Antimicrobial surfaces grafted random copolymers with REDV peptide beneficial for endothelialization

Abstract

Polycarbonate urethane (PCU) elastomeric materials have been developed for vascular prosthesis applications, because of their excellent mechanical and physical properties. However, thrombosis and inflammation often limit their usage as small-diameter vascular grafts. Herein, we focused on the design and functionalization of a PCU elastomer with enhanced hemocompatibility, rapid endothelialization and antimicrobial properties. An atom transfer radical polymerization (ATRP) technique was utilized to graft random copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and eugenyl methacrylate (EgMA) onto a PCU surface, and subsequently the cysteine-terminated CREDV peptide sequence was directly linked onto the surface by a thiol-ene click reaction to prepare a series of REDV peptide functionalized surfaces. The chemical compositions of the modified surfaces were quantified by X-ray photoelectron spectroscopy (XPS), and the hydrophilicity was evaluated by water contact analysis and water uptake.The surface hemocompatibility was verified by platelet adhesion assays, and the results demonstrated that platelet adhesion was significantly reduced on the modified surface. More importantly, the functionalized surfaces with high hydrophilicity and cell specific adhesive REDV peptide could selectively enhance the adhesion and proliferation of human umbilical vein endothelial cells (HUVECs) but they suppressed these behaviors in human arterial smooth muscle cells (HASMCs). Moreover, these surfaces showed excellent antibacterial properties, which originate from the EgMA moieties of the copolymers. The successful fabrication of multifunctional surfaces with excellent hemocompatibility, rapid endothelialization, and good antimicrobial activity through a feasible route could be an attractive platform for tissue engineering applications.

Biofunctionalized Electrospun PCL‐PIBMD/SF Vascular Grafts with PEG and Cell‐Adhesive Peptides for Endothelialization

“…These results can be attributed to the EC‐selective adhesion ability of the peptides. REDV and CAG peptides not only have high affinity toward HUVECs compared with HASMCs, but also can promote the adhesion and migration of HUVECs . PEG endowed the modified surfaces with proper surface wettability, meanwhile REDV and CAG peptides selectively adhered HUVECs rather than HASMCs.…”

“…Polyethylene glycol (PEG) and other hydrophilic polymers can inhibit platelet adhesion and nonspecific protein adsorption, thus enhancing hemocompatibility. The second main approach is to enhance the attachment of endothelial cells (ECs) on biomaterial surface and consequently induce the rapid endothelialization of vascular grafts . ECs play a key role in maintaining the normal physiological functions of blood vessels.…”

Peptide‐Functionalized Polyurethane Coatings Prepared via Grafting‐To Strategy to Selectively Promote Endothelialization

“…Covalent immobilization of REDV peptides on surfaces through “graft‐from” approach was also reported. [7b,10] In this approach, an oligomer or polymer was grown from the surface, followed by chemical conjugation of REDV peptide to the oligomer or polymer. “Graft from” approach is well known to be capable of creating dense polymer brushes, but control over polymer structure and precise characterization of polymer brushes are difficult to achieve.…”

Combinatorial functionalization with bisurea‐peptides and antifouling bisurea additives of a supramolecular elastomeric biomaterial

“…Nonetheless, inconsistent results have been reported for the efficacy of REDV functionalization. Some studies report improved adhesion of endothelial cells but do not compare to RGD or other peptides for functionalization, or adhesion of other mammalian cell types., or show unexpected failed refunctionalization for other cell‐types with RGD . Other studies also unexpectedly show reduced endothelial cell adhesion on REDV functionalized surfaces compared to RGD …”

“…Besides peptides such as RGD, which induce cell adhesion in general, peptide sequences have been discovered for which specific cell types have an increased affinity over other cell types, due to increased expression of the binding motif on these cells . The REDV peptide, for which endothelial cell‐specificity has been reported, attributed to binding to integrin α4β1, has been extensively applied to enhance endothelialization of biomaterials . In another approach, a peptide derived from stromal cell derived factor‐1α (SDF1α), a chemoattractant of lymphocytes, monocytes, and progenitors cells, has been applied for improved in situ cellularization…”