Regenerative Therapy最新文献

{"title":"Printable biomaterials for 3D brain regenerative scaffolds: An in vivo biocompatibility assessment","authors":"Maylis Combeau ,&nbsp;Nina Colitti ,&nbsp;Julien Clauzel ,&nbsp;Franck Desmoulin ,&nbsp;Adrien Brilhault ,&nbsp;Juliette Fitremann ,&nbsp;Mickaël Chabbert ,&nbsp;Matthew L. Becker ,&nbsp;Sébastien Blanquer ,&nbsp;Lorenne Robert ,&nbsp;Melissa Parny ,&nbsp;Isabelle Raymond-Letron ,&nbsp;Carla Cirillo ,&nbsp;Isabelle Loubinoux","doi":"10.1016/j.reth.2025.08.008","DOIUrl":"10.1016/j.reth.2025.08.008","url":null,"abstract":"<div><h3>Background</h3><div>Brain regeneration after injury is a challenge being tackled by numerous therapeutic strategies in pre-clinical development. There is growing interest in scaffolds implanted in brain lesions. Developments in 3D printing offer the possibility of designing complex structures of varying compositions adapted to tissue anatomy.</div></div><div><h3>Methods</h3><div>This feasibility study assessed the cerebral biocompatibility of four bioeliminable Digital Light Processing (DLP) printed materials in the rat model: gelatin methacrylate (GelMA), poly(ethylene glycol)diacrylate (PEGDA) mixed with GelMA (PEGDA-GelMA), poly(trimethylene carbonate) trimethacrylate (PTMC-tMA) and an ABA triblock copolymer of polypropylene fumarate-b-poly γ-methyl ε-caprolactone-b-polypropylene fumarate (P(PF-MCL-PF)). Their tolerance was compared to that of polydioxanone Ethicon (PDSII), a neurosurgery suture component commonly used in clinical practice. A one-month MRI and behavioral follow-up aided in safety assessment.</div></div><div><h3>Results</h3><div>High-resolution T2 MRI imaging effectively captured the scaffold structures and demonstrated its non-invasive utility in monitoring degradability. PDSII served as a control of the acceptable inflammatory response to implantable foreign bodies. GelMA, PEGDA-GelMA and PTMC-tMA did not affect the permissive glial barrier, promoted cell migration, and neovascularization without additional perilesional microglial inflammation (median mean of 6.5 %, compared to 8.2 % for the PDSII control). However, the GelMA scaffold core was not colonized and allowed a limited neuronal progenitors recruitment. The rigidity of PTMC-tMA facilitated insertion, but posed histological issues. The brain hardly reacted to the P(PF-MCL-PF).</div></div><div><h3>Conclusion</h3><div>All these materials can serve as a basis for brain regeneration. PEGDA-GelMA emerged as a promising candidate for intracerebral implantation, combining biophysical and bioprinting advantages while maintaining an acceptable level of inflammation compared with clinically used suture, paving the way for innovative therapies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 641-655"},"PeriodicalIF":3.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conditioned plasma promotes full-thickness skin defect healing in a rat model","authors":"Majid Zamani ,&nbsp;Saeid Kaviani ,&nbsp;Mehdi Yousefi ,&nbsp;Saeid Abroun ,&nbsp;Mohammad Hojjat-Farsangi ,&nbsp;Behzad Pourabbas","doi":"10.1016/j.reth.2025.08.003","DOIUrl":"10.1016/j.reth.2025.08.003","url":null,"abstract":"<div><h3>Introduction</h3><div>Blood derivatives may enhance wound healing, but each possesses distinct characteristics and has yielded varying outcomes in patient treatment. This research seeks to examine the efficacy of conditioned plasma (CP) using polylactic acid (PLA) coated beads and to compare it with CP using bare beads and platelet-rich plasma (PRP) in the context of acute wound healing.</div></div><div><h3>Methods</h3><div>Blood was collected from 7 volunteer donors in three tubes containing ACD anticoagulant, PLA coated, or bare beads and incubated for 6 h at 37 °C. The concentration of VEGF, PDGF, TGF-β, IL-1β, IL-13, and IL-1Ra were measured by ELISA. Full-thickness wounds were made on the back of rats. PRP, CP with PLA-coated bead or bare beads, and phosphate buffer saline as control were administered to the wound area. Wound closure rate at days 3, 7, 10, and 14; epithelialization, fibroblast cells, inflammatory cells infiltration, new collagen formation, new vessel, and immunohistochemistry (CD31, α-SMA) were measured 14 days after the incision.</div></div><div><h3>Results</h3><div>The concentration of VEGF, PDGF, TGF-β, IL1-β, and IL-1Ra was significantly higher in CPs than in PRP (<em>p</em> &lt; 0.05). CP with PLA-coated beads promoted wound closure and improved skin wound healing (<em>p</em> &lt; 0.05), which was associated with enhanced epithelialization, fibroblast cell proliferation, new collagen formation, and reduced inflammatory cells infiltration. Immunohistochemistry showed an increase in CD31 and α-SMA levels in the treatment groups compared to the control group, but this increase was insignificant (<em>p</em> &gt; 0.05).</div></div><div><h3>Conclusion</h3><div>CP promotes wound healing by increasing epithelialization, fibroblast proliferation, collagen synthesis and deposition, and reducing inflammatory cells infiltration.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 629-640"},"PeriodicalIF":3.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles-delivered circDB promotes ischemic muscle repair through the miR-34a/USP7/Notch1 signaling pathway","authors":"Lijuan Jiao ,&nbsp;Qingfang Han ,&nbsp;Yan Xu ,&nbsp;Wenjie Chen ,&nbsp;Tonggan Lu ,&nbsp;Huiling Zhang ,&nbsp;Anqi Zhou ,&nbsp;Weiliang Wu ,&nbsp;Yu Zhang ,&nbsp;Ao Li ,&nbsp;Yangxin Li","doi":"10.1016/j.reth.2025.08.009","DOIUrl":"10.1016/j.reth.2025.08.009","url":null,"abstract":"<div><h3>Introduction</h3><div>The incidence of lower limb ischemic diseases has been rising steadily in recent years, often leading to severe outcomes such as limb amputation. Given the limited availability of effective treatments, there is a critical need for novel therapeutic strategies. This study explores the reparative role and underlying mechanisms of extracellular vesicles derived from human umbilical cord mesenchymal stem cells (UMSC-EVs) in promoting ischemic hindlimb recovery through the delivery of circular RNA circDB.</div></div><div><h3>Methods</h3><div>A hindlimb ischemia model was established in C57BL/6 mice <em>via</em> femoral artery ligation, followed by intramuscular injections of extracellular vesicles derived from either untreated UMSCs (NC-EVs) or UMSCs transfected with si-circDB (si-EVs). Functional recovery was assessed using Laser Doppler imaging for blood flow, grip strength tests, and treadmill endurance evaluations. Molecular analyses included Western blot and qRT-PCR for USP7 and Notch1 expression, EdU assays for myoblast proliferation, and co-immunoprecipitation to confirm USP7-Notch1 interactions. <em>In vitro</em>, C2C12 myoblasts were cultured under hypoxic conditions for 48 h to mimic ischemia, and their proliferation and signaling were studied using similar techniques. Bioinformatics tools (CircBank, TargetScan) were used to analyze circDB-miR-34a interactions.</div></div><div><h3>Results</h3><div>We found that circDB expression is markedly reduced in ischemic hindlimb tissues and is closely associated with tissue repair. In a murine hindlimb ischemia model, localized injection of UMSC-EVs into ischemic muscle significantly enhanced blood flow recovery, improved muscle function, and increased expression of USP7 and Notch1. Additionally, a hypoxia-induced myoblast injury model <em>in vitro</em> revealed that UMSC-EVs delivering circDB promoted myoblast proliferation <em>via</em> the miR-34a/USP7/Notch1 signaling axis.</div></div><div><h3>Conclusion</h3><div>Extracellular vesicles circDB enhances ischemic muscle repair by modulating the miR-34a/USP7/Notch1 pathway. These findings highlight a novel mechanism by which UMSC-derived extracellular vesicles facilitate muscle regeneration and suggest a promising therapeutic approach for lower limb ischemic diseases.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 616-628"},"PeriodicalIF":3.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of long-shelf-life allogeneic adipose-derived mesenchymal stem cell line-derived platelet-like cells for refractory foot ulcers: A translational preclinical and phase 1/2a study","authors":"Hideaki Obara ,&nbsp;Kentaro Matsubara ,&nbsp;Naoki Fujimura ,&nbsp;Yumiko Matsubara ,&nbsp;Yukako Ono-Uruga ,&nbsp;Masaki Yazawa ,&nbsp;Jun Okui ,&nbsp;Yasunori Sato ,&nbsp;Yuko Kitagawa","doi":"10.1016/j.reth.2025.08.006","DOIUrl":"10.1016/j.reth.2025.08.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Refractory foot ulcers, characterized by prolonged healing and frequent recurrences, challenge existing therapies such as revascularization and compression, which typically fail to prevent amputation. We developed adipose-derived mesenchymal stem cell line-derived platelet-like cells (ASCL-PLCs) for refractory ulcers that are long-lasting and readily available.</div></div><div><h3>Methods</h3><div>A translational preclinical investigation and phase 1/2a first-in-human clinical study assessed the safety and efficacy of a novel allogeneic ASCL-PLC treatment for refractory foot ulcers. In the pre-clinical phase, ASCL-PLCs were cryopreserved for 9 months and then thawed to measure cytokine release after calcium chloride stimulation. The therapeutic efficacy was evaluated in a diabetic mouse wound model, comparing ASCL-PLC treatment with vehicle control. The clinical trial involved topically applying ASCL-PLCs (1.5 × 10⁸ cells/cm²) to the ulcers of four patients (two ischemic, two venous) on days 0, 14, and 28, with safety and efficacy monitored based on adverse events, ulcer size reduction, epithelialization time, and pain score changes.</div></div><div><h3>Results</h3><div>ASCL-PLCs maintained considerable cytokine-releasing activity even after long-term cryopreservation. In the diabetic mouse skin defect model, treatment with ASCL-PLCs substantially enhanced wound closure compared with the controls, demonstrating potent wound-healing capabilities. In the clinical trial, all patients exhibited notable ulcer size reduction without serious adverse events; three achieved epithelialization within 6 months, along with improvements in pain and quality of life without a negative impact on local blood flow.</div></div><div><h3>Conclusions</h3><div>ASCL-PLCs are safe and a promising therapeutic option for refractory ulcers and can potentially reduce amputation rates, improve patient outcomes, and minimize the socioeconomic impact due to chronic wounds. Their long shelf life and cryopreservation stability make wound management practical and accessible. Moreover, their efficacy with simple topical application suggests a minimally invasive strategy suitable for outpatient care. Further large-scale trials are recommended.</div><div>This study was registered with the Japan Registry of Clinical Trials (jRCT ID: jRCTa030200053; on June 18, 2020, <span><span>https://jrct.mhlw.go.jp/en-latest-detail/jRCTa030200053</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 606-615"},"PeriodicalIF":3.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem/progenitor cell dynamics during salivary gland development and regeneration demonstrated by the double pulse-chase paradigm","authors":"Shusuke Ohshima ,&nbsp;Angela Quispe-Salcedo ,&nbsp;Hiroko Ida-Yonemochi ,&nbsp;Yushi Ueki ,&nbsp;Arata Horii ,&nbsp;Hayato Ohshima","doi":"10.1016/j.reth.2025.08.007","DOIUrl":"10.1016/j.reth.2025.08.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Active and quiescent stem cells coexist in hair follicles and intestinal crypts; however, their localization and differentiation potential in the salivary dynamics are unknown. This study aimed to clarify the cellular dynamics that occur during salivary gland development and regeneration in the duct ligation model with a focus on the role of label retaining cells (LRCs), presumably quiescent stem cells, in these processes.</div></div><div><h3>Methods</h3><div>Doxycycline-inducible TetOP-histone 2B (H2B)-green fluorescent protein (GFP) transgenic mice [GFP expression was induced during embryonic day 15 (E15)–postnatal day 7 (P7)] followed by EdU (5-ethynyl-2′-deoxyuridine) administration at P10–14 to chase the LRCs during development. In addition, LRCs were labeled with GFP immediately before salivary gland duct ligation and EdU was administered after the ligation was released to chase the LRCs with GFP and EdU during tissue repair.</div></div><div><h3>Results and conclusions</h3><div>During development, GFP (+) EdU (−) LRCs were abundant in striated duct cells (SDCs) and GFP (+) EdU (+) LRCs were primarily localized to the intercalated duct cells (IDCs) at P21. Labeling of the GFP (+) LRCs faded as well as the EdU (+) LRCs at P70. During tissue repair, GFP (+) EdU (+) LRCs were colocalized in the IDCs and myoepithelium cells (MECs), whereas the GFP (+) EdU (+) acinar cells (ACs) appeared over time. These results suggest that salivary gland quiescent stem/progenitor cells are present in the IDCs during development and that quiescent stem/progenitor cells in the IDCs and MECs differentiate into ACs during tissue repair.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 595-605"},"PeriodicalIF":3.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models","authors":"Hamid Khan ,&nbsp;Hammad Riaz ,&nbsp;Adeel Ahmed ,&nbsp;Mubin Mustafa Kiyani ,&nbsp;Sahibzada Muhammad Jawad ,&nbsp;Syed Shahab Ud Din Shah ,&nbsp;Turki Abualait ,&nbsp;Fawaz Al-hussain ,&nbsp;Hong-Tao Li ,&nbsp;Shahid Bashir","doi":"10.1016/j.reth.2025.07.009","DOIUrl":"10.1016/j.reth.2025.07.009","url":null,"abstract":"<div><div>Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by the death of motor neurons in the spinal cord and brain regions, leading to a reduced survival rate in patients. Nearly 20 gene mutations are associated with ALS, with SOD1, FUS, TARDBP, and C9orf72 mutations being more common. Ninety percent of ALS cases are related to sporadic ALS, while the remaining 10 % are associated with familial ALS. CRISPR/Cas9, a genome engineering technology known as clustered regularly interspaced short palindromic repeats/CRISPR-associated system 9, has the potential for gene editing and for studying the underlying mechanisms of ALS in mouse models. This technique enables neuroscientists to reverse mutations found in ALS mouse models, providing new hope for understanding the complexities of ALS. Additionally, this tool can create mutations to probe the functional changes of genetic diseases. Using CRISPR/Cas9 with an in vivo delivery method involving adeno-associated vectors, it is possible to silence mutations in the SOD1-linked ALS mouse model. Some limitations related to CRISPR/Cas9 have been discussed in previous studies and need to be addressed before clinical trials can proceed. In this review-based study, we summarise the latest research on CRISPR/Cas9 genome editing for ALS in mouse models and discuss its limitations and future prospects as well.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 575-583"},"PeriodicalIF":3.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144830685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tanshinone IIA suppresses fibro-adipogenic progenitor differentiation and attenuates fat infiltration in rotator cuff injury via Wnt/β-catenin pathway","authors":"Yumei Zhang ,&nbsp;Xinghua Li ,&nbsp;Rui Zhang ,&nbsp;Minhui Wang ,&nbsp;Tihui Wang ,&nbsp;Guanfeng Liu ,&nbsp;Amila Kuati ,&nbsp;Wenhua Mao","doi":"10.1016/j.reth.2025.08.004","DOIUrl":"10.1016/j.reth.2025.08.004","url":null,"abstract":"<div><h3>Background</h3><div>Fibro-adipogenic progenitors (FAPs) contribute to excessive muscular fatty infiltration after rotator cuff tears (RCT), impairing shoulder function. Tanshinone IIA (Tan IIA), a major active compound from Salvia miltiorrhiza Bunge, has known anti-adipogenic effects, yet its impact on FAP adipogenesis remains unclear.</div></div><div><h3>Methods</h3><div>Human FAPs from rotator cuff muscles were isolated via FACS, cultured, and treated with Tan IIA. Adipogenic differentiation was assessed with Oil Red O staining and RT-qPCR for lipid accumulation and gene expression. Single-cell RNA sequencing identified affected FAP subpopulations, while pathway analysis and Western blots confirmed Wnt/β-catenin pathway activation. β-catenin inhibitors KYA1797K and XAV-939 were then applied to evaluate pathway specificity. In vivo, RCT models received Tan IIA treatment, with Plin1 staining and triglyceride quantification measuring fatty infiltration, and gait and treadmill tests assessing shoulder function.</div></div><div><h3>Results</h3><div>Tan IIA reduced adipogenic differentiation of FAPs in vitro, as shown by Oil Red O staining and RT-qPCR. Single-cell RNA sequencing indicated that Tan IIA reduced adipogenic potential in specific FAP populations. Enrichment analysis and Western blot results confirmed Wnt/β-catenin pathway activation by Tan IIA. Anti-adipogenic effects were reversed with β-catenin inhibitors. In vivo, Tan IIA significantly reduced muscular fatty infiltration and improved shoulder function in RCT models.</div></div><div><h3>Conclusion</h3><div>Tan IIA inhibits FAP adipogenesis through Wnt/β-catenin signaling activation, reducing fatty infiltration and enhancing shoulder function in RCT, suggesting Tan IIA as a potential treatment.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 584-594"},"PeriodicalIF":3.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144830687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From an Antimicrobial Agent to a constituent of 3D Printed Heterogenous Scaffolds Stimulating Bone Characteristics: An In-vitro and Animal model evaluation","authors":"Shahad Ahmed Daood ,&nbsp;Martha Then Xin Yi ,&nbsp;Nicole Wen Ce Mun ,&nbsp;Sharjeel Ilyas ,&nbsp;Lee Yin Shien ,&nbsp;Oh Jia En ,&nbsp;Syed Saad Bin Qasim ,&nbsp;Yichen Dai ,&nbsp;Galvinderjeet Kaur Grewal ,&nbsp;Ng Mei Liit ,&nbsp;Gopu Sriram ,&nbsp;Malikarjuna Rao Pichika ,&nbsp;Kit-Kay Mak ,&nbsp;Ranjeet Ajit Bapat ,&nbsp;Zeeshan Sheikh ,&nbsp;Umer Daood","doi":"10.1016/j.reth.2025.08.001","DOIUrl":"10.1016/j.reth.2025.08.001","url":null,"abstract":"<div><div>This paper describes a promising candidate molecule, investigates the pattern of scaffold composition which arises and assesses the effect of the agent on its mechanical properties.</div></div><div><h3>Methods</h3><div>Scaffold samples were fabricated using a commercial extrusion bioprinter equipped with a pneumatic printhead fitted with a 21G conical nozzle. The Pore Printability Index, and the area and perimeter of the pore within the grid patterns were quantified using ImageJ software (NIH, USA). Mechanical properties of scaffolds were assessed using atomic force microscopy. The phase composition and crystal structures were analyzed using X-ray diffraction and Raman mapping. Morphologies of human gingival fibroblastic cells were examined using scanning electron microscopy. Lactobacillus biofilms were generated for cytolysin peptide cleavage. A rabbit bone defect model with scaffold implantations was used to provide histologic specimens for measuring percentages of bone trabeculae, collagen fibers and inflammatory cells along with granulation tissue. The Primeway Total RNA Extraction Kit was used for RNA extraction.</div></div><div><h3>Results</h3><div>All bioink formulations demonstrated successful printing of 3D grid and solid square patterned scaffolds achieving Pr values exceeding 0.9. _{<strong>0.1</strong> <strong>%</strong>}<strong>K21</strong> group showed the highest elastic modulus. XRD revealed a pattern producing around 90 % β-tricalcium phosphate displaying two peaks at 2θ angles. 0.1 % K21 and _{<strong>0.1</strong> <strong>%</strong>}<strong>CHX</strong> did not alter scaffold's pore size and porosity. _{<strong>0.1</strong> <strong>%</strong>}<strong>K21</strong> group exhibited highest ratio (62.5 ± 6.1 θ), significantly surpassing control. Surface morphologies of cells were also well retained. TEM image shows a sequence of structural changes in fibroblastic cell structure when exposed to K21. 0.1 % K21 proved to be critical in completely eradicating the biofilm. <strong>_0.K21</strong> group closed the openings of wound areas completely. Correlation coefficient of gene expression levels demonstrates sample variations and recurring instances among groupings.</div></div><div><h3>Conclusion</h3><div>3D-printing technologies with _{<strong>0.1</strong> <strong>%</strong>}<strong>K21</strong> represent a significant advancement over conventional regenerative medicine techniques for bone-related treatments.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 558-574"},"PeriodicalIF":3.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144826956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogel in musculoskeletal diseases: Unraveling trends, research foci, and future trajectories via bibliometric insights (from 2000 to 2025)","authors":"Weibei Sheng ,&nbsp;Siyang Cao ,&nbsp;Haotian Qin ,&nbsp;Peng Liu ,&nbsp;Deli Wang ,&nbsp;Jian Weng ,&nbsp;Hui Zeng ,&nbsp;Fei Yu","doi":"10.1016/j.reth.2025.08.002","DOIUrl":"10.1016/j.reth.2025.08.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Hydrogels, owing to their excellent biocompatibility, tunable physicochemical properties, and ability to mimic the extracellular matrix, have emerged as promising materials for the treatment of musculoskeletal disorders, including osteoarthritis, intervertebral disc degeneration, and bone injuries. Recent advancements in smart hydrogels and multifunctional composites have further broadened their applications in drug delivery, tissue engineering, and regenerative medicine. However, despite growing interest in this field, current reviews often lack systematic, data-driven insights into the evolving research landscape.</div></div><div><h3>Methods</h3><div>To address this gap, we conducted a bibliometric analysis using CiteSpace and VOSviewer to quantitatively map the development of hydrogel-related research in musculoskeletal disorders over the past two decades. Key parameters analyzed included publication trends, influential countries and institutions, collaborative networks, keyword evolution, and research hotspots.</div></div><div><h3>Results</h3><div>Our analysis revealed a steady growth in publications, with China and the United States emerging as leading contributors. Prominent institutions and authors were identified, along with landmark publications that have shaped the field. Keyword co-occurrence analysis highlighted emerging themes such as injectable hydrogels, 3D bioprinting, and osteochondral regeneration. The most frequently studied disease targets included osteoarthritis, intervertebral disc degeneration, and bone defect repair.</div></div><div><h3>Conclusions</h3><div>This comprehensive bibliometric overview offers valuable insights into the current status and future directions of hydrogel research in musculoskeletal disorders. It highlights key trends, influential contributors, and emerging hotspots, providing a solid foundation for advancing interdisciplinary collaborations and accelerating the clinical translation of hydrogel-based therapies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 544-557"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The therapeutic potential of neuroglobin-overexpressing human neural stem cells in a photothrombosis model","authors":"Eun-Jung Yoon ,&nbsp;Jiwon Jeong ,&nbsp;Jisu An ,&nbsp;Yunseo Choi ,&nbsp;Dongsun Park","doi":"10.1016/j.reth.2025.07.013","DOIUrl":"10.1016/j.reth.2025.07.013","url":null,"abstract":"<div><h3>Background</h3><div>Neuroglobin (NGB) is an oxygen-binding protein with neuroprotective properties under hypoxic and ischemic conditions. It promotes cell survival, reduces oxidative stress, and activates survival-related signaling pathways. This study aimed to evaluate whether overexpression of NGB in human neural stem cells (F3.NGB) could enhance their regenerative potential and therapeutic efficacy in photothrombosis model.</div></div><div><h3>Methods</h3><div>F3 cells were genetically engineered to overexpress NGB. In vitro proliferation and migration were assessed using CCK-8, colony forming, and scratch-based wound healing assays. In vivo, a photothrombosis-induced stroke model was used to evaluate infarct volume, transplanted cell migration and differentiation, and activation of proliferation-related signaling pathways following intravenous transplantation of F3.NGB cells.</div></div><div><h3>Results</h3><div>NGB overexpression significantly enhanced the proliferative capacity of F3 cells, and F3.NGB cells promoted N2A cell proliferation and actively migrated in co-culture conditions. In vivo, transplantation of F3.NGB cells resulted in a significant reduction in infarct volume compared with that in the controls. Western blot analysis showed increased activation of PI3K/AKT, mTOR, and ERK signaling pathways, with decreased PTEN expression. Immunohistochemical staining confirmed that F3.NGB cells migrated to the infarcted region, differentiated into neurons and astrocytes, and showed strong Ki67 positivity, indicating active proliferation at the injury site.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate that F3.NGB cells reduce ischemic brain damage primarily by enhancing cell proliferation, and also migrate to the injury site and undergo differentiation into neurons or astrocytes. These results suggest that F3.NGB cell-based therapy may contribute to the development of advanced regenerative strategies for the treatment of ischemic stroke.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 515-524"},"PeriodicalIF":3.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}