Inflammatory Microenvironment of Skin Wounds.

Zhen Wang, Fang Qi, Han Luo, Guangchao Xu, Dali Wang
Author Information
  1. Zhen Wang: Department of Plastic Surgery and Burns, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
  2. Fang Qi: Department of Plastic Surgery and Burns, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
  3. Han Luo: Department of Plastic Surgery and Burns, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
  4. Guangchao Xu: Department of Plastic Surgery and Burns, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
  5. Dali Wang: Department of Plastic Surgery and Burns, Affiliated Hospital of Zunyi Medical University, Zunyi, China.

Abstract

Wound healing is a dynamic and highly regulated process that can be separated into three overlapping and interdependent phases: inflammation, proliferation, and remodelling. This review focuses on the inflammation stage, as it is the key stage of wound healing and plays a vital role in the local immune response and determines the progression of wound healing. inflammatory cells, the main effector cells of the inflammatory response, have been widely studied, but little attention has been paid to the immunomodulatory effects of wound healing in non-inflammatory cells and the extracellular matrix. In this review, we attempt to deepen our understanding of the wound-healing microenvironment in the inflammatory stage by focusing on the interactions between cells and the extracellular matrix, as well as their role in regulating the immune response during the inflammatory stage. We hope our findings will provide new ideas for promoting tissue regeneration through immune regulation.

Keywords

References

  1. Acta Cir Bras. 2015 Apr;30(4):289-95 [PMID: 25923262]
  2. J Invest Dermatol. 2012 Feb;132(2):458-65 [PMID: 21993557]
  3. Semin Immunol. 2018 Jun;37:85-97 [PMID: 29454575]
  4. J Surg Res. 2020 Feb;246:213-223 [PMID: 31606511]
  5. Front Immunol. 2018 Feb 01;9:93 [PMID: 29449841]
  6. Matrix Biol. 2019 Jan;75-76:12-26 [PMID: 29330022]
  7. J Wound Care. 2017 Jul 2;26(7):381-397 [PMID: 28704150]
  8. J Tissue Eng Regen Med. 2020 Mar;14(3):424-440 [PMID: 31826321]
  9. Plast Surg Int. 2013;2013:243853 [PMID: 23766899]
  10. Clin Cosmet Investig Dermatol. 2021 Jun 25;14:715-721 [PMID: 34211289]
  11. Pharmacol Ther. 2015 Mar;147:123-135 [PMID: 25448040]
  12. PLoS One. 2020 Aug 18;15(8):e0237746 [PMID: 32810144]
  13. Medicine (Baltimore). 2019 Feb;98(6):e14392 [PMID: 30732182]
  14. J Dermatol Sci. 2019 Dec;96(3):159-167 [PMID: 31761388]
  15. Lancet. 2016 Jun 25;387(10038):2655-2664 [PMID: 26775126]
  16. Am J Pathol. 2009 Jul;175(1):132-47 [PMID: 19528348]
  17. Front Immunol. 2018 Jun 04;9:1099 [PMID: 29915573]
  18. Curr Rheumatol Rep. 2018 Mar 17;20(4):17 [PMID: 29550962]
  19. Acta Biomater. 2017 Apr 15;53:13-28 [PMID: 28119112]
  20. Matrix Biol Plus. 2020 Apr 22;6-7:100037 [PMID: 33543031]
  21. Monogr Oral Sci. 2014;24:52-60 [PMID: 24862594]
  22. J Biol Chem. 2000 Apr 14;275(15):11058-63 [PMID: 10753909]
  23. J Biol Chem. 2019 Sep 27;294(39):14370-14382 [PMID: 31395659]
  24. Methods Mol Biol. 2016;1423:3-15 [PMID: 27142005]
  25. Semin Immunopathol. 2017 Feb;39(2):153-163 [PMID: 27456849]
  26. J Wound Care. 2015 Mar;24(3):149-56 [PMID: 25764960]
  27. Semin Immunol. 2013 Feb;25(1):73-8 [PMID: 23768898]
  28. Curr Opin Hematol. 2015 Jan;22(1):53-9 [PMID: 25427141]
  29. Platelets. 2018 Sep;29(6):556-568 [PMID: 29442539]
  30. J Dermatol Surg Oncol. 1979 Jun;5(6):477-81 [PMID: 379076]
  31. Trends Biotechnol. 2009 Mar;27(3):158-67 [PMID: 19187989]
  32. J Dermatolog Treat. 2013 Apr;24(2):141-7 [PMID: 22007700]
  33. Clin Dev Immunol. 2012;2012:534291 [PMID: 23346185]
  34. Int J Mol Sci. 2020 Oct 28;21(21): [PMID: 33126494]
  35. JAMA Netw Open. 2021 Sep 1;4(9):e2122607 [PMID: 34477854]
  36. Medicine (Baltimore). 2017 Jun;96(22):e6881 [PMID: 28562537]
  37. Thromb Res. 2019 Jul;179:56-63 [PMID: 31078121]
  38. Nature. 1962 Jan 20;193:293-4 [PMID: 14007593]
  39. Physiol Rev. 2019 Jan 1;99(1):665-706 [PMID: 30475656]
  40. ACS Biomater Sci Eng. 2018 Apr 9;4(4):1176-1192 [PMID: 33418655]
  41. FASEB J. 2012 Jan;26(1):376-86 [PMID: 21926236]
  42. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17253-8 [PMID: 24101477]
  43. J Exp Med. 2010 Dec 20;207(13):2921-30 [PMID: 21115688]
  44. Pancreas. 2020 Jul;49(6):830-836 [PMID: 32541639]
  45. Front Biosci. 2007 May 01;12:2849-68 [PMID: 17485264]
  46. Wound Repair Regen. 1999 Mar-Apr;7(2):79-89 [PMID: 10231509]
  47. Blood. 2021 Jun 10;137(23):3151-3152 [PMID: 33940613]
  48. J Pharm Pharm Sci. 2015;18(1):53-60 [PMID: 25877441]
  49. Adv Skin Wound Care. 2010 Aug;23(8):369-79; quiz 380-1 [PMID: 20631603]
  50. Vascul Pharmacol. 2015 Aug;71:31-6 [PMID: 25869514]
  51. Acta Histochem. 2021 Oct;123(7):151789 [PMID: 34560403]
  52. Matrix Biol. 2017 Jul;60-61:38-56 [PMID: 27932299]
  53. J Immunol. 1999 Apr 15;162(8):4849-57 [PMID: 10202029]
  54. ACS Biomater Sci Eng. 2015 Jul 13;1(7):481-493 [PMID: 26280020]
  55. J Immunol. 2014 Apr 1;192(7):3355-64 [PMID: 24591374]
  56. Immunol Rev. 2016 Sep;273(1):61-75 [PMID: 27558328]
  57. Nat Rev Immunol. 2016 May 27;16(6):378-91 [PMID: 27231052]
  58. J Immunol. 2010 Apr 1;184(7):3964-77 [PMID: 20176743]
  59. Immunology. 2021 May;163(1):98-104 [PMID: 33496963]
  60. Biomolecules. 2021 May 08;11(5): [PMID: 34066746]
  61. Plast Reconstr Surg. 2014 Sep;134(3):459-467 [PMID: 24814421]
  62. Nature. 2020 Jul;583(7815):296-302 [PMID: 32612232]
  63. Front Immunol. 2018 Nov 15;9:2650 [PMID: 30524429]
  64. Semin Cell Dev Biol. 2017 Jan;61:3-11 [PMID: 27521521]
  65. Nat Methods. 2021 Aug;18(8):912-920 [PMID: 34253926]
  66. J Dermatol. 1998 Dec;25(12):805-11 [PMID: 9990773]
  67. Dev Dyn. 2020 Jul;249(7):834-846 [PMID: 32314465]
  68. FEBS J. 2020 Jul;287(13):2636-2646 [PMID: 32145148]
  69. Soft Matter. 2021 Nov 24;17(45):10274-10285 [PMID: 34137758]
  70. Nature. 1996 May 2;381(6577):77-80 [PMID: 8609993]
  71. Matrix Biol. 2017 Jul;60-61:124-140 [PMID: 27534610]
  72. Am J Pathol. 2001 Aug;159(2):399-403 [PMID: 11485896]
  73. J Wound Care. 2009 Apr;18(4):145-50 [PMID: 19349934]
  74. Acta Pharmacol Sin. 2019 Apr;40(4):468-476 [PMID: 30446735]
  75. Front Immunol. 2018 May 14;9:1059 [PMID: 29868019]
  76. Clin Sci (Lond). 2019 Feb 18;133(4):565-582 [PMID: 30626731]
  77. PLoS One. 2017 Jan 20;12(1):e0170500 [PMID: 28107529]
  78. Anat Rec (Hoboken). 2020 Jun;303(6):1624-1629 [PMID: 30980479]
  79. Wound Repair Regen. 2021 Nov;29(6):988-995 [PMID: 34546614]
  80. Science. 2004 Mar 5;303(5663):1532-5 [PMID: 15001782]
  81. EXCLI J. 2021 Jan 07;20:52-79 [PMID: 33510592]
  82. Open Life Sci. 2021 Oct 06;16(1):1091-1100 [PMID: 34708153]
  83. Exp Dermatol. 2019 Apr;28(4):464-471 [PMID: 29105155]
  84. Cytokine. 2017 Oct;98:79-86 [PMID: 28325629]
  85. J Invest Dermatol. 2020 Apr;140(4):901-911.e11 [PMID: 31568772]
  86. Curr Biol. 2020 Jul 20;30(14):R828-R830 [PMID: 32693082]
  87. Biochim Biophys Acta. 2013 Jul;1832(7):1005-17 [PMID: 23220258]
  88. J Clin Invest. 2019 Feb 1;129(2):712-726 [PMID: 30640176]
  89. Pathol Biol (Paris). 2014 Apr;62(2):91-5 [PMID: 24650524]
  90. Immunol Rev. 2021 Jul;302(1):299-320 [PMID: 34164824]
  91. Front Immunol. 2014 Nov 04;5:510 [PMID: 25408693]
  92. Mech Dev. 2017 Apr;144(Pt A):43-52 [PMID: 27989746]
  93. Clin Immunol. 2018 Dec;197:96-106 [PMID: 30217791]
  94. Proc Soc Exp Biol Med. 1971 Oct;138(1):350-2 [PMID: 5125534]
  95. J Immunol. 2016 Mar 1;196(5):2010-4 [PMID: 26826250]
  96. Int J Mol Sci. 2020 Aug 01;21(15): [PMID: 32752284]
  97. Inflamm Res. 2020 Apr;69(4):347-363 [PMID: 32146517]
  98. Immunology. 2019 Jul;157(3):190-197 [PMID: 30866049]
  99. J Cell Biol. 2016 Nov 21;215(4):445-456 [PMID: 27872252]
  100. Transplant Proc. 2004 Jul-Aug;36(6):1709-13 [PMID: 15350459]
  101. Int Arch Allergy Immunol. 2010;151(1):80-8 [PMID: 19672099]
  102. Br J Dermatol. 2019 Sep;181(3):593-594 [PMID: 31124130]
  103. Bull Exp Biol Med. 2020 Nov;170(1):128-134 [PMID: 33231804]
  104. J Dermatol. 2000 Apr;27(4):258-63 [PMID: 10824490]
  105. Int J Mol Sci. 2021 Feb 16;22(4): [PMID: 33669239]
  106. Immunol Res. 2013 Dec;57(1-3):222-8 [PMID: 24277309]
  107. Thromb Haemost. 2016 Sep 27;116(4):605-12 [PMID: 27384503]
  108. J Wound Care. 2017 May 1;26(Sup5):S1-S43 [PMID: 28475468]
  109. Clin Rev Allergy Immunol. 2020 Jun;58(3):298-312 [PMID: 30729428]
  110. Plast Reconstr Surg. 2012 Sep;130(3):523-529 [PMID: 22929237]
  111. J Burn Care Res. 2017 Sep/Oct;38(5):e796-e806 [PMID: 28447971]
  112. Nat Rev Immunol. 2009 Oct;9(10):679-91 [PMID: 19763149]
  113. Diabetes. 2016 Jul;65(7):2006-19 [PMID: 27207516]
  114. J Leukoc Biol. 2020 Jul;108(1):377-396 [PMID: 32202340]
  115. Eur J Microbiol Immunol (Bp). 2017 Aug 19;7(3):151-157 [PMID: 29034104]
  116. Carbohydr Polym. 2022 Apr 1;281:119020 [PMID: 35074102]
  117. Immunol Lett. 2018 Aug;200:43-51 [PMID: 29969603]
  118. Int Wound J. 2014 Apr;11(2):129-37 [PMID: 23834253]
  119. Front Immunol. 2020 Mar 10;11:413 [PMID: 32210976]
  120. Trends Immunol. 2001 Apr;22(4):199-204 [PMID: 11274925]
  121. Arch Immunol Ther Exp (Warsz). 2006 Nov-Dec;54(6):367-74 [PMID: 17122884]
  122. Arterioscler Thromb Vasc Biol. 1998 Sep;18(9):1363-70 [PMID: 9743223]
  123. Clin Cosmet Investig Dermatol. 2019 Jul 15;12:519-532 [PMID: 31410045]
  124. Am J Pathol. 2018 Mar;188(3):696-714 [PMID: 29248462]
  125. Nat Commun. 2021 May 31;12(1):3256 [PMID: 34059671]
  126. Biomed Mater. 2021 Mar 01;16(3): [PMID: 33571971]
  127. Wound Repair Regen. 2014 Mar-Apr;22(2):174-86 [PMID: 24611980]
  128. Semin Cell Dev Biol. 2021 Nov;119:111-118 [PMID: 34183242]
  129. Eur J Immunol. 2020 Sep;50(9):1335-1349 [PMID: 32306381]
  130. Int J Mol Sci. 2017 Dec 23;19(1): [PMID: 29295520]
  131. Subcell Biochem. 2017;82:405-456 [PMID: 28101869]
  132. Front Immunol. 2018 Feb 26;9:350 [PMID: 29535726]
  133. J Immunol. 2015 Feb 1;194(3):1285-91 [PMID: 25548229]
  134. Transl Res. 2021 Oct;236:109-116 [PMID: 34089902]
  135. J Burn Care Res. 2014 Jan-Feb;35(1):46-53 [PMID: 24270084]
  136. Front Immunol. 2019 Jul 26;10:1731 [PMID: 31402914]
  137. J Invest Dermatol. 2006 Jun;126(6):1403-9 [PMID: 16543894]
  138. Front Immunol. 2021 Feb 25;12:614347 [PMID: 33717100]
  139. J Leukoc Biol. 2000 Feb;67(2):149-59 [PMID: 10670574]
  140. Burns Trauma. 2021 Jun 23;9:tkab009 [PMID: 34212060]
  141. J Appl Toxicol. 2021 Apr;41(4):561-571 [PMID: 33058278]
  142. Front Immunol. 2021 Nov 02;12:767319 [PMID: 34795674]
  143. Wound Repair Regen. 2015 Jul-Aug;23(4):456-64 [PMID: 25857996]
  144. Int Wound J. 2015 Jun;12(3):313-6 [PMID: 23742140]
  145. PLoS One. 2017 Jul 13;12(7):e0180333 [PMID: 28704477]
  146. J Plast Surg Hand Surg. 2013 Apr;47(2):89-92 [PMID: 23356944]
  147. Exp Dermatol. 2013 Aug;22(8):507-10 [PMID: 23802591]
  148. Biomed Pharmacother. 2019 Sep;117:109191 [PMID: 31387187]
  149. Physiology (Bethesda). 2011 Oct;26(5):334-47 [PMID: 22013192]
  150. Antibodies (Basel). 2020 Dec 01;9(4): [PMID: 33271774]
  151. Trials. 2019 Oct 28;20(1):612 [PMID: 31661012]
  152. Diabetes Technol Ther. 2007 Dec;9(6):535-44 [PMID: 18034608]
  153. J Invest Dermatol. 2019 Nov;139(11):2313-2323.e8 [PMID: 31129057]
  154. Front Immunol. 2012 May 25;3:120 [PMID: 22654879]
  155. Matrix Biol. 2017 Jul;60-61:1-4 [PMID: 28527902]
  156. Trends Immunol. 2005 Mar;26(3):150-6 [PMID: 15745857]
  157. Clin Rev Allergy Immunol. 2020 Jun;58(3):342-365 [PMID: 31828527]
  158. Biol Chem. 2021 Aug 16;402(11):1289-1307 [PMID: 34390641]
  159. Nat Immunol. 2010 Sep;11(9):785-97 [PMID: 20720586]
  160. J Wound Care. 2005 Jun;14(6):273-6 [PMID: 15974414]
  161. Int J Mol Sci. 2016 Dec 11;17(12): [PMID: 27973441]
  162. Medicina (Kaunas). 2021 Oct 08;57(10): [PMID: 34684109]
  163. J Immunol. 2017 Jul 1;199(1):17-24 [PMID: 28630109]
  164. Int J Mol Sci. 2020 Nov 20;21(22): [PMID: 33233704]
  165. Plast Surg Int. 2013;2013:146764 [PMID: 23984063]
  166. J Mol Med (Berl). 2016 Aug;94(8):943-55 [PMID: 26960761]
  167. Semin Immunopathol. 2007 Apr;29(1):15-26 [PMID: 17621951]
  168. J Mater Chem B. 2021 Feb 15;9(5):1395-1405 [PMID: 33462572]
  169. Ann N Y Acad Sci. 2001;936:355-67 [PMID: 11460492]
  170. Immunol Cell Biol. 2019 Mar;97(3):258-267 [PMID: 30746824]

MeSH Term

Extracellular Matrix
Humans
Immunomodulation
Inflammation
Soft Tissue Injuries
Wound Healing

Word Cloud

Created with Highcharts 10.0.0cellshealinginflammatorystagewoundimmuneresponseextracellularmatrixinflammationreviewroleInflammatorynon-inflammatorymicroenvironmentWounddynamichighlyregulatedprocesscanseparatedthreeoverlappinginterdependentphases:proliferationremodellingfocuseskeyplaysvitallocaldeterminesprogressionmaineffectorwidelystudiedlittleattentionpaidimmunomodulatoryeffectsattemptdeepenunderstandingwound-healingfocusinginteractionswellregulatinghopefindingswillprovidenewideaspromotingtissueregenerationregulationMicroenvironmentSkinWounds

Similar Articles

Cited By (45)