Tissue Engineering Part A最新文献

{"title":"Regenerative Healing.","authors":"Michael V Sefton, Malcolm King, Alexandra King","doi":"10.1177/19373341251392179","DOIUrl":"10.1177/19373341251392179","url":null,"abstract":"<p><p>Indigenous health and wellness encompasses physical, mental, emotional, and spiritual well-being, with a focus on \"the interconnectedness of these aspects and the importance of community and cultural practices.\" \"Regenerative healing,\" as distinct from \"Regenerative medicine,\" is a similarly wholistic term that has emerged from conversations with selected First Nations and Métis Knowledge Holders from across Canada.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"589-591"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental Study of Umbilical Cord Graft and Established Sling Materials for Frontalis Suspension.","authors":"Dayoon Cho, Myeong-Kyu Lee, Sae Rom Lee, Ja-Young Kwon, Jin Sook Yoon","doi":"10.1177/19373341251398493","DOIUrl":"10.1177/19373341251398493","url":null,"abstract":"<p><p>Frontalis suspension surgery is the preferred treatment option for patients with poor levator function ptosis. This procedure connects the affected eyelid to the brow using sling material, harnessing the action of the frontalis muscle to elevate the upper eyelid. Various sling materials have been used, most commonly silicone rods and fascia lata. However, both have notable limitations: silicone rods carry a relatively high risk of postoperative inflammation and ptosis recurrence, while fascia lata, due to its low elasticity, may cause blinking dysfunction and exposure keratopathy. Additionally, fascia lata harvesting poses challenges in young children. Therefore, there is a need for an alternative human tissue sling material that is both readily available and capable of overcoming the limitations of established sling materials. This study aimed to evaluate the viability of human umbilical cord grafts as a novel sling material for frontalis suspension surgery in ptosis patients. We developed a new method for dissecting and dehydrating umbilical cord tissue and assessed its mechanical and histological properties using uniaxial tensile testing and histological analysis. Untreated umbilical cord grafts exhibited mechanical strength (15.9546 ± 2.6117 N) and strain (96.8674 ± 3.6707%) values intermediate between those of silicone rod and fascia lata. Alcohol dehydration significantly increased ultimate tensile strength and maximum strain, ultimate strength values exceeding those of silicone rod. These grafts withstood forces exceeding those generated during forced blinking, outperforming silicone rod in strength and exhibiting greater elasticity than fascia lata. Histological analysis revealed abundant collagen and glycosaminoglycans within Wharton's jelly, alongside elastic fiber-rich regions in vessel walls. The presence of these extracellular matrix components likely underlies the grafts' favorable mechanical properties. Overall, umbilical cord grafts may emerge as a promising alternative to conventional sling materials in ptosis surgery, potentially addressing limitations in material availability.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"630-638"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-BMSC Spheroids Enhance Bone Repair Associated with H-Type Vessels and Immunomodulation.","authors":"Sheng-Tao Zhao, Yao-Wen Zhang, Yi-Hui Pan, Xiang-Zhen Yan","doi":"10.1177/19373341261473151","DOIUrl":"https://doi.org/10.1177/19373341261473151","url":null,"abstract":"<p><p>The therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) in bone tissue engineering (BTE) is compromised by functional decline during conventional two-dimensional (2D) expansion. We hypothesized that chitosan film-based three-dimensional (3D) culture rejuvenates BMSC potency, synergistically promoting angiogenesis and immunomodulation for vascularized bone regeneration. Mouse BMSCs were cultured into spheroids on chitosan films. Their stemness, proliferation, migration, senescence, osteogenic, and proangiogenic potential were compared with 2D cultures. Paracrine effects were evaluated by treating human umbilical vein endothelial cells (HUVECs) and RAW264.7 macrophages with BMSC-conditioned medium (CM). <i>In vivo</i>, gelatin methacryloyl (GelMA) hydrogel-encapsulated 3D-BMSC spheroids were implanted into mouse critical-size cranial defects. Compared to 2D counterparts, 3D-BMSCs exhibited increased stemness, proliferation, migration, delayed senescence, osteogenic differentiation, and enhanced proangiogenic potential. We observed that conditioned medium from 3D-BMSCs (3D-CM) was associated with <i>in vitro</i> angiogenesis and orchestrated a proreparative microenvironment by promoting M2 macrophage polarization and suppressing M1 inflammation. <i>In vivo</i>, GelMA + 3D-BMSC spheroids achieved greater bone regeneration, which was accompanied by a proreparative immune microenvironment and enhanced CD31/EMCN-positive H-type-like vessel formation. This chitosan film-based 3D culture system effectively augments BMSC therapeutic potency, simultaneously enhancing intrinsic cell properties and orchestrating a proregenerative microenvironment, thereby offering a promising experimental platform for critical-sized bone defect repair.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261473151"},"PeriodicalIF":2.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148686314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC00687 Regulates PRDX2 Expression in High Glucose-Induced Nonunion after Digital Replantation.","authors":"Xiangying Wang, Xin He","doi":"10.1177/19373341251381372","DOIUrl":"10.1177/19373341251381372","url":null,"abstract":"<p><p>Diabetic nonunion is a major clinical challenge with unclear molecular mechanisms. This study systematically investigated the key genes and molecular mechanisms of bone nonunion after finger replantation induced by high glucose using Gene Expression Omnibus (GEO), bioinformatics, and experimental analyses. In total, 179 differentially expressed mRNAs and one lncRNA (DElncRNA) were identified using the GEO dataset. Functional enrichment analysis showed that these genes were mainly involved in the regulation of autophagy and metabolism. Protein-protein interaction network analysis identified five core genes (Peroxiredoxin 2 [PRDX2], FK506 binding protein 8 [FKBP8], SHANK-associated RH domain interactor [SHARPIN], WD repeat domain 45 [WDR45], and gamma-aminobutyric acid type A receptor-associated protein like 2 [GABARAPL2]), three of which exhibited good binding affinities for potential therapeutic agents. Immune infiltration analysis revealed significant differences in the CD8+ T cell proportions between nonunion and healthy samples. We constructed a competitive endogenous RNA network (long intergenic non-protein coding RNA 687 [LINC00687]-miR-4443-PRDX2) and verified its direct regulatory interaction using a dual-luciferase reporter assay. FKBP8, PRDX2, SHARPIN, WDR45, and GABARAPL2 were overexpressed in tissue samples from patients with type 2 diabetes mellitus fracture nonunion. Animal experiments further confirmed that LINC00687 upregulated PRDX2 expression by sponging miR-4443 in a hyperglycemic environment, thereby inhibiting bone healing. This study not only identified PRDX2 and other genes as potential biomarkers of diabetic nonunion but also clarified the regulatory role of the LINC00687/miR-4443/PRDX2 axis in hyperglycemia-induced nonunion, providing a new molecular target for clinical prevention and treatment.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"517-528"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-Engineered Endothelial Keratoplasty with Controlled Cell Density: Toward Super TEEKs.","authors":"Inès Aouimeur, Louise Coulomb, Sofiane Fraine, Zhiguo He, Guillaume Bonnet, Tomy Sagnial, Gauthier Travers, Sédao Xxx, Cyril Mauclair, Anaick Moisan, Philippe Gain, Gilles Thuret, Corantin Maurin","doi":"10.1177/19373341251381346","DOIUrl":"10.1177/19373341251381346","url":null,"abstract":"<p><p>Over the past 20 years, endothelial keratoplasty procedures have revolutionized the treatment of corneal endothelial disorders. These conditions have now become the leading indication for corneal transplantation in Western countries and account for half of all donor cornea usage. Despite their undeniable success, the global shortage of donor tissues and major disparities between nations justify the development of alternatives to donor grafts. Cell therapy using injections of suspended endothelial cells has proven effective, and tissue-engineered endothelial keratoplasty (TEEK), comprising a membrane coated with cultured endothelial cells, is under development to better mimic the native endothelial graft. Our team utilizes a femtosecond-laser-cut lens capsule disc as a bioengineering scaffold, taking advantage of this novel tissue's biocompatibility, transparency, curvature, and availability. In the present study, we provide proof of concept, in 12 TEEKs, that it is possible to control the final endothelial cell density (ECD) by varying the seeding density per mm². Cell characterization was performed through morphometric analysis of the endothelial mosaic stained with anti-NCAM (a lateral membrane marker used as a differentiation marker), using the CellPose artificial intelligence algorithm specifically trained for <i>in vitro</i> endothelium segmentation. Five criteria related to pleomorphism, polymorphism, and elongation were combined into a single endothelial quality score. The median cell viability at 28 days of culture, assessed by Hoechst 33342 and Calcein-AM staining, reached 98% (range: 83-99%). The median viable ECD (number of live cells per surface unit) in the highest-density group was 3.245 cells/mm² (range: 2.778-3.753), paving the way for the bioengineering of supra-physiological TEEKs, or \"super TEEKs\".</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"529-537"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Seeding Density Effects on Cardiac Organoid Health and Functionality for Toxicity Studies.","authors":"Anirudha Harihara, Khashayar Moshksayan, Nima Momtahan, Adela Ben-Yakar, Janet Zoldan","doi":"10.1177/19373341251392244","DOIUrl":"10.1177/19373341251392244","url":null,"abstract":"<p><p>Development of relevant human induced pluripotent stem cell-derived cardiac organoids is essential to recapitulate myocardium physiology and functionality for the assessment of drug-induced toxicity evaluations. However, the optimal conditions for culturing self-aggregating multicellular cardiac organoids are not well-elucidated, particularly the impact of noncardiomyocytes. In this study, we generated cardiac organoids at varying seeding densities to formulate organoids that meet or exceed the biological diffusion limit. We assessed their morphology, gene expression profiles, beating functionality, viability, and mitochondrial activity over time. Our results show that organoid sizes stabilize by 7 days of culture, regardless of seeding density. However, organoids seeded with 20,000 cells retained a more optimal cardiac signature that promotes cardiac maturity and minimizes fibrotic tendencies, especially when cultured for longer than 7 days. While all organoid populations maintained their beating functionalities, those seeded with 80,000 cells exhibited greater cell shedding and increased apoptosis at long-term culture. In contrast, minimal apoptosis was observed in organoids seeded with 20,000 cells after 7 days. Mitochondrial staining further revealed that organoids seeded with 20,000 cells consistently demonstrated higher metabolic activity. Taken together, organoids seeded with 20,000 cells and cultured for 7 days yielded the healthiest morphology, transcriptional signature, and viability while maintaining robust beating kinetics. Importantly, the organoid model identified in this study demonstrated a selectivity index (SI) that is over an order of magnitude larger than that of two-dimensional cultures, showing improved sensitivity to clinically relevant doxorubicin-induced cardiotoxicity, enabling more accurate dose-response evaluations that better reflect therapeutic conditions.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"570-581"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13024569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of TGF-β in Tubule Cells Increases Respiration via Upregulation of Respiratory Genes.","authors":"Kuniko Hunter, Shuvo Roy, Alissa Ice, Rachel C Evans, Roy Zent, William H Fissell","doi":"10.1177/19373341251389007","DOIUrl":"10.1177/19373341251389007","url":null,"abstract":"<p><strong>Background: </strong>Renal tubule cells lose differentiated characteristics in artificial culture, limiting their application in medical research and cell therapy. We previously showed that adding inhibitors of transforming growth factor-β (TGF-β) signaling to cell culture media increased specific transport functions characteristic of differentiated tubule cells. Transport in proximal tubule cells is energetically demanding; <i>in vivo</i>, these cells rely primarily on oxidative phosphorylation of fatty acids for adenosine triphosphate (ATP) generation. We examined whether TGF-β inhibition, with or without metformin, altered glycolysis and oxidative phosphorylation compared with standard culture conditions.</p><p><strong>Approach: </strong>Primary renal tubule cells (PRTC) were cultured with or without an inhibitor of TGF-β receptor I and with or without metformin in a 2 × 2 factorial design. First, expression of proteins in fatty acid transport and the electron transport chain was compared between conditions. The relative contributions of glycolysis and oxidative phosphorylation to ATP generation were assessed by extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). We also tested substrate-specific contributions using inhibitors of pyruvate, glutamine, and carnitine mitochondrial entry. Finally, OCR and transport were measured after 48 weeks in culture to determine durability of culture phenotype.</p><p><strong>Results: </strong>Metformin and SB431542 increased expression and phosphorylation of proteins in the electron transport chain and involved in fatty acid transport. Metformin and TGF-β inhibition increased oxidative phosphorylation. Metformin decreased glucose dependency, while combination with TGF-β inhibition increased fatty acid dependency. Differences in OCR and transport between treatment conditions persisted at 48 weeks in culture.</p><p><strong>Discussion: </strong>Renal tubule cell transport is energetically demanding, so cellular differentiation requires matching increases in energetic machinery. We found that metformin and inhibition of TGF-β increased oxygen consumption and utilization of fatty acids in cultured primary tubule cells. These data support the hypothesis that TGF-β inhibition <i>in vitro</i> not only increases expression of a broad array of transporters characteristic of the proximal tubule, as we previously showed, but also improves the supply of energy to support active transport.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"559-569"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiation of iPS Cells into Periodontal Ligament Cells.","authors":"Yufan Wu, Kengo Iwasaki, Yurie Taniguchi, Isao Ishikawa, Yoshiya Hashimoto","doi":"10.1177/19373341251389015","DOIUrl":"10.1177/19373341251389015","url":null,"abstract":"<p><p>Periodontal ligament (PDL) is a thin connective tissue that connects the tooth to the bony socket and plays a crucial role in the regeneration and maintenance of homeostasis of periodontal tissues by supplying stem/progenitor cells. Induced pluripotent stem cells (iPSCs) are highly anticipated in regenerative medicine because of their differentiation potential into a wide variety of cell types. In this study, we investigated the effects of humoral factors on iPSC differentiation by culturing iPSCs in the presence of PDL cell-derived culture supernatants. Changes in gene expression were analyzed using quantitative real-time PCR, reverse-transcription PCR, and RNA sequencing. The marker protein expression on the cell surface was assessed using flow cytometry. Periodontal regeneration was verified by microcomputed tomography and histomorphological observation in a periodontal defect model using male F344/NJcl-<i>rnu</i>/<i>rnu</i> rats. When iPSCs were cultured in the PDL culture supernatant, some cells formed clumps, and spindle-shaped cells grew out from them. Upon passaging, spindle cells increased further, and by the fifth passage, these cells occupied the entire culture. These cells (iPS-PDLs) expressed genes such as periostin and Asporin/PLAP1, and their comprehensive gene expression patterns resembled those of PDL cells. iPS-PDL cells exhibited a cell surface antigen profile of CD90+, CD73+, CD105+, CD44+, CD29+, CD14-, CD34-, CD45-, and CD19- and differentiation potential into osteoblasts, adipocytes, and chondrocytes. Transplantation of iPS-PDLs into rat periodontal defects increased the height of newly formed bone and enhanced periodontal tissue regeneration after 4 weeks. Our results showed that iPSCs differentiated into cells with properties similar to those of PDL cells in the presence of humoral factors of cultured PDL cells. Additionally, the transplantation of iPS-PDL cells into periodontal defects induces periodontal tissue regeneration. These findings provide valuable insights for developing novel periodontal regenerative therapies using iPSCs.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"548-558"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of Low-Dose Carbon Monoxide in Promoting Osseointegration.","authors":"Jiahe Li, Liang Zhou, Mingxiao Liu, Tianyu Huang, Xian He","doi":"10.1177/19373341251383864","DOIUrl":"10.1177/19373341251383864","url":null,"abstract":"<p><p>Successful osseointegration is crucial for dental implant stability, yet it remains challenging due to adverse local microenvironments, particularly infection and inflammation. While carbon monoxide (CO) has been recognized as a promising gaseous signaling molecule with diverse therapeutic properties, its clinical application faces significant limitations due to dose control challenges. To address this issue, we developed a polyetheretherketone (PEEK)-based photo-responsive implant system with surface-immobilized manganese carbonyl nanocrystals, enabling precisely controlled near-infrared light-triggered CO release. The system demonstrated efficient photoresponsiveness, achieving 13.83 ± 1.16 μM CO release within 10 min under optimal illumination conditions. <i>In vitro</i> studies revealed that low-dose CO significantly enhanced bone marrow mesenchymal stem cell osteogenic differentiation with upregulated expression of key markers, including Runx2, ALP, and OCN. In a rat femoral defect model, implants with controlled CO release exhibited significantly improved osseointegration. Comprehensive biosafety assessments confirmed the system's excellent biocompatibility without detectable organ toxicity. This research provides compelling evidence for controlled low-dose CO as an innovative strategy to enhance osseointegration, offering new possibilities for dental and orthopedic implant development, particularly for challenging clinical scenarios with compromised bone healing.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"538-547"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages Primed with Hyaluronic Acid Promote Bone Regeneration in Mouse Peri-Implantitis Model.","authors":"Yumi Miwa, Naoki Tsuji, Kazuto Hoshi, Atsuhiko Hikita","doi":"10.1177/19373341261473146","DOIUrl":"https://doi.org/10.1177/19373341261473146","url":null,"abstract":"<p><p>Peri-implantitis is characterized by bacterial infection and progressive destruction of surrounding tissues, with limited long-term therapeutic strategies. Although macrophages could have therapeutic effects on peri-implantitis, macrophage-based cell therapies have yet to be widely applied in clinical settings. In this study, we developed a macrophage-based approach using hyaluronic acid (HA)-mediated priming and evaluated its <i>in vitro</i> functions and therapeutic efficacy in a mouse model of peri-implantitis. Mouse spleen-derived macrophages were cultured with HA (1.5, 1.8, or 2.0 MDa), and phenotypes were analyzed by Reverse transcription quantitative polymerase chain reaction (RT-qPCR) (inducible nitric oxide synthase [iNOS], tumor necrosis factor-α [TNFα], vascular endothelial growth factor [VEGF], Dectin-1) and flow cytometry (F4/80, VEGF, Dectin-1). Phagocytic and migratory capacities were evaluated, and endothelial cell (HUEhT-2) migration was examined. <i>In vivo</i>, HA-treated macrophages were locally injected into a ligature-induced peri-implantitis model and assessed histologically. HA treatment of macrophages suppressed M1-related (iNOS, TNF-α) and M2a, b, c-related (Dectin-1) gene expression while enhancing the M2d-related gene (VEGF). Flow cytometry revealed an increased proportion of M2d-like cells (Dectin-1^-/VEGF⁺). HA priming enhanced macrophage phagocytic and migratory capacities and promoted HUEhT-2 migration. <i>In vivo</i>, the HA-treated macrophage group exhibited reduced fibrotic tissue formation and enhanced alveolar bone regeneration, particularly in the MΦ18 group. HA-mediated priming modulates macrophage phenotype and function, supporting its therapeutic potential.Impact StatementThe treatment for peri-implantitis includes infection control and tissue regeneration. Although macrophages exerting anti-infectious and regenerative activities could mitigate peri-implantitis, macrophage-based cell therapies have not yet been widely applied in clinical settings. In this study, we demonstrated the therapeutic efficacy of hyaluronic acid-primed macrophages in a mouse model of peri-implantitis. Our findings not only provide insights into the establishment of new therapies for peri-implantitis but also potentially enhance clinical applications of macrophage-based cell therapies for a wide range of diseases.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261473146"},"PeriodicalIF":2.8,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}