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Cell-based cytokine patch for localized immunomodulation and accelerated healing in rodent and porcine wounds

Abstract

Wounds can become chronic if the biological processes that coordinate tissue repair, including immune cell activity and matrix remodelling, become dysregulated. Current treatments mainly focus on a wound’s physical properties, such as moisture and pressure, and do not restore the disrupted molecular pathways. Here we show a removable patch containing engineered human cells that continuously release native cytokines and that can accelerate healing in rodent and porcine full-thickness wounds. The patch is a polydimethylsiloxane structure that houses alginate-encapsulated human retinal epithelial cells engineered to secrete individual cytokines relevant to tissue repair. Once placed on the wound bed, the cells remain viable and locally release the cytokines over several days. Delivery of interleukin 10, interleukin 12 and transforming growth factor-beta accelerates wound healing in mice and pigs, with accompanying changes in gene expression linked to tissue repair, including pathways involved in skin development and collagen organization. This work suggests that localized, cell-based cytokine delivery may enable future wound treatments that directly modulate the cellular programs governing tissue repair.

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Fig. 1: A patch for localized delivery of cytokines to a wound bed.
The alternative text for this image may have been generated using AI.
Fig. 2: IL10, IL12 and TGF-β delivered from the patch accelerates wound healing in a murine wound model.
The alternative text for this image may have been generated using AI.
Fig. 3: IL10, IL12 and TGF-β delivered from the patch affects immune cell composition in the wound bed and upregulates transcripts important for wound healing.
The alternative text for this image may have been generated using AI.
Fig. 4: IL10, IL12 and TGF-β delivered from the patch upregulates pathways associated with wound healing.
The alternative text for this image may have been generated using AI.
Fig. 5: IL10, IL12 and TGF-β delivered from the patch accelerates wound healing in a porcine wound model.
The alternative text for this image may have been generated using AI.

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Data availability

Sequencing data for the murine scRNA-seq, murine bulk RNA-seq and pig bulk RNA-seq are available from the Sequence Read Archive with accession number PRJNA1436584. Any additional information is available from the corresponding author with reasonable request. Source data are provided with this paper.

References

  1. Sawaya, A. P. et al. Deregulated immune cell recruitment orchestrated by FOXM1 impairs human diabetic wound healing. Nat. Commun. 11, 4678 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Khanna, S. et al. Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PLoS ONE 5, e9539 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Nussbaum, S. R. et al. An economic evaluation of the impact, cost, and medicare policy implications of chronic nonhealing wounds. Value Health 21, 27–32 (2018).

    Article  PubMed  Google Scholar 

  5. Rodrigues, M., Kosaric, N., Bonham, C. A. & Gurtner, G. C. Wound healing: a cellular perspective. Physiol. Rev. 99, 665–706 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. De Rooij, L. et al. Negative pressure wound therapy does not decrease postoperative wound complications in patients undergoing mastectomy and flap fixation. Sci. Rep. 11, 9620 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Löndahl, M., Katzman, P., Nilsson, A. & Hammarlund, C. Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care 33, 998–1003 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Patton, D. et al. A meta-review of the impact of compression therapy on venous leg ulcer healing. Int. Wound J. 20, 430–447 (2023).

    Article  PubMed  Google Scholar 

  9. Caravaggi, C. et al. HYAFF 11-based autologous dermal and epidermal grafts in the treatment of noninfected diabetic plantar and dorsal foot ulcers: a prospective, multicenter, controlled, randomized clinical trial. Diabetes Care 26, 2853–2859 (2003).

    Article  PubMed  Google Scholar 

  10. Edmonds, M. & European and Australian Apligraf Diabetic Foot Ulcer Study Group. Apligraf in the treatment of neuropathic diabetic foot ulcers. Int. J. Low. Extrem. Wounds 8, 11–18 (2009).

  11. Didomenico, L., Landsman, A. R., Emch, K. J. & Landsman, A. A prospective comparison of diabetic foot ulcers treated with either a cryopreserved skin allograft or a bioengineered skin substitute. Wounds 23, 184–189 (2011).

    PubMed  Google Scholar 

  12. Cytokines in the balance. Nat. Immunol. 20, 1557 (2019).

  13. Kohli, K., Pillarisetty, V. G. & Kim, T. S. Key chemokines direct migration of immune cells in solid tumors. Cancer Gene Ther. 29, 10–21 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Carmeliet, P. & Jain, R. K. Molecular mechanisms and clinical applications of angiogenesis. Nature 473, 298–307 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. King, A., Balaji, S., Le, L. D., Crombleholme, T. M. & Keswani, S. G. Regenerative wound healing: the role of interleukin-10. Adv. Wound Care 3, 315–323 (2014).

    Article  Google Scholar 

  16. Kieran, I. et al. Interleukin-10 reduces scar formation in both animal and human cutaneous wounds: results of two preclinical and phase II randomized control studies. Wound Repair Regen. 21, 428–436 (2013).

    Article  PubMed  Google Scholar 

  17. Hamza, T., Barnett, J. B. & Li, B. Interleukin 12 a key immunoregulatory cytokine in infection applications. Int. J. Mol. Sci. 11, 789–806 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Xiao, T., Yan, Z., Xiao, S. & Xia, Y. Proinflammatory cytokines regulate epidermal stem cells in wound epithelialization. Stem Cell Res. Ther. 11, 232 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Barrientos, S., Stojadinovic, O., Golinko, M. S., Brem, H. & Tomic-Canic, M. PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing. Wound Repair Regen. 16, 585–601 (2008).

    Article  PubMed  Google Scholar 

  20. Hirshberg, J., Coleman, J., Marchant, B. & Rees, R. S. TGF-beta3 in the treatment of pressure ulcers: a preliminary report. Adv. Skin Wound Care 14, 91–95 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Roberts, N. J., Zhou, S., Diaz, L. A. & Holdhoff, M. Systemic use of tumor necrosis factor alpha as an anticancer agent. Oncotarget 2, 739–751 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Haicheur, N. et al. Cytokines and soluble cytokine receptor induction after IL-12 administration in cancer patients. Clin. Exp. Immunol. 119, 28–37 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cohen, J. IL-12 deaths: explanation and a puzzle. Science 270, 908 (1995).

    Article  CAS  PubMed  Google Scholar 

  24. Vazquez-Lombardi, R., Roome, B. & Christ, D. Molecular engineering of therapeutic cytokines. Antibodies 2, 426–451 (2013).

    Article  Google Scholar 

  25. Darwin, E. & Tomic-Canic, M. Healing chronic wounds: current challenges and potential solutions. Curr. Dermatol. Rep. 7, 296–302 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Miranda, I. et al. Properties and applications of PDMS for biomedical engineering: a review. J. Funct. Biomater. 13, 2 (2022).

    Article  CAS  Google Scholar 

  27. Lee, K. Y. & Mooney, D. J. Alginate: properties and biomedical applications. Prog. Polym. Sci. 37, 106–126 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sieving, P. A. et al. Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proc. Natl Acad. Sci. USA 103, 3896–3901 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Dunn, L. et al. Murine model of wound healing. J. Vis. Exp. 2013, e50265 (2013).

    Google Scholar 

  30. Masson-Meyers, D. S. et al. Experimental models and methods for cutaneous wound healing assessment. Int. J. Exp. Pathol. 101, 21–37 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Singer, A. J. & McClain, S. A. Development of a porcine excisional wound model. Acad. Emerg. Med. 10, 1029–1033 (2003).

    Article  PubMed  Google Scholar 

  32. Nash, A. M. et al. Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors. Sci. Adv. 8, 1032 (2022).

    Article  Google Scholar 

  33. Kauper, K. et al. Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases. Invest. Ophthalmol. Vis. Sci. 53, 7484–7491 (2012).

    Article  CAS  PubMed  Google Scholar 

  34. Eriksdotter-Jönhagen, M. et al. Encapsulated cell biodelivery of nerve growth factor to the basal forebrain in patients with Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 33, 18–28 (2012).

    Article  PubMed  Google Scholar 

  35. Dunn, K. C., Aotaki-Keen, A. E., Putkey, F. R. & Hjelmeland, L. M. ARPE-19, a human retinal pigment epithelial cell line with differentiated properties. Exp. Eye Res. 62, 155–170 (1996).

    Article  CAS  PubMed  Google Scholar 

  36. Yousef, H., Ahangar, E. R. & Varacallo, M. Physiology, Thermal Regulation (StatPearls, 2023); https://www.ncbi.nlm.nih.gov/books/NBK499843/

  37. Crum, R. J. et al. Transcriptomic, proteomic, and morphologic characterization of healing in volumetric muscle loss. Tissue Eng A 28, 941–957 (2022).

    Article  CAS  Google Scholar 

  38. Zou, J. J. et al. Structure-function analysis of the p35 subunit of mouse interleukin 12. J. Biol. Chem. 270, 5864–5871 (1995).

    Article  CAS  PubMed  Google Scholar 

  39. Chen, L., Mirza, R., Kwon, Y., DiPietro, L. A. & Koh, T. J. The murine excisional wound model: contraction revisited. Wound Repair Regen. 23, 874–877 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Hao, Y. et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol. 42, 293–304 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Satija, R., Farrell, J. A., Gennert, D., Schier, A. F. & Regev, A. Spatial reconstruction of single-cell gene expression data. Nat. Biotechnol. 33, 495–502 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411–420 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888–1902.e21 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587.e29 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jew, B. et al. Accurate estimation of cell composition in bulk expression through robust integration of single-cell information. Nat. Commun. 11, 1971 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chen, J. et al. Complement factor D regulates collagen type I expression and fibroblast migration to enhance human tendon repair and healing outcomes. Front. Immunol. 14, 1225957 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kuivaniemi, H. & Tromp, G. Type III collagen (COL3A1): gene and protein structure, tissue distribution, and associated diseases. Gene 707, 151–171 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Denigris, J., Yao, Q., Birk, E. K. & Birk, D. E. Altered dermal fibroblast behavior in a collagen V haploinsufficient murine model of classic Ehlers-Danlos syndrome. Connect. Tissue Res. 57, 1–9 (2016).

    Article  CAS  PubMed  Google Scholar 

  49. Park, A. C. et al. Deficits in Col5a2 expression result in novel skin and adipose abnormalities and predisposition to aortic aneurysms and dissections. Am. J. Pathol. 187, 2300–2311 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Theocharidis, G. et al. Type VI collagen regulates dermal matrix assembly and fibroblast motility. J. Invest. Dermatol. 136, 74–83 (2016).

    Article  CAS  PubMed  Google Scholar 

  51. Pyo, M. et al. HSP47, a collagen-specific chaperone protein, is a limiting factor for type I collagen secretion in aged skin. J. Dermatol. Sci. 86, e92 (2017).

    Article  Google Scholar 

  52. Engelhardt, E. et al. Chemokines IL-8, GROα, MCP-1, IP-10, and Mig are sequentially and differentially expressed during phase-specific infiltration of leukocyte subsets in human wound healing. Am. J. Pathol. 153, 1849–1860 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ishi, S. et al. Cutaneous wound healing promoted by topical administration of heat-killed Lactobacillus plantarum KB131 and possible contribution of CARD9-mediated signaling. Sci. Rep. 13, 15917 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ridiandries, A., Tan, J. T. M. & Bursill, C. A. The role of chemokines in wound healing. Int. J. Mol. Sci. 19, 3217 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Wietecha, M. S. et al. Activin-mediated alterations of the fibroblast transcriptome and matrisome control the biomechanical properties of skin wounds. Nat. Commun. 11, 2604 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wang, G. et al. Bacteria induce skin regeneration via IL-1β signaling. Cell Host Microbe 29, 777–791 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Jones, A. M. et al. The clinical significance and impact of interleukin 15 on keratinocyte cell growth and migration. Int. J. Mol. Med. 38, 679–686 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hsu, J. Y. C. et al. Matrix metalloproteinase-2 facilitates wound healing events that promote functional recovery after spinal cord injury. J. Neurosci. 26, 9841–9850 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Le, H. T. et al. Platelet factor 4 (CXCL4/PF4) upregulates matrix metalloproteinase-2 (MMP-2) in gingival fibroblasts. Sci. Rep. 12, 18636 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gu, M. et al. Chemokine platelet factor 4 accelerates peripheral nerve regeneration by regulating Schwann cell activation and axon elongation. Neural Regen. Res. 19, 190–195 (2023).

    Article  Google Scholar 

  61. Huguier, V. et al. Oncostatin M exerts a protective effect against excessive scarring by counteracting the inductive effect of TGFβ1 on fibrosis markers. Sci. Rep. 9, 2113 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  62. DiPietro, L. A., Burdick, M., Low, Q. E., Kunkel, S. L. & Strieter, R. M. MIP-1alpha as a critical macrophage chemoattractant in murine wound repair. J. Clin. Invest. 101, 1693–1698 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Li, Y., Jalili, R. B. & Ghahary, A. Accelerating skin wound healing by M-CSF through generating SSEA-1 and -3 stem cells in the injured sites. Sci. Rep. 6, 28979 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Wang, J.-M. et al. Boosting UPR transcriptional activator XBP1 accelerates acute wound healing. PNAS Nexus 2, pgad050 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Wu, M. et al. Essential roles for early growth response transcription factor Egr-1 in tissue fibrosis and wound healing. Am. J. Pathol. 175, 1041–1055 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Silva, W. N. et al. Macrophage-derived GPNMB accelerates skin healing. Exp. Dermatol. 27, 630–635 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Inoue, Y. et al. Macrophage-specific, mafb-deficient mice showed delayed skin wound healing. Int. J. Mol. Sci. 23, 9346 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Caley, M. P., Martins, V. L. C. & O’Toole, E. A. Metalloproteinases and wound healing. Adv. Wound Care 4, 225–234 (2015).

    Article  Google Scholar 

  69. Hwang, S. J. et al. Human collagen alpha-2 type I stimulates collagen synthesis, wound healing, and elastin production in normal human dermal fibroblasts (HDFs). BMB Rep. 53, 539 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Xie, Z. et al. Gene set knowledge discovery with Enrichr. Curr. Protoc. 1, e90 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kuleshov, M. V. et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 44, W90–W97 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Chen, E. Y. et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics 14, 128 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Browaeys, R., Saelens, W. & Saeys, Y. NicheNet: modeling intercellular communication by linking ligands to target genes. Nat. Methods 17, 159–162 (2019).

    Article  PubMed  Google Scholar 

  74. Shi, G. et al. Platelet factor 4 mediates vascular smooth muscle cell injury responses. Blood 121, 4417–4427 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Tantilertanant, Y. et al. Cyclic tensile force-upregulated IL6 increases MMP3 expression by human periodontal ligament cells. Arch. Oral Biol. 107, 104495 (2019).

    Article  CAS  PubMed  Google Scholar 

  76. Liu, M., Wilson, N. O., Hibbert, J. M. & Stiles, J. K. STAT3 Regulates MMP3 in heme-induced endothelial cell apoptosis. PLoS ONE 8, e71366 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Buka, R. J. et al. PF4 activates the c-Mpl–Jak2 pathway in platelets. Blood 143, 64–69 (2023).

    Article  Google Scholar 

  78. Dinca, S. C. et al. Novel mechanism for OSM-promoted extracellular matrix remodeling in breast cancer: LOXL2 upregulation and subsequent ECM alignment. Breast Cancer Res. 23, 56 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Cuevas, E. P. et al. LOXL2 drives epithelial-mesenchymal transition via activation of IRE1-XBP1 signalling pathway. Sci. Rep. 7, 44988 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kuo, T. Y. et al. Skin wound healing assessment via an optimized wound array model in miniature pigs. Sci. Rep. 12, 445 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Sakamoto, M. et al. Cultured human epidermis combined with meshed skin autografts accelerates epithelialization and granulation tissue formation in a rat model. Ann. Plast. Surg. 78, 651–658 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Matias, M. A., Saunus, J. M., Ivanovski, S., Walsh, L. J. & Farah, C. S. Accelerated wound healing phenotype in Interleukin 12/23 deficient mice. J. Inflamm. 8, 39 (2011).

    Article  CAS  Google Scholar 

  83. Abu-Khalaf, J. M., Al-Ghussain, L. & Al-Halhouli, A. Fabrication of stretchable circuits on polydimethylsiloxane (PDMS) pre-stretched substrates by inkjet printing silver nanoparticles. Materials 11, 2377 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Denis, M. C. & Huber, B. T. Native and recombinant interleukin-2, two functionally distinct molecules. Mol. Immunol. 40, 279–286 (2003).

    Article  CAS  PubMed  Google Scholar 

  85. Li, Q. et al. Advances of hydrogel combined with stem cells in promoting chronic wound healing. Front. Chem. 10, 1038839 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Srifa, W. et al. Cas9-AAV6-engineered human mesenchymal stromal cells improved cutaneous wound healing in diabetic mice. Nat. Commun. 11, 2470 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Freedman, B. R. et al. Breakthrough treatments for accelerated wound healing. Sci. Adv. 9, eade7007 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Patil, P. et al. Reactive oxygen species–degradable polythioketal urethane foam dressings to promote porcine skin wound repair. Sci. Transl. Med. 14, eabm6586 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Notodihardjo, S. C. et al. A comparison of the wound healing process after the application of three dermal substitutes with or without basic fibzroblast growth factor impregnation in diabetic mice. J. Plast. Reconstr. Aesthet. Surg. 73, 1547–1555 (2020).

    Article  PubMed  Google Scholar 

  90. Larouche, J., Sheoran, S., Maruyama, K. & Martino, M. M. Immune regulation of skin wound healing: mechanisms and novel therapeutic targets. Adv. Wound Care 7, 209–231 (2018).

    Article  Google Scholar 

  91. Barrientos, S., Stojadinovic, O., Golinko, M. S., Brem, H. & Tomic-Canic, M. Growth factors and cytokines in wound healing. Wound Repair Regen. 16, 585–601 (2008).

    Article  PubMed  Google Scholar 

  92. Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Beeton, C., Garcia, A. & Chandy, K. G. Drawing blood from rats through the saphenous vein and by cardiac puncture. J. Vis. Exp. https://doi.org/10.3791/266 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Bankhead, P. et al. QuPath: open source software for digital pathology imtypes of age analysis. Sci. Rep. 7, 16878 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Patel, H. et al. nf-core/rnaseq: nf-core/rnaseq v3.14.0 - Hassium Honey Badger. Zenodo https://doi.org/10.5281/zenodo.10471647 (2024).

  96. Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by Defense Advanced Research Projects Agency (D20AC00002) for O.V., T.C.-K., S.F.B. and B.N.B. We thank R. Crum and M. Lebaudy for their assistance with the canine surgery.

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Authors

Contributions

C.C.S., E.L.K. and O.V. designed the studies. C.C.S., E.L.K, G.A., S.J., S.F., M.N.B., D.V., M.K. and G.M.D. conducted the experiments. R.G. designed the device form. C.C.S. and E.L.K. analysed data, carried out statistical analyses and prepared displays communicating datasets. O.V., T.C.-K., S.F.B. and B.N.B. provided advice and technical support throughout. O.V. supervised the study. C.C.S. wrote the paper with assistance from E.L.K, S.J., B.N.B., S.F.B. and O.V. All authors discussed the results and the preparation of the paper.

Corresponding author

Correspondence to Omid Veiseh.

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Competing interests

C.C.S., T.C.K. and O.V. declare interests via patents filed by Rice University and Carnegie Mellon University on the wound patch described in this paper. C.C.S., T.C.K. and O.V. hold equity in and are cofounders of Curada Bio. The other authors declare no competing interests.

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Schreib, C.C., Kelley, E.L., Audia, G. et al. Cell-based cytokine patch for localized immunomodulation and accelerated healing in rodent and porcine wounds. Nat. Biomed. Eng (2026). https://doi.org/10.1038/s41551-026-01687-7

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