Engineering Edgeless Human Skin with Enhanced Biomechanical Properties

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Jan 27

PMID 36706190

Authors

Alberto Pappalardo

David Alvarez Cespedes

Shuyang Fang

Abigail R Herschman

Eun Young Jeon

Kristin M Myers

Jeffrey W Kysar

Hasan Erbil Abaci

Affiliations

Soon will be listed here.

Abstract

Despite the advancements in skin bioengineering, 3D skin constructs are still produced as flat tissues with open edges, disregarding the fully enclosed geometry of human skin. Therefore, they do not effectively cover anatomically complex body sites, e.g., hands. Here, we challenge the prevailing paradigm by engineering the skin as a fully enclosed 3D tissue that can be shaped after a body part and seamlessly transplanted as a biological clothing. Our wearable edgeless skin constructs (WESCs) show enhanced dermal extracellular matrix (ECM) deposition and mechanical properties compared to conventional constructs. WESCs display region-specific cell/ECM alignment, as well as physiologic anisotropic mechanical properties. WESCs replace the skin in full-thickness wounds of challenging body sites (e.g., mouse hindlimbs) with minimal suturing and shorter surgery time. This study provides a compelling technology that may substantially improve wound care and suggests that the recapitulation of the tissue macroanatomy can lead to enhanced biological function.

Citing Articles

A perspective: Regeneration of soft and hard tissues in the oral cavity, from research to clinical practice.

Puterman I, Fien M, Mesquida J, Ginebreda I, Bauza G, Somerman M Front Dent Med. 2025; 4:1242547.

PMID: 39916909 PMC: 11797814. DOI: 10.3389/fdmed.2023.1242547.

Organoids in skin wound healing.

Wang Z, Zhao F, Lang H, Ren H, Zhang Q, Huang X Burns Trauma. 2025; 13:tkae077.

PMID: 39759541 PMC: 11697111. DOI: 10.1093/burnst/tkae077.

Diversity of human skin three-dimensional organotypic cultures.

Jia Y, Atwood S Curr Opin Genet Dev. 2024; 89:102275.

PMID: 39536613 PMC: 11881886. DOI: 10.1016/j.gde.2024.102275.

A biopsy-sized 3D skin model with a perifollicular vascular plexus enables studying immune cell trafficking in the skin.

Shah K, Garriga-Cerda L, Pappalardo A, Sorrells L, Jeong H, Lee C Biofabrication. 2024; 16(4).

PMID: 38941996 PMC: 11244652. DOI: 10.1088/1758-5090/ad5d1a.

Vascularized 3D Human Skin Models in the Forefront of Dermatological Research.

Rimal R, Muduli S, Desai P, Marquez A, Moller M, Platzman I Adv Healthc Mater. 2024; 13(9):e2303351.

PMID: 38277705 PMC: 11468127. DOI: 10.1002/adhm.202303351.

References

Nilforoushzadeh M, Sisakht M, Amirkhani M, Seifalian A, Banafshe H, Verdi J . Engineered skin graft with stromal vascular fraction cells encapsulated in fibrin-collagen hydrogel: A clinical study for diabetic wound healing. J Tissue Eng Regen Med. 2019; 14(3):424-440. DOI: 10.1002/term.3003. View

Gangatirkar P, Paquet-Fifield S, Li A, Rossi R, Kaur P . Establishment of 3D organotypic cultures using human neonatal epidermal cells. Nat Protoc. 2007; 2(1):178-86. DOI: 10.1038/nprot.2006.448. View

Korosec A, Frech S, Gesslbauer B, Vierhapper M, Radtke C, Petzelbauer P . Lineage Identity and Location within the Dermis Determine the Function of Papillary and Reticular Fibroblasts in Human Skin. J Invest Dermatol. 2018; 139(2):342-351. DOI: 10.1016/j.jid.2018.07.033. View

Muller Q, Beaudet M, De Serres-Berard T, Bellenfant S, Flacher V, Berthod F . Development of an innervated tissue-engineered skin with human sensory neurons and Schwann cells differentiated from iPS cells. Acta Biomater. 2018; 82:93-101. DOI: 10.1016/j.actbio.2018.10.011. View

Abaci H, Gledhill K, Guo Z, Christiano A, Shuler M . Pumpless microfluidic platform for drug testing on human skin equivalents. Lab Chip. 2014; 15(3):882-8. PMC: 4305008. DOI: 10.1039/c4lc00999a. View

Boyce S, Kagan R, Greenhalgh D, Warner P, Yakuboff K, Palmieri T . Cultured skin substitutes reduce requirements for harvesting of skin autograft for closure of excised, full-thickness burns. J Trauma. 2006; 60(4):821-9. DOI: 10.1097/01.ta.0000196802.91829.cc. View

Radermacher P, Haouzi P . A mouse is not a rat is not a man: species-specific metabolic responses to sepsis - a nail in the coffin of murine models for critical care research?. Intensive Care Med Exp. 2015; 1(1):26. PMC: 4796700. DOI: 10.1186/2197-425X-1-7. View

Hedley S, Layton C, Heaton M, Chakrabarty K, Dawson R, Gawkrodger D . Fibroblasts play a regulatory role in the control of pigmentation in reconstructed human skin from skin types I and II. Pigment Cell Res. 2002; 15(1):49-56. DOI: 10.1034/j.1600-0749.2002.00067.x. View

Gledhill K, Guo Z, Umegaki-Arao N, Higgins C, Itoh M, Christiano A . Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells. PLoS One. 2015; 10(8):e0136713. PMC: 4550351. DOI: 10.1371/journal.pone.0136713. View

10.

Ascension A, Fuertes-Alvarez S, Ibanez-Sole O, Izeta A, Arauzo-Bravo M . Human Dermal Fibroblast Subpopulations Are Conserved across Single-Cell RNA Sequencing Studies. J Invest Dermatol. 2021; 141(7):1735-1744.e35. DOI: 10.1016/j.jid.2020.11.028. View

11.

Joodaki H, Panzer M . Skin mechanical properties and modeling: A review. Proc Inst Mech Eng H. 2018; 232(4):323-343. DOI: 10.1177/0954411918759801. View

12.

Biggs L, Kim C, Miroshnikova Y, Wickstrom S . Mechanical Forces in the Skin: Roles in Tissue Architecture, Stability, and Function. J Invest Dermatol. 2019; 140(2):284-290. DOI: 10.1016/j.jid.2019.06.137. View

13.

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

14.

Sander E, Lynch K, Boyce S . Development of the mechanical properties of engineered skin substitutes after grafting to full-thickness wounds. J Biomech Eng. 2013; 136(5):051008. PMC: 4023834. DOI: 10.1115/1.4026290. View

15.

Kim B, Gao G, Kim J, Cho D . 3D Cell Printing of Perfusable Vascularized Human Skin Equivalent Composed of Epidermis, Dermis, and Hypodermis for Better Structural Recapitulation of Native Skin. Adv Healthc Mater. 2018; 8(7):e1801019. DOI: 10.1002/adhm.201801019. View

16.

Kollmannsberger P, Bidan C, Dunlop J, Fratzl P, Vogel V . Tensile forces drive a reversible fibroblast-to-myofibroblast transition during tissue growth in engineered clefts. Sci Adv. 2018; 4(1):eaao4881. PMC: 5771696. DOI: 10.1126/sciadv.aao4881. View

17.

Kosten I, Spiekstra S, de Gruijl T, Gibbs S . MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure. Toxicol Appl Pharmacol. 2015; 287(1):35-42. DOI: 10.1016/j.taap.2015.05.017. View

18.

Tsutsui K, Machida H, Nakagawa A, Ahn K, Morita R, Sekiguchi K . Mapping the molecular and structural specialization of the skin basement membrane for inter-tissue interactions. Nat Commun. 2021; 12(1):2577. PMC: 8110968. DOI: 10.1038/s41467-021-22881-y. View

19.

Bourland J, Fradette J, Auger F . Tissue-engineered 3D melanoma model with blood and lymphatic capillaries for drug development. Sci Rep. 2018; 8(1):13191. PMC: 6123405. DOI: 10.1038/s41598-018-31502-6. View

20.

Baltazar T, Merola J, Catarino C, Xie C, Kirkiles-Smith N, Lee V . Three Dimensional Bioprinting of a Vascularized and Perfusable Skin Graft Using Human Keratinocytes, Fibroblasts, Pericytes, and Endothelial Cells. Tissue Eng Part A. 2019; 26(5-6):227-238. PMC: 7476394. DOI: 10.1089/ten.TEA.2019.0201. View