to anti-Gal antibodies leaked from ruptured capillaries. The binding of anti-Gal to α-gal epitopes on the α-gal nanoparticles activates the complement system to release complement cleavage chemotactic peptides such as C5a, C3a that recruit macrophages and microglia. These recruited cells bind to the anti-Gal coated α-gal nanoparticles and are further polarized into the M2 state. <b>B.</b> Recruited M2 macrophages and microglia secrete neuroprotective and pro-healing factors to promote tissue repair, neovascularization and axonal regeneration (<b>C.</b>).</p>\u0000","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":"1 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atelocollagen Scaffold Enhances Cartilage Regeneration in Osteochondral Defects: A Study in Rabbits.","authors":"Ji-Chul Yoo, Man Soo Kim, Sueen Sohn, Sang Hun Woo, Yu Ri Choi, Andrew S Kwak, Dong Shin Lee","doi":"10.1007/s13770-023-00589-y","DOIUrl":"10.1007/s13770-023-00589-y","url":null,"abstract":"<p><strong>Background: </strong>To enhance articular cartilage healing, microfractures (Mfx) and bone marrow aspirate concentrate (BMAC) are commonly used, and some form of scaffold is often used together to increase its efficacy. Herein, we compared the efficacy of atelocollagen scaffold to that of collagen scaffold when used with Mfx or BMAC on osteochondral defect of animal.</p><p><strong>Methods: </strong>This experiment was designed in two stages, and therapeutic effects of Mfx and BMAC were respectively evaluated when used with atelocollagen or collagen scaffold. Femoral condyle defects were artificially created in male New Zealand White rabbits, and in each stage, 12 rabbits were randomly allocated into three treatment groups: test group with additional atelocollagen scaffold, the positive control group with collagen scaffold, and the negative control group. Then, for 12 weeks, macroscopic and histological evaluations were performed.</p><p><strong>Results: </strong>At 12 weeks, defects in the test group were fully regenerated with normal cartilage-like tissue, and were well integrated with the surrounding cartilage at both stages experiment, whereas defects in the control groups were not fully filled with regenerated tissue, and the tissue appeared as fibrous tissue. Histologically, the regenerated tissue in the test group showed a statistically significant improvement compared to the positive and negative control groups, achieving a similar structure as normal articular cartilage.</p><p><strong>Conclusion: </strong>The results showed that implantation of the atelocollagen scaffold enhanced cartilage regeneration following osteochondral defects in rabbits. This suggests that the atelocollagen scaffold can be used with Mfx or BMAC for effective regeneration of osteochondral defects.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"329-339"},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10825099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49682614","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":"Synovium-Derived Mesenchymal Stem Cell-Based Scaffold-Free Fibrocartilage Engineering for Bone-Tendon Interface Healing in an Anterior Cruciate Ligament Reconstruction Model.","authors":"Sujin Noh, Sang Jin Lee, James J Yoo, Yong Jun Jin, Hee-Woong Yun, Byoung-Hyun Min, Jae-Young Park, Do Young Park","doi":"10.1007/s13770-023-00593-2","DOIUrl":"10.1007/s13770-023-00593-2","url":null,"abstract":"<p><strong>Background: </strong>Current tendon and ligament reconstruction surgeries rely on scar tissue healing which differs from native bone-to-tendon interface (BTI) tissue. We aimed to engineer Synovium-derived mesenchymal stem cells (Sy-MSCs) based scaffold-free fibrocartilage constructs and investigate in vivo bone-tendon interface (BTI) healing efficacy in a rat anterior cruciate ligament (ACL) reconstruction model.</p><p><strong>Methods: </strong>Sy-MSCs were isolated from knee joint of rats. Scaffold-free sy-MSC constructs were fabricated and cultured in differentiation media including  TGF-β-only, CTGF-only, and TGF-β + CTGF. Collagenase treatment on tendon grafts was optimized to improve cell-to-graft integration. The effects of fibrocartilage differentiation and collagenase treatment on BTI integration was assessed by conducting histological staining, cell adhesion assay, and tensile testing. Finally, histological and biomechanical analyses were used to evaluate in vivo efficacy of fibrocartilage construct in a rat ACL reconstruction model.</p><p><strong>Results: </strong>Fibrocartilage-like features were observed with in the scaffold-free sy-MSC constructs when applying TGF-β and CTGF concurrently. Fifteen minutes collagenase treatment increased cellular attachment 1.9-fold compared to the Control group without affecting tensile strength. The failure stress was highest in the Col + D + group (22.494 ± 13.74 Kpa) compared to other groups at integration analysis in vitro. The ACL Recon + FC group exhibited a significant 88% increase in estimated stiffness (p = 0.0102) compared to the ACL Recon group at the 4-week postoperative period.</p><p><strong>Conclusion: </strong>Scaffold-free, fibrocartilage engineering together with tendon collagenase treatment enhanced fibrocartilaginous BTI healing in ACL reconstruction.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"341-351"},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10825091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49682617","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":"Understanding the Multi-Functional Role of TCTP in the Regeneration Process of Earthworm, Perionyx excavatus.","authors":"Kamarajan Rajagopalan, Jackson Durairaj Selvan Christyraj, Karthikeyan Subbiahanadar Chelladurai, Puja Das, Karthikeyan Mahendran, Logeshwari Nagarajan, Saritha Gunalan","doi":"10.1007/s13770-023-00599-w","DOIUrl":"10.1007/s13770-023-00599-w","url":null,"abstract":"<p><strong>Background: </strong>Regeneration is a highly complex process that requires the coordination of numerous molecular events, and identifying the key ruler that governs is important to investigate. While it has been shown that TCTP is a multi-functional protein that regulates cell proliferation, differentiation, apoptosis, anti-apoptosis, stem cell maintenance, and immune responses, but only a few studies associated to regeneration have been reported. To investigate the multi-functional role of TCTP in regeneration, the earthworm Perionyx excavatus was chosen.</p><p><strong>Methods: </strong>Through pharmacological suppression of TCTP, amputation, histology, molecular docking, and western blotting, the multi-function role of TCTP involved in regeneration is revealed.</p><p><strong>Results: </strong>Amputational studies show that P. excavatus is a clitellum-independent regenerating earthworm resulting in two functional worms upon amputation. Arresting cell cycle at the G1/S boundary using 2 mM Thymidine confirms that P. excavatus execute both epimorphosis and morphallaxis regeneration mode. The pharmacological suppression of TCTP using buclizine results in regeneration suppression. Following the combinatorial injection of 2 mM Thymidine and buclizine, the earthworm regeneration is completely blocked, which suggests a critical functional role of TCTP in morphallaxis. The pharmacological inhibition of TCTP also suppresses the key proteins involved in regeneration: Wnt3a (stem cell marker), PCNA (cell proliferation) and YAP1 (Hippo signalling) but augments the expression of cellular stress protein p53.</p><p><strong>Conclusion: </strong>The collective results indicate that TCTP synchronously is involved in the process of stem cell activation, cell proliferation, morphallaxis, and organ development in the regeneration event.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"353-366"},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10825100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71486437","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":"Bulk Modification with Inorganic Particles and Immobilization of Extracellular Vesicles onto PDO Composite for Facial Rejuvenation.","authors":"Seung-Woon Baek, Dong Min Kim, Semi Lee, Duck Hyun Song, Gi-Min Park, Chun Gwon Park, Dong Keun Han","doi":"10.1007/s13770-023-00622-0","DOIUrl":"10.1007/s13770-023-00622-0","url":null,"abstract":"<p><strong>Background: </strong>The skin, a vital organ protecting against microorganisms and dehydration, undergoes structural decline with aging, leading to visible issues such as wrinkles and sagging. Reduced blood vessels exacerbate vulnerability, hindering optimal cellular function and compromising skin health. Polydioxanone (PDO) biomaterials address aging concerns but produce acidic byproducts, causing inflammation. Inorganic particles and nitric oxide (NO) play crucial roles in inhibiting inflammation and promoting skin regeneration. Stem cell-derived extracellular vesicles (EVs) contribute to intercellular communication, offering the potential to enhance cell functions. The study proposes a method to enhance PDO-based medical devices by incorporating inorganic particles and immobilizing EVs, focusing on facial rejuvenation, anti-inflammatory response, collagen formation, and angiogenesis.</p><p><strong>Method: </strong>PDO composites with inorganic particles such as magnesium hydroxide (MH) and zinc oxide (ZO) were prepared and followed by EV immobilization. Comprehensive characterization included biocompatibility, anti-inflammation, collagen formation ability, and angiogenesis ability.</p><p><strong>Results: </strong>Bulk-modified PDO composites demonstrated even dispersion of inorganic particles, pH neutralization, and enhanced biocompatibility. EVs immobilized on the composite surface exhibited spherical morphology. Inflammation-related gene expressions decreased, emphasizing anti-inflammatory effects. Collagen-related gene and protein expressions increased, showcasing collagen formation ability. In addition, angiogenic capabilities were notably improved, indicating potential for skin rejuvenation.</p><p><strong>Conclusion: </strong>The study successfully developed and characterized PDO composites with inorganic particles and EVs, demonstrating promising attributes for medical applications. These composites exhibit biocompatibility, anti-inflammatory properties, collagen formation ability, and angiogenic potential, suggesting their utility in skin rejuvenation and tissue engineering. Further research and clinical validation are essential.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"199-208"},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10825105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521934","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":"Application of Cartilage Extracellular Matrix to Enhance Therapeutic Efficacy of Methotrexate.","authors":"Jeong-Woo Seo, Sung-Han Jo, Seon-Hwa Kim, Byeong-Hoon Choi, Hongsik Cho, James J Yoo, Sang-Hyug Park","doi":"10.1007/s13770-023-00587-0","DOIUrl":"10.1007/s13770-023-00587-0","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is characterized by chronic inflammation and joint damage. Methotrexate (MTX), a commonly used disease-modifying anti-rheumatic drug (DMARD) used in RA treatment. However, the continued use of DMARDs can cause adverse effects and result in limited therapeutic efficacy. Cartilage extracellular matrix (CECM) has anti-inflammatory and anti-vascular effects and promotes stem cell migration, adhesion, and differentiation into cartilage cells.</p><p><strong>Methods: </strong>CECM was assessed the dsDNA, glycosaminoglycan, collagen contents and FT-IR spectrum of CECM. Furthermore, we determined the effects of CECM and MTX on cytocompatibility in the SW 982 cells and RAW 264.7 cells. The anti-inflammatory effects of CECM and MTX were assessed using macrophage cells. Finally, we examined the in vivo effects of CECM in combination with MTX on anti-inflammation control and cartilage degradation in collagen-induced arthritis model. Anti-inflammation control and cartilage degradation were assessed by measuring the serum levels of RA-related cytokines and histology.</p><p><strong>Results: </strong>CECM in combination with MTX had no effect on SW 982, effectively suppressing only RAW 264.7 activity. Moreover, anti-inflammatory effects were enhanced when low-dose MTX was combined with CECM. In a collagen-induced arthritis model, low-dose MTX combined with CECM remarkably reduced RA-related and pro-inflammatory cytokine levels in the blood. Additionally, low-dose MTX combined with CECM exerted the best cartilage-preservation effects compared to those observed in the other therapy groups.</p><p><strong>Conclusion: </strong>Using CECM as an adjuvant in RA treatment can augment the therapeutic effects of MTX, reduce existing drug adverse effects, and promote joint tissue regeneration.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"209-221"},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10825102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41213794","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}