Co–Cr–Mo alloy binding peptide as molecular glue for constructing biomedical surfaces

The mechanical properties of Co–Cr–Mo (CCM) alloys are advantageous in various biomedical applications. However, because of their bioinert surface, CCM alloys exhibit poor endothelial cell attachment properties; thus, problems of biocompatibility remain. In this study, we aimed to improve the biocompatibility of the CCM alloy surface using solid-binding peptides. We selected peptides with high binding affinity for cast CCM alloy surfaces through in vitro evolution by the phage display method. The peptides were functionalized on the CCM alloy surfaces by simple immersion in the peptide solution. The peptide bound to both cast and 3D-printed CCMs with the same affinity. The peptides linked to the amino acid motif that promotes cell adhesion, and improved the attachment of endothelial cells on the 3D-printed CCM in serum and serum-free conditions. Hence, CCM-binding peptides are attractive tools for constructing a biofunctional surface on CCM-based biodevices.

Hypoxia Induced Heparan Sulfate Primes the Extracellular Matrix for Endothelial Cell Recruitment by Facilitating VEGF-Fibronectin Interactions

Vascular endothelial growth factor-A (VEGF) is critical for the development, growth, and survival of blood vessels. Retinal pigmented epithelial (RPE) cells are a major source of VEGF in the retina, with evidence that the extracellular matrix (ECM)-binding forms are particularly important. VEGF associates with fibronectin in the ECM to mediate distinct signals in endothelial cells that are required for full angiogenic activity. Hypoxia stimulates VEGF expression and angiogenesis; however, little is known about whether hypoxia also affects VEGF deposition within the ECM. Therefore, we investigated the role of hypoxia in modulating VEGF-ECM interactions using a primary retinal cell culture model. We found that retinal endothelial cell attachment to RPE cell layers was enhanced in cells maintained under hypoxic conditions. Furthermore, we found that agents that disrupt VEGF-fibronectin interactions inhibited endothelial cell attachment to RPE cells. We also found that hypoxia induced a general change in the chemical structure of the HS produced by the RPE cells, which correlated to changes in the deposition of VEGF in the ECM, and we further identified preferential binding of VEGFR2 over VEGFR1 to VEGF laden-fibronectin matrices. Collectively, these results indicate that hypoxia-induced HS may prime fibronectin for VEGF deposition and endothelial cell recruitment by promoting VEGF-VEGFR2 interactions as a potential means to control angiogenesis in the retina and other tissues.

Surface characterization, hemo- and cytocompatibility of segmented poly(dimethylsiloxane)-based polyurethanes

Segmented polyurethanes based on poly(dimethylsiloxane), currently used for biomedical applications, have sub-optimal biocompatibility which reduces their efficacy. Improving the endothelial cell attachment and blood-contacting properties of PDMS-based copolymers would substantially improve their clinical applications. We have studied the surface properties and in vitro biocompatibility of two series of segmented poly(urethane-dimethylsiloxane)s (SPU-PDMS) based on hydroxypropyl- and hydroxyethoxypropyl- terminated PDMS with potential applications in blood-contacting medical devices. SPU-PDMS copolymers were characterized by contact angle measurements, surface free energy determination (calculated using the van Oss-Chaudhury-Good and Owens-Wendt methods), and atomic force microscopy. The biocompatibility of copolymers was evaluated using an endothelial EA.hy926 cell line by direct contact assay, before and after pre-treatment of copolymers with multicomponent protein mixture, as well as by a competitive blood-protein adsorption assay. The obtained results suggested good blood compatibility of synthesized copolymers. All copolymers exhibited good resistance to fibrinogen adsorption and all favored albumin adsorption. Copolymers based on hydroxyethoxypropyl-PDMS had lower hydrophobicity, higher surface free energy, and better microphase separation in comparison with hydroxypropyl-PDMS-based copolymers, which promoted better endothelial cell attachment and growth on the surface of these polymers as compared to hydroxypropyl-PDMS-based copolymers. The results showed that SPU-PDMS copolymers display good surface properties, depending on the type of soft PDMS segments, which can be tailored for biomedical application requirements such as biomedical devices for short- and long-term uses.