A volar skin excisional wound model for in situ evaluation of multiple-appendage regeneration and innervation

Huanhuan Gao; Yiqiong Liu; Ziwei Shi; Hongliang Zhang; Mengyang Wang; Huating Chen; Yan Li; Shaifei Ji; Jiangbing Xiang; Wei Pi; Laixian Zhou; Yiyue Hong; Lu Wu; Aizhen Cai; Xiaobing Fu; Xiaoyan Sun

doi:10.1093/burnst/tkad027

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A volar skin excisional wound model for in situ evaluation of multiple-appendage regeneration and innervation

更新时间：2023-08-29

- A volar skin excisional wound model for in situ evaluation of multiple-appendage regeneration and innervation
- Burns & Trauma Vol. 11, Issue 1, (2023)
- 作者机构：
  
  1. Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center
  2. Chinese Academy of Medical Sciences
  3. Institute of Chemistry, Chinese Academy of Sciences
  4. Research Institute of General Surgery
  5. the First Medical Center, PLA General Hospital
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkad027
  CLC：
- Published：2023，
  
  Published Online：29 June 2023，
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Huanhuan Gao, Yiqiong Liu, Ziwei Shi, Hongliang Zhang, Mengyang Wang, Huating Chen, Yan Li, Shaifei Ji, Jiangbing Xiang, Wei Pi, Laixian Zhou, Yiyue Hong, Lu Wu, Aizhen Cai, Xiaobing Fu, Xiaoyan Sun, A volar skin excisional wound model for in situ evaluation of multiple-appendage regeneration and innervation, Burns & Trauma, Volume 11, 2023, tkad027, https://doi.org/10.1093/burnst/tkad027
DOI：

Huanhuan Gao, Yiqiong Liu, Ziwei Shi, Hongliang Zhang, Mengyang Wang, Huating Chen, Yan Li, Shaifei Ji, Jiangbing Xiang, Wei Pi, Laixian Zhou, Yiyue Hong, Lu Wu, Aizhen Cai, Xiaobing Fu, Xiaoyan Sun, A volar skin excisional wound model for in situ evaluation of multiple-appendage regeneration and innervation, Burns & Trauma, Volume 11, 2023, tkad027, https://doi.org/10.1093/burnst/tkad027 DOI：

摘要

Abstract

BackgroundPromoting rapid wound healing with functional recovery of all skin appendages is the main goal of regenerative medicine. So far current methodologies

including the commonly used back excisional wound model (BEWM) and paw skin scald wound model

are focused on assessing the regeneration of either hair follicles (HFs) or sweat glands (SwGs). How to achieve de novo appendage regeneration by synchronized evaluation of HFs

SwGs and sebaceous glands (SeGs) is still challenging. Here

we developed a volar skin excisional wound model (VEWM) that is suitable for examining cutaneous wound healing with multiple-appendage restoration

as well as innervation

providing a new research paradigm for the perfect regeneration of skin wounds.MethodsMacroscopic observation

iodine–starch test

morphological staining and qRT-PCR analysis were used to detect the existence of HFs

SwGs

SeGs and distribution of nerve fibres in the volar skin. Wound healing process monitoring

HE/Masson staining

fractal analysis and behavioral response assessment were performed to verify that VEWM could mimic the pathological process and outcomes of human scar formation and sensory function impairment.ResultsHFs are limited to the inter-footpads. SwGs are densely distributed in the footpads

scattered in the IFPs. The volar skin is richly innervated. The wound area of the VEWM at 1

7 and 10 days after the operation is respectively 89.17% ± 2.52%

71.72% ± 3.79%

55.09 % ± 4.94% and 35.74% ± 4.05%

and the final scar area accounts for 47.80% ± 6.22% of the initial wound. While the wound area of BEWM at 1

7 and 10 days after the operation are respectively 61.94% ± 5.34%

51.26% ± 4.89%

12.63% ± 2.86% and 6.14% ± 2.84%

and the final scar area accounts for 4.33% ± 2.67% of the initial wound. Fractal analysis of the post-traumatic repair site for VEWM vs human was performed: lacunarity values

0.040 ± 0.012 vs 0.038 ± 0.014; fractal dimension values

1.870 ± 0.237 vs 1.903 ± 0.163. Sensory nerve function of normal skin vs post-traumatic repair site was assessed: mechanical threshold

1.05 ± 0.52 vs 4.90 g ± 0.80; response rate to pinprick

100% vs 71.67% ± 19.92%

and temperature threshold

50.34°C ± 3.11°C vs 52.13°C ± 3.54°C.ConclusionsVEWM closely reflects the pathological features of human wound healing and can be applied for skin multiple-appendages regeneration and innervation evaluation.

关键词

Keywords

Wound healingAnimal modelMultiple appendagesInnervationRegeneration evaluationHair folliclesSweat glandSebaceous gland

references

1.Jung EG, Augustin M. Dermatologie.Georg Thieme Verlag, 2005. https://books.google.com.hk/books?id=9CwPDA2MXOgC.

2.Woodby B, Penta K, Pecorelli A, Lila MA, Valacchi G. Skin health from the inside out. Annu Rev Food Sci Technol. 2020;11:235–54. https://doi.org/10.1146/annurev-food-032519-051722.

3.Gravitz L. Skin. Nature. 2018;563:S83. https://doi.org/10.1038/d41586-018-07428-4.

4.Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: a cellular perspective. Physiol Rev. 2019;99:665–706. https://doi.org/10.1152/physrev.00067.2017.

5.Fu X. State policy for managing chronic skin wounds in China. Wound Repair Regen. 2020;28:576–7. https://doi.org/10.1111/wrr.12808.

6.Horch KW, Tuckett RP, Burgess PR. A key to the classification of cutaneous mechanoreceptors. J Invest Dermatol. 1977;69:75–82. https://doi.org/10.1111/1523-1747.ep12497887.

7.Björklund H, Dalsgaard CJ, Jonsson CE, Hermansson A. Sensory and autonomic innervation of non-hairy and hairy human skin. An immunohistochemical study. Cell Tissue Res. 1986;243:51–7. https://doi.org/10.1007/bf00221851.

8.Zhang Y, Enhejirigala, Yao B, Li Z, Song W, Li J, et al. Using bioprinting and spheroid culture to create a skin model with sweat glands and hair follicles. Burns Trauma. 2021;9:tkab013. https://doi.org/10.1093/burnst/tkab013.

9.Yao C, Zhou Y, Wang H, Deng F, Chen Y, Zhu X, et al. Adipose-derived stem cells alleviate radiation-induced dermatitis by suppressing apoptosis and downregulating cathepsin F expression. Stem Cell Res Ther. 2021;12:447. https://doi.org/10.1186/s13287-021-02516-1.

10.Sun X, Xiang J, Chen R, Geng Z, Wang L, Liu Y, et al. Sweat gland organoids originating from reprogrammed epidermal keratinocytes functionally recapitulated damaged skin. Adv Sci (Weinh). 2021;8:e2103079. https://doi.org/10.1002/advs.202103079.

11.Lee J, Rabbani CC, Gao H, Steinhart MR, Woodruff BM, Pflum ZE, et al. Hair-bearing human skin generated entirely from pluripotent stem cells. Nature. 2020;582:399–404. https://doi.org/10.1038/s41586-020-2352-3.

12.Qi C, Xu L, Deng Y, Wang G, Wang Z, Wang L. Sericin hydrogels promote skin wound healing with effective regeneration of hair follicles and sebaceous glands after complete loss of epidermis and dermis. Biomater Sci. 2018;6:2859–70. https://doi.org/10.1039/c8bm00934a.

13.Shen K, Wang XJ, Liu KT, Li SH, Li J, Zhang JX, et al. Effects of exosomes from human adipose-derived mesenchymal stem cells on inflammatory response of mouse RAW264.7 cells and wound healing of full-thickness skin defects in mice. Zhonghua Shao Shang Za Zhi. 2022;38:215–26. https://doi.org/10.3760/cma.j.cn501120-20201116-00477.

14.Mascharak S, Talbott HE, Januszyk M, Griffin M, Chen K, Davitt MF, et al. Multi-omic analysis reveals divergent molecular events in scarring and regenerative wound healing. Cell Stem Cell. 2022;29:315–327.e6. https://doi.org/10.1016/j.stem.2021.12.011.

15.Wang G, Sweren E, Liu H, Wier E, Alphonse MP, Chen R, et al. Bacteria induce skin regeneration via IL-1β signaling. Cell Host Microbe. 2021;29:777–91.e6. https://doi.org/10.1016/j.chom.2021.03.003.

16.Mascharak S, des Jardins-Park HE, Davitt MF, Griffin M, Borrelli MR, Moore AL, et al. Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring. Science. 2021;372:356–62. https://doi.org/10.1126/science.aba2374.

17.Phan QM, Fine GM, Salz L, Herrera GG, Wildman B, Driskell IM, et al. Lef1 expression in fibroblasts maintains developmental potential in adult skin to regenerate wounds. elife. 2020;9:1–19. https://doi.org/10.7554/eLife.60066.

18.Kolter J, Feuerstein R, Zeis P, Hagemeyer N, Paterson N, d'Errico P, et al. A subset of skin macrophages contributes to the surveillance and regeneration of local nerves. Immunity. 2019;50:1482–97.e7. https://doi.org/10.1016/j.immuni.2019.05.009.

19.Willyard C. Unlocking the secrets of scar-free skin healing. Nature. 2018;563:S86–s8. https://doi.org/10.1038/d41586-018-07430-w.

20.Nishiguchi MA, Spencer CA, Leung DH, Leung TH. Aging suppresses skin-derived circulating SDF1 to promote full-thickness tissue regeneration. Cell Rep. 2018;24:3383–92.e5. https://doi.org/10.1016/j.celrep.2018.08.054.

21.Rinkevich Y, Walmsley GG, Hu MS, Maan ZN, Newman AM, Drukker M, et al. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential. Science. 2015;348:aaa2151. https://doi.org/10.1126/science.aaa2151.

22.Yuan X, Duan X, Li Z, Yao B, Enhejirigala, Song W, et al. Collagen triple helix repeat containing-1 promotes functional recovery of sweat glands by inducing adjacent microvascular network reconstruction in vivo. Burns Trauma. 2022;10:tkac035. https://doi.org/10.1093/burnst/tkac035.

23.Wang X, Ge J, Tredget EE, Wu Y. The mouse excisional wound splinting model, including applications for stem cell transplantation. Nat Protoc. 2013;8:302–9. https://doi.org/10.1038/nprot.2013.002.

24.Jiang D, Correa-Gallegos D, Christ S, Stefanska A, Liu J, Ramesh P, et al. Two succeeding fibroblastic lineages drive dermal development and the transition from regeneration to scarring. Nat Cell Biol. 2018;20:422–31. https://doi.org/10.1038/s41556-018-0073-8.

25.Aldea D, Atsuta Y, Kokalari B, Schaffner SF, Prasasya RD, Aharoni A, et al. Repeated mutation of a developmental enhancer contributed to human thermoregulatory evolution. Proc Natl Acad Sci U S A. 2021;118:1–10. https://doi.org/10.1073/pnas.2021722118.

26.Kamberov YG, Wang S, Tan J, Gerbault P, Wark A, Tan L, et al. Modeling recent human evolution in mice by expression of a selected EDAR variant. Cell. 2013;152:691–702. https://doi.org/10.1016/j.cell.2013.01.016.

27.Wada M, Takagaki T. A simple and accurate method for detecting the secretion of sweat. Tohoku J Exp Med. 1948;49:284.

28.Deuis JR, Vetter I. The thermal probe test: a novel behavioral assay to quantify thermal paw withdrawal thresholds in mice. Temperature (Austin). 2016;3:199–207. https://doi.org/10.1080/23328940.2016.1157668.

29.Gladman SJ, Huang W, Lim SN, Dyall SC, Boddy S, Kang JX, et al. Improved outcome after peripheral nerve injury in mice with increased levels of endogenous ω-3 polyunsaturated fatty acids. J Neurosci. 2012;32:563–71. https://doi.org/10.1523/jneurosci.3371-11.2012.

30.Nanmo A, Yan L, Asaba T, Wan L, Kageyama T, Fukuda J. Bioprinting of hair follicle germs for hair regenerative medicine. Acta Biomater. 2022;1–10. https://doi.org/10.1016/j.actbio.2022.06.021.

31.Chen P, Miao Y, Zhang F, Fan Z, Huang J, Mao X, et al. Tissue engineering ECM-enriched controllable vascularized human microtissue for hair regenerative medicine using a biomimetic developmental approach. J Adv Res. 2022;38:77–89. https://doi.org/10.1016/j.jare.2021.09.010.

32.Hu S, Li Z, Lutz H, Huang K, Su T, Cores J, et al. Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling. Sci Adv. 2020;6:eaba1685. https://doi.org/10.1126/sciadv.aba1685.

33.Abaci HE, Coffman A, Doucet Y, Chen J, Jacków J, Wang E, et al. Tissue engineering of human hair follicles using a biomimetic developmental approach. Nat Commun. 2018;9:5301. https://doi.org/10.1038/s41467-018-07579-y.

34.Snippert HJ, Haegebarth A, Kasper M, Jaks V, van Es JH, Barker N, et al. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science. 2010;327:1385–9. https://doi.org/10.1126/science.1184733.

35.Nowak JA, Polak L, Pasolli HA, Fuchs E. Hair follicle stem cells are specified and function in early skin morphogenesis. Cell Stem Cell. 2008;3:33–43. https://doi.org/10.1016/j.stem.2008.05.009.

36.Horsley V, O'Carroll D, Tooze R, Ohinata Y, Saitou M, Obukhanych T, et al. Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Cell. 2006;126:597–609. https://doi.org/10.1016/j.cell.2006.06.048.

37.Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014;6:265sr6. https://doi.org/10.1126/scitranslmed.3009337.

38.Coulson-Thomas VJ, Gesteira TF, Esko J, Kao W. Heparan sulfate regulates hair follicle and sebaceous gland morphogenesis and homeostasis. J Biol Chem. 2014;289:25211–26. https://doi.org/10.1074/jbc.M114.572511.

39.Xu Y, Hong Y, Xu M, Ma K, Fu X, Zhang M, et al. Role of keratinocyte growth factor in the differentiation of sweat gland-like cells from human umbilical cord-derived mesenchymal stem cells. Stem Cells Transl Med. 2016;5:106–16. https://doi.org/10.5966/sctm.2015-0081.

40.Huang S, Yao B, Xie J, Fu X. 3D bioprinted extracellular matrix mimics facilitate directed differentiation of epithelial progenitors for sweat gland regeneration. Acta Biomater. 2016;32:170–7. https://doi.org/10.1016/j.actbio.2015.12.039.

41.Cai S, Pan Y, Han B, Sun TZ, Sheng ZY, Fu XB. Transplantation of human bone marrow-derived mesenchymal stem cells transfected with ectodysplasin for regeneration of sweat glands. Chin Med J. 2011;124:2260–8.

42.Sheng Z, Fu X, Cai S, Lei Y, Sun T, Bai X, et al. Regeneration of functional sweat gland-like structures by transplanted differentiated bone marrow mesenchymal stem cells. Wound Repair Regen. 2009;17:427–35. https://doi.org/10.1111/j.1524-475X.2009.00474.x.

43.Bovell DL. The evolution of eccrine sweat gland research towards developing a model for human sweat gland function. Exp Dermatol. 2018;27:544–50. https://doi.org/10.1111/exd.13556.

44.Huang S, Lu G, Wu Y, Jirigala E, Xu Y, Ma K, et al. Mesenchymal stem cells delivered in a microsphere-based engineered skin contribute to cutaneous wound healing and sweat gland repair. J Dermatol Sci. 2012;66:29–36. https://doi.org/10.1016/j.jdermsci.2012.02.002.

45.Huang S, Xu Y, Wu C, Sha D, Fu X. In vitro constitution and in vivo implantation of engineered skin constructs with sweat glands. Biomaterials. 2010;31:5520–5. https://doi.org/10.1016/j.biomaterials.2010.03.060.

46.Blais M, Grenier M, Berthod F. Improvement of nerve regeneration in tissue-engineered skin enriched with schwann cells. J Invest Dermatol. 2009;129:2895–900. https://doi.org/10.1038/jid.2009.159.

47.Caissie R, Gingras M, Champigny MF, Berthod F. In vivo enhancement of sensory perception recovery in a tissue-engineered skin enriched with laminin. Biomaterials. 2006;27:2988–93. https://doi.org/10.1016/j.biomaterials.2006.01.014.

48.Girard D, Laverdet B, Buhe V, Trouillas M, Ghazi K, Alexaline MM, et al. Biotechnological Management of Skin Burn Injuries: challenges and perspectives in wound healing and sensory recovery. Tissue Eng Part B Rev. 2017;23:59–82. https://doi.org/10.1089/ten.TEB.2016.0195.

49.Murthy SE, Loud MC, Daou I, Marshall KL, Schwaller F, Kühnemund J, et al. The mechanosensitive ion channel Piezo2 mediates sensitivity to mechanical pain in mice. Sci Transl Med. 2018;10:1–22. https://doi.org/10.1126/scitranslmed.aat9897.

50.Chen Z, Zhao J, Yan Y, Zhang L, Du L, Liu X, et al. Differential distribution and genetic determination of eccrine sweat glands and hair follicles in the volar skin of C57BL/6 mice and SD rats. BMC Vet Res. 2022;18:316. https://doi.org/10.1186/s12917-022-03416-z.

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