Wound repair and regeneration

Geoffrey C. Gurtner; Sabine Werner; Yann Barrandon; Michael T. Longaker

doi:10.1038/nature07039

journal article May 14, 2008

Wound repair and regeneration

Geoffrey C. Gurtner

Sabine Werner Yann Barrandon Michael T. Longaker

Nature Vol. 453 No. 7193 pp. 314-321 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/nature07039

Topics

No keywords indexed for this article. Browse by subject →

References

86

[1]

Singer, A. J. & Clark, R. A. Cutaneous wound healing. N. Engl. J. Med. 341, 738–746 (1999). 10.1056/nejm199909023411006

[2]

Aarabi, S., Longaker, M. T. & Gurtner, G. C. Hypertrophic scar formation following burns and trauma: new approaches to treatment. PLoS Med. 4, e234 (2007). 10.1371/journal.pmed.0040234

[3]

Konigova, R. & Rychterova, V. Marjolin's ulcer. Acta Chir. Plast. 42, 91–94 (2000).

[4]

Trent, J. T. & Kirsner, R. S. Wounds and malignancy. Adv. Skin Wound Care 16, 31–34 (2003). 10.1097/00129334-200301000-00014

[5]

Colwell, A. S., Longaker, M. T. & Lorenz, H. P. Fetal wound healing. Front. Biosci. 8, s1240–s1248 (2003). 10.2741/1183

[6]

Gurtner, G. C., Callaghan, M. J. & Longaker, M. T. Progress and potential for regenerative medicine. Annu. Rev. Med. 58, 299–312 (2007). 10.1146/annurev.med.58.082405.095329

[7]

National Heart, Lung, and Blood Institute. Morbidity & Mortality: 2002 Chart Book on Cardiovascular, Lung, and Blood Diseases (US Department of Health and Human Services, Bethesda, 2002).

[8]

Anderson, R. N. & Smith, B. L. Deaths: leading causes for 2001. Natl Vital Stat. Rep. 52 (9), 1–85 (2003).

[9]

Selman, M., King, T. E. & Pardo, A. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann. Intern. Med. 134, 136–151 (2001). 10.7326/0003-4819-134-2-200101160-00015

[10]

Mescher, A. L. & Neff, A. W. Regenerative capacity and the developing immune system. Adv. Biochem. Eng. Biotechnol. 93, 39–66 (2005).

[11]

Klein, L. et al. Pharmacologic therapy for patients with chronic heart failure and reduced systolic function: review of trials and practical considerations. Am. J. Cardiol. 91, 18F–40F (2003). 10.1016/s0002-9149(02)03336-2

[12]

Nichols, S. A., Dirks, W., Pearse, J. S. & King, N. Early evolution of animal cell signaling and adhesion genes. Proc. Natl Acad. Sci.USA 103, 12451–12456 (2006). 10.1073/pnas.0604065103

[13]

Adamska, M. et al. The evolutionary origin of hedgehog proteins. Curr. Biol. 17, R836–R837 (2007). 10.1016/j.cub.2007.08.010

[14]

Adamska, M. et al. Wnt and TGF-β expression in the sponge Amphimedon queenslandica and the origin of metazoan embryonic patterning. PLoS ONE 2, e1031 (2007). 10.1371/journal.pone.0001031

[15]

Adamska, M. et al. The evolutionary origin of hedgehog proteins. Curr. Biol. 17, R836–R837 (2007). 10.1016/j.cub.2007.08.010

[16]

Woolner, S., Jacinto, A. & Martin, P. The small GTPase Rac plays multiple roles in epithelial sheet fusion — dynamic studies of Drosophila dorsal closure. Dev. Biol. 282, 163–173 (2005). 10.1016/j.ydbio.2005.03.005

[17]

Samakovlis, C. et al. Genetic control of epithelial tube fusion during Drosophila tracheal development. Development 122, 3531–3536 (1996).This paper shows that the molecular machinery involved in dorsal closure in D. melanogaster embryos is also used during wound closure. 10.1242/dev.122.11.3531

[18]

Wood, W. et al. Wound healing recapitulates morphogenesis in Drosophila embryos. Nature Cell Biol. 4, 907–912 (2002). 10.1038/ncb875

[19]

Woolley, K. & Martin, P. Conserved mechanisms of repair: from damaged single cells to wounds in multicellular tissues. Bioessays 22, 911–919 (2000). 10.1002/1521-1878(200010)22:10<911::aid-bies6>3.0.co;2-v

[20]

Martin, P. & Parkhurst, S. M. Parallels between tissue repair and embryo morphogenesis. Development 131, 3021–3034 (2004). 10.1242/dev.01253

[21]

Suzuki, M., Satoh, A., Ide, H. & Tamura, K. Nerve-dependent and -independent events in blastema formation during Xenopus froglet limb regeneration. Dev. Biol. 286, 361–375 (2005). 10.1016/j.ydbio.2005.08.021

[22]

Brockes, J. P. & Kumar, A. Plasticity and reprogramming of differentiated cells in amphibian regeneration. Nature Rev. Mol. Cell Biol. 3, 566–574 (2002). 10.1038/nrm881

[23]

Endo, T., Bryant, S. V. & Gardiner, D. M. A stepwise model system for limb regeneration. Dev. Biol. 270, 135–145 (2004). 10.1016/j.ydbio.2004.02.016

[24]

Kumar, A., Godwin, J. W., Gates, P. B., Garza-Garcia, A. A. & Brockes, J. P. Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate. Science 318, 772–777 (2007). This study found that the nerve dependence of limb regeneration results from nerves producing the protein nAG, which is a ligand for Prod 1 at the surface of blastemal cells, stimulating their proliferation. 10.1126/science.1147710

[25]

Ánchez Alvarado, A. Planarian regeneration: its end is its beginning. Cell 124, 241–245 (2006). 10.1016/j.cell.2006.01.012

[26]

Klapka, N. & Müller, H. W. Collagen matrix in spinal cord injury. J. Neurotrauma 23, 422 (2006). 10.1089/neu.2006.23.422

[27]

Stichel, C. C. & Müller, H. W. The CNS lesion scar: new vistas on an old regeneration barrier. Cell Tissue Res. 294, 1–9 (1998). 10.1007/s004410051151

[28]

Grose, R. & Werner, S. Wound-healing studies in transgenic and knockout mice. Mol. Biotechnol. 28, 147–166 (2004). 10.1385/mb:28:2:147

[29]

Martin, P. & Leibovich, S. J. Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol. 15, 599–607 (2005). This review comprehensively synthesizes the voluminous literature on the role of the inflammatory process in wound repair, and the authors suggest that eliminating some physical components might ultimately improve tissue regeneration. 10.1016/j.tcb.2005.09.002

[30]

Martin, P. et al. Wound healing in the PU.1 null mouse — tissue repair is not dependent on inflammatory cells. Curr. Biol. 13, 1122–1128 (2003). 10.1016/s0960-9822(03)00396-8

[31]

Werner, S. & Grose, R. Regulation of wound healing by growth factors and cytokines. Physiol. Rev. 83, 835–870 (2003). 10.1152/physrev.2003.83.3.835

[32]

Galiano, R. D. et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am. J. Pathol. 164, 1935–1947 (2004). 10.1016/s0002-9440(10)63754-6

[33]

Bluff, J. E., Ferguson, M. W. J., O'Kane, S. & Ireland, G. Bone marrow-derived endothelial progenitor cells do not contribute significantly to new vessels during incisional wound healing. Exp. Hematol. 35, 500–506 (2007). 10.1016/j.exphem.2006.10.016

[34]

Opalenik, S. R. & Davidson, J. M. Fibroblast differentiation of bone marrow-derived cells during wound repair. FASEB J. 19, 1561–1563 (2005). 10.1096/fj.04-2978fje

[35]

Werner, S., Krieg, T. & Smola, H. Keratinocyte–fibroblast interactions in wound healing. J. Invest. Dermatol. 127, 998–1008 (2007). 10.1038/sj.jid.5700786

[36]

Szabowski, A. et al. c-Jun and JunB antagonistically control cytokine-regulated mesenchymal–epidermal interaction in skin. Cell 103, 745–755 (2000). 10.1016/s0092-8674(00)00178-1

[37]

Lovvorn, H. N. et al. Relative distribution and crosslinking of collagen distinguish fetal from adult sheep wound repair. J. Pediatr. Surg. 34, 218–223 (1999). 10.1016/s0022-3468(99)90261-0

[38]

Levenson, S. M. et al. The healing of rat skin wounds. Ann. Surg. 161, 293–308 (1965). 10.1097/00000658-196502000-00019

[39]

Comparative Genomics of the Eukaryotes

Gerald M. Rubin, Mark D. Yandell, Jennifer R. Wortman et al.

Science 2000 10.1126/science.287.5461.2204

[40]

Cole, J., Tsou, R., Wallace, K., Gibran, N. & Isik, F. Early gene expression profile of human skin to injury using high-density cDNA microarrays. Wound Repair Regen. 9, 360–370 (2001). 10.1046/j.1524-475x.2001.00360.x

[41]

Cooper, L., Johnson, C., Burslem, F. & Martin, P. Wound healing and inflammation genes revealed by array analysis of 'macrophageless' PU.1 null mice. Genome Biol. 6, R5 (2005). 10.1186/gb-2004-6-1-r5

[42]

Chang, H. Y. et al. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol. 2, E7 (2004). 10.1371/journal.pbio.0020007

[43]

Raja, K., Sivamani, M. S., Garcia, R. R. & Isseroff, R. R. Wound re-epithelialization: modulating keratinocyte migration in wound healing. Front. Biosci. 12, 2849–2868 (2007). 10.2741/2277

[44]

Chmielowiec, J. et al. c-Met is essential for wound healing in the skin. J. Cell Biol. 177, 151–162 (2007). This paper describes the essential role of the HGF receptor, MET, in wound re-epithelialization: cells deficient in this protein cannot contribute to the formation of a neo-epidermis. 10.1083/jcb.200701086

[45]

Werner, S. et al. The function of KGF in morphogenesis of epithelium and reepithelialization of wounds. Science 266, 819–822 (1994). This study was the first to use genetically modified mice to study wound repair. 10.1126/science.7973639

[46]

Braun, S., auf dem Keller, U., Steiling, H. & Werner, S. Fibroblast growth factors in epithelial repair and cytoprotection. Phil. Trans. R. Soc. Lond. B 359, 753–757 (2004). 10.1098/rstb.2004.1464

[47]

Jameson, J. et al. A role for skin γδ T cells in wound repair. Science 296, 747–749 (2002). 10.1126/science.1069639

[48]

Shirakata, Y. et al. Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing. J. Cell Sci. 118, 2363–2370 (2005). 10.1242/jcs.02346

[49]

Schäfer, M. & Werner, S. Transcriptional control of wound repair. Annu. Rev. Cell Dev. Biol. 23, 69–92 (2007). 10.1146/annurev.cellbio.23.090506.123609

[50]

Li, G. et al. c-Jun is essential for organization of the epidermal leading edge. Dev. Cell 4, 865–877 (2003). 10.1016/s1534-5807(03)00159-x

Showing 50 of 86 references

Cited By

5,590

Engineering Multiscale Scaffold‐Free Mimetic Environments Within Microfibrous Scaffolds Enhances Tendon Regeneration

Chiao‐Yu Tseng, Yen‐Ching Yang · 2026

Small Structures

Sulfonated chitosan hydrogels reprogram the inflammatory niche for accelerated skin regeneration

Peng Ding, Yingsong Zhao · 2026

Colloids and Surfaces A: Physicoche...

Hydrogel-immobilized coacervate droplets enable microenvironment-responsive sustained drug release to accelerate diabetic foot ulcers healing

Hao Li, Ruinan Wang · 2026

Journal of Controlled Release

Magnesium-based barrier membrane for guided bone regeneration: From bedside to bench and back again

Ping Li, Jiahao Chen · 2026

Biomaterials

Axolotl skin mechanics–biomimetic hydrogel promotes scarless wound healing associated with macrophage polarisation via Piezo1/YAP signalling

Manping Lin, Shaowen Cheng · 2026

Biomaterials

Mechanically promotes diabetic wound healing via restoring wound contractility

Jia Li, Li Xiao · 2026

Chemical Engineering Journal

Decoding wound healing: cellular insights and technological advances

Kayleigh A. Berthiaume Fox, Emily R. Galvin · 2026

npj Biomedical Innovations

Impact of Staphylococcus aureus intramammary infection on cellular proliferation and apoptosis on developing mammary glands of pregnant dairy heifers

M.X.S. Oliveira, K.M. Enger · 2026

Journal of Dairy Science

Procyanidin capsules attenuate PI3K/AKT-mediated mitochondrial dysfunction and accelerate skin wound healing in diabetic mice

Yifan Ping, Jiaying Wang · 2026

Materials Today Bio

Multifunctional nanocomposite hydrogel dressing with synergistic photothermal/photodynamic/electrostimulation therapy for accelerated infected wound healing

Shiyu Wang, Jianyang Shi · 2026

Composites Part A: Applied Science...

Standardized Centella asiatica extract (ECa 233) mitigates chlorhexidine-induced cytotoxicity and promotes oral wound repair via immunomodulation and angiogenesis

Nattapon Rotpenpian, Duangchewan Puengsurin · 2026

Archives of Oral Biology

Role of CTGF-LRP1 in impaired healing of cesarean section incisions

Chuqing He, Shunna Ge · 2026

Nature Communications

Uterine closure after cesarean delivery: surgical technique, biological rationale, and clinical implications

Emmanuel Bujold, Roberto Romero · 2026

American Journal of Obstetrics and...

Nanozyme‐Reinforced Hydrogel Spray as a Reactive Oxygen Species‐Driven Oxygenator to Accelerate Diabetic Wound Healing

Hao Li, Shuzhen Wei · 2025

Advanced Materials

Peptide-driven approaches in advanced wound healing materials

Chen Zhang, Gautam Sethi · 2025

Drug Discovery Today

Piezoelectric nanocomposite electrospun dressings: Tailoring mechanics for scar-free wound recovery

Chao Zhang, Wei Song · 2025

Biomaterials Advances

Antibacterial hydrogels for bacteria-infected wound treatment

Wenhan Li, Quanchi Chen · 2025

Biomedical Technology

Rapid restoration of cell phenotype and matrix forming capacity following transient nuclear softening

Ryan C. Locke, Liane M. Miller · 2025

Acta Biomaterialia

Cell migration in diabetic wound healing: Molecular mechanisms and therapeutic strategies (Review)

Jielin Song, Tong Zhao · 2025

International Journal of Molecular...

Recent Advances in Asymmetric Wettability Dressings for Wound Exudate Management

Fang Wang, Wenqing He · 2025

Research

Metrics

5,590

Citations

86

References

Details

Published: May 14, 2008
Vol/Issue: 453(7193)
Pages: 314-321
License: View

Authors

Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA

Cite This Article

Geoffrey C. Gurtner, Sabine Werner, Yann Barrandon, et al. (2008). Wound repair and regeneration. Nature, 453(7193), 314-321. https://doi.org/10.1038/nature07039

Wound repair and regeneration

You May Also Like