{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T02:37:34Z","timestamp":1794278254697,"version":"4.9.0"},"reference-count":122,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The core pathology of chronic non-healing wounds is the dysfunction of wound-repair cells\u2014a molecular defect that conventional passive therapies can hardly correct at its root. Cell reprogramming techniques, by actively rewriting cell identity, have therefore brought a paradigm shift to wound repair. Herein, we propose a systematic \u201cfour-dimensional technology toolbox\u201d for wound cell reprogramming, comprising transcription factor-mediated, small-molecule-induced, epigenetic and metabolic regulation, and nanomaterial-assisted delivery. Using this toolbox as the main thread, we comprehensively integrate three core cell-identity reprogramming strategies: fibroblasts (from a profibrotic scar-forming phenotype to a pro-regenerative repair-competent phenotype), keratinocytes (restoring the endogenous regenerative capacity of keratinocytes to reconstruct the epidermal barrier), and macrophages (from a pro-inflammatory pathological state to a reparative homeostatic phenotype). Remedying the principal weaknesses of existing reviews\u2014overemphasis on technique listing, weak mechanistic integration, and lack of translational critique\u2014we dissect the key molecular mechanisms layer by layer and critically evaluate the core clinical-translation bottlenecks, including safety, spatiotemporal precision, and model systems. Finally, we spotlight emerging frontiers such as single-cell multi-omics navigation, AI-driven temporally programmed smart materials, and trained immunity, and discuss how they propel the field from proof-of-concept toward a precision systems-engineering paradigm of \u201cpersonalized diagnosis \u2192 intelligent sequential delivery \u2192 closed-loop healing monitoring\u201d. This work not only offers a novel intervention paradigm for the core challenges of treating chronic non-healing wounds like diabetic foot ulcers, but also delivers a panoramic theoretical framework and practical guidance for precision reprogramming therapy\u2014from fundamental mechanisms to clinical translation.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1892931","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T04:21:23Z","timestamp":1784521283000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Reprogramming the wound microenvironment: identity remodeling strategies for fibroblasts, keratinocytes, and macrophages"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Department of Hand surgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Department of Pediatric Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Department of Hand surgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Department of Pediatric Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Department of Hand surgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Department of Pediatric Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Department of Hand surgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Department of Pediatric Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Luzhou Key Laboratory for Prevention and Treatment of Orthopedic Diseases Through Integrated Traditional Chinese and Western Medicine","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglong","family":"Wang","sequence":"additional","affiliation":[{"name":"Mianyang Orthopaedic Hospital","place":["Mianyang, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huirong","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Department of Hand surgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Department of Pediatric Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1001\/jama.2023.10578","article-title":"Diabetic foot ulcers","volume":"330","author":"Armstrong","year":"2023","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2022.31.10.882","article-title":"Impaired wound healing in diabetes","volume":"31","author":"Swoboda","year":"2022","journal-title":"J Wound Care"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2023.0149","article-title":"Macrophage and neutrophil dysfunction in diabetic wounds","volume":"13","author":"Clayton","year":"2024","journal-title":"Adv Wound Care"},{"key":"B4","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/dmrr.2700","article-title":"IWGDF guidance on use of interventions to enhance the healing of chronic ulcers of the foot in diabetes","volume":"32","author":"Game","year":"2015","journal-title":"Diabetes\/Metabolism Res Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-019-00495-x","article-title":"Diabetic foot ulcers: Appraising standard of care and reviewing new trends in management","volume":"21","author":"Aldana","year":"2019","journal-title":"Am J Clin Dermatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25073702","article-title":"Bioengineering skin substitutes for wound management\u2014perspectives and challenges","volume":"25","author":"Kondej","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0477-4","article-title":"In vivo reprogramming of wound-resident cells generates skin epithelial tissue","volume":"561","author":"Kurita","year":"2018","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.30574\/msabp.2025.15.2.0052","article-title":"Origin and evolution of induced pluripotent stem cells (IPSCs)","volume":"15","author":"Bandyopadhyay","year":"2025","journal-title":"Magna Scientia Advanced Biol Pharm"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/pcmedi\/pbac004","article-title":"Tumorigenicity risk of iPSCs in vivo: nip it in the bud","volume":"5","author":"Zhong","year":"2022","journal-title":"Precis Clin Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-025-10929-1","article-title":"Direct lineage reprogramming of fibroblasts into functional keratinocyte-like cells via BMI1 and FGFR2b for diabetic wound repair","volume":"21","author":"Ma","year":"2025","journal-title":"Stem Cell Rev Rep"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2842","article-title":"Reduction of fibrosis and scar formation by partial reprogramming in vivo","volume":"36","author":"Doeser","year":"2018","journal-title":"Stem Cells"},{"key":"B12","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/bs.pmbts.2023.01.001","article-title":"Mechanisms of DNA methylation and histone modifications","volume":"197","author":"Acharjee","year":"2023","journal-title":"Prog Mol Biol Transl Sci"},{"key":"B13","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/s41576-023-00580-2","article-title":"Methods and applications for single-cell and spatial multi-omics","volume":"24","author":"Vandereyken","year":"2023","journal-title":"Nat Rev Genet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12943-024-02064-1","article-title":"Decoding the spatiotemporal heterogeneity of tumor-associated macrophages","volume":"23","author":"Chu","year":"2024","journal-title":"Mol Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00335-z","article-title":"Direct cell reprogramming: approaches, mechanisms and progress","volume":"22","author":"Wang","year":"2021","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.8","article-title":"A decade of transcription factor-mediated reprogramming to pluripotency","volume":"17","author":"Takahashi","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1016\/j.cell.2016.11.052","article-title":"In vivo amelioration of age-associated hallmarks by partial reprogramming","volume":"167","author":"Ocampo","year":"2016","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1089\/cell.2014.0089","article-title":"Transdifferentiation of fibroblasts by defined factors","volume":"17","author":"Zhao","year":"2015","journal-title":"Cell Reprogramming"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.182844","article-title":"Reprogramming of epidermal keratinocytes by PITX1 transforms the cutaneous cellular landscape and promotes wound healing","volume":"9","author":"Overmiller","year":"2024","journal-title":"JCI Insight"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2017.07.003","article-title":"Chemical reprogramming and transdifferentiation","volume":"46","author":"Xie","year":"2017","journal-title":"Curr Opin Genet Dev"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2305085120","article-title":"Pharmacological YAP activation promotes regenerative repair of cutaneous wounds","volume":"120","author":"Grzelak","year":"2023","journal-title":"Proc Natl Acad Sci"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/smsc.202500140","article-title":"Sustained-release sitagliptin microneedles for scar prevention via fibroblast-to-adipocyte conversion","volume":"5","author":"Zhang","year":"2025","journal-title":"Small Sci"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.07.031","article-title":"Targeted silencing of Engrailed-1 reprograms profibrotic fibroblast lineage for scarless wound healing","volume":"33","author":"Xu","year":"2025","journal-title":"Mol Ther"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s44321-025-00265-9","article-title":"Chemical reprogramming ameliorates cellular hallmarks of aging and extends lifespan","volume":"17","author":"Schoenfeldt","year":"2025","journal-title":"EMBO Mol Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2337\/db23-0258","article-title":"Reepithelialization of diabetic skin and mucosal wounds is rescued by treatment with epigenetic inhibitors","volume":"73","author":"Yang","year":"2023","journal-title":"Diabetes"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.114988","article-title":"Epigenetic orchestration of RNA m6A methylation in wound healing and post-wound events","volume":"21","author":"Zhang","year":"2025","journal-title":"Int J Biol Sci"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1639650","article-title":"Long-term hyperglycaemia exerts contrasting effects on M1- and M2-like macrophages","volume":"16","author":"Margaryan","year":"2025","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70035","article-title":"Compressive forces induce epigenetic activation of aged human dermal fibroblasts through ERK signaling pathway","volume":"24","author":"Liu","year":"2025","journal-title":"Aging Cell"},{"key":"B30","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.actbio.2021.06.023","article-title":"From influenza to COVID-19: Lipid nanoparticle mRNA vaccines at the frontiers of infectious diseases","volume":"131","author":"Pilkington","year":"2021","journal-title":"Acta Biomater"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2322935121","article-title":"Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle-mRNA formulation","volume":"121","author":"Wang","year":"2024","journal-title":"PNAS"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03786-0","article-title":"Triple-targeting miRNA-loaded core-shell nanoparticles in injectable hydrogel enable coordinated diabetic wound repair","volume":"23","author":"Guo","year":"2025","journal-title":"J Nanobiotechnol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122848","article-title":"Immunomodulatory hydrogel orchestrates pro-regenerative response of macrophages and angiogenesis for chronic wound healing","volume":"314","author":"Kuan","year":"2024","journal-title":"Biomaterials"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S50046","article-title":"Fibroblasts and myofibroblasts in wound healing","volume":"7","author":"Darby","year":"2014","journal-title":"Clin Cosmetic Investigational Dermatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.70014","article-title":"Overview of oxidative stress and inflammation in diabetes","volume":"16","author":"Weinberg Sibony","year":"2024","journal-title":"J Diabetes"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/6649314","article-title":"Similarities between tumour immune response and chronic wound microenvironment: Influence of mesenchymal stromal\/stem cells","volume":"2021","author":"Peta","year":"2021","journal-title":"J Immunol Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.03.783","article-title":"769 single cell transcriptomics reveals dermal fibroblast heterogeneity and a progenitor population that shapes fibroblast heterogeneity","volume":"140","author":"Chen","year":"2020","journal-title":"J Invest Dermatol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.jid.2024.06.1281","article-title":"Integrated single-cell analysis reveals spatially and temporally dynamic heterogeneity in fibroblast states during wound healing","volume":"145","author":"Almet","year":"2024","journal-title":"J Invest Dermatol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2024.110982","article-title":"Single-cell RNA sequencing reveals the heterogeneity of myofibroblasts in wound repair","volume":"117","author":"Liu","year":"2024","journal-title":"Genomics"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00799-2","article-title":"Cardiac fibroblasts and mechanosensation in heart development, health and disease","volume":"20","author":"Pesce","year":"2022","journal-title":"Nat Rev Cardiol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/01.gox.0001015136.74818.64","article-title":"11. Piezo inhibition prevents and rescues scarring by targeting the adipocyte to fibroblast transition","volume":"12","author":"Griffin","year":"2024","journal-title":"Plast Reconstructive Surg Global Open"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/life14030377","article-title":"Roles of mechanosensitive channel Piezo1 in wound healing and scar formation","volume":"14","author":"Rennekampff","year":"2024","journal-title":"Life"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1097\/01.gox.0001015212.91741.03","article-title":"30. The remodeling phase of wound healing: A multi-omic approach","volume":"12","author":"He","year":"2024","journal-title":"Plast Reconstructive Surg Global Open"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1097\/01.xcs.0000894508.92389.a2","article-title":"Inhibition of Yes-associated protein promotes skin wound regeneration in large animals","volume":"235","author":"Januszyk","year":"2022","journal-title":"J Am Coll Surgeons"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2869","DOI":"10.1016\/j.jid.2025.03.039","article-title":"Piezo1-mediated calcium flux transfers mechanosignal to Yes-associated protein to stimulate matrix production in keloid","volume":"145","author":"Liao","year":"2025","journal-title":"J Invest Dermatol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e17-01-0014","article-title":"Mechanical regulation of cardiac fibroblast profibrotic phenotypes","volume":"28","author":"Herum","year":"2017","journal-title":"Mol Biol Cell"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202517631","article-title":"ECM-stiffness mediated persistent fibroblast activation requires integrin and formin dependent chromatin remodeling","author":"Packirisamy","year":"2026","journal-title":"Adv Sci"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106570","article-title":"Changes in nascent chromatin structure regulate activation of the pro-fibrotic transcriptome and myofibroblast emergence in organ fibrosis","volume":"26","author":"Basta","year":"2023","journal-title":"iScience"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202303369","article-title":"Actomyosin activity and Piezo1 activity synergistically drive urinary system fibroblast activation","volume":"10","author":"Chen","year":"2023","journal-title":"Adv Sci"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2024.03.274","article-title":"Impaired epigenetic reprogramming prevents fibroblast to myofibroblast transition in diabetic wounds","volume":"79","author":"Davis","year":"2024","journal-title":"J Vasc Surg"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-eular.3792","article-title":"Sat0318 epigenetic regulation of FRA2 by JMJD3 regulates fibroblast activation in systemic sclerosis","volume":"76","author":"Bergmann","year":"2017","journal-title":"Ann Rheumatic Dis"},{"key":"B52","doi-asserted-by":"publisher","first-page":"33117","DOI":"10.1038\/s41598-025-17114-x","article-title":"Effects of Slit2 on hypertrophic scar formation: an in vitro study in fibroblasts","volume":"15","author":"Cui","year":"2025","journal-title":"Sci Rep"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1126\/science.aai8792","article-title":"Regeneration of fat cells from myofibroblasts during wound healing","volume":"355","author":"Plikus","year":"2017","journal-title":"Science"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.12659\/msm.928933","article-title":"Functional dissection of CD26 and its pharmacological inhibition by sitagliptin during skin wound healing","volume":"27","author":"Jiang","year":"2021","journal-title":"Med Sci Monit"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14032","article-title":"Implanting mechanically reprogrammed fibroblasts for aged tissue regeneration and wound healing","volume":"23","author":"Roy","year":"2023","journal-title":"Aging Cell"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.26502\/jbsb.5107054","article-title":"Role of transcription factors and microRNAs in regulating fibroblast reprogramming in wound healing","volume":"6","author":"Rai","year":"2023","journal-title":"J Bioinf Syst Biol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2021.0030","article-title":"Keratinocyte growth factor-based strategies for wound re-epithelialization","volume":"28","author":"B\u00e1rtolo","year":"2021","journal-title":"Tissue Eng Part B Rev"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.2174\/0113862073314510240612101052","article-title":"Promoter hypermethylation downregulates miR-125b-5p and miR-199b-5p targeting of \u0394Np63, resulting in PI3K\/AKT\/mTOR pathway activation and keratinocyte differentiation","volume":"28","author":"Ding","year":"2024","journal-title":"Comb Chem High Throughput Screening"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2025.1547044","article-title":"Towards propagation of epidermal cells for wound repair: glass, as cell culture substrate, enhances proliferation and migration of human keratinocytes","volume":"13","author":"Shahin","year":"2025","journal-title":"Front Bioeng Biotechnol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.ads0594","article-title":"HDAC5 deacetylates cytosolic ACTN4 during skin reepithelialization and represents a therapeutic target for chronic wound healing","volume":"17","author":"Zhang","year":"2025","journal-title":"Sci Transl Med"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.179017","article-title":"The STAT3\/SETDB2 axis dictates NF-\u03baB\u2013mediated inflammation in macrophages during wound repair","volume":"9","author":"Mangum","year":"2024","journal-title":"JCI Insight"},{"key":"B62","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/s41467-025-67456-3","article-title":"IL-17A is increased in diabetic wounds and impairs keratinocyte function via histone demethylase JMJD3","volume":"17","author":"Moon","year":"2025","journal-title":"Nat Commun"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1974175","article-title":"m6A reader YTHDC1 modulates autophagy by targeting SQSTM1 in diabetic skin","volume":"18","author":"Liang","year":"2022","journal-title":"Autophagy"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2025.101787","article-title":"Lactylation-driven METTL3 regulates wound healing by enhancing m6A\/HNRNPA2B1\/DNMT1 signaling in keratinocytes","volume":"13","author":"Hu","year":"2025","journal-title":"Genes Dis"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2025.1593390","article-title":"A comprehensive characterization of metabolic signatures-hypoxia, glycolysis, and lactylation-in non-healing diabetic foot ulcers","volume":"12","author":"Hu","year":"2025","journal-title":"Front Mol Biosci"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-022-02280-6","article-title":"Expression of PKM2 in wound keratinocytes is coupled to angiogenesis during skin repair in vivo and in HaCaT keratinocytes in vitro","volume":"101","author":"Sych","year":"2023","journal-title":"J Mol Med (Berlin Germany)"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1468301","article-title":"Sequencing of messenger RNA in the healing process of diabetes foot ulcer","volume":"15","author":"Wang","year":"2024","journal-title":"Front Endocrinol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b20-00587","article-title":"Human induced pluripotent stem cell-based skin for assessing transdermal drug permeability and irritancy","volume":"44","author":"Naito","year":"2020","journal-title":"Biol Pharm Bull"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v15.i11.2177","article-title":"Macrophages: key players in diabetic wound healing","volume":"15","author":"Zhou","year":"2024","journal-title":"World J Diabetes"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02993","article-title":"New insights on the role of lipid metabolism in the metabolic reprogramming of macrophages","volume":"10","author":"Batista-Gonzalez","year":"2020","journal-title":"Front Immunol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2025.101780","article-title":"Dynamic multistage nanozyme hydrogel reprograms diabetic wound microenvironment: synergistic oxidative stress alleviation and mitochondrial restoration","volume":"32","author":"Yan","year":"2025","journal-title":"Mater Today Bio"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.23407","article-title":"Mitochondrial dysfunction and oxidative stress in diabetic wound","volume":"37","author":"Jiang","year":"2023","journal-title":"J Biochem Mol Toxicol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01462","article-title":"The metabolic signature of macrophage responses","volume":"10","author":"Viola","year":"2019","journal-title":"Front Immunol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s11658-023-00503-3","article-title":"Metabolite itaconate in host immunoregulation and defense","volume":"28","author":"Yang","year":"2023","journal-title":"Cell Mol Biol Lett"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1101\/2025.05.12.653532","article-title":"SIRT4 controls macrophage function and wound healing through control of protein itaconylation in mice","author":"Anderson","year":"2025","journal-title":"bioRxiv"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2025.1638356","article-title":"KDM5A, a H3K4me3 demethylase, regulates skin wound healing by promoting M2 macrophage polarization via suppression of Socs1","volume":"16","author":"Zhang","year":"2025","journal-title":"Front Physiol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202504920","article-title":"Restoring histone acetylation accelerates diabetic wound repair by improving the spatiotemporal dynamics of macrophages","volume":"12","author":"Singh","year":"2025","journal-title":"Adv Sci"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining trained immunity and its role in health and disease","volume":"20","author":"Netea","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1098","article-title":"Trained immunity: a program of innate immune memory in health and disease","volume":"352","author":"Netea","year":"2016","journal-title":"Science"},{"key":"B80","doi-asserted-by":"publisher","first-page":"10580","DOI":"10.1038\/s41467-025-65659-2","article-title":"A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models","volume":"16","author":"Lv","year":"2025","journal-title":"Nat Commun"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01479-0","article-title":"Macrophage function in adipose tissue homeostasis and metabolic inflammation","volume":"24","author":"Chavakis","year":"2023","journal-title":"Nat Immunol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"88","DOI":"10.3390\/polym13010088","article-title":"Modulation of macrophages M1\/M2 polarization using carbohydrate-functionalized polymeric nanoparticles","volume":"13","author":"Andrade","year":"2020","journal-title":"Polymers"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1078\/0171-2985-00089","article-title":"Binding properties of the mannose receptor","volume":"204","author":"Martinez-Pomares","year":"2001","journal-title":"Immunobiology"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adw3834","article-title":"Cascade-targeting pH\/ROS microneedles promote scarless diabetic wound healing by macrophage metaboimmune reprogramming","volume":"11","author":"Yang","year":"2025","journal-title":"Sci Adv"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.115.162628","article-title":"Monitoring therapy response of experimental arthritis with radiolabeled tracers targeting fibroblasts, macrophages, or integrin \u03b1v\u03b23g","volume":"57","author":"Terry","year":"2016","journal-title":"J Nucl Med Off Publication Soc Nucl Med"},{"key":"B86","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/s41467-020-14433-7","article-title":"Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase","volume":"11","author":"Palmieri","year":"2020","journal-title":"Nat Commun"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.5c19664","article-title":"Mitochondrial-targeting drug-loaded nanoparticles reprogram macrophage metabolism via ROS\/NO co-elimination for diabetic wound healing","volume":"17","author":"Zhou","year":"2025","journal-title":"ACS Appl Materials Interfaces"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbaf092","article-title":"L-arginine-loaded microneedle patch enhances diabetic wound healing by regulating macrophage polarisation and mitochondrial homeostasis","volume":"12","author":"Wang","year":"2025","journal-title":"Regener Biomater"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123869","article-title":"Macrophage cell therapy enabled by interleukin-4 mRNA-loaded lipid nanoparticles to sustain a pro-reparative phenotype in inflammatory injuries","volume":"328","author":"O'Brien","year":"2025","journal-title":"Biomaterials"},{"key":"B90","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/s10735-025-10407-5","article-title":"Exosomes from miR-21-5p-modified adipose-derived stem cells promote wound healing by regulating M2 macrophage polarization in a rodent model of pressure ulcer","volume":"56","author":"Su","year":"2025","journal-title":"J Mol Histol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173090","article-title":"Macrophage M1\/M2 polarization","volume":"877","author":"Yunna","year":"2020","journal-title":"Eur J Pharmacol"},{"key":"B92","doi-asserted-by":"publisher","first-page":"359","DOI":"10.3390\/vaccines9040359","article-title":"Lipid-based nanoparticles in the clinic and clinical trials: from cancer nanomedicine to COVID-19 vaccines","volume":"9","author":"Thi","year":"2021","journal-title":"Vaccines"},{"key":"B93","doi-asserted-by":"publisher","first-page":"937","DOI":"10.3390\/vaccines11050937","article-title":"Validation of an HPLC-CAD method for determination of lipid content in LNP-encapsulated COVID-19 mRNA vaccines","volume":"11","author":"Yu","year":"2023","journal-title":"Vaccines"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2025.1693937","article-title":"Single-cell transcriptome analysis profiles cellular dynamics and transcriptional changes in diabetic wound tissues following ESWT treatment","volume":"16","author":"Li","year":"2025","journal-title":"Front Physiol"},{"key":"B95","article-title":"Gene regulatory networks at single-cell resolution: an approach to exploring the impact of genomic regulation on cellular heterogeneity","volume-title":"University of Cambridge","author":"Xu","year":"2023"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1413299111","article-title":"Dynamic regulation of human endogenous retroviruses mediates factor-induced reprogramming and differentiation potential","volume":"111","author":"Ohnuki","year":"2014","journal-title":"PNAS"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1038\/nm1613","article-title":"Endothelial-to-mesenchymal transition contributes to cardiac fibrosis","volume":"13","author":"Zeisberg","year":"2007","journal-title":"Nat Med"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.024","article-title":"Tissue-resident macrophage ontogeny and homeostasis","volume":"44","author":"Ginhoux","year":"2016","journal-title":"Immunity"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.70","article-title":"A guide to immunometabolism for immunologists","volume":"16","author":"O\u2019Neill","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05008-z","article-title":"HIF-1\u03b1-mediated metabolic reprogramming in wound macrophages sustains diabetic wound healing impairment","volume":"11","author":"Liu","year":"2019","journal-title":"Sci Transl Med"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.06.008","article-title":"The MSC: an injury drugstore","volume":"9","author":"Caplan","year":"2011","journal-title":"Cell Stem Cell"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.11.012","article-title":"An essential role for senescent cells in wound healing through secretion of PDGF-AA","volume":"31","author":"Demaria","year":"2014","journal-title":"Dev Cell"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2848","article-title":"Lineage tracing and genetic ablation of ADAM12+ perivascular cells identify a major source of profibrotic cells during acute tissue injury","volume":"18","author":"Dulauroy","year":"2012","journal-title":"Nat Med"},{"key":"B104","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1016\/j.stem.2020.03.013","article-title":"Dermal adipocyte lipolysis and myofibroblast conversion are required for efficient skin repair","volume":"26","author":"Shook","year":"2020","journal-title":"Cell Stem Cell"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-316356","article-title":"An important role of lymphatic vessel activation in limiting acute inflammation","volume":"117","author":"Huggenberger","year":"2011","journal-title":"Blood"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2024.102482","article-title":"Development and characterization of contraction-suppressed full-thickness skin wound model in rabbits","volume":"90","author":"Sharun","year":"2024","journal-title":"Tissue Cell"},{"key":"B107","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41586-020-2352-3","article-title":"Hair-bearing human skin generated entirely from pluripotent stem cells","volume":"582","author":"Lee","year":"2020","journal-title":"Nature"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2019.1071","article-title":"Microfluidic platforms for wound healing analysis","volume":"10","author":"Sivaraj","year":"2021","journal-title":"Adv Wound Care (New Rochelle)"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.040","article-title":"The stromal intervention: regulation of immunity and inflammation at the epithelial-mesenchymal barrier","volume":"168","author":"Nowarski","year":"2017","journal-title":"Cell"},{"key":"B110","doi-asserted-by":"publisher","first-page":"4007","DOI":"10.1016\/j.cell.2021.05.012","article-title":"Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring","volume":"184","author":"Mascharak","year":"2021","journal-title":"Cell"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2026.116631","article-title":"Revisiting CCL22 in autoimmune diseases: pathogenesis and clinical implications","volume":"179","author":"Zhang","year":"2026","journal-title":"Int Immunopharmacol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkad047","article-title":"Metabolic reprogramming in skin wound healing","volume":"12","author":"Wang","year":"2024","journal-title":"Burns Trauma"},{"key":"B113","doi-asserted-by":"publisher","first-page":"369","DOI":"10.3892\/mmr.2022.12886","article-title":"Dedifferentiation and in vivo reprogramming of committed cells in wound repair (Review)","volume":"26","author":"Guo","year":"2022","journal-title":"Mol Med Rep"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/j.molp.2026.03.005","article-title":"WIND1 controls cell fate transition through coordinately integrating histone acetylation and deacetylation-mediated transcriptional reprogramming during somatic embryogenesis","volume":"19","author":"Iwase","year":"2026","journal-title":"Mol Plant"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252313128","article-title":"An unbiased approach to identifying cellular reprogramming-inducible enhancers","volume":"25","author":"Klagkou","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.682143","article-title":"A scarless healing tale: Comparing homeostasis and wound healing of oral mucosa with skin and oesophagus","volume":"9","author":"Pereira","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2025.107527","article-title":"Post-transcriptional regulation of diabetic wound healing by junctional adhesion molecule A\/miR-106b axis","volume":"51","author":"Gong","year":"2025","journal-title":"Burns"},{"key":"B118","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels","volume":"330","author":"Coste","year":"2010","journal-title":"Science"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1038\/nature10137","article-title":"Role of YAP\/TAZ in mechanotransduction","volume":"474","author":"Dupont","year":"2011","journal-title":"Nature"},{"key":"B120","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1016\/j.cell.2017.10.008","article-title":"Force triggers YAP nuclear entry by regulating transport across nuclear pores","volume":"171","author":"Elosegui-Artola","year":"2017","journal-title":"Cell"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00300.2014","article-title":"Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis","volume":"308","author":"Liu","year":"2015","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba2374","article-title":"Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring","volume":"372","author":"Mascharak","year":"2021","journal-title":"Science"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1892931\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T04:21:25Z","timestamp":1784521285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1892931\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":122,"alternative-id":["10.3389\/fimmu.2026.1892931"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1892931","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]},"article-number":"1892931"}}