Obstruction of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice

Yunxia Chen , Xiaorong Zhang , Zhihui Liu , Jiacai Yang , Cheng Chen , Jue Wang , Zengjun Yang , Lei He , Pengcheng Xu , Xiaohong Hu , Gaoxing Luo , Weifeng He

Burns & Trauma ›› 2021, Vol. 9 ›› Issue (1) : tkab004

PDF (3258KB)
Burns & Trauma ›› 2021, Vol. 9 ›› Issue (1) :tkab004 DOI: 10.1093/burnst/tkab004
Research Article
research-article
Obstruction of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice
Author information +
History +
PDF (3258KB)

Abstract

Background: Delayed wound healing remains a common but challenging problem in patients with acute or chronic wound following accidental scald burn injury. However, the systematic and detailed evaluation of the scald burn injury, including second-degree deep scald (SDDS) and third-degree scald (TDS), is still unclear. The present study aims to analyze the wound-healing speed, the formation of granulation tissue, and the healing quality after cutaneous damage. Methods: In order to assess SDDS and TDS, the models of SDDS and TDS were established using a scald instrument in C57BL/6 mice. Furthermore, an excisional wound was administered on the dorsal surface in mice (Cut group). The wound-healing rate was first analyzed at days 0, 3, 5, 7, 15 and 27, with the Cut group as a control. Then, on the full-thickness wounds, hematoxylin and eosin (H&E) staining, Masson staining, Sirius red staining, Victoria blue staining and immunohistochemistry were performed to examine re-epithelialization, the formation of granulation tissue, vascularization, inflammatory infiltration and the healing quality at different time points in the Cut, SDDS and TDS groups. Results: The presented data revealed that the wound-healing rate was higher in the Cut group, when compared with the SDDS and TDS groups. H&E staining showed that re-epithelialization, formation of granulation tissue and inflammatory infiltration were greater in the Cut group, when compared with the SDDS and TDS groups. Immunohistochemistry revealed that the number of CD31, vascular endothelial growth factor A, transforming growth factor-β and α-smooth muscle actin reached preferential peak in the Cut group, when compared with other groups. In addition, Masson staining, Sirius red staining, Victoria blue staining, Gordon-Sweets staining and stress analysis indicated that the ratio of collagen I to III, reticular fibers, failure stress, Young’s modulus and failure length in the SDDS group were similar to those in the normal group, suggesting that healing quality was better in the SDDS group, when compared with the Cut and TDS groups. Conclusion: Overall, the investigators first administered a comprehensive analysis in the Cut, SDDS and TDS groups through in vivo experiments, which further proved that the obstacle of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice.

Keywords

Burn wound healing / Second-degree deep scald / Third-degree scald / Re-epithelialization / Granulation tissue / Healing quality

Cite this article

Download citation ▾
Yunxia Chen, Xiaorong Zhang, Zhihui Liu, Jiacai Yang, Cheng Chen, Jue Wang, Zengjun Yang, Lei He, Pengcheng Xu, Xiaohong Hu, Gaoxing Luo, Weifeng He. Obstruction of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice. Burns & Trauma, 2021, 9 (1) : tkab004 DOI:10.1093/burnst/tkab004

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Sheikholeslam M, Wright MEE, Jeschke MG, Amini-Nik S. Biomaterials for skin substitutes. Adv Healthc Mater. 2018; 7. https://doi.org/10.1002/adhm.201700897

[2]

Xu HL, Chen PP, Wang LF, Tong MQ, Ou ZH, Zhao YZ, et al. Skin-permeable liposome improved stability and permeability of bFGF against skin of mice with deep second degree scald to promote hair follicle neogenesis through inhibition of scar formation. Colloids Surf B Biointerfaces. 2018; 172: 573-85.

[3]

Andrews CJ, Kimble RM, Kempf M, Cuttle L. Evidence-based injury prediction data for the water temperature and duration of exposure for clinically relevant deep dermal scald injuries. Wound Repair Regen. 2017; 25: 792-804.

[4]

Piperigkou Z, Gotte M, Theocharis AD, Karamanos NK. Insights into the key roles of epigenetics in matrix macromolecules-associated wound healing. Adv Drug Deliv Rev. 2018; 129: 16-36.

[5]

Amini-Nik S, Yousuf Y, Jeschke MG. Scar management in burn injuries using drug delivery and molecular signaling: current treatments and future directions. Adv Drug Deliv Rev. 2018; 123: 135-54.

[6]

Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011; 17: 113-25.

[7]

Berman B, Maderal A, Raphael B. Hypertrophic scars: pathophysiology, classification, and treatment. Dermatol Surg. 2017; 43: S3-18.

[8]

Greaves NS, Ashcroft KJ, Baguneid M, Bayat A.Current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during acute wound healing. J Dermatol Sci. 2013; 72: 206-17.

[9]

Boldeanu L, Boldeanu MV, Bogdan M, Meca AD, Coman CG, Buca BR, et al. Immunological approaches and therapy in burns (Review). Exp Ther Med. 2020; 20: 2361-7.

[10]

Rosenblum G, Meroueh SO, Kleifeld O, Brown S, Singson SP, Fridman R, et al. Structural basis for potent slow binding inhibition of human matrix metalloproteinase-2 (MMP-2). J Biol Chem. 2003; 278: 27009-15.

[11]

Song Y, Li Y, Xiao Y, Hu W, Wang X, Wang P, et al. Neutralization of interleukin-17A alleviates burn-induced intestinal barrier disruption via reducing pro-inflammatory cytokines in a mouse model. Burns Trauma. 2019; 7: 37.

[12]

Ricard-Blum S. The collagen family. Cold Spring Harb Perspect Biol. 2011; 3(1): a004978.

[13]

Exposito JY, Valcourt U, Cluzel C, Lethias C. The fibrillar collagen family. Int J Mol Sci. 2010; 11: 407-26.

[14]

Kasuya A, Tokura Y. Attempts to accelerate wound healing. J Dermatol Sci. 2014; 76: 169-72.

[15]

Davison-Kotler E, Marshall WS, Garcia-Gareta E. Sources of collagen for biomaterials in skin wound healing. Bioengineering (Basel). 2019; 6(3): 56.

[16]

João de Masi ECD, Campos AC, João de Masi FD, Ratti MA, Ike IS, João de Masi RD. The influence of growth factors on skin wound healing in rats. Braz J Otorhinolaryngol. 2016; 82: 512-21.

[17]

Zarei F, Soleimaninejad M. Role of growth factors and biomaterials in wound healing. Artif Cells Nanomed Biotechnol. 2018; 46: 906-11.

[18]

Xu P, Wu Y, Zhou L, Yang Z, Zhang X, Hu X, et al. Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization. Burns Trauma. 2020; 8: tkaa028. https://doi.org/10.1093/burnst/tkaa028

[19]

Rehman SRU, Augustine R, Zahid AA, Ahmed R, Tariq M, Hasan A. Reduced graphene oxide incorporated GelMA hydrogel promotes angiogenesis for wound healing applications. Int J Nanomedicine. 2019; 14: 9603-17.

[20]

Kargozar S, Baino F, Hamzehlou S, Hamblin MR, Mozafari M. Nanotechnology for angiogenesis: opportunities and challenges. Chem Soc Rev. 2020; 49: 5008-57.

[21]

Noishiki C, Yuge S, Ando K, Wakayama Y, Mochizuki N, Ogawa R, et al. Live imaging of angiogenesis during cutaneous wound healing in adult zebrafish. Angiogenesis. 2019; 22: 341-54.

[22]

Giatsidis G, Cheng L, Haddad A, Ji K, Succar J, Lancerotto L, et al. Noninvasive induction of angiogenesis in tissues by external suction: sequential optimization for use in reconstructive surgery. Angiogenesis. 2018; 21: 61-78.

[23]

Yin H, Chen CY, Liu YW, Tan YJ, Deng ZL, Yang F, et al. Synechococcus elongatus PCC7942 secretes extracellular vesicles to accelerate cutaneous wound healing by promoting angiogenesis. Theranostics. 2019; 9: 2678-93.

[24]

Chen C-Y, Rao S-S, Ren L, Hu X-K, Tan Y-J, Hu Y, et al. Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics. 2018; 8: 1607-23.

[25]

Whittam AJ, Maan ZN, Duscher D, Barrera JA, Hu MS, Fischer LH, et al. Small molecule inhibition of dipeptidyl peptidase-4 enhances bone marrow progenitor cell function and angiogenesis in diabetic wounds. Transl Res. 2019; 205: 51-63.

[26]

Enciso N, Avedillo L, Fermin ML, Fragio C, Tejero C. Cutaneous wound healing: canine allogeneic ASC therapy. Stem Cell Res Ther. 2020; 11: 261.

[27]

Scherer SS, Pietramaggiori G, Mathews JC, Chan R, Fiorina P, Orgill DP. Wound healing kinetics of the genetically diabetic mouse. Wounds. 2008; 20: 18-28.

[28]

Yang X, Guo JL, Han J, Si RJ, Liu PP, Zhang ZR, Wang AM, Zhang J. Chitosan hydrogel encapsulated with LL-37 peptide promotes deep tissue injury healing in a mouse model. Mil Med Res. 2020; 7(1): 20. doi: 10.1186/s40779-020-00249-5. PMID: 32321591; PMCID: PMC7175584.

[29]

Yang L, Witten TM, Pidaparti RM. A biomechanical model of wound contraction and scar formation. J Theor Biol. 2013; 332: 228-48.

[30]

Zeng XL, Sun L, Zheng HQ, Wang GL, Du YH, Lv XF, et al. Smooth muscle-specific TMEM16A expression protects against angiotensin II-induced cerebrovascular remodeling via suppressing extracellular matrix deposition. J Mol Cell Cardiol. 2019; 134: 131-43.

[31]

Cohen BE, Geronemus RG, McDaniel DH, Brauer JA. The role of elastic fibers in scar formation and treatment. Dermatol Surg. 2017; 43: S19-24.

[32]

Ruszczak Z. Effect of collagen matrices on dermal wound healing. Adv Drug Deliv Rev. 2003; 55: 1595-611.

[33]

Boudreau NJ, Jones PL. Extracellular matrix and integrin signalling: the shape of things to come. Biochem J. 1999; 339: 481-8.

[34]

Hinz B, McCulloch CA, Coelho NM. Mechanical regulation of myofibroblast phenoconversion and collagen contraction. Exp Cell Res. 2019; 379: 119-28.

[35]

Ribatti D, Tamma R. Giulio Gabbiani and the discovery of myofibroblasts. Inflamm Res. 2019; 68: 241-5.

[36]

Tang J, Saito T. Biocompatibility of novel type I collagen purified from tilapia fish scale: an in vitro comparative study. Biomed Res Int. 2015; 2015: 139476. https://doi.org/10.1155/2015/139476

[37]

Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015; 33: 257-90.

[38]

Grünert SC, Elling R, Maag B, Wortmann SB, Derks TGJ, Hannibal L, et al. Improved inflammatory bowel disease, wound healing and normal oxidative burst under treatment with empagliflozin in glycogen storage disease type Ib. Orphanet J Rare Dis. 2020; 15: 218.

[39]

Kim KW, Ryu JS, Kim JY, Kim MK. Preserved corneal lamellar grafting reduces inflammation and promotes wound healing in a scleral defect rabbit model. Transl Vis Sci Technol. 2020; 9: 38.

[40]

Singampalli KL, Balaji S, Wang X, Parikh UM, Kaul A, Gilley J, et al. The role of an IL-10/hyaluronan axis in dermal wound healing. Front Cell Dev Biol. 2020; 8: 636.

[41]

Rivera L, Pandika M, Bergers G. Escape mechanisms from antiangiogenic therapy: an immune cell’s perspective. Adv Exp Med Biol. 2014; 772: 83-99.

[42]

Loretelli C, Ben Nasr M, Giatsidis G, Bassi R, Lancerotto L, D’Addio F, et al. Embryonic stem cell extracts improve wound healing in diabetic mice. Acta Diabetol. 2020; 57: 883-90.

PDF (3258KB)

17

Accesses

0

Citation

Detail

Sections
Recommended

/

〈 〉