Regenerative Therapy最新文献

{"title":"Corrigendum to ‘Transplantation of chemically induced liver progenitors in Nagase analbuminemic rats under liver regenerative stimulus’ [Regen Ther 30 (2025) 1–8]","authors":"Masayuki Fukumoto, Akihiko Soyama, Daisuke Miyamoto, Takanobu Hara, Hajime Matsushima, Hajime Imamura, Mampei Yamashita, Tomohiko Adachi, Kengo Kanetaka, Susumu Eguchi","doi":"10.1016/j.reth.2025.09.013","DOIUrl":"10.1016/j.reth.2025.09.013","url":null,"abstract":"","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Page 910"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319878","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":"Effects and the mechanism of pine pollen polysaccharides on diabetic wound healing in vitro and in vivo","authors":"Lan Chen ,&nbsp;Lifang Zhu ,&nbsp;Yu Cao","doi":"10.1016/j.reth.2025.06.009","DOIUrl":"10.1016/j.reth.2025.06.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Pine pollen polysaccharides (PPPS) has anti-inflammatory, immunomodulatory, anti-oxidant, hypoglycemic, and anti-bacterial properties. PPPS can accelerate wound healing in mouse cutaneous wounds, yet it is unclear whether PPPS can promote diabetic wound healing.</div></div><div><h3>Methods</h3><div>Fibroblasts, keratinocytes, and human umbilical vein endothelial cells (HUVECs) were stimulated with high glucose (HG) to mimic hyperglycemic environment. Cell viability, apoptosis, migration, and angiogenesis were assessed by cell counting, Western blot, transwell migration, and tube formation assays. Neutrophil extracellular traps (NETs) and macrophage polarization were analyzed by immunofluorescence and flow cytometry. Streptozotocin-induced diabetes mellitus (DM) mice were subjected to skin wounds and PPPS administration to validate the role of PPPS in diabetic wound healing.</div></div><div><h3>Results</h3><div>PPPS treatment impaired HG-induced viability reduction, apoptosis promotion, and migration repression of fibroblasts, keratinocytes, and HUVECs, accompanied by promotion of angiogenesis of HUVECs under HG stimulation. Specifically, PPPS treatment facilitated NET degradation and suppressed macrophage M1 polarization. Furthermore, PPPS accelerated diabetic wound healing in DM mice, along with decreased citrullinated H3 and PAD4 protein levels and elevated CD31 protein levels, suggesting that PPPS facilitated re-epithelialization and vascularization and reduced NETs.</div></div><div><h3>Conclusions</h3><div>PPPS accelerates diabetic wound healing via mediating NETs and the polarization of M1-type macrophages, providing new insights into the promoting role of PPPS in diabetic wound healing.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 241-251"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470221","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":"Transplantation of adipose-derived stem cell aggregates via hydrogel microspheres that incorporate growth factors increases muscle strength","authors":"Tomohiro Abe ,&nbsp;Emiko Tanaka Isomura ,&nbsp;Toshie Kuwahara ,&nbsp;Ryo Mitsui ,&nbsp;Makoto Matsukawa ,&nbsp;Kiyoko Nakagawa ,&nbsp;Susumu Tanaka ,&nbsp;Yasuhiko Tabata","doi":"10.1016/j.reth.2025.05.016","DOIUrl":"10.1016/j.reth.2025.05.016","url":null,"abstract":"<div><h3>Introduction</h3><div>Stem cell transplantation is widely employed to treat various diseases, and adipose-derived mesenchymal stem cells (ASCs) are used for allogeneic xenotransplantation. However, muscle function post stem cell transplantation remains largely understudied. Therefore, we aimed to investigate the optimal conditions for the transplantation of ASC aggregates of gelatin hydrogel microparticles incorporating growth factors. We further aimed to establish a method for improving muscle function via ASC implantation combined with muscle loading through treadmill running.</div></div><div><h3>Methods</h3><div>Mouse ASCs suspended in various solutions were transplanted into the soleus muscles. The strength of each mouse was measured using a digital force gauge after a muscle load was applied using a treadmill.</div></div><div><h3>Results</h3><div>Platelet-rich growth factor-BB (PDGF-BB) effectively facilitated the expression of MYO-D in the ASCs. Moreover, the injection of cell aggregates rather than suspensions enhanced cell retention. Transplantation of ASC-aggregate gelatin hydrogel microparticles incorporating PDGF-BB in combination with muscle load using a treadmill enhanced mouse muscle function.</div></div><div><h3>Conclusions</h3><div>ASC aggregates with growth factor transplantation likely enhance cell retention. Moreover, they likely improve muscle function and load. Thus, our findings provide new avenues for cell regeneration therapy in muscle rehabilitation.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 299-308"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514364","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":"Transplantation of chemically induced liver progenitors in Nagase analbuminemic rats under liver regenerative stimulus","authors":"Masayuki Fukumoto,&nbsp;Akihiko Soyama,&nbsp;Daisuke Miyamoto,&nbsp;Takanobu Hara,&nbsp;Hajime Matsushima,&nbsp;Hajime Imamura,&nbsp;Mampei Yamashita,&nbsp;Tomohiko Adachi,&nbsp;Kengo Kanetaka,&nbsp;Susumu Eguchi","doi":"10.1016/j.reth.2025.04.015","DOIUrl":"10.1016/j.reth.2025.04.015","url":null,"abstract":"<div><div>We have explored chemically induced liver progenitors (CLiP) as a potential therapeutic agent for liver diseases because their proliferative capacity <em>in vitro</em>. Therefore, we hypothesized the potential treatment with CLiP transplantation (Tx) could be effective and be enhanced with liver regenerative stimulus for metabolic liver diseases.</div></div><div><h3>Methods</h3><div>Male Sprague Dawley rats were used for mature hepatocytes (HEP) isolation to induce CLiP using 3 small molecules cocktail (ROCK-inhibitor, TGF beta-1 inhibitor, GSK3 inhibitor). Harvested rat CLiP (1 × 10⁶) were transplanted to the posterior lobe of the liver (30 % of whole liver) of Nagase analbuminemic rats (NAR) through portal vein injection. One week later, portal venous branch to non-transplanted lobe was ligated to induce liver regeneration in CLiP bearing liver lobe (portal branch ligation: PBL). Only CLiP Tx or HEP Tx of same dose were used as control groups. Serial measurement of serum albumin level was measured by ELISA method. All NARs were subject to immunosuppression therapy using tacrolimus s.q. 3 days per week.</div></div><div><h3>Results</h3><div>After HEP Tx especially with PBL, serum albumin level was significantly elevated. However, even with PBL, CLiP Tx group did not show significant increase in serum albumin. CLiP were surrounded by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) positive cells in portal veins suggesting that CLiP were exposed to the risk of innate immunity.</div></div><div><h3>Conclusion</h3><div>Although CLiP respond to growth factors and proliferate better than HEP <em>in vitro</em>, their behavior <em>in vivo</em> in response to liver regenerative stimulus were not similar to <em>in vitro</em> probably because of less immaturity of receptors and/or high immunogenicity as compared to HEP.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 1-8"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923045","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":"Sustained release of canine mesenchymal stem/stromal cell-derived extracellular vesicles rescues motor function in rodent spinal cord injury models","authors":"Hidetaka Nishida ,&nbsp;Haruhi Matsuura ,&nbsp;Karin Yoshizaki ,&nbsp;Yusuke Sakaguchi ,&nbsp;Takeshi Izawa ,&nbsp;Hikaru Sonoda ,&nbsp;Kazuya Edamura ,&nbsp;Yasuhiko Tabata","doi":"10.1016/j.reth.2025.05.014","DOIUrl":"10.1016/j.reth.2025.05.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Extracellular vesicles (EVs) are expected to be a novel promotes in regenerative therapy. EVs derived from canine mesenchymal stromal/stem cells (MSCs) have been shown to play an important role in tissue repair. For clinical application of EV therapy, a major challenge is to find scalable methods for EV collection and to facilitate continuing local EV action. The aim of this study is to develop collection methods for EVs derived from canine MSCs using anion exchange chromatography (AEX), and to determine the therapeutic effects of sustained release of EVs from cationized gelatin hydrogels in rats with spinal cord injury (SCI).</div></div><div><h3>Methods</h3><div>Canine MSC-derived EVs were isolated from the culture supernatant by AEX. Lipopolysaccharide-stimulated BV-2 cells were used to determine the immunomodulatory effect of EVs. Distinct cross-linked cationized gelatin hydrogels were created by thermal dehydration. The amount of EVs captured by and released from hydrogels were measured using ELISA for CD63. The effects of sustained release of EVs on SCI in rats were evaluated via motor function and cavity volume.</div></div><div><h3>Results</h3><div>EVs were collected from the culture supernatant of canine MSCs using AEX. Canine MSC derived EVs collected by AEX significantly reduced the expression levels of IL-1β and IL-6 in BV-2 cells induced by LPS. Sustained release of EVs from cationized hydrogels led to significant improvement of locomotion in SCI rats relative to the control group at 14- and 28-days post-injury. Cavity formation in the spinal cord with sustained release of EVs was significantly less than in the control group.</div></div><div><h3>Conclusions</h3><div>Canine MSC derived EVs cultured in serum-free medium using AEX were successfully collected. Sustained release of canine MSC derived EVs suppresses cavity formation in the spinal cord after SCI and promotes improvement in motor function.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 164-172"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261767","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":"Trehalose enhances neuronal differentiation with VEGF secretion in human iPSC-derived neural stem/progenitor cells","authors":"Sean K. Roose ,&nbsp;Yoichi Mizukami ,&nbsp;Jun Muto ,&nbsp;Hideyuki Okano ,&nbsp;Masaya Nakamura ,&nbsp;Narihito Nagoshi","doi":"10.1016/j.reth.2025.06.012","DOIUrl":"10.1016/j.reth.2025.06.012","url":null,"abstract":"<div><h3>Introduction</h3><div>Cell transplantation therapy has emerged as a promising approach in regenerative medicine for treating neurological diseases. Neural stem/progenitor cell (NS/PC) transplantation has demonstrated therapeutic efficacy; however, its potential remains limited by suboptimal differentiation and insufficient secretion of pro-healing growth factors. Trehalose, a glucose disaccharide, has been shown to exert neuroprotective effects by inducing autophagy and stabilizing cellular structures. Recent studies suggest that trehalose can modulate growth factor secretion through the CDKN1A/p21 pathway. However, its impact on human induced pluripotent stem cell-derived NS/PCs (hiPSC-NS/PCs) remains unclear. This study investigates the effect of trehalose on neuronal differentiation, cell viability, and growth factor expression in hiPSC-NS/PCs to explore its potential in enhancing transplantation therapy.</div></div><div><h3>Methods</h3><div>hiPSC-NS/PCs were cultured as neurospheres and treated with trehalose (10 mg/ml or 40 mg/ml) for 7 days. Cell viability was assessed using CellTiter Glo® assay. Gene expression analysis was conducted via qRT-PCR and RNA-seq, particularly focusing on <em>CDKN1A</em>, <em>VEGFA</em>, <em>FGF2</em>, and <em>BDNF</em>. Protein expression of SOX2 was analyzed via western blotting. Neurite outgrowth was evaluated using MAP2 immunostaining following differentiation. Statistical significance was set at p &lt; 0.05.</div></div><div><h3>Results</h3><div>Treatment with 10 mg/ml trehalose upregulated <em>CDKN1A</em> expression and promoted neuronal differentiation, as evidenced by reduced SOX2 expression and enhanced neurite outgrowth. RNA-seq analysis revealed the activation of growth factor-related pathways, including <em>VEGFA</em> upregulation, which persisted even after trehalose withdrawal (p = 0.016). However, high concentration (40 mg/ml) significantly reduced cell viability (p = 0.032), suggesting dose-dependent cytotoxicity.</div></div><div><h3>Conclusion</h3><div>Trehalose enhances neuronal differentiation and <em>VEGFA</em> secretion in hiPSC-NS/PCs, potentially augmenting the efficacy of transplantation therapy. These findings suggest that trehalose may serve as a valuable adjunct for neural regeneration, though optimal dosing must be determined to balance differentiation enhancement and cell viability. Further <em>in vivo</em> studies are warranted to validate its clinical applicability.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 268-277"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479963","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":"Development of pyrogen-free utensils for cell culture by combining ozone/hydrogen peroxide mixed gas sterilization with steam-washing technology","authors":"Shaimaa Ibrahim ,&nbsp;Yasuo Nakamura ,&nbsp;Emi Sugizaki ,&nbsp;Genki Koyama ,&nbsp;Zhiping Chen ,&nbsp;Shiori Tamura ,&nbsp;Haruka Shinohara ,&nbsp;Kenya Sato ,&nbsp;Yoh-ichi Tagawa ,&nbsp;Erika Sasaki ,&nbsp;Hiroyuki Tomari ,&nbsp;Masaaki Tanino ,&nbsp;Yuji Haishima","doi":"10.1016/j.reth.2025.05.015","DOIUrl":"10.1016/j.reth.2025.05.015","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this study was to develop disposable cell culture utensils with improved cleanliness.</div></div><div><h3>Methods</h3><div>Pyrogen contamination levels were evaluated using a direct human cell-based pyrogen test (HCPT). Pyrogen inactivation tests were performed using low-temperature ozone/hydrogen peroxide mixed gas treatment. Residual hydrogen peroxide was quantified using a commercially available measurement kit, and the effectiveness of vacuum drying and steam washing in removing the residual hydrogen peroxide was evaluated. The physicochemical properties of the materials were analyzed by measuring FI-IR spectra, static contact angles, and tensile strength.</div></div><div><h3>Results</h3><div>The HCPT of commercially available pyrogen-free products showed that two out of eight pipette chips were contaminated with pyrogen exceeding the limit of quantitation. For the well plates and conical tubes, two out of eleven and four out of ten of the products, respectively, were identified as pyrogen-positive. Some products were contaminated with trace amounts of pyrogen. Pyrogens present in these products were inactivated to below the limit of detection by ozone/hydrogen peroxide mixed gas treatment at 50 °C. Residual hydrogen peroxide on the surface of the products after the treatment, that exhibits strong oxidative effects to cultured cells, was removed to almost the limit of detection by sequential vacuum drying (80 °C/24 h) and steam-washing at 50 °C. Polypropylene and polystyrene, as raw materials for the products, were physicochemically stable for mixed gas treatment.</div></div><div><h3>Conclusion</h3><div>These results suggest that the production of cell culture utensils containing no pyrogen and with no influence on the cell culture is now possible by installing these technologies in the manufacturing process, instead of the radiation sterilization currently used.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 157-163"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254778","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":"2025-12-01","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":"Assessment of permeability in deep tissue capillaries using a new method reflects the nutrient supply status in a healthy heart","authors":"Mio Nakamura ,&nbsp;Yurika Yoshida-Kikkawa ,&nbsp;Kousuke Sugiura ,&nbsp;Yoko Itakura ,&nbsp;Kensuke Ohse ,&nbsp;Norihiko Sasaki ,&nbsp;Yuzuru Ito ,&nbsp;Masashi Toyoda","doi":"10.1016/j.reth.2025.10.005","DOIUrl":"10.1016/j.reth.2025.10.005","url":null,"abstract":"<div><h3>Introduction</h3><div>The <em>in vitro</em> organoid model is a valuable tool for studying organ development and disease. However, a key current challenge is the absence of a functional vascular compartment, which results from limited understanding of capillary function <em>in vivo</em>. Multisystem disorders involve physiological abnormalities that affect different organs in various ways. Notably, women have a higher prevalence of microvessel disease in the heart compared to men. This is because, until now, there has been no way to detect or evaluate the material exchange functions carried out by capillaries deep within healthy heart tissue.</div></div><div><h3>Methods</h3><div>To detect fluorescent material leaking from intracardiac microvessels deep within the left ventricular wall under healthy conditions, female mice were injected with fluorescent dextran via the tail vein. The heart tissue was quickly removed, frozen, sliced, and examined directly under fluorescence. Additionally, the extent of the fluorescent substance diffusion was measured in young and aged female mice.</div></div><div><h3>Results</h3><div>We observed fluorescent substances leaking from deep heart capillaries under healthy conditions. We then developed a method to measure capillary permeability by assessing the diffusion area. Furthermore, this method showed that the permeability of capillaries in the hearts of aged female mice was lower than that of young female mice.</div></div><div><h3>Conclusion</h3><div>We have developed a method to assess capillary permeability in deep tissue. This research will improve our understanding of how capillaries exchange substances and support tissue function. This new method will not only provide new insights into studies of cardiac disease risk and sex differences, but also assist in developing more advanced <em>in vitro</em> models. It will further aid in refining the best cell transplantation techniques.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 900-909"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319877","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":"Sulfated hyaluronic acid for wound repair: Mechanisms, materials, and translational challenges","authors":"Min Lin ,&nbsp;Danni Zhou ,&nbsp;Kaixuan Chen ,&nbsp;Hankang Jiang ,&nbsp;Wenjie Chen ,&nbsp;Jing Wu ,&nbsp;Guizhi Zhu ,&nbsp;Kailei Xu ,&nbsp;Peng Wei","doi":"10.1016/j.reth.2025.10.006","DOIUrl":"10.1016/j.reth.2025.10.006","url":null,"abstract":"<div><div>Sulfated hyaluronic acid (sHA) is emerging as a promising biomaterial for advanced wound dressings because it combines the intrinsic biocompatibility and extracellular matrix (ECM)-like hydration of hyaluronic acid (HA) with added chemical functionality that enhances stability and bioactivity. Chronic wounds, particularly diabetic ulcer, —remain a major clinical challenge due to persistent inflammation, protease/reactive oxygen species (ROS)-rich microenvironments, impaired angiogenesis, and poor growth-factor retention; native HA is limited by rapid enzymatic degradation, low protein affinity, and potentially pro-inflammatory low-molecular fragments, motivating strategies to introduce sulfate groups onto HA to tune its interactions with cells and proteins. In this review, we performed a comprehensive literature review of the biological functions and applications of sHA in wound healing. Key results demonstrate that sHA significantly enhances anti-inflammatory responses, promotes sustained release of cationic therapeutics, improves angiogenesis, and reduces fibrosis. Furthermore, sHA-functionalized hydrogels accelerate diabetic wound healing by modulating macrophage polarization, enhancing re-epithelialization, and supporting vascularization. In further, we also offered a practical roadmap for researchers and clinicians to rationally design next-generation sHA-based dressings with improved reproducibility, controlled release, and safety.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 956-968"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319874","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}