1.Cell adhesive peptides functionalized on CoCr alloy stimulate endothelialization and prevent thrombogenesis and restenosis.
Castellanos MI;Guillem-Marti J;Mas-Moruno C;Díaz-Ricart M;Escolar G;Ginebra MP;Gil FJ;Pegueroles M;Manero JM J Biomed Mater Res A. 2017 Apr;105(4):973-983. doi: 10.1002/jbm.a.35988. Epub 2017 Jan 18.
Immobilization of bioactive peptide sequences on CoCr surfaces is an effective route to improve endothelialization, which is of great interest for cardiovascular stents. In this work, we explored the effect of physical and covalent immoblization of RGDS, YIGSR and their equimolar combination peptides on endothelial cells (EC) and smooth muscle cell (SMC) adhesion and on thrombogenicity. We extensively investigated using RT-qPCR, the expression by ECs cultured on functionalised CoCr surfaces of different genes. Genes relevant for adhesion (ICAM-1 and VCAM-1), vascularization (VEGFA, VEGFR-1 and VEGFR-2) and anti-thrombogenicity (tPA and eNOS) were over-expressed in the ECs grown to covalently functionalized CoCr surfaces compared to physisorbed and control surfaces. Pro-thrombogenic genes expression (PAI-1 and vWF) decreased over time. Cell co-cultures of ECs/SMCs found that functionalization increased the amount of adhered ECs onto modified surfaces compared to plain CoCr, independently of the used peptide and the strategy of immobilization. SMCs adhered less compared to ECs in all surfaces. All studied peptides showed a lower platelet cell adhesion compared to TCPS. Covalent functionalization of CoCr surfaces with an equimolar combination of RGDS and YIGSR represented prevailing strategy to enhance the early stages of ECs adhesion and proliferation, while preventing SMCs and platelet adhesion.
2.Phorbol ester induces a transient increase in alpha(5)beta(1)-mediated adhesion of the megakaryoblastic cell line CHRF 288-11.
Conran N;Hemming FW Platelets. 1999;10(2-3):117-23.
This study investigated the mechanism by which treatment of the CHRF 288-11 megakaryoblastic cell line with phorbol myristate acetate caused a transient increase in adhesion. The adhesion to tissue culture plastic occurred within 4 h and could be reversed by treatment with RGDS-peptide suggesting the involvement of one or more RGD-binding integrins. Ligand-binding adhesion assays suggested that PMA-induced CHRF 288-11 cells had very little affinity for fibrinogen, a low affinity for vitronectin and a much higher affinity for fibronectin. Further adhesion assays performed in the presence of various integrin antagonists or inhibiting monoclonal antibodies demonstrated that the fibronectin-mediated cell adhesion is via the alpha beta , fibronectin receptor, integrin. Flow cytometrical investigations showed that this increase in alpha(5)beta(1)-adhesion on CHRF 288-11 cells following PMA stimulation was not brought about by an increase in alpha(5)beta(1)-integrin expression and inferred that increased adhesion is achieved by an increase in alpha(5)beta(1) ligand-binding function. These findings confirm other reports using different cells that the expression and function of integrins may play an important role in megakaryocytopoiesis.
3.Angiopoietin-1 peptide QHREDGS promotes osteoblast differentiation, bone matrix deposition and mineralization on biomedical materials.
Feric N;Cheng CC;Goh MC;Dudnyk V;Di Tizio V;Radisic M Biomater Sci. 2014 Oct 1;2(10):1384-1398.
Bone loss occurs as a consequence of a variety of diseases as well as from traumatic injuries, and often requires therapeutic intervention. Strategies for repairing and replacing damaged and/or lost bone tissue include the use of biomaterials and medical implant devices with and without osteoinductive coatings. The soluble growth factor angiopoietin-1 (Ang-1) has been found to promote cell adhesion and survival in a range of cell types including cardiac myocytes, endothelial cells and fibroblasts through an integrin-dependent mechanism. Furthermore, the short sequence QHREDGS has been identified as the integrin-binding sequence of Ang-1 and as a synthetic peptide has been found to possess similar integrin-dependent effects as Ang-1 in the aforementioned cell types. Integrins have been implicated in osteoblast differentiation and bone mineralization, processes critical to bone regeneration. By binding integrins on the osteoblast surface, QHREDGS could promote cell survival and adhesion, as well as conceivably osteoblast differentiation and bone mineralization. Here we immobilized QHREDGS onto polyacrylate (PA)-coated titanium (Ti) plates and polyethylene glycol (PEG) hydrogels. The osteoblast differentiation marker, alkaline phosphatase, peaked in activity 4-12 days earlier on the QHREDGS-immobilized PA-coated Ti plates than on the unimmobilized, DGQESHR (scrambled)- and RGDS-immobilized surfaces.
