Tissue engineering and regenerative medicine最新文献

{"title":"Injectable Human Acellular Adipose Matrix with Crosslinked Hyaluronic Acid and Carboxymethyl Cellulose Gels for Soft Tissue Augmentation.","authors":"Si Youn Kim, Jung Ki Lee, Soon Won Jung, Kee-Won Lee, Seung Yong Song","doi":"10.1007/s13770-025-00715-y","DOIUrl":"10.1007/s13770-025-00715-y","url":null,"abstract":"<p><strong>Background: </strong>Fillers have become a viable treatment option for addressing volume deficits, whether for aesthetic purposes or due to trauma or congenital deformities. While most fillers effectively maintain volume, promoting adipogenesis remains a significant challenge. This study investigated a biomaterial designed to maintain volume both in the short and long term while promoting adipose tissue formation, focusing on the biological properties of a human acellular adipose matrix (AAM) combined with crosslinked hyaluronic acid (HA) and carboxymethyl cellulose (CMC) gels.</p><p><strong>Methods: </strong>The AAM was prepared through delipidation and decellularization and evaluated for residual fat and cells. To assess its performance, the AAM was compared with conventional collagen scaffolds for the proliferation and adipogenic differentiation of human adipose-derived stem cells(hADSCs) in vitro. An injectable AAM filler was developed by combining AAM with crosslinked HA and CMC gels for the desired rheological properties. Over 12 weeks, the AAM filler, conventional HA filler, and adipose tissue were compared in a nude mice model, assessing volume retention, cell incorporation, and adipogenesis.</p><p><strong>Results: </strong>The AAM showed effective fat and cell removal and promoted the viability and adipogenic differentiation of hADSCs in vitro. The AAM filler exhibited six times higher viscosity than HA filler. It also outperformed both HA filler and adipose tissue in volume retention and cell incorporation, and new adipose tissue formation.</p><p><strong>Conclusions: </strong>These results suggest that AAM filler is a promising biomaterial for soft tissue augmentation, particularly in applications requiring volume retention and adipogenesis.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"647-660"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626184","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":"Exosomes Extracted from Human Umbilical Cord MSCs Contribute to Osteoarthritic Cartilage and Chondrocytes Repair Through Enhancing Autophagy While Suppressing the Wnt/β-Catenin Pathway.","authors":"Shangzhu Qin, Aijie Zhang, Lian Duan, Fang Lin, Mingcai Zhao","doi":"10.1007/s13770-025-00716-x","DOIUrl":"10.1007/s13770-025-00716-x","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA), a widespread chronic joint disorder mainly affecting the elderly, currently lacks a definitive cure. This study investigated the efficacy of exosomes (Exos) extracted from human umbilical cord MSCs (hucMSCs) in the treatment of OA, and preliminarily explored the mechanisms.</p><p><strong>Methods: </strong>A rat osteoarthritis model was constructed by surgical induction. The cartilage morphology was observed after pathological staining; expression of cartilage matrix protein, autophagy-related protein and β-catenin were detected by immunohistochemistry; and inflammatory factors in serum were tested by ELISA. In cellular experiments, human primary chondrocytes were induced with IL-1β to build the OA microenvironment. The levels of relevant proteins in each group were analyzed.</p><p><strong>Results: </strong>Comparing to the OA model, the Exos treatment showed positive effects in reducing OARSI score and Mankin score, decreasing joint space stenosis, promoting matrix synthesis, increasing autophagy, and decreasing β-catenin. The results of the cellular experiments were consistent with those from the animal experiments. However, the Wnt/β-catenin pathway was greatly activated, the levels of matrix proteins and autophagy were distinctly reduced in the Exos + LiCl group comparing to the exosome-treated group.</p><p><strong>Conclusion: </strong>hucMSCs-Exos effectively attenuated the pathological damage of OA cartilage and chondrocytes, promoted the synthesis of cartilage matrix, reduced inflammation, suppressed the Wnt/β-catenin pathway, and enhanced autophagy which promoted the repair of OA cartilage.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"719-733"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061903","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":"Au@Pt Nanoparticles Enhance Maturation and Contraction of Mouse Embryonic Stem Cells-Derived and Neonatal Mouse Cardiomyocytes.","authors":"Shuai Dong, Kangli Guo, Nana Zhao, Yan Xu","doi":"10.1007/s13770-025-00724-x","DOIUrl":"10.1007/s13770-025-00724-x","url":null,"abstract":"<p><strong>Background: </strong>Cardiomyocytes derived from pluripotent stem cells (PSCs) hold great promise in heart damage repair in vivo and drug screening in vitro. However, PSC-derived cardiomyocytes exhibit immature structural and functional properties, which hinder their widespread application. To address this challenge, we designed bimetallic gold-platinum nanoparticles (Au@Pt NPs) endowed with intrinsic oxidase-like, peroxidase-like, and catalase-like activities and high electrical conductivity for promoting cardiomyocyte maturation.</p><p><strong>Methods: </strong>Mouse embryonic stem cell (ESC)-derived and neonatal mouse cardiomyocytes were used to evaluate the effects of Au@Pt NPs on cardiomyocyte maturation. The expression and alignment of cardiomyocyte myofibril proteins were analyzed by qRT-PCR, western blot, and immunofluorescence staining. Cellular functionality was analyzed by the multi-electrode array.</p><p><strong>Results: </strong>By adding Au@Pt NPs at different stages of cardiac differentiation of mouse ESCs, we found that treatment with Au@Pt NPs at the late stage could promote the maturation of differentiated cardiomyocytes, evidenced by increased expression of mature myofibril protein isoforms, more aligned myofibrils, and enhanced sarcomere length. Additionally, Au@Pt NPs can enhance the expression of mature sarcomere components, increase sarcomere length, and significantly boost beating amplitude and conduction velocity in neonatal mouse cardiomyocytes. Furthermore, Au@Pt NPs promoted cell cycle arrest, increased intracellular reactive oxygen species levels, and promoted contractility by inducing the ERK1/2 signaling pathway.</p><p><strong>Conclusion: </strong>Our results indicate that the bimetallic Au@Pt NPs with intrinsic oxidase-like, peroxidase-like, and catalase-like activities and high electrical conductivity could promote the maturation of ESCs-derived and neonatal mouse cardiomyocytes, providing a promising approach for cardiomyocyte maturation and cell therapy for cardiovascular disease.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"611-625"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111249","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":"Physicochemical Modulation Strategies for Mass Production of Extracellular Vesicle.","authors":"Hyoeun Park, Young-Kwon Seo, Yoshie Arai, Soo-Hong Lee","doi":"10.1007/s13770-025-00726-9","DOIUrl":"10.1007/s13770-025-00726-9","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs) have attracted expanded attention as vehicles for the diagnosis and therapy of diseases and regenerative medicine due to their biocompatibility, efficient cellular uptake ability, and capacity to transport biologically active molecules. However, the low secretion yield of EVs and the challenges of large-scale production remain the main barriers to their extensive clinical use.</p><p><strong>Methods and results: </strong>This review explores recent strategies to enhance EV production in cell culture systems, focusing on chemical stimulation, mechanical stimulation, and structural stimulation. First, we review chemical stimulation strategies for modulating culture conditions using chemical stimulation, including nutrient composition, pH, temperature, oxygen levels, intracellular cholesterol, and oxidative stress. Second, we examine mechanical stimulation strategies, including shear stress, irradiation, and ultrasound. Third, we explore structural stimulation strategies, such as three-dimensional (3D) culture systems involving spheroid-based culture, as well as the use of bioreactors and scaffolds. In addition, cell-derived nanovesicles containing cell membrane and cellular component, which can be more easily mass-produced compared to EVs, are proposed as an alternative to EVs.</p><p><strong>Conclusion: </strong>Future research should focus on developing cost-effective and scalable EV production methods while improving purification techniques to ensure a high yield without compromising functional integrity. Moreover, integrating optimized stimulation strategies-such as refining 3D culture systems, bioreactor designs, and mechanical stimulation methods-could further enhance EV secretion. Addressing these challenges is essential for advancing EV-based applications in both research and clinical practice.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"569-591"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226726","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":"Fabrication of 3D Biofunctional Magnetic Scaffolds by Combining Fused Deposition Modelling and Inkjet Printing of Superparamagnetic Iron Oxide Nanoparticles.","authors":"Manuel Estévez, Elisa Batoni, Mónica Cicuéndez, Amedeo Franco Bonatti, Tamara Fernández-Marcelo, Carmelo De Maria, Blanca González, Isabel Izquierdo-Barba, Giovanni Vozzi","doi":"10.1007/s13770-025-00711-2","DOIUrl":"10.1007/s13770-025-00711-2","url":null,"abstract":"<p><strong>Background: </strong>Recently, magnetic composite biomaterials have raised attention in bone tissue engineering as the application of dynamic magnetic fields proved to modulate the proliferation and differentiation of several cell types.</p><p><strong>Methods: </strong>This study presents a novel method to fabricate biofunctional magnetic scaffolds by the deposition of superparamagnetic iron oxide nanoparticles (SPIONs) through thermal Drop-On-Demand inkjet printing on three-dimensional (3D) printed scaffolds. Firstly, 3D scaffolds based on thermoplastic polymeric composed by poly-L-lactic acid/poly-caprolactone/poly(3-hydroxybutyrate-co-3-hydroxyvalerate) were fabricated by Fused Deposition Modelling. Then, in a second step, SPIONs were incorporated onto the surface of the scaffolds by inkjet printing following a designed 2D pattern.</p><p><strong>Results: </strong>A complete characterization of the resulting magnetic scaffolds was carried out attending to the surface SPIONs deposits, demonstrating the accuracy and versatility of the production technique, as well as the stability under physiological conditions and the magnetic properties. Biological evaluation with human bone marrow mesenchymal stems cells demonstrated biocompatibility of the scaffolds and increased osteogenic capability under the application of a magnetic field, due to the activation of mechanotransduction processes.</p><p><strong>Conclusion: </strong>These results show that the developed 3D magnetic biofunctional scaffolds can be a very promising tool for advanced and personalised bone regeneration treatments.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"627-646"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658717","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":"Recent Advances in Three-Dimensional In Vitro Models for Studies of Liver Fibrosis.","authors":"Kyun Yoo Chi, Gyeongmin Kim, Jeong Sang Son, Jiyou Han, Jong-Hoon Kim","doi":"10.1007/s13770-025-00719-8","DOIUrl":"10.1007/s13770-025-00719-8","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis is a reversible but complex pathological condition associated with chronic liver diseases, affecting over 1.5 billion people worldwide. It is characterized by excessive extracellular matrix deposition resulting from sustained liver injury, often advancing to cirrhosis and cancer. As its progression involves various cell types and pathogenic factors, understanding the intricate mechanisms is essential for the development of effective therapies. In this context, extensive efforts have been made to establish three-dimensional (3D) in vitro platforms that mimic the progression of liver fibrosis.</p><p><strong>Methods: </strong>This review outlines the pathophysiology of liver fibrosis and highlights recent advancements in 3D in vitro liver models, including spheroids, organoids, assembloids, bioprinted constructs, and microfluidic systems. It further assesses their biological relevance, with particular focus on their capacity to reproduce fibrosis-related characteristics.</p><p><strong>Results: </strong>3D in vitro liver models offer significant advantages over conventional two-dimensional cultures. Although each model exhibits unique strengths, they collectively recapitulate key fibrotic features, such as extracellular matrix remodeling, hepatic stellate cell activation, and collagen deposition, in a physiologically relevant 3D setting. In particular, multilineage liver organoids and assembloids integrate architectural complexity with scalability, enabling deeper mechanistic insights and supporting therapeutic evaluation with improved translational relevance.</p><p><strong>Conclusion: </strong>3D in vitro liver models represent a promising strategy to bridge the gap between in vitro studies and in vivo realities by faithfully replicating liver-specific architecture and microenvironments. With enhanced reproducibility through standardized protocols, these models hold great potential for advancing drug discovery and facilitating the development of personalized therapies for liver fibrosis.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"593-609"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019052","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":"Corneal Endothelium Regeneration with Decellularized Porcine Corneal Extracellular Matrix Scaffolds.","authors":"Cha Yeon Kim, Cholong Jeong, Hun Lee, Changmo Hwang","doi":"10.1007/s13770-025-00734-9","DOIUrl":"10.1007/s13770-025-00734-9","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the structural, biochemical, and functional performance of decellularized porcine corneal extracellular matrix (dECM) scaffolds for engineering human corneal endothelium.</p><p><strong>Methods: </strong>Porcine corneas were decellularized using either 0.3% sodium dodecyl sulfate (SDS) or 1.5 M sodium chloride (NaCl), followed by enzymatic nucleic acid digestion. Histological and biochemical analyses were performed to assess decellularization efficiency and extracellular matrix preservation. Human corneal endothelial cells (hCECs) were cultured on SDS-dECM scaffolds to evaluate cytocompatibility, morphology, and functional outcomes. Therapeutic efficacy was further assessed using a rabbit model of corneal endothelial dystrophy (CED).</p><p><strong>Results: </strong>SDS-treated corneas showed superior nuclear clearance (residual DNA: 123.60 ± 8.92 ng/mg) compared to NaCl (146.15 ± 5.49 ng/mg), with 95.2% retention of sulfated glycosaminoglycans (sGAGs) and moderate collagen loss (40% of native). In contrast, NaCl better preserved collagen (100% of native) but exhibited incomplete decellularization and lower sGAG retention (71.0%). In vitro, hCECs cultured on SDS-dECM exhibited progressive proliferation, with cell viability surpassing that of TCPS by day 14 (389.01 ± 5.68 vs. 359.65 ± 7.92, p < 0.05). Immunofluorescence confirmed polygonal morphology and ZO-1 expression, indicating intact barrier phenotype. Transparency of dECM scaffolds improved with hCEC culture, with light transmittance at 400 nm increasing from 65.82% (acellular) to 90.13% (double-sided culture). In vivo transplantation of hCEC-seeded SDS-dECM resulted in dose-dependent corneal clarity restoration, with the high-dose group achieving transparency and pachymetry comparable to normal corneas (thickness ~ 602 µm, grading score 0.00 ± 0.00) by 16 weeks.</p><p><strong>Conclusions: </strong>SDS-dECM scaffolds demonstrated excellent biocompatibility and functional support for human corneal endothelial cells, both in vitro and in vivo. These findings support their potential use as bioengineered alternatives to donor corneas for treating endothelial dysfunction.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"735-746"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326879","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":"Exosomes of Human Fetal Cartilage Progenitor Cells (hFCPCs) Inhibited Interleukin-1β (IL-1β)-Induced Osteoarthritis Phenotype via miR-125b-5p In Vitro.","authors":"JuHyeok Lee, Jiyoung Lee, Byung Hyune Choi","doi":"10.1007/s13770-025-00720-1","DOIUrl":"10.1007/s13770-025-00720-1","url":null,"abstract":"<p><strong>Background: </strong>This study investigated anti-inflammatory effects of exosomes derived from human fetal cartilage progenitor cells (hFCPC-Exo) and their microRNAs (miRNAs) on the osteoarthritis (OA) phenotype in vitro in comparison with exosomes from bone marrow mesenchymal stem cells (MSC-Exo).</p><p><strong>Methods: </strong>SW982 cells (synoviocytes) or hFCPCs (chondrocytes) were stimulated with 10 ng/mL IL-1β to mimic OA phenotypes. The effects of hFCPC-Exo and MSC-Exo were compared by measuring the expression of inflammatory cytokines and an anti-inflammatory protein. miRNA profiles of hFCPC-Exo and MSC-Exo were analyzed using a 2588 human miRNA dataset, and miRNAs potentially involved in the anti-inflammatory effect of hFCPC-Exo were selected. miRNA mimics and antisense inhibitors were used to investigate the role of selected miRNAs in the IL-1β signaling pathways.</p><p><strong>Results: </strong>Both hFCPC-Exo and MSC-Exo significantly decreased the expression of inflammatory cytokines (IL-1β, IL-6, and MCP-1), while slightly increased an anti-inflammatory protein (SOCS1) in IL-1β-treated SW982 cells. miRNA sequencing revealed anti-inflammatory miRNAs present in large amounts in both hFCPC-Exo and MSC-Exo. Among them, miR-125b-5p mimic significantly suppressed the expression of inflammatory cytokines induced by IL-1β, while anti-sense inhibitor of miR-125b-5p efficiently blocked anti-inflammatory effects of hFCPC-Exo. Both hFCPC-Exo and miR-125b-5p inhibited IκBα down-regulation and -NF-κB stabilization in IL-1β-treated SW982 cells. Additionally, hFCPC-Exo and miR-125b-5p showed similar effects on IL-1β-treated hFCPCs as an OA model in chondrocytes by down-regulating the expression of IL-1β, MMP13, and ADAMTS-5 and up-regulating the expression of aggrecan (ACAN) and type II collagen (COL2A1).</p><p><strong>Conclusion: </strong>This study demonstrated that hFCPC-Exo exhibits anti-inflammatory effects on IL-1β-treated synoviocytes and chondrocytes in vitro possibly by down-regulating the IL-1β-TRAF6-NF-κB pathway via anti-inflammatory miRNAs such as miR-125b-5p.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"691-703"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080432","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":"Correction: Exosomes of Human Fetal Cartilage Progenitor Cells (hFCPCs) Inhibited Interleukin-1β (IL-1β)-Induced Osteoarthritis Phenotype via miR-125b-5p In Vitro.","authors":"JuHyeok Lee, Jiyoung Lee, Byung Hyune Choi","doi":"10.1007/s13770-025-00740-x","DOIUrl":"10.1007/s13770-025-00740-x","url":null,"abstract":"","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476794","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":"Stepwise Administration of Bone-Targeted Lipid Nanoparticles Encapsulating Valproic Acid and TUDCA Facilitates In Vivo Direct Reprogramming for Osteoporosis Treatment.","authors":"Hyoeun Park, Woong Jin Cho, Jiseong Kim, Hyejong Choi, Inho Baek, Youngjin Kim, Deogil Kim, Byoung Ju Kim, Yoshie Arai, Soo-Hong Lee","doi":"10.1007/s13770-025-00738-5","DOIUrl":"https://doi.org/10.1007/s13770-025-00738-5","url":null,"abstract":"<p><strong>Background: </strong>The ultimate goal of regenerative medicine is to restore damaged tissues to a healthy state in the body. Direct reprogramming, also referred to as transdifferentiation, holds significant therapeutic potential by converting abundant somatic cells, such as fibroblasts, into functionally distinct cell types for tissue regeneration. Despite its potential applications in regenerative medicine, direct reprogramming faces major challenges, including low efficiency and poor In vivo applicability. In this study, we propose a novel therapeutic strategy for osteoporosis based on In vivo direct reprogramming using a stepwise delivery approach that first enhances cellular stemness and subsequently induces osteogenic transdifferentiation. Enhancing stemness in lineage-committed cells facilitates their conversion into other functional cell types.</p><p><strong>Method: </strong>To investigate the efficiency of direct reprogramming via stepwise delivery, we utilized valproic acid (VPA) and tauroursodeoxycholic acid (TUDCA) as reprogramming and bone-stimulating factors, respectively. VPA increased the expression of stemness genes, including Oct4, Nanog, and Sox2, and subsequent treatment of TUDCA enhanced the expression of osteogenic genes in the mouse fibroblast. Targeted delivery of these factors to fibroblasts surrounding bone tissue, enabling subsequent direct reprogramming into osteoblasts, was achieved using bisphosphonate (BP)-conjugated lipid nanoparticles as carriers.</p><p><strong>Results: </strong>Our findings demonstrate that sequential induction of cell reprogramming and tissue regeneration through stepwise administration of VPA and TUDCA significantly enhances therapeutic efficacy in a mouse model of osteoporosis compared to their simultaneous administration.</p><p><strong>Conclusion: </strong>This stepwise bone-targeted drug delivery system presents a promising strategy for osteoporosis treatment via In vivo direct reprogramming.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476795","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}