Abstract
Cell migration in three-dimensional environment is extremely important for tissue regeneration and other biological processes. In this work, a model system was developed to study how endothelial cells (ECs) migrate into photo-responsive hydrogels under the presence of pro-inflammatory macrophages. The hydrogel was synthesized from hyaluronic acid grafted with coumarin and methacrylate moieties by both carbon–carbon covalent linking and coumarin dimerization under UV irradiation at 365 nm. The structure of the hydrogel was conveniently modulated by UV irradiation at 254 nm to decompose the coumarin dimers, leading to the significant decrease of modulus and increase of swelling ratio and mesh size. Under the presence of M1 macrophages, ECs were induced to migrate into the hydrogels with a different degree. A significant larger net displacement of ECs was found in the softer hydrogel obtained by irradiation with UV at 254 nm than in the stiffer original one at day 7.
Highlights
Cell migration is referred to the movement of cells in response to specific external signals including biochemical factors and changes in extracellular matrix (ECM) [1]
The M2 phenotype induced by IL-4, IL-10 and IL-3 can secrete cytokines such as matrix metalloprotease-9 (MMP-9), transforming growth factor-b (TGF-b), and platelet-derived growth factor-BB (PDGF-BB) to accelerate the process of tissue regeneration
7-Hydroxy-coumarin was reacted with epichlorohydrin to synthesize epoxypropoxy coumarin (EPC) via the substitution reaction (Scheme 1A), whose structure was confirmed by 1H NMR spectroscopy (Fig. 1A) (500 MHz, CDCl3) [29]
Summary
Cell migration is referred to the movement of cells in response to specific external signals including biochemical factors and changes in extracellular matrix (ECM) [1]. One of the creative ways to achieve this goal is to regulate the inflammatory response after biomaterials are implanted by applying different phenotypes of macrophages [5,6,7]. Macrophages of different phenotypes have been recognized, including the pro-inflammatory phenotype (M1, the ‘classic phenotype’), and the anti-inflammatory/regulatory phenotypes (M2) [9]. The M2 phenotype induced by IL-4, IL-10 and IL-3 can secrete cytokines such as matrix metalloprotease-9 (MMP-9), transforming growth factor-b (TGF-b), and platelet-derived growth factor-BB (PDGF-BB) to accelerate the process of tissue regeneration. Both types of macrophages can induce cell migration in a different way [11]
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