Vascularization strategies for human skin tissue engineering via 3D bioprinting
The skin is composed of many cells that are organized into different layers and connected by dense and complex vascular networks. This creates a dynamic microenvironment in which cells interact within the matrix. Significant advancements have been made in this field over the past decade, and various strategies have been developed for accelerating and enhancing skin regeneration. The primary challenge for successful skin grafts is the integration of the functional vasculature, which can supply essential nutrients and oxygen to cell-laden structures and damaged native tissues. An inadequate vascular network can lead to ischemia, which can cause slow wound healing—particularly in the case of chronic skin conditions. Therefore, blood vessel formation remains one of the most significant obstacles that skin tissue engineering must overcome to create vascularized skin tissue substitutes with specific living cells. Technological advances can augment effective vascularization. The three-dimensional (3D) bioprinting platform is a promising technology that allows precise deposition of living cells and bioactive materials. The application of this technology to skin tissue engineering can provide solutions for augmenting pre-vascularization in engineered in vitro skin models and in vivo skin substitutes. This review presents the significance of skin vascularization in in vitro modeling and in vivo wound healing. Various strategies and related applications involving 3D bioprinting technology are introduced for the biofabrication of enhanced vascularized skin in vitro and in vivo, followed by a discussion of their limitations and future research directions.
- Talikowska M, Fu X, Lisak G. Application of conducting polymers to wound care and skin tissue engineering: a review. Biosens Bioelectron. 2019;135:50-63. doi: 10.1016/j.bios.2019.04.001
- Fenner J, Clark RAF. Anatomy, physiology, histology, and immunohistochemistry of human skin. In: Skin Tissue Engineering and Regenerative Medicine. New York: Elsevier; 2016:1-17. doi: 10.1016/B978-0-12-801654-1.00001-2
- Pittman RN. Regulation of Tissue Oxygenation. San Rafael, CA:Morgan & Claypool Life Sciences; 2011:1-100. doi: 10.4199/c00029ed1v01y201103isp017
- Arroyo JA, Winn VD. Vasculogenesis and Angiogenesis in the IUGR Placenta. In: Seminars in Perinatology. New York: Elsevier; 2008:172-177. doi: 10.1053/j.semperi.2008.02.006
- Chouhan D, Dey N, Bhardwaj N, Mandal BB. Emerging and innovative approaches for wound healing and skin regeneration: current status and advances. Biomaterials. 2019;216:119267. doi: 10.1016/j.biomaterials.2019.119267
- Winter GD. Effect of air exposure and occlusion on experimental human skin wounds. Nature. 1963;200: 378-379. doi: 10.1038/200377a0
- Dhivya S, Padma VV, Santhini E. Wound dressings–a review. BioMedicine. 2015;5(4):22. doi: 10.7603/s40681-015-0022-9
- Kamoun EA, Kenawy E-RS, Chen X. A review on polymeric hydrogel membranes for wound dressing applications: PVA-based hydrogel dressings. J Adv Res. 2017;8(3): 217-233. doi: 10.1016/j.jare.2017.01.005
- Ahmed S, Ali A, Sheikh J. A review on chitosan centred scaffolds and their applications in tissue engineering. Int J Biol Macromol. 2018;116:849-862. doi: 10.1016/j.ijbiomac.2018.04.176
- Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407(6801):249-257. doi: 10.1038/35025220
- Jain R, Au P, Tam J, Duda DG, Fukumura D. Engineering vascularized tissue. Nat Biotechnol. 2005;23(7):821. doi: 10.1038/nbt0705-821
- Bouhadir KH, Mooney DJ. Promoting angiogenesis in engineered tissues. J Drug Targeting. 2001;9(6):397-406. doi: 10.3109/10611860108998775
- Utzinger U, Baggett B, Weiss JA, Hoying JB, Edgar LT. Large-scale time series microscopy of neovessel growth during angiogenesis. Angiogenesis. 2015;18:219-232. doi: 10.1007/s10456-015-9461-x
- Malda J, Rouwkema J, Martens D, et al. Oxygen gradients in tissue‐engineered PEGT/PBT cartilaginous constructs: measurement and modeling. Biotechnol Bioeng. 2004;86(1):9-18. doi: 10.1002/bit.20038
- Hsu Y-C, Li L, Fuchs E. Emerging interactions between skin stem cells and their niches. Nat Med. 2014;20(8):847-856. doi: 10.1038/nm.3643
- Nguyen AV, Soulika AM. The dynamics of the skin’s immune system. Int J Mol Sci. 2019;20(8):1811. doi: 10.3390/ijms20081811
- Abdo JM, Sopko NA, Milner SM. The applied anatomy of human skin: A model for regeneration. Wound Med. 2020;28:100179. doi: 10.1016/j.wndm.2020.100179
- Roger M, Fullard N, Costello L, et al. Bioengineering the microanatomy of human skin. J Anat. 2019;234(4):438-455. doi: 10.1111/joa.12942
- Pincelli C, Marconi A. Keratinocyte stem cells: friends and foes. J Cell Physiol. 2010;225(2):310-315. doi: 10.1002/jcp.22275
- Clayton K, Vallejo AF, Davies J, Sirvent S, Polak ME. Langerhans cells—programmed by the epidermis. Front Immunol. 2017;8:1676. doi: 10.3389/fimmu.2017.01676
- Haeberle H, Lumpkin EA. Merkel cells in somatosensation. Chemosens Percept. 2008;1:110-118. doi: 10.1007/s12078-008-9012-6
- Roig-Rosello E, Rousselle P. The human epidermal basement membrane: a shaped and cell instructive platform that aging slowly alters. Biomolecules. 2020;10(12):1607. doi: 10.3390/biom10121607
- Prost-Squarcioni C, Fraitag S, Heller M, Boehm N. Functional histology of dermis. Ann Dermatol Venereol. 2008:1S5-20. doi: 10.1016/s0151-9638(08)70206-0
- Grinnell F. Fibroblast biology in three-dimensional collagen matrices. Trends Cell Biol. 2003;13(5):264-269. doi: 10.1016/s0962-8924(03)00057-6
- Muiznieks LD, Keeley FW. Molecular assembly and mechanical properties of the extracellular matrix: a fibrous protein perspective. Biochim Biophys Acta. 2013;1832(7):866-875. doi: 10.1016/j.bbadis.2012.11.022
- Moon TC, Befus AD, Kulka M. Mast cell mediators: their differential release and the secretory pathways involved. Front Immunol. 2014;5:569. doi: 10.3389/fimmu.2014.00569
- Driskell RR, Jahoda CA, Chuong CM, Watt FM, Horsley V. Defining dermal adipose tissue. Exp Dermatol. 2014;23(9):629-631. doi: 10.1111/exd.12450
- Driskell RR, Jahoda CA, Chuong CM, Watt FM, Horsley V. Defining dermal adipose tissue. Exp. Dermatol. 2014; 23(9):629-631. doi: 10.1111/exd.12450
- Frueh FS, Menger MD, Lindenblatt N, Giovanoli P, Laschke MW. Current and emerging vascularization strategies in skin tissue engineering. Crit Rev Biotechnol. 2016;37(5): 613-625. doi: 10.1080/07388551.2016.1209157
- Hendrickx B, Vranckx JJ, Luttun A. Cell-based vascularization strategies for skin tissue engineering. Tissue Eng Part B Rev. 2011;17(1):13-24. doi: 10.1089/ten.teb.2010.0315
- Laschke MW, Menger MD. Prevascularization in tissue engineering: current concepts and future directions. Biotechnol Adv. 2016;34(2):112-121. doi: 10.1016/j.biotechadv.2015.12.004
- Laschke M, Menger M. Vascularization in tissue engineering: angiogenesis versus inosculation. Eur Surg Res. 2012;48(2):85-92. doi: 10.1159/000336876
- Johnson KE, Wilgus TA. Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair. Adv Wound Care. 2014;3(10):647-661. doi: 10.1089/wound.2013.0517
- Kolte D, McClung JA, Aronow WS. Chapter 6 - Vasculogenesis and angiogenesis. In: Translational Research in Coronary Artery Disease. New York: Elsevier; 2016:49-65. doi: 10.1016/B978-0-12-802385-3.00006-1
- Demidova-Rice TN, Durham JT, Herman IM. Wound healing angiogenesis: innovations and challenges in acute and chronic wound healing. Adv Wound Care. 2012;1(1):17-22. doi: 10.1089/wound.2011.0308
- Heller M, Bauer HK, Schwab R, et al. The impact of intercellular communication for the generation of complex multicellular prevascularized tissue equivalents. J Biomed Mater Res Part A. 2020;108(3):734-748. doi: 10.1002/jbm.a.36853
- Liew AWL, Zhang Y. In vitro pre-vascularization strategies for tissue engineered constructs–Bioprinting and others. Int J Bioprint. 2017;3(1). doi: 10.18063/iib.2017.01.008
- Tomasina C, Bodet T, Mota C, Moroni L, Camarero- Espinosa S. Bioprinting vasculature: materials, cells and emergent techniques. Materials. 2019;12(17):2701. doi: 10.3390/ma12172701
- Yang G, Mahadik B, Choi JY, Fisher JP. Vascularization in tissue engineering: fundamentals and state-of-art. Prog Biomed Eng. 2020;2(1):012002. doi: 10.1088/2516-1091/ab5637
- Richardson RJ. Parallels between vertebrate cardiac and cutaneous wound healing and regeneration. Npj Regener Med. 2018;3(1):21. doi: 10.1038/s41536-018-0059-y
- Chandra P, Atala A. Engineering blood vessels and vascularized tissues: technology trends and potential clinical applications. Clin Sci. 2019;133(9):1115-1135. doi: 10.1042/cs20180155
- Min S, Ko IK, Yoo JJ. State-of-the-art strategies for the vascularization of three-dimensional engineered organs. Vasc Spec Int. 2019;35(2):77. doi: 10.5758/vsi.2019.35.2.77
- Sharma D, Ross D, Wang G, Jia W, Kirkpatrick SJ, Zhao F. Upgrading prevascularization in tissue engineering: a review of strategies for promoting highly organized microvascular network formation. Acta Biomater. 2019;95:112-130. doi: 10.1016/j.actbio.2019.03.016
- Takei T, Sakai S, Yoshida M. In vitro formation of vascular-like networks using hydrogels. J Biosci Bioeng. 2016;122(5):519-527. doi: 10.1016/j.jbiosc.2016.03.023
- Wong HK, Lam CRI, Wen F, et al. Novel method to improve vascularization of tissue engineered constructs with biodegradable fibers. Biofabrication. 2016;8(1):015004. doi: 10.1088/1758-5090/8/1/015004
- Datta P, Ayan B, Ozbolat IT. Bioprinting for vascular and vascularized tissue biofabrication. Acta Biomater. 2017; 51:1-20. doi: 10.1016/j.actbio.2017.01.035
- Herrmann M, Binder A, Menzel U, Zeiter S, Alini M, Verrier S. CD34/CD133 enriched bone marrow progenitor cells promote neovascularization of tissue engineered constructs in vivo. Stem Cell Res. 2014;13(3):465-477. doi: 10.1016/j.scr.2014.10.005
- Kniebs C, Kreimendahl F, Köpf M, Fischer H, Jockenhoevel S, Thiebes AL. Influence of different cell types and sources on pre-vascularisation in fibrin and agarose–collagen gels. Organogenesis. 2020;16(1):14-26. doi: 10.1080/15476278.2019.1697597
- Liu X, Chen W, Zhang C, et al. Co-seeding human endothelial cells with human-induced pluripotent stem cell-derived mesenchymal stem cells on calcium phosphate scaffold enhances osteogenesis and vascularization in rats. Tissue Eng Part A. 2017;23(11-12):546-555. doi: 10.1089/ten.tea.2016.0485
- Rouwkema J, Khademhosseini A. Vascularization and angiogenesis in tissue engineering: beyond creating static networks. Trends Biotechnol. 2016;34(9):733-745. doi: 10.1016/j.tibtech.2016.03.002
- Sarker M, Chen X, Schreyer D. Experimental approaches to vascularisation within tissue engineering constructs. J Biomater Sci. 2015;26(12):683-734. doi: 10.1080/09205063.2015.1059018
- Xiao X, Wang W, Liu D, et al. The promotion of angiogenesis induced by three-dimensional porous beta-tricalcium phosphate scaffold with different interconnection sizes via activation of PI3K/Akt pathways. Sci Rep. 2015;5(1): 9409. doi: 10.1038/srep09409
- Xie R, Zheng W, Guan L, Ai Y, Liang Q. Engineering of hydrogel materials with perfusable microchannels for building vascularized tissues. Small. 2020;16(15): 1902838. doi: 10.1002/smll.201902838
- Blatchley MR, Hall F, Wang S, Pruitt HC, Gerecht S. Hypoxia and matrix viscoelasticity sequentially regulate endothelial progenitor cluster-based vasculogenesis. Sci Adv. 2019;5(3):eaau7518. doi: 10.1126/sciadv.aau7518
- Auger FA, Gibot L, Lacroix D. The pivotal role of vascularization in tissue engineering. Annu Rev Biomed Eng. 2013;15:177-200. doi: 10.1146/annurev-bioeng-071812-152428
- Phua QH, Han HA, Soh B-S. Translational stem cell therapy: vascularized skin grafts in skin repair and regeneration. J Transl Med. 2021;19:1-11. doi: 10.1186/s12967-021-02752-2
- Gao C, Lu C, Qiao H, et al. Strategies for vascularized skin models in vitro. Biomater Sci. 2022;10(17):4724-4739. doi: 10.1039/d2bm00784c
- Baldwin J, Antille M, Bonda U, et al. In vitro pre-vascularisation of tissue-engineered constructs A co-culture perspective. Vasc Cell. 2014;6:1-16. doi: 10.1186/2045-824x-6-13
- Costa-Almeida R, Granja P, Soares R, Guerreiro S. Cellular strategies to promote vascularisation in tissue engineering applications. Eur Cell Mater. 2014;28:51-66. doi: 10.22203/ecm.v028a05
- Heller M, Frerick-Ochs E, Bauer H-K, et al. Tissue engineered pre-vascularized buccal mucosa equivalents utilizing a primary triculture of epithelial cells, endothelial cells and fibroblasts. Biomaterials. 2016;77:207-215. doi: 10.1016/j.biomaterials.2015.10.073
- Um Min Allah N, Berahim Z, Ahmad A, Kannan TP. Biological interaction between human gingival fibroblasts and vascular endothelial cells for angiogenesis: a co-culture perspective. Tissue Eng Regener Med. 2017;14:495-505. doi: 10.1007/s13770-017-0065-y
- Weinandy S, Laffar S, Unger RE, et al. Biofunctionalized microfiber-assisted formation of intrinsic three-dimensional capillary-like structures. Tissue Eng Part A. 2014;20(13- 14):1858-1869. doi: 10.1089/ten.tea.2013.0330
- Miyazaki H, Tsunoi Y, Akagi T, Sato S, Akashi M, Saitoh D. A novel strategy to engineer pre-vascularized 3-dimensional skin substitutes to achieve efficient, functional engraftment. Sci Rep. 2019;9(1):7797. doi: 10.1038/s41598-019-44113-6
- Costa-Almeida R, Gomez-Lazaro M, Ramalho C, Granja PL, Soares R, Guerreiro SG. Fibroblast-endothelial partners for vascularization strategies in tissue engineering. Tissue Eng Part A. 2015;21(5-6):1055-1065. doi: 10.1089/ten.tea.2014.0443
- Morin KT, Tranquillo RT. In vitro models of angiogenesis and vasculogenesis in fibrin gel. Exp Cell Res. 2013;319(16): 2409-2417. doi: 10.1016/j.yexcr.2013.06.006
- Wan X, Bovornchutichai P, Cui Z, O’Neill E, Ye H. Morphological analysis of human umbilical vein endothelial cells co-cultured with ovarian cancer cells in 3D: an oncogenic angiogenesis assay. PLoS One. 2017;12(7):e0180296. doi: 10.1371/journal.pone.0180296
- Ren L, Ma D, Liu B, et al. Preparation of three-dimensional vascularized MSC cell sheet constructs for tissue regeneration. BioMed Res Int. 2014;2014. doi: 10.1155/2014/301279
- Liu X, Michael S, Bharti K, Ferrer M, Song MJ. A biofabricated vascularized skin model of atopic dermatitis for preclinical studies. Biofabrication. 2020;12(3):035002. doi: 10.1088/1758-5090/ab76a1
- Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32(8):773-785. doi: 10.1038/nbt.2958
- Ng WL, Wang S, Yeong WY, Naing MW. Skin bioprinting: impending reality or fantasy? Trends Biotechnol. 2016;34(9):689-699. doi: 10.1016/j.tibtech.2016.04.006
- Guillotin B, Guillemot F. Cell patterning technologies for organotypic tissue fabrication. Trends Biotechnol. 2011;29(4):183-190. doi: 10.1016/j.tibtech.2010.12.008
- Lee W, Debasitis JC, Lee VK, et al. Multi-layered culture of human skin fibroblasts and keratinocytes through three-dimensional freeform fabrication. Biomaterials. 2009;30(8):1587-1595. doi: 10.1016/j.biomaterials.2008.12.009
- Binder KW, Zhao W, Aboushwareb T, Dice D, Atala A, Yoo JJ. In situ bioprinting of the skin for burns. J Am Coll Surg. 2010;211(3):S76. doi: 10.1016/j.jamcollsurg.2010.06.198
- Koch L, Deiwick A, Schlie S, et al. Skin tissue generation by laser cell printing. Biotechnol Bioeng. 2012;109(7): 1855-1863. doi: 10.1002/bit.24455
- Richards D, Jia J, Yost M, Markwald R, Mei Y. 3D bioprinting for vascularized tissue fabrication. Ann Biomed Eng. 2017;45:132-147. doi: 10.1007/s10439-016-1653-z
- Yu J, Park SA, Kim WD, et al. Current advances in 3D bioprinting technology and its applications for tissue engineering. Polymers. 2020;12(12):2958. doi: 10.3390/polym12122958
- Klebe RJ. Cytoscribing: a method for micropositioning cells and the construction of two-and three-dimensional synthetic tissues. Exp Cell Res. 1988;179(2):362-373. doi: 10.1016/0014-4827(88)90275-3
- Zikulnig J, Kosel J. Fabrication technologies for flexible printed sensors. In: Encyclopedia of Sensors and Biosensors. New York: Elsevier; 2023:33–50. doi: 10.1016/b978-0-12-822548-6.00010-8
- Cui X, Boland T. Human microvasculature fabrication using thermal inkjet printing technology. Biomaterials. 2009;30(31):6221-6227. doi: 10.1016/j.biomaterials.2009.07.056
- Malda J, Visser J, Melchels FP, et al. 25th anniversary article: engineering hydrogels for biofabrication. Adv Mater. 2013;25(36):5011-5028. doi: 10.1002/adma.201302042
- Cui X, Boland T, DD’Lima D, Lotz MK. Thermal inkjet printing in tissue engineering and regenerative medicine. Recent Pat Drug Delivery Formulation. 2012;6(2):149-155. doi: 10.2174/187221112800672949
- Cui X, Dean D, Ruggeri ZM, Boland T. Cell damage evaluation of thermal inkjet printed Chinese hamster ovary cells. Biotechnol Bioeng. 2010;106(6):963-969. doi: 10.1002/bit.22762
- Ning L, Chen X. A brief review of extrusion‐based tissue scaffold bio‐printing. Biotechnol J. 2017;12(8):1600671. doi: 10.1002/biot.201600671
- Kim BS, Lee J-S, Gao G, Cho D-W. Direct 3D cell-printing of human skin with functional transwell system. Biofabrication. 2017;9(2):025034. doi: 10.1088/1758-5090/aa71c8
- Ramasamy S, Davoodi P, Vijayavenkataraman S, et al. Optimized construction of a full thickness human skin equivalent using 3D bioprinting and a PCL/collagen dermal scaffold. Bioprinting. 2021;21:e00123. doi: 10.1016/j.bprint.2020.e00123
- Park JH, Ahn M, Park SH, et al. 3D bioprinting of a trachea-mimetic cellular construct of a clinically relevant size. Biomaterials. 2021;279:121246. doi: 10.1016/j.biomaterials.2021.121246
- Choi Y-J, Jun Y-J, Kim DY, et al. A 3D cell printed muscle construct with tissue-derived bioink for the treatment of volumetric muscle loss. Biomaterials. 2019;206:160-169. doi: 10.1016/j.biomaterials.2019.03.036
- Kang H-W, Lee SJ, Ko IK, Kengla C, Yoo JJ, Atala A. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat Biotechnol. 2016;34(3): 312-319. doi: 10.1038/nbt.3413
- Ma Y, Wang Y, Chen D, et al. 3D bioprinting of a gradient stiffened gelatin–alginate hydrogel with adipose-derived stem cells for full-thickness skin regeneration. J Mater Chem B. 2023;11(13):2989-3000. doi: 10.1039/d2tb02200a
- Pati F, Jang J, Ha D-H, et al. Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat Commun. 2014;5(1):3935. doi: 10.1038/ncomms4935
- Ahn M, Cho WW, Lee H, et al. Engineering of uniform epidermal layers via sacrificial gelatin bioink‐assisted 3D extrusion bioprinting of skin. Adv Healthc Mater. 2023:2301015. doi: 10.1002/adhm.202301015
- Odde DJ, Renn MJ. Laser-guided direct writing for applications in biotechnology. Trends Biotechnol. 1999;17(10):385-389. doi: 10.1016/s0167-7799(99)01355-4
- Derakhshanfar S, Mbeleck R, Xu K, Zhang X, Zhong W, Xing M. 3D bioprinting for biomedical devices and tissue engineering: a review of recent trends and advances. Bioact Mater. 2018;3(2):144-156. doi: 10.1016/j.bioactmat.2017.11.008
- Li H, Tan C, Li L. Review of 3D printable hydrogels and constructs. Mater Des. 2018;159:20-38. doi: 101016/jmatdes201808023
- Donderwinkel I, Van Hest JC, Cameron NR. Bio-inks for 3D bioprinting: recent advances and future prospects. Polym Chem. 2017;8(31):4451-4471. doi: 10.1039/C7PY00826K
- Catros S, Guillotin B, Bačáková M, Fricain J-C, Guillemot F. Effect of laser energy, substrate film thickness and bioink viscosity on viability of endothelial cells printed by laser-assisted bioprinting. Appl Surf Sci. 2011;257(12): 5142-5147. doi: 10.1016/j.apsusc.2010.11.049
- Magalhães LSS, Santos FEP, Elias CdMV, et al. Printing 3D hydrogel structures employing low-cost stereolithography technology. J Funct Biomater. 2020;11(1):12. doi: 10.3390/jfb11010012
- Choi KY, Ajiteru O, Hong H, et al. A digital light processing 3D-printed artificial skin model and full-thickness wound models using silk fibroin bioink. Acta Biomater. 2023;164:159-174. doi: 10.1016/j.actbio.2023.04.034
- Zhang G, Zhang Z, Cao G, et al. Engineered dermis loaded with confining forces promotes full-thickness wound healing by enhancing vascularisation and epithelialisation. Acta Biomater. 2023;170:464-478. doi: 10.1016/j.actbio.2023.08.049
- Xu T, Binder KW, Albanna MZ, et al. Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications. Biofabrication. 2012;5(1):015001. doi: 10.1088/1758-5082/5/1/015001
- Gudapati H, Dey M, Ozbolat I. A comprehensive review on droplet-based bioprinting: past, present and future. Biomaterials. 2016;102:20-42. doi: 10.1016/j.biomaterials.2016.06.012
- LaBarge W, Morales A, Pretorius D, Kahn-Krell AM, Kannappan R, Zhang J. Scaffold-free bioprinter utilizing layer-by-layer printing of cellular spheroids. Micromachines. 2019;10(9):570. doi: 10.3390/mi10090570
- Hakimi N, Cheng R, Leng L, et al. Handheld skin printer: in situ formation of planar biomaterials and tissues. Lab Chip. 2018;18(10):1440-1451. doi: 10.1039/c7lc01236e
- Vijayavenkataraman S, Lu W, Fuh J. 3D bioprinting of skin: a state-of-the-art review on modelling, materials, and processes. Biofabrication. 2016;8(3):032001. doi: 10.1088/1758-5090/8/3/032001
- Matai I, Kaur G, Seyedsalehi A, McClinton A, Laurencin CT. Progress in 3D bioprinting technology for tissue/organ regenerative engineering. Biomaterials. 2020;226:119536. doi: 10.1016/j.biomaterials.2019.119536
- Ning L, Gil CJ, Hwang B, et al. Biomechanical factors in three-dimensional tissue bioprinting. Appl Phys Rev. 2020;7(4):041319. doi: 10.1016/j.biomaterials.2019.119536
- Zorlutuna P, Vrana NE, Khademhosseini A. The expanding world of tissue engineering: the building blocks and new applications of tissue engineered constructs. IEEE Rev Biomed Eng. 2012;6:47-62. doi: 10.1109/rbme.2012.2233468
- Wang Y, Kankala RK, Ou C, Chen A, Yang Z. Advances in hydrogel-based vascularized tissues for tissue repair and drug screening. Bioact Mater. 2022;9:198-220. doi: 10.1016/j.bioactmat.2021.07.005
- Bedell ML, Navara AM, Du Y, Zhang S, Mikos AG. Polymeric systems for bioprinting. Chem Rev. 2020;120(19): 10744-10792. doi: 10.1021/acs.chemrev.9b00834
- Nyström A, Bruckner‐Tuderman L. Matrix molecules and skin biology. In: Seminars in Cell & Developmental Biology. New York: Elsevier; 2019;89:136-146. doi: 10.1016/j.semcdb.2018.07.025
- Wells A, Nuschke A, Yates CC. Skin tissue repair: matrix microenvironmental influences. Matrix Biol. 2016; 49:25-36. doi: 10.1016/j.matbio.2015.08.001
- Dzobo K, Motaung KSCM, Adesida A. Recent trends in decellularized extracellular matrix bioinks for 3D printing: an updated review. Int J Mol Sci. 2019;20(18):4628. doi: 10.3390/ijms20184628
- Kim BS, Das S, Jang J, Cho D-W. Decellularized extracellular matrix-based bioinks for engineering tissue-and organ-specific microenvironments. Chem Rev. 2020;120(19): 10608-10661. doi: 10.1021/acs.chemrev.9b00808
- Choudhury D, Tun HW, Wang T, Naing MW. Organ-derived decellularized extracellular matrix: a game changer for bioink manufacturing? Trends Biotechnol. 2018;36(8):787-805. doi: 10.1016/j.tibtech.2018.03.003
- Kim BS, Kim H, Gao G, Jang J, Cho D-W. Decellularized extracellular matrix: a step towards the next generation source for bioink manufacturing. Biofabrication. 2017;9(3):034104. doi: 10.1088/1758-5090/aa7e98
- Kim BS, Kwon YW, Kong J-S, et al. 3D cell printing of in vitro stabilized skin model and in vivo pre-vascularized skin patch using tissue-specific extracellular matrix bioink: A step towards advanced skin tissue engineering. Biomaterials. 2018;168:38-53. doi: 10.1016/j.biomaterials.2018.03.040
- Jorgensen AM, Chou Z, Gillispie G, et al. Decellularized skin extracellular matrix (dsECM) improves the physical and biological properties of fibrinogen hydrogel for skin bioprinting applications. Nanomaterials. 2020;10(8):1484. doi: 10.3390/nano10081484
- Zhang Q, Johnson JA, Dunne LW, et al. Decellularized skin/ adipose tissue flap matrix for engineering vascularized composite soft tissue flaps. Acta Biomater. 2016;35:166-184. doi: 10.1016/j.actbio.2016.02.017
- Parmaksiz M, Elçin AE, Elçin YM. Decellularized bSIS-ECM as a regenerative biomaterial for skin wound repair. Skin Stem Cell Methods Protoc. 2019:175-185. doi: 10.1007/7651_2018_147
- Abaci A, Guvendiren M. Designing decellularized extracellular matrix‐based bioinks for 3D bioprinting. Adv Healthc Mater. 2020;9(24):2000734. doi: 10.1002/adhm.202000734
- Velasco D, Quílez C, Garcia M, del Cañizo JF, Jorcano JL. 3D human skin bioprinting: a view from the bio side. J 3D Print Med. 2018:141-162. doi: 10.2217/3dp-2018-0008
- Hayden P, Ayehunie S, Jackson G, et al. In vitro skin equivalent models for toxicity testing. In: Alternative Toxicological Methods. Boca Raton, FL: CRC Press; 2003:229-247. doi: 10.1201/9780203008799.ch20
- Schmook FP, Meingassner JG, Billich A. Comparison of human skin or epidermis models with human and animal skin in in-vitro percutaneous absorption. Int J Pharm. 2001;215(1-2):51-56. doi: 10.1016/s0378-5173(00)00665-7
- Almeida A, Sarmento B, Rodrigues F. Insights on in vitro models for safety and toxicity assessment of cosmetic ingredients. Int J Pharm. 2017;519(1-2):178-185. doi: 10.1016/j.ijpharm.2017.01.024
- Liebsch M, Grune B, Seiler A, et al. Alternatives to animal testing: current status and future perspectives. Arch Toxicol. 2011;85:841-858. doi: 10.1007/s00204-011-0718-x
- Yanez M, Rincon J, Dones A, De Maria C, Gonzales R, Boland T. In vivo assessment of printed microvasculature in a bilayer skin graft to treat full-thickness wounds. Tissue Eng Part A. 2015;21(1-2):224-233. doi: 10.1089/ten.tea.2013.0561
- Kim BS, Gao G, Kim JY, Cho DW. 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. 2019;8(7):1801019. doi: 10.1002/adhm.201801019
- Abaci HE, Coffman A, Doucet Y, et al. Tissue engineering of human hair follicles using a biomimetic developmental approach. Nat Commun. 2018;9(1):5301. doi: 10.1038/s41467-018-07579-y
- Pontiggia L, Van Hengel IA, Klar A, et al. Bioprinting and plastic compression of large pigmented and vascularized human dermo-epidermal skin substitutes by means of a new robotic platform. J Tissue Eng. 2022;13:20417314221088513. doi: 10.1177/20417314221088513
- Naomi R, Ridzuan PM, Bahari H. Current insights into collagen type I. Polymers. 2021;13(16):2642. doi: 10.3390/polym13162642
- Zhang X, Li J, Ye P, Gao G, Hubbell K, Cui X. Coculture of mesenchymal stem cells and endothelial cells enhances host tissue integration and epidermis maturation through AKT activation in gelatin methacryloyl hydrogel-based skin model. Acta Biomater. 2017;59: 317-326. doi: 10.1016/j.actbio.2017.07.001
- Baltazar T, Merola J, Catarino C, et al. Three dimensional bioprinting of a vascularized and perfusable skin graft using human keratinocytes, fibroblasts, pericytes, and endothelial cells. Tissue Eng Part A. 2020;26(5-6):227-238. doi: 10.1089/ten.tea.2019.0201
- Kolesky DB, Homan KA, Skylar-Scott MA, Lewis JA. Three-dimensional bioprinting of thick vascularized tissues. Proc Natl Acad Sci. 2016;113(12):3179-3184. doi: 10.1073/pnas.1521342113
- Ng WL, Qi JTZ, Yeong WY, Naing MW. Proof-of-concept: 3D bioprinting of pigmented human skin constructs. Biofabrication. 2018;10(2):025005. doi: 10.1088/1758-5090/aa9e1e
- Ma J, Qin C, Wu J, et al. 3D printing of strontium silicate microcylinder‐containing multicellular biomaterial inks for vascularized skin regeneration. Adv Healthc Mater. 2021;10(16):2100523. doi: 10.1002/adhm.202100523
- Heinemann S, Coradin T, Desimone MF. Bio-inspired silica–collagen materials: applications and perspectives in the medical field. Biomater Sci. 2013;1(7):688-702. doi: 10.1039/c3bm00014a
- Desimone MF, Hélary C, Mosser G, Giraud-Guille M-M, Livage J, Coradin T. Fibroblast encapsulation in hybrid silica–collagen hydrogels. J Mater Chem. 2010;20(4): 666-668. doi: 10.1039/B921572G
- Desimone MF, Hélary C, Rietveld IB, et al. Silica–collagen bionanocomposites as three-dimensional scaffolds for fibroblast immobilization. Acta Biomater. 2010;6(10): 3998-4004. doi: 10.1016/j.actbio.2010.05.014
- Pouroutzidou GK, Liverani L, Theocharidou A, et al. Synthesis and characterization of mesoporous mg-and sr-doped nanoparticles for moxifloxacin drug delivery in promising tissue engineering applications. Int J Mol Sci. 2021;22(2):577. doi: 10.3390/ijms22020577
- Mao L, Xia L, Chang J, et al. The synergistic effects of Sr and Si bioactive ions on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration. Acta Biomater. 2017;61:217-232. doi: 10.1016/j.actbio.2017.08.015
- Dikici S, Claeyssens F, MacNeil S. Bioengineering vascular networks to study angiogenesis and vascularization of physiologically relevant tissue models in vitro. ACS Biomater Sci Eng. 2020;6(6):3513-3528. doi: 10.1021/acsbiomaterials.0c00191
- Abaci HE, Guo Z, Coffman A, et al. Human skin constructs with spatially controlled vasculature using primary and iPSC‐derived endothelial cells. Adv Healthc Mater. 2016;5(14):1800-1807. doi: 10.1002/adhm.201500936
- Schneider J, Biedermann T, Widmer D, et al. Matriderm® versus Integra®: a comparative experimental study. Burns. 2009;35(1):51-57. doi: 10.1016/j.burns.2008.07.018
- Choi SW, Zhang Y, MacEwan MR, Xia Y. Neovascularization in biodegradable inverse opal scaffolds with uniform and precisely controlled pore sizes. Adv Healthc Mater. 2013;2(1):145-154. doi: 10.1002/adhm.201200106
- van Zuijlen PP, Vloemans JF, van Trier AJ, et al. Dermal substitution in acute burns and reconstructive surgery: a subjective and objective long-term follow-up. Plast Reconstr Surg. 2001;108(7):1938-1946. doi: 10.1097/00006534-200112000-00014
- Ring A, Langer S, Schaffran A, et al. Enhanced neovascularization of dermis substitutes via low-pressure plasma-mediated surface activation. Burns. 2010;36(8):1222-1227. doi: 10.1016/j.burns.2010.03.002
- Shaterian A, Borboa A, Sawada R, et al. Real-time analysis of the kinetics of angiogenesis and vascular permeability in an animal model of wound healing. Burns. 2009;35(6):811-817. doi: 10.1016/j.burns.2008.12.012
- Supp DM, Boyce ST. Engineered skin substitutes: practices and potentials. Clin Dermatol. 2005;23(4):403-412. doi: 10.1016/j.clindermatol.2004.07.023
- Cam C, Zhu S, Truong NF, Scumpia PO, Segura T. Systematic evaluation of natural scaffolds in cutaneous wound healing. J Mater Chem B. 2015;3(40):7986-7992. doi: 10.1039/c5tb00807g
- Griffin M, Naderi N, Kalaskar D, Seifalian A, Butler P. Argon plasma surface modification promotes the therapeutic angiogenesis and tissue formation of tissue-engineered scaffolds in vivo by adipose-derived stem cells. Stem Cell Res Ther. 2019;10:1-14. doi: 10.1186/s13287-019-1195-z
- Liu Q, Huang Y, Lan Y, et al. Acceleration of skin regeneration in full‐thickness burns by incorporation of bFGF‐loaded alginate microspheres into a CMCS–PVA hydrogel. J Tissue Eng Regener Med. 2017;11(5):1562-1573. doi: 10.1002/term.2057
- Guo R, Xu S, Ma L, Huang A, Gao C. Enhanced angiogenesis of gene-activated dermal equivalent for treatment of full thickness incisional wounds in a porcine model. Biomaterials. 2010;31(28):7308-7320. doi: 10.1016/j.biomaterials.2010.06.013
- Guo R, Xu S, Ma L, Huang A, Gao C. The healing of full-thickness burns treated by using plasmid DNA encoding VEGF-165 activated collagen–chitosan dermal equivalents. Biomaterials. 2011;32(4):1019-1031. doi: 10.1016/j.biomaterials.2010.08.087
- Yang Y, Xia T, Chen F, et al. Electrospun fibers with plasmid bFGF polyplex loadings promote skin wound healing in diabetic rats. Mol Pharm. 2012;9(1):48-58. doi: 10.1021/mp200246b
- Reckhenrich AK, Hopfner U, Krötz F, et al. Bioactivation of dermal scaffolds with a non-viral copolymer-protected gene vector. Biomaterials. 2011;32(7):1996-2003. doi: 10.1016/j.biomaterials.2010.11.022
- Scherer SS, Pietramaggiori G, Matthews J, et al. Poly-N-acetyl glucosamine nanofibers: a new bioactive material to enhance diabetic wound healing by cell migration and angiogenesis. Ann Surg. 2009;250(2):322-330. doi: 10.1097/sla.0b013e3181ae9d45
- Zhao S, Li L, Wang H, et al. Wound dressings composed of copper-doped borate bioactive glass microfibers stimulate angiogenesis and heal full-thickness skin defects in a rodent model. Biomaterials. 2015;53:379-391. doi: 10.1016/j.biomaterials.2015.02.112
- Wang X, You C, Hu X, et al. The roles of knitted mesh-reinforced collagen–chitosan hybrid scaffold in the one-step repair of full-thickness skin defects in rats. Acta Biomater. 2013;9(8):7822-7832. doi: 10.1016/j.actbio.2013.04.017
- Sun G, Zhang X, Shen Y-I, et al. Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing. Proc Natl Acad Sci. 2011;108(52):20976-20981. doi: 10.1073/pnas.1115973108
- Hohlfeld J, de Buys Roessingh A, Hirt-Burri N, et al. Tissue engineered fetal skin constructs for paediatric burns. Lancet. 2005;366(9488):840-842. doi: 10.1016/s0140-6736(05)67107-3
- Tonello C, Zavan B, Cortivo R, Brun P, Panfilo S, Abatangelo G. In vitro reconstruction of human dermal equivalent enriched with endothelial cells. Biomaterials. 2003;24(7):1205-1211. doi: 10.1016/s0142-9612(02)00450-7
- Hudon V, Berthod F, Black A, Damour O, Germain L, Auger F. A tissue‐engineered endothelialized dermis to study the modulation of angiogenic and angiostatic molecules on capillary‐like tube formation in vitro. Br J Dermatol. 2003;148(6):1094-1104. doi: 10.1046/j.1365-2133.2003.05298.x
- Black AF, Berthod F, L’Heureux N, Germain L, Auger FA. In vitro reconstruction of a human capillary‐like network in a tissue‐engineered skin equivalent. FASEB J. 1998;12(13):1331-1340. doi: 10.1046/j.1365-2133.2003.05298.x
- Tremblay P-L, Hudon V, Berthod F, Germain L, Auger FA. Inosculation of tissue-engineered capillaries with the host’s vasculature in a reconstructed skin transplanted on mice. Am J Transplant. 2005;5(5):1002-1010. doi: 10.1111/j.1600-6143.2005.00790.x
- Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964-966. doi: 10.1126/science.275.5302.964
- Sander AL, Jakob H, Henrich D, et al. Systemic transplantation of progenitor cells accelerates wound epithelialization and neovascularization in the hairless mouse ear wound model. J Surg Res. 2011;165(1):165-170. doi: 10.1016/j.jss.2009.07.003
- Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood. 2004;104(9):2752-2760. doi: 10.1182/blood-2004-04-1396
- Kaushal S, Amiel GE, Guleserian KJ, et al. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med. 2001;7(9):1035-1040. doi: 10.1038/nm0901-1035
- Hendrickx B, Verdonck K, Van den Berge S, et al. Integration of blood outgrowth endothelial cells in dermal fibroblast sheets promotes full thickness wound healing. Stem Cell. 2010;28(7):1165-1177. doi: 10.1002/stem.445
- Tiruvannamalai Annamalai R, Rioja AY, Putnam AJ, Stegemann JP. Vascular network formation by human microvascular endothelial cells in modular fibrin microtissues. ACS Biomater Sci Eng. 2016;2(11):1914-1925. doi: 10.1021/acsbiomaterials.6b00274
- Kinnaird T, Stabile E, Burnett M, et al. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res. 2004;94(5):678-685. doi: 10.1161/01.res.0000118601.37875.ac
- Yoshikawa T, Mitsuno H, Nonaka I, et al. Wound therapy by marrow mesenchymal cell transplantation. Plast Reconstr Surg. 2008;121(3):860-877. doi: 10.1097/01.prs.0000299922.96006.24
- Moioli EK, Clark PA, Chen M, et al. Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. PLoS One. 2008;3(12):e3922. doi: 10.1371/journal.pone.0003922
- Liu P, Deng Z, Han S, et al. Tissue‐engineered skin containing mesenchymal stem cells improves burn wounds. Artif Organs. 2008;32(12):925-931. doi: 10.1111/j.1525-1594.2008.00654.x
- Altman AM, Yan Y, Matthias N, et al. IFATS collection: human adipose-derived stem cells seeded on a silk fibroin-chitosan scaffold enhance wound repair in a murine soft tissue injury model. Stem Cell. 2009;27(1):250-258. doi: 10.1634/stemcells.2008-0178
- Gang E, Jeong J, Han S, Yan Q, Jeon C, Kim H. In vitro endothelial potential of human UC blood-derived mesenchymal stem cells. Cytotherapy. 2006;8(3): 215-227. doi: 10.1080/14653240600735933
- Koponen JK, Kekarainen T, Heinonen SE, et al. Umbilical cord blood–derived progenitor cells enhance muscle regeneration in mouse hindlimb ischemia model. Mol Ther. 2007;15(12):2172-2177. doi: 10.1038/sj.mt.6300302
- Wang Z, Zheng L, Lian C, Qi Y, Li W, Wang S. Human umbilical cord-derived mesenchymal stem cells relieve hind limb ischemia by promoting angiogenesis in mice. Stem Cell Dev. 2019;28(20):1384-1397. doi: 10.1089/scd.2019.0115
- Chen X, Yue Z, Winberg PC, Lou Y-R, Beirne S, Wallace GG. 3D bioprinting dermal-like structures using species-specific ulvan. Biomater Sci. 2021;9(7):2424-2438. doi: 10.1039/d0bm01784a
- Liu P, Shen H, Zhi Y, et al. 3D bioprinting and in vitro study of bilayered membranous construct with human cells-laden alginate/gelatin composite hydrogels. Colloid Surf B. 2019;181:1026-1034. doi: 10.1016/j.colsurfb.2019.06.069
- Lee V, Singh G, Trasatti JP, et al. Design and fabrication of human skin by three-dimensional bioprinting. Tissue Eng Part C. 2014;20(6):473-484. doi: 10.1089/ten.tec.2013.0335
- Shi Y, Xing T, Zhang H, et al. Tyrosinase-doped bioink for 3D bioprinting of living skin constructs. Biomed Mater. 2018;13(3):035008. doi: 10.1088/1748-605x/aaa5b6
- 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;32:170-177. doi: 10.1016/j.actbio.2015.12.039
- Wang S, Xiong Y, Chen J, et al. Three dimensional printing bilayer membrane scaffold promotes wound healing. Front Bioeng Biotechnol. 2019;7:348. doi: 10.3389/fbioe.2019.00348
- Zidarič T, Milojević M, Gradišnik L, Stana Kleinschek K, Maver U, Maver T. Polysaccharide-based bioink formulation for 3D bioprinting of an in vitro model of the human dermis. Nanomaterials. 2020;10(4):733. doi: 10.3390/nano10040733
- Intini C, Elviri L, Cabral J, et al. 3D-printed chitosan-based scaffolds: an in vitro study of human skin cell growth and an in-vivo wound healing evaluation in experimental diabetes in rats. Carbohydr Polym. 2018;199: 593-602. doi: 10.1016/j.carbpol.2018.07.057
- Ng WL, Yeong WY, Naing MW. Development of polyelectrolyte chitosan-gelatin hydrogels for skin bioprinting. Procedia Cirp. 2016;49:105-112. doi: 10.1016/j.procir.2015.09.002
- Cubo N, Garcia M, Del Canizo JF, Velasco D, Jorcano JL. 3D bioprinting of functional human skin: production and in vivo analysis. Biofabrication. 2016;9(1):015006. doi: 10.1088/1758-5090/9/1/015006
- Hafezi F, Shorter S, Tabriz AG, et al. Bioprinting and preliminary testing of highly reproducible novel bioink for potential skin regeneration. Pharmaceutics. 2020;12(6):550. doi: 10.3390/pharmaceutics12060550
- Kwak H, Shin S, Lee H, Hyun J. Formation of a keratin layer with silk fibroin-polyethylene glycol composite hydrogel fabricated by digital light processing 3D printing. J Ind Eng Chem. 2019;72:232-240. doi: 10.1016/j.jiec.2018.12.023
- Azadmanesh F, Pourmadadi M, Zavar Reza J, Yazdian F, Omidi M, Haghirosadat BF. Synthesis of a novel nanocomposite containing chitosan as a three‐dimensional printed wound dressing technique: Emphasis on gene expression. Biotechnol Prog. 2021;37(4):e3132. doi: 10.1002/btpr.3132