Controlled co-immobilization of EGF and VEGF to optimize vascular cell survival

Abstract

Growth factors (GFs) are potent signaling molecules that act in a coordinated manner in physiological processes such as tissue healing or angiogenesis. Co-immobilizing GFs on materials while preserving their bioactivity still represents a major challenge in the field of tissue regeneration and bioactive implants. In this study, we explore the potential of an oriented immobilization technique based on two high affinity peptides, namely the Ecoil and Kcoil, to allow for the simultaneous capture of the epidermal growth factor (EGF) and the vascular endothelial growth factor (VEGF) on a chondroitin sulfate coating. This glycosaminoglycan layer was selected as it promotes cell adhesion but reduces non-specific adsorption of plasma proteins. We demonstrate here that both Ecoiltagged GFs can be successfully immobilized on chondroitin sulfate surfaces that had been pre-decorated with the Kcoil peptide. As shown by direct ELISA, changing the incubation concentration of the various GFs enabled to control their grafted amount.Moreover, cell survival studies with endothelial and smooth muscle cells confirmed that our oriented tethering strategy preserved GF bioactivity. Of salient interest, coimmobilizing EGF and VEGF led to better cell survival compared to each GF captured alone, suggesting a synergistic effect of these GFs. Altogether, these results demonstrate the potential of coiled-coil oriented GF tethering for the co-immobilization of macromolecules; it thus open the way to the generation of biomaterials surfaces with fine-tuned biological properties.

The effects of icariin on wound healing of extraction sites with administration of zoledronic and dexamethasone: A rat model study

“…Previous studies have shown that ICA promoted VEGF and ZA inhibited wound healing and the expression of VEGF, which were in accordance with our study. VEGF is one of the growth factors that are of great importance in soft tissue repair and angiogenesis . So the decreased VEGF may be a reason for the delayed healing and ICA promoted wound healing by increasing VEGF expression.…”

Multifunctional biomaterial coatings: synthetic challenges and biological activity

“…The strong electrostatic interaction to a negatively charged E-coil permits the modular tethering of two growth factors ( Figure 6A; Table 3, line n). Thereby, survival of HUVEC and human aortic smooth muscle cells (AoSMC) could be synergistically increased (Lequoy et al, 2016).…”

“…Interestingly, Ao et al could demonstrate that a layer-by-layer system can be stabilized by crosslinking the charged layers of collagen and hyaluronic acid through the generation of an amide bond (Ao et al, 2013). In addition, differently charged peptide helices, which can build a coiled coil, can be used for a directed presentation of molecules for several biochemical applications (Reinhardt et al, 2014;Lequoy et al, 2016). An advantage of peptide self-assembly strategies is the generation of highly modular fibrils that can additionally create a structural ECM-mimetic to support cell adhesion (Collier, 2008;Jung et al, 2011;Ceylan et al, 2012).…”

“…Thereby the authors could achieve the induction of osteogenic differentiation (of MG-63 cells) by excretion of BMP-2 and a lowered bacterial growth by the release of gentamicin . Lowered protein adsorption and platelet adhesion can be mediated by GAGs such as chondroitin sulfate (Thalla The strong interaction between a K-coil and an E-coil is used to immobilize VEGF (PDB: 1VPF) and epidermal growth factor (EGF, pdb 1JL9) on covalently immobilized chondroitin sulfate (Lequoy et al, 2016). (B) Heparin was immobilized covalently by silanization.…”

“…Bioinert PEG-surfaces showed an inhibition of electrostat. Cell viability↑ Lequoy et al (2016) PEG, polyethylene glycol; OEG, oligoethylene glycol; PS, polystyrene; SDF-1, stromal cell-derived factor; ICAM-1, intercellular adhesion molecule 1; BMP-2, bone morphogenetic protein; VEGF, vascular endothelial growth factor; EGF, epidermal growth factor; PET, polyethylene terephthalate; ad., adsorption; electrostat., electrostatic; CS, chondroitin sulfate; different., differentiation;…”