Abstract
Endothelialization by materials provides a promising approach for the rapid re-endothelialization of a cardiovascular implantation. Although previous studies have focused on improving endothelialization through the immobilization of bioactive molecules onto the surface of biodegradable implants, comparative studies of effective surface modification have not yet been reported. Here, we conducted a comparative study on the surface modification of poly(lactide-co-glycolide) (PLGA)-based composites to graft mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) using three different materials, fibronectin (FN), polyethylenimine (PEI), and polydopamine (PDA), which have different bond strengths of ligand–receptor interaction, ionic bond, and covalent bond, respectively. Further in vitro analysis exhibited that MSC-EVs released from all modified films sustainably, but the MSC-EVs grafted onto the surface coated with PEI are more effective than other groups in increasing angiogenesis and reducing the inflammatory responses in endothelial cells. Therefore, the overall results demonstrated that PEI is a desirable coating reagent for the immobilization of MSC-EVs on the surface of biodegradable implants.
Highlights
Cardiovascular disease is currently identified as a major cause of morbidity and mortality worldwide, and this situation is expected to continue for years to come, placing a significant strain on global health resources [1]
We investigated the effects of differential affinity immobilization of MSCderived extracellular vesicles (EVs) on poly(lactide-co-glycolide) (PLGA) composite films using surface coating with fibronectin (FN), polyethylenimine (PEI), and polydopamine (PDA) on the restoration of endothelial function (Scheme 1)
We previously established that PLGA-based biodegradable implants containing magnesium hydroxide (MH) effectively alleviated the adverse effects induced by acidic PLGA byproducts [30,31]
Summary
Cardiovascular disease is currently identified as a major cause of morbidity and mortality worldwide, and this situation is expected to continue for years to come, placing a significant strain on global health resources [1]. The endothelium retains a non-adhesive and non-thrombotic surface on which blood cells slide with minimal interaction with the ECs. During inflammation, ECs are activated in response to pro-inflammatory stimuli that promote a robust increase in the expression level of cell adhesion molecules (CAMs) [7,8]. Circulating leukocytes are attached to the inflamed endothelium, where they firmly interact through various classes of CAMs. The initial rolling process of leukocytes is mediated mainly by the selectins expressed on activated ECs and P-selectin glycoprotein ligand-1 (PSGL-1) on the leukocyte surface, whereas firmer adhesion is mediated largely by vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on the ECs [9,10,11]. The inhibition of adhesion and recruitment of leukocytes to ECs could have a beneficial effect on inflammatory vascular diseases
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