Academic Journal
Reprogramming the wound microenvironment: identity remodeling strategies for fibroblasts, keratinocytes, and macrophages.
| Τίτλος: | Reprogramming the wound microenvironment: identity remodeling strategies for fibroblasts, keratinocytes, and macrophages. |
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| Συγγραφείς: | Wang J; Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Department of Hand surgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Department of Pediatric Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China., Chen M; Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Department of Hand surgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Department of Pediatric Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China., Wei J; Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Department of Hand surgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Department of Pediatric Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China., Chen X; Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Department of Hand surgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Department of Pediatric Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Luzhou Key Laboratory for Prevention and Treatment of Orthopedic Diseases Through Integrated Traditional Chinese and Western Medicine, Luzhou, Sichuan, China., Wang C; Mianyang Orthopaedic Hospital, Mianyang, Sichuan, China., Feng H; Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Department of Hand surgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Department of Pediatric Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China. |
| Πηγή: | Frontiers in immunology [Front Immunol] 2026 Jul 20; Vol. 17, pp. 1892931. Date of Electronic Publication: 2026 Jul 20 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| Ιατρικοί όροι (MeSH): | Macrophages*/metabolism , Macrophages*/physiology , Keratinocytes*/metabolism , Keratinocytes*/physiology , Fibroblasts*/metabolism , Fibroblasts*/physiology , Cellular Reprogramming* , Wound Healing* , Cellular Microenvironment*, Humans ; Animals |
| Περίληψη: | The core pathology of chronic non-healing wounds is the dysfunction of wound-repair cells-a 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 "four-dimensional technology toolbox" 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-overemphasis on technique listing, weak mechanistic integration, and lack of translational critique-we 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 "personalized diagnosis → intelligent sequential delivery → closed-loop healing monitoring". 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-from fundamental mechanisms to clinical translation. (Copyright © 2026 Wang, Chen, Wei, Chen, Wang and Feng.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
| Contributed Indexing: | Keywords: cell reprogramming; epigenetic regulation; fibroblasts; keratinocytes; macrophages; metabolic reprogramming; trained immunity; wound repair |
| Entry Date(s): | Date Created: 20260804 Date Completed: 20260804 Latest Revision: 20260804 |
| Update Code: | 20260804 |
| PubMed Central ID: | PMC13429392 |
| DOI: | 10.3389/fimmu.2026.1892931 |
| PMID: | 42548532 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2026.1892931 |