50. Treloar KK, Simpson MJ, Binder BJ, McElwain SDL, Baker RE. Assessing the role of spatial correlations during collective cell spreading. Sci Rep 2014; 4: 5713. 51. Monsuur HN, Boink MA, Weijers EM, Roffel S, Breetveld M, Gefen A et al. Methods to study differences in cell mobility during skin wound healing in vitro. J Biomech 2016; 49: 1381-7. 52. Hewitt NJ, Edwards RJ, Fritsche E, Goebel C, Aeby P, Scheel J et al. Use of human in vitro skin models for accurate and ethical risk assessment: metabolic considerations. Toxicol Sci 2013; 133: 209–217. 53. Butler PD, Ly DP, Longaker MT, Yang GP. Use of organotypic coculture to study keloid biology. Am J Surg 2008; 195: 144-8. 54. Phan TT, Lim IJ, Aalami O, Lorget F, Khoo A, Tan EK et al. Smad3 signalling plays an important role in keloid pathogenesis via epithelial-mesenchymal interactions. J Pathol 2005; 207: 232-42. 55. Boyden S. The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. J Exp Med 1962; 115: 453–466. 56. Chen WL, Kuo KT, Chou TY, Chen CL, Wang CH, Wei YH, Wang LS. The role of cytochrome c oxidase subunit Va in nonsmall cell lung carcinoma cells: association with migration, invasion and prediction of distant metastasis. BMC Cancer 2012; 12: 273.
intracellular antibodies: identification of hnRNP-K as a potential target for metastasis. Proc Natl Acad Sci USA 2007; 104: 8983–8988. 71. Chigurupati S, Arumugam TV, Son TG, Lathia JD, Jameel S, Mughal MR et al. Involvement of notch signaling in wound healing. PLoS One 2007; 2: e1167. 72. U, Hauge C, Frank SR, Jensen CJ, Duda K, Nielsen JV et al. RSK is a principal effector of the RAS-ERK pathway for eliciting a coordinate promotile/invasive gene program and phenotype in epithelial cells. Mol Cell 2009; 35: 511–522. 73. Zhang S, Cao Z, Tian H, Shen G, Ma Y, Xie H et al. SKLB1002, a novel potent inhibitor of VEGF receptor 2 signaling, inhibits angiogenesis and tumor growth in vivo. Clin Cancer Res 2011; 17: 4439–4450. 74. Wu CS, Wu PH, Fang AH, Lan CC. inhibits the enhancing effects of transforming growth factor (TGF)-beta1 on collagen expression and TGF-beta/ Smad signalling in keloid fibroblasts: implication for new therapeutic approach, B J Dermatol 2012; 167: 532–541. 75. Mendoza-Naranjo A, Cormie OP, Serrano AE, Hu R, O’Neill S, Wang CM et al. Targeting Cx43 and N-cadherin, which are abnormally upregulated in venous leg ulcers, influences migration, adhesion and activation of Rho GTPases. PLoS One 2012; 7: e37374. 76. Xu W, Jong Hong S, Jia S, Zhao Y, Galiano RD, Mustoe TA. Application of a
Figure 5: In vivo models. Flowchart depicting the two categories of ex vivo models and the types of wounds used; patients (surgical wounds, incisional wounds, excisional wounds, donor site wounds) and human volunteers (Incisional wounds, excisional biopsy wounds, scratch, blister tape stripping and burns). Figure 6: In vivo assays. A diagram to demonstrate the assays including invasive (gene and protein studies) and non-invasive devices and those used for specific healing parameters. Supplementary Figures Supplementary Figure S1: In vitro assays. A diagram to demonstrate the different assays for migration, invasion proliferation and senescence.