Bioinspired Collagen Scaffold Loaded with bFGF-Overexpressing Human Mesenchymal Stromal Cells Accelerating Diabetic Skin Wound Healing via HIF-1 Signal Pathway Regulated Neovascularization.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 101504991 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1944-8252 (Electronic) Linking ISSN: 19448244 NLM ISO Abbreviation: ACS Appl Mater Interfaces Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, D.C. : American Chemical Society
    • Subject Terms:
      Wound Healing*/drug effects ; Mesenchymal Stem Cells*/metabolism ; Fibroblast Growth Factor 2*/chemistry ; Fibroblast Growth Factor 2*/pharmacology ; Collagen*/chemistry ; Diabetes Mellitus, Experimental* ; Tissue Scaffolds*/chemistry ; Skin*/pathology ; Neovascularization, Physiologic*/drug effects ; Signal Transduction*; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Hypoxia-Inducible Factor 1/metabolism
    • Abstract:
      The healing of severe chronic skin wounds in chronic diabetic patients is still a huge clinical challenge due to complex regeneration processes and control signals. Therefore, a single approach is difficult in obtaining satisfactory therapeutic efficacy for severe diabetic skin wounds. In this study, we adopted a composite strategy for diabetic skin wound healing. First, we fabricated a collagen-based biomimetic skin scaffold. The human basic fibroblast growth factor (bFGF) gene was electrically transduced into human umbilical cord mesenchymal stromal cells (UC-MSCs), and the stable bFGF-overexpressing UC-MSCs (bFGF-MSCs) clones were screened out. Then, an inspired collagen scaffold loaded with bFGF-MSCs was applied to treat full-thickness skin incision wounds in a streptozotocin-induced diabetic rat model. The mechanism of skin damage repair in diabetes mellitus was investigated using RNA-Seq and Western blot assays. The bioinspired collagen scaffold demonstrated good biocompatibility for skin-regeneration-associated cells such as human fibroblast (HFs) and endothelial cells (ECs). The bioinspired collagen scaffold loaded with bFGF-MSCs accelerated the diabetic full-thickness incision wound healing including cell proliferation enhancement, collagen deposition, and re-epithelialization, compared with other treatments. We also showed that the inspired skin scaffold could enhance the in vitro tube formation of ECs and the early angiogenesis process of the wound tissue in vivo . Further findings revealed enhanced angiogenic potential in ECs stimulated by bFGF-MSCs, evidenced by increased AKT phosphorylation and elevated HIF-1α and HIF-1β levels, indicating the activation of HIF-1 pathways in diabetic wound healing. Based on the superior biocompatibility and bioactivity, the novel bioinspired skin healing materials composed of the collagen scaffold and bFGF-MSCs will be promising for healing diabetic skin wounds and even other refractory tissue regenerations. The bioinspired collagen scaffold loaded with bFGF-MSCs could accelerate diabetic wound healing via neovascularization by activating HIF-1 pathways.
    • References:
      J Surg Res. 1988 Jul;45(1):145-53. (PMID: 3392988)
      Rev Endocr Metab Disord. 2019 Jun;20(2):207-217. (PMID: 30937614)
      N Engl J Med. 1999 Sep 2;341(10):738-46. (PMID: 10471461)
      Stem Cell Res Ther. 2021 Aug 21;12(1):468. (PMID: 34419172)
      Stem Cells. 2007 Oct;25(10):2648-59. (PMID: 17615264)
      Cells. 2021 Sep 09;10(9):. (PMID: 34572020)
      Eur J Med Res. 2017 Mar 24;22(1):11. (PMID: 28340602)
      Macromol Biosci. 2018 Nov;18(11):e1800086. (PMID: 30160040)
      Eur J Dermatol. 2009 Sep-Oct;19(5):461-8. (PMID: 19638336)
      Free Radic Biol Med. 2020 Nov 20;160:447-457. (PMID: 32853721)
      Prog Retin Eye Res. 2022 Jul;89:101039. (PMID: 34991965)
      Biomater Res. 2016 Apr 01;20:9. (PMID: 27042331)
      Semin Plast Surg. 2021 Aug;35(3):153-158. (PMID: 34526862)
      Stem Cells Transl Med. 2016 Oct;5(10):1425-1439. (PMID: 27388239)
      N Engl J Med. 2017 Jun 15;376(24):2367-2375. (PMID: 28614678)
      Adv Skin Wound Care. 2004 Jan-Feb;17(1):24-35. (PMID: 14752324)
      Hum Cell. 2023 Jul;36(4):1253-1264. (PMID: 37067766)
      J R Soc Med. 2017 Mar;110(3):104-109. (PMID: 28116957)
      Life Sci. 2021 Mar 1;268:118932. (PMID: 33400933)
      ACS Nano. 2018 Feb 27;12(2):1023-1032. (PMID: 29406741)
      Acta Biomater. 2018 Jan 15;66:325-334. (PMID: 29203426)
      Nature. 2008 May 15;453(7193):314-21. (PMID: 18480812)
      Nat Commun. 2021 Jun 7;12(1):3363. (PMID: 34099651)
      Biomed Pharmacother. 2019 Apr;112:108615. (PMID: 30784919)
      Wound Repair Regen. 2019 Jul;27(4):324-334. (PMID: 30817065)
      Artif Cells Nanomed Biotechnol. 2013 Jun;41(3):202-12. (PMID: 23316788)
      Acc Chem Res. 2021 Mar 2;54(5):1080-1093. (PMID: 33596041)
      Cells. 2021 Jul 08;10(7):. (PMID: 34359898)
      Biomed Pharmacother. 2018 Nov;107:625-633. (PMID: 30118878)
      J Cell Mol Med. 2005 Jan-Mar;9(1):59-71. (PMID: 15784165)
      Diabetes. 2013 Jul;62(7):2588-94. (PMID: 23423568)
      J Nanobiotechnology. 2020 May 6;18(1):68. (PMID: 32375794)
      Lancet. 2005 Nov 12;366(9498):1719-24. (PMID: 16291066)
      Biomaterials. 2021 Aug;275:120963. (PMID: 34153785)
      Diabetes Care. 1995 Jan;18(1):64-9. (PMID: 7698050)
      Bull Math Biol. 2013 Aug;75(8):1377-99. (PMID: 23494144)
      Cell Biosci. 2022 Jul 12;12(1):105. (PMID: 35831878)
      Cell. 2007 Jun 29;129(7):1261-74. (PMID: 17604717)
      Mol Med Rep. 2018 Oct;18(4):3547-3554. (PMID: 30106145)
      Front Immunol. 2022 Mar 01;13:789274. (PMID: 35300324)
      Cardiovasc Res. 2000 May;46(2):250-6. (PMID: 10773228)
      J Nanobiotechnology. 2021 May 8;19(1):131. (PMID: 33964948)
      Carbohydr Polym. 2022 Jul 15;288:119404. (PMID: 35450656)
      Front Pharmacol. 2020 Aug 07;11:1193. (PMID: 32848793)
      Br J Pharmacol. 2012 Jun;166(3):877-94. (PMID: 22352879)
      Eur Rev Med Pharmacol Sci. 2015;19(14):2666-70. (PMID: 26221898)
      Stem Cell Res Ther. 2020 Jan 28;11(1):39. (PMID: 31992364)
      Stem Cell Res Ther. 2018 Jul 4;9(1):177. (PMID: 29973264)
      J Control Release. 2020 Nov 10;327:61-69. (PMID: 32768629)
    • Contributed Indexing:
      Keywords: bFGF; collagen scaffold; diabetic wound healing; mesenchymal stromal cells
    • Accession Number:
      103107-01-3 (Fibroblast Growth Factor 2)
      9007-34-5 (Collagen)
      0 (Hypoxia-Inducible Factor 1, alpha Subunit)
      0 (Hypoxia-Inducible Factor 1)
    • Publication Date:
      Date Created: 20240821 Date Completed: 20240905 Latest Revision: 20240910
    • Publication Date:
      20240910
    • Accession Number:
      PMC11378764
    • Accession Number:
      10.1021/acsami.4c08174
    • Accession Number:
      39165237