A Volar Skin Excisional Wound Model for Evaluation of Multiple-appendage Regeneration and Innervation

Overview

Journal Burns Trauma

Publisher Oxford University Press

Date 2023 Jul 3

PMID 37397511

Authors

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

Affiliations

Soon will be listed here.

Abstract

Background: Promoting 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 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.

Methods: Macroscopic 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.

Results: HFs 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, 3, 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, 3, 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 human was performed: lacunarity values, 0.040 ± 0.012 0.038 ± 0.014; fractal dimension values, 1.870 ± 0.237 1.903 ± 0.163. Sensory nerve function of normal skin post-traumatic repair site was assessed: mechanical threshold, 1.05 ± 0.52 4.90 g ± 0.80; response rate to pinprick, 100% 71.67% ± 19.92%, and temperature threshold, 50.34°C ± 3.11°C 52.13°C ± 3.54°C.

Conclusions: VEWM closely reflects the pathological features of human wound healing and can be applied for skin multiple-appendages regeneration and innervation evaluation.

Citing Articles

Human-Induced Pluripotent Stem Cells in Plastic and Reconstructive Surgery.

Hadzimustafic N, DElia A, Shamoun V, Haykal S Int J Mol Sci. 2024; 25(3).

PMID: 38339142 PMC: 10855589. DOI: 10.3390/ijms25031863.

Cocktail Cell-Reprogrammed Hydrogel Microspheres Achieving Scarless Hair Follicle Regeneration.

Ji S, Li Y, Xiang L, Liu M, Xiong M, Cui W Adv Sci (Weinh). 2024; 11(12):e2306305.

PMID: 38225741 PMC: 10966561. DOI: 10.1002/advs.202306305.

References

Caissie R, Gingras M, Champigny M, Berthod F . In vivo enhancement of sensory perception recovery in a tissue-engineered skin enriched with laminin. Biomaterials. 2006; 27(15):2988-93. DOI: 10.1016/j.biomaterials.2006.01.014. View

Sun X, Xiang J, Chen R, Geng Z, Wang L, Liu Y . Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin. Adv Sci (Weinh). 2021; 8(22):e2103079. PMC: 8596119. DOI: 10.1002/advs.202103079. View

Rodrigues M, Kosaric N, Bonham C, Gurtner G . Wound Healing: A Cellular Perspective. Physiol Rev. 2018; 99(1):665-706. PMC: 6442927. DOI: 10.1152/physrev.00067.2017. View

Lee J, Rabbani C, Gao H, Steinhart M, Woodruff B, Pflum Z . Hair-bearing human skin generated entirely from pluripotent stem cells. Nature. 2020; 582(7812):399-404. PMC: 7593871. DOI: 10.1038/s41586-020-2352-3. View

Sheng Z, Fu X, Cai S, Lei Y, Sun T, Bai X . Regeneration of functional sweat gland-like structures by transplanted differentiated bone marrow mesenchymal stem cells. Wound Repair Regen. 2009; 17(3):427-35. DOI: 10.1111/j.1524-475X.2009.00474.x. View

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(21):5520-5. DOI: 10.1016/j.biomaterials.2010.03.060. View

Woodby B, Penta K, Pecorelli A, Lila M, Valacchi G . Skin Health from the Inside Out. Annu Rev Food Sci Technol. 2020; 11:235-254. DOI: 10.1146/annurev-food-032519-051722. View

Chen Z, Zhao J, Yan Y, Zhang L, Du L, Liu X . 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(1):316. PMC: 9380334. DOI: 10.1186/s12917-022-03416-z. View

Cai S, Pan Y, Han B, Sun T, Sheng Z, Fu X . Transplantation of human bone marrow-derived mesenchymal stem cells transfected with ectodysplasin for regeneration of sweat glands. Chin Med J (Engl). 2011; 124(15):2260-8. View

10.

Kamberov Y, Wang S, Tan J, Gerbault P, Wark A, Tan L . Modeling recent human evolution in mice by expression of a selected EDAR variant. Cell. 2013; 152(4):691-702. PMC: 3575602. DOI: 10.1016/j.cell.2013.01.016. View

11.

Nowak J, Polak L, Pasolli H, Fuchs E . Hair follicle stem cells are specified and function in early skin morphogenesis. Cell Stem Cell. 2008; 3(1):33-43. PMC: 2877596. DOI: 10.1016/j.stem.2008.05.009. View

12.

Horsley V, OCarroll D, Tooze R, Ohinata Y, Saitou M, Obukhanych T . Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Cell. 2006; 126(3):597-609. PMC: 2424190. DOI: 10.1016/j.cell.2006.06.048. View

13.

Wang G, Sweren E, Liu H, Wier E, Alphonse M, Chen R . Bacteria induce skin regeneration via IL-1β signaling. Cell Host Microbe. 2021; 29(5):777-791.e6. PMC: 8122070. DOI: 10.1016/j.chom.2021.03.003. View

14.

Gladman S, Huang W, Lim S, Dyall S, Boddy S, Kang J . Improved outcome after peripheral nerve injury in mice with increased levels of endogenous ω-3 polyunsaturated fatty acids. J Neurosci. 2012; 32(2):563-71. PMC: 6621061. DOI: 10.1523/JNEUROSCI.3371-11.2012. View

15.

Abaci H, Coffman A, Doucet Y, Chen J, Jackow J, Wang E . Tissue engineering of human hair follicles using a biomimetic developmental approach. Nat Commun. 2018; 9(1):5301. PMC: 6294003. DOI: 10.1038/s41467-018-07579-y. View

16.

Eming S, Martin P, Tomic-Canic M . Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014; 6(265):265sr6. PMC: 4973620. DOI: 10.1126/scitranslmed.3009337. View

17.

Yao C, Zhou Y, Wang H, Deng F, Chen Y, Zhu X . Adipose-derived stem cells alleviate radiation-induced dermatitis by suppressing apoptosis and downregulating cathepsin F expression. Stem Cell Res Ther. 2021; 12(1):447. PMC: 8351374. DOI: 10.1186/s13287-021-02516-1. View

18.

Aldea D, Atsuta Y, Kokalari B, Schaffner S, Prasasya R, Aharoni A . Repeated mutation of a developmental enhancer contributed to human thermoregulatory evolution. Proc Natl Acad Sci U S A. 2021; 118(16). PMC: 8072367. DOI: 10.1073/pnas.2021722118. View

19.

Blais M, Grenier M, Berthod F . Improvement of nerve regeneration in tissue-engineered skin enriched with schwann cells. J Invest Dermatol. 2009; 129(12):2895-900. DOI: 10.1038/jid.2009.159. View

20.

Kolter J, Feuerstein R, Zeis P, Hagemeyer N, Paterson N, dErrico P . A Subset of Skin Macrophages Contributes to the Surveillance and Regeneration of Local Nerves. Immunity. 2019; 50(6):1482-1497.e7. DOI: 10.1016/j.immuni.2019.05.009. View