Microfluidic and Lab-on-a-Chip Systems for Cutaneous Wound Healing Studies
Abstract
:1. Introduction
2. A Brief Overview of Wound Healing: Process, Cells, and Pathways
3. Conventional In Vitro Wound Healing Assays
4. Advanced Microfluidic Wound-Healing Assays
4.1. Exclusion
4.2. Enzymatic Depletion
4.3. Physical Depletion
5. Outlook
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Singer, C.R. Cutaneous wound healing. N. Engl. J. Med. 1999, 341, 738–746. [Google Scholar] [CrossRef] [PubMed]
- Guo, S.; DiPietro, L.A. Factors Affecting Wound Healing. J. Dent. Res. 2010, 89, 219–229. [Google Scholar] [CrossRef] [PubMed]
- Gurtner, G.C.; Werner, S.; Barrandon, Y.; Longaker, M.T. Wound repair and regeneration. Nat. Cell Biol. 2008, 453, 314–321. [Google Scholar] [CrossRef] [PubMed]
- Sorg, H.; Tilkorn, D.J.; Hager, S.; Hauser, J.; Mirastschijski, U. Skin Wound Healing: An Update on the Current Knowledge and Concepts. Eur. Surg. Res. 2017, 58, 81–94. [Google Scholar] [CrossRef]
- Stamm, A.; Reimers, K.; Strauß, S.; Vogt, P.; Scheper, T.; Pepelanova, I. In vitro wound healing assays—State of the art. BioNanoMaterials 2016, 17, 79–87. [Google Scholar] [CrossRef]
- Bielefeld, K.A.; Amini-Nik, S.; Alman, B.A. Cutaneous wound healing: Recruiting developmental pathways for regeneration. Cell. Mol. Life Sci. 2012, 70, 2059–2081. [Google Scholar] [CrossRef] [Green Version]
- Werner, S.; Grose, R. Regulation of Wound Healing by Growth Factors and Cytokines. Physiol. Rev. 2003, 83, 835–870. [Google Scholar] [CrossRef]
- Martin, P. Wound Healing--Aiming for Perfect Skin Regeneration. Science 1997, 276, 75–81. [Google Scholar] [CrossRef]
- Falanga, V. Wound healing and its impairment in the diabetic foot. Lancet 2005, 366, 1736–1743. [Google Scholar] [CrossRef]
- Cristina, A.; Gonzalez, D.O. Wound healing—A literature review. An. Bras. Dermatol. 2016, 91, 614–620. [Google Scholar]
- Li, J.; Chen, J.; Kirsner, R. Pathophysiology of acute wound healing. Clin. Dermatol. 2007, 25, 9–18. [Google Scholar] [CrossRef]
- Qing, C. The molecular biology in wound healing & non-healing wound. Chin. J. Traumatol. 2017, 20, 189–193. [Google Scholar] [CrossRef]
- Werner, S.; Krieg, T.; Smola, H. Keratinocyte–Fibroblast Interactions in Wound Healing. J. Investig. Dermatol. 2007, 127, 998–1008. [Google Scholar] [CrossRef] [Green Version]
- Busra, F.M.; Lokanathan, Y.; Nadzir, M.M.; Saim, A.; Idrus, R.B.H.; Chowdhury, S.R. Attachment, Proliferation, and Morphological Properties of Human Dermal Fibroblasts on Ovine Tendon Collagen Scaffolds: A Comparative Study. Malays. J. Med. Sci. 2017, 24, 33–43. [Google Scholar] [CrossRef]
- Loots, M.A.M.; Lamme, E.N.; Mekkes, J.R.; Bos, J.D.; Middelkoop, E. Cultured fibroblasts from chronic diabetic wounds on the lower extremity (non-insulin-dependent diabetes mellitus) show disturbed proliferation. Arch. Dermatol. Res. 1999, 291, 93–99. [Google Scholar] [CrossRef]
- Brem, H.; Golinko, M.S.; Stojadinovic, O.; Kodra, A.; Diegelmann, R.F.; Vukelic, S.; Entero, H.; Coppock, D.L.; Tomic-Canic, M. Primary cultured fibroblasts derived from patients with chronic wounds: A methodology to produce human cell lines and test putative growth factor therapy such as GMCSF. J. Transl. Med. 2008, 6, 75. [Google Scholar] [CrossRef] [Green Version]
- Lee, N.-Y.; Cho, K.-H. The effects of epidermal keratinocytes and dermal fibroblasts on the formation of cutaneous basement membrane in three-dimensional culture systems. Arch. Dermatol. Res. 2004, 296, 296–302. [Google Scholar] [CrossRef]
- Ramirez, H.L.; Patel, S.B.; Pastar, I. The Role of TGFβ Signaling in Wound Epithelialization. Adv. Wound Care 2014, 3, 482–491. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barrientos, S.; Stojadinovic, O.; Golinko, M.S.; Brem, H.; Tomic-Canic, M. PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing. Wound Repair Regen. 2008, 16, 585–601. [Google Scholar] [CrossRef]
- Teven, C.M.; Farina, E.M.; Rivas, J.; Reid, R.R. Fibroblast growth factor (FGF) signaling in development and skeletal diseases. Genes Dis. 2014, 1, 199–213. [Google Scholar] [CrossRef] [Green Version]
- Grada, A.; Otero-Vinas, M.; Prieto-Castrillo, F.; Obagi, Z.; Falanga, V. Research Techniques Made Simple: Analysis of Collective Cell Migration Using the Wound Healing Assay. J. Investig. Dermatol. 2017, 137, e11–e16. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jonkman, J.E.N.; Cathcart, J.A.; Xu, F.; Bartolini, M.E.; Amon, J.E.; Stevens, K.M.; Colarusso, P. An introduction to the wound healing assay using live-cell microscopy. Cell Adhes. Migr. 2014, 8, 440–451. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Escámez, M.J.; García, M.; Larcher, F.; Meana, A.; Muñoz, E.; Jorcano, J.L.; Del Río, M. An in vivo model of wound healing in genetically modified skin-humanized mice. J. Investig. Dermatol. 2004, 123, 1182–1191. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shrivastav, A.; Mishra, A.K.; Ali, S.S.; Ahmad, A.; Abuzinadah, M.F.; Khan, N.A. In vivo models for assesment of wound healing potential: A systematic review. Wound Med. 2018, 20, 43–53. [Google Scholar] [CrossRef]
- Schneider, M.K.; Ioanas, H.-I.; Xandry, J.; Rudin, M. An in vivo wound healing model for the characterization of the angiogenic process and its modulation by pharmacological interventions. Sci. Rep. 2019, 9, 6004. [Google Scholar] [CrossRef]
- Jain, P.; Worthylake, R.A.; Alahari, S.K. Quantitative Analysis of Random Migration of Cells Using Time-lapse Video Microscopy. J. Vis. Exp. 2012, 1–11. [Google Scholar] [CrossRef] [Green Version]
- Gao, A.; Tian, Y.; Shi, Z.; Yu, L. A cost-effective microdevice bridges microfluidic and conventional in vitro scratch/wound-healing assay for personalized therapy validation. BioChip J. 2016, 10, 56–64. [Google Scholar] [CrossRef]
- Zhang, M.; Li, H.; Ma, H.; Qin, J. A simple microfluidic strategy for cell migration assay in an in vitro wound-healing model. Wound Repair Regen. 2013, 21, 897–903. [Google Scholar] [CrossRef]
- Van Kilsdonk, J.W.J.; Bogaard, E.H.V.D.; Jansen, P.A.M.; Bos, C.; Bergers, M.; Schalkwijk, J. An in vitro wound healing model for evaluation of dermal substitutes. Wound Repair Regen. 2013, 21, 890–896. [Google Scholar] [CrossRef]
- Ueck, C.; Volksdorf, T.; Houdek, P.; Vidal-y-Sy, S.; Sehner, S.; Ellinger, B.; Lobmann, R.; Larena-Avellaneda, A.; Reinshagen, K.; Ridderbusch, I.; et al. Comparison of In-Vitro and Ex-Vivo Wound Healing Assays for the Investigation of Diabetic Wound Healing and Demonstration of a Beneficial Effect of a Triterpene Extract. PLoS ONE 2017, 12, e0169028. [Google Scholar] [CrossRef]
- Topman, G.; Shoham, N.; Sharabani-Yosef, O.; Lin, F.-H.; Gefen, A. A new technique for studying directional cell migration in a hydrogel-based three-dimensional matrix for tissue engineering model systems. Micron 2013, 51, 9–12. [Google Scholar] [CrossRef]
- Muniandy, K.; Gothai, S.; Tan, W.S.; Kumar, S.S.; Esa, N.M.; Chandramohan, G.; Al-Numair, K.S.; Arulselvan, P. In Vitro Wound Healing Potential of Stem Extract of Alternanthera sessilis. Evid. Based Complement. Altern. Med. 2018, 2018, 1–13. [Google Scholar] [CrossRef] [Green Version]
- Justus, C.R.; Leffler, N.; Ruiz-Echevarria, M.; Yang, L.V. In vitro Cell Migration and Invasion Assays. J. Vis. Exp. 2014, e51046. [Google Scholar] [CrossRef] [Green Version]
- Joshi, P.N. Cells and Organs on Chip—A Revolutionary Platform for Biomedicine. Lab. Chip Fabr. Appl. 2016, 77–79. [Google Scholar] [CrossRef] [Green Version]
- Huh, D. A Human Breathing Lung-on-a-Chip. Ann. Am. Thorac. Soc. 2015, 12, S42–S44. [Google Scholar] [CrossRef]
- Felder, M.; Trueeb, B.; Stucki, A.O.; Borcard, S.; Stucki, J.D.; Schnyder, B.; Geiser, T.; Guenat, O.T. Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-On-A-Chip. Front. Bioeng. Biotechnol. 2019, 7, 3. [Google Scholar] [CrossRef]
- Subramaniam, A.; Sethuraman, S. Biomedical Applications of Nondegradable Polymers. Nat. Synth. Biomed. Polym. 2014, 301–308. [Google Scholar] [CrossRef]
- Deal, H.E.; Brown, A.C.; Daniele, M.A. Microphysiological systems for the modeling of wound healing and evaluation of pro-healing therapies. J. Mater. Chem. B 2020, 8, 7062–7075. [Google Scholar] [CrossRef]
- Biglari, S.; Le, T.Y.L.; Tan, R.P.; Wise, S.; Zambon, A.; Codolo, G.; De Bernard, M.; Warkiani, M.; Schindeler, A.; Naficy, S.; et al. Simulating Inflammation in a Wound Microenvironment Using a Dermal Wound-on-a-Chip Model. Adv. Health Mater. 2019, 8, e1801307. [Google Scholar] [CrossRef] [Green Version]
- Cheng, S.-Y.; Heilman, S.; Wasserman, M.; Archer, S.; Shuler, M.L.; Wu, M. A hydrogel-based microfluidic device for the studies of directed cell migration. Lab. Chip 2007, 7, 763–769. [Google Scholar] [CrossRef]
- Chen, Y.-C.; Allen, S.G.; Ingram, P.N.; Buckanovich, R.J.; Merajver, S.D.; Yoon, E. Single-cell Migration Chip for Chemotaxis-based Microfluidic Selection of Heterogeneous Cell Populations. Sci. Rep. 2015, 5, 9980. [Google Scholar] [CrossRef]
- Poujade, M.; Grasland-Mongrain, E.; Hertzog, A.; Jouanneau, J.; Chavrier, P.; Ladoux, B.; Buguin, A.; Silberzan, P. Collective migration of an epithelial monolayer in response to a model wound. Proc. Natl. Acad. Sci. USA 2007, 104, 15988–15993. [Google Scholar] [CrossRef] [Green Version]
- Nie, F.-Q.; Yamada, M.; Kobayashi, J.; Yamato, M.; Kikuchi, A.; Okano, T. On-chip cell migration assay using microfluidic channels. Biomaterials 2007, 28, 4017–4022. [Google Scholar] [CrossRef] [PubMed]
- Lin, J.-Y.; Lo, K.-Y.; Sun, Y.-S. A microfluidics-based wound-healing assay for studying the effects of shear stresses, wound widths, and chemicals on the wound-healing process. Sci. Rep. 2019, 9, 20016. [Google Scholar] [CrossRef]
- Conant, C.G.; Nevill, J.T.; Schwartz, M.; Ionescu-Zanetti, C. Wound Healing Assays in Well Plate–Coupled Microfluidic Devices with Controlled Parallel Flow. J. Lab. Autom. 2010, 15, 52–57. [Google Scholar] [CrossRef]
- Wei, Y.; Chen, F.; Zhang, T.; Chen, D.; Jia, X.; Wang, J.; Guo, W.; Chen, J. A Tubing-Free Microfluidic Wound Healing Assay Enabling the Quantification of Vascular Smooth Muscle Cell Migration. Sci. Rep. 2015, 5, 14049. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Conde, A.J.; Salvatierra, E.; Podhajcer, O.; Fraigi, L.; Madrid, R.E. Wound healing assay in a low-cost microfluidic platform. J. Phys. Conf. Ser. 2013, 477, 012035. [Google Scholar] [CrossRef] [Green Version]
- Lee, I.; Kim, D.; Park, G.-L.; Jeon, T.-J.; Kim, S.M. Investigation of wound healing process guided by nano-scale topographic patterns integrated within a microfluidic system. PLoS ONE 2018, 13, e0201418. [Google Scholar] [CrossRef]
- Van der Meer, A.; Vermeul, K.; Poot, A.A.; Feijen, J.; Vermes, I. A microfluidic wound-healing assay for quantifying endothelial cell migration. Am. J. Physiol. Circ. Physiol. 2010, 298, H719–H725. [Google Scholar] [CrossRef] [Green Version]
- Murrell, M.; Kamm, R.; Matsudaira, P. Tension, Free Space, and Cell Damage in a Microfluidic Wound Healing Assay. PLoS ONE 2011, 6, e24283. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jeong, G.S.; Kwon, G.H.; Kang, A.R.; Jung, B.Y.; Park, Y.; Chung, S.; Lee, S.-H. Microfluidic assay of endothelial cell migration in 3D interpenetrating polymer semi-network HA-Collagen hydrogel. Biomed. Microdevices 2011, 13, 717–723. [Google Scholar] [CrossRef]
- Shih, H.-C.; Lee, T.-A.; Wu, H.-M.; Ko, P.-L.; Liao, W.-H.; Tung, Y.-C. Microfluidic Collective Cell Migration Assay for Study of Endothelial Cell Proliferation and Migration under Combinations of Oxygen Gradients, Tensions, and Drug Treatments. Sci. Rep. 2019, 9, 8234. [Google Scholar] [CrossRef]
- Sticker, D.; Lechner, S.; Jungreuthmayer, C.; Zanghellini, J.; Ertl, P. Microfluidic Migration and Wound Healing Assay Based on Mechanically Induced Injuries of Defined and Highly Reproducible Areas. Anal. Chem. 2017, 89, 2326–2333. [Google Scholar] [CrossRef]
- Monfared, G.S.; Ertl, P.; Rothbauer, M. An on-chip wound healing assay fabricated by xurography for evaluation of dermal fibroblast cell migration and wound closure. Sci. Rep. 2020, 10, 16192. [Google Scholar] [CrossRef]
Assay Type | Microdevice Material | Cell Types | Ref. |
---|---|---|---|
Cell Exclusion | PDMS and glass | Gastric epithelial GES-1 cells | [28] |
PDMS, glass, and cell-culture plastic | Epithelial cells | [42] | |
PDMS | Human melanoma cells | [27] | |
Enzymatic cell depletion | PDMS and polystyrene | NIH-3T3 fibroblasts | [43] |
PMMA | NIH-3T3 fibroblasts | [44] | |
PDMS and cell-culture plastic | Rat epithelial cells | [45] | |
PDMS and glass | VSMCs | [46] | |
PMMA | Human melanoma cells | [47] | |
PDMS and PUA | NIH-3T3 fibroblasts | [48] | |
PDMS and glass | HUVECs | [49] | |
PDMS | Moues epithelial Cells | [50] | |
PDMS | HUVECs | [51] | |
PDMS | HUVECs | [52] | |
Physical cell depletion | PDMS and glass | HUVECs | [53] |
PDMS and glass | HDFs | [54] |
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Shabestani Monfared, G.; Ertl, P.; Rothbauer, M. Microfluidic and Lab-on-a-Chip Systems for Cutaneous Wound Healing Studies. Pharmaceutics 2021, 13, 793. https://doi.org/10.3390/pharmaceutics13060793
Shabestani Monfared G, Ertl P, Rothbauer M. Microfluidic and Lab-on-a-Chip Systems for Cutaneous Wound Healing Studies. Pharmaceutics. 2021; 13(6):793. https://doi.org/10.3390/pharmaceutics13060793
Chicago/Turabian StyleShabestani Monfared, Ghazal, Peter Ertl, and Mario Rothbauer. 2021. "Microfluidic and Lab-on-a-Chip Systems for Cutaneous Wound Healing Studies" Pharmaceutics 13, no. 6: 793. https://doi.org/10.3390/pharmaceutics13060793
APA StyleShabestani Monfared, G., Ertl, P., & Rothbauer, M. (2021). Microfluidic and Lab-on-a-Chip Systems for Cutaneous Wound Healing Studies. Pharmaceutics, 13(6), 793. https://doi.org/10.3390/pharmaceutics13060793