Antifouling polymer layers containing extracellular matrix-derived peptide motifs offer promising new options for biomimetic surface engineering. In this contribution, we report the design of antifouling vascular grafts bearing biofunctional peptide motifs for tissue regeneration applications based on hierarchical polymer brushes. Hierarchical diblock poly(methyl ether oligo(ethylene glycol) methacrylate-block-glycidyl methacrylate) brushes bearing azide groups (poly(MeOEGMA-block-GMA-N3)) were grown by surface-initiated atom transfer radical polymerization (SI-ATRP) and functionalized with biomimetic RGD peptide sequences. Varying the conditions of copper-catalyzed alkyne-azide "click" reaction allowed for the immobilization of RGD peptides in a wide surface concentration range. The synthesized hierarchical polymer brushes bearing peptide motifs were characterized in detail using various surface sensitive physicochemical methods. The hierarchical brushes presenting the RGD sequences provided excellent cell adhesion properties and at the same time remained resistant to fouling from blood plasma. The synthesis of anti-fouling hierarchical brushes bearing 1.2 × 103 nmol/cm2 RGD biomimetic sequences has been adapted for the surface modification of commercially available grafts of woven polyethylene terephthalate (PET) fibers. The fiber mesh was endowed with polymerization initiator groups via aminolysis and acylation reactions optimized for the material. The obtained bioactive antifouling vascular grafts promoted the specific adhesion and growth of endothelial cells, thus providing a potential avenue for endothelialization of artificial conduits.

Institute of Macromolecular Chemistry Czech Academy of Sciences Heyrovsky sq 2 162 06 Prague Czech Republic

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Basson M. Cardiovascular disease. Nature. 2008;451:903. doi: 10.1038/451903a. DOI

Drury J.L., Mooney D.J. Hydrogels for tissue engineering: Scaffold design variables and applications. Biomaterials. 2003;24:4337–4351. doi: 10.1016/S0142-9612(03)00340-5. PubMed DOI

Yang S., Leong K.-F., Du Z., Chua C.-K. The Design of Scaffolds for Use in Tissue Engineering. Part II. Rapid Prototyping Techniques. Tissue Eng. 2002;8:1–11. doi: 10.1089/107632702753503009. PubMed DOI

Singh C., Wong C., Wang X. Medical Textiles as Vascular Implants and Their Success to Mimic Natural Arteries. J. Funct. Biomater. 2015;6:500–525. doi: 10.3390/jfb6030500. PubMed DOI PMC

Ratner B.D. The blood compatibility catastrophe. J. Biomed. Mat. Res. 1993;27:283–287. doi: 10.1002/jbm.820270302. PubMed DOI

Gorbet M.B., Sefton M.V. Biomaterial-associated thrombosis: Roles of coagulation factors, complement, platelets and leukocytes. Biomaterials. 2004;25:5681–5703. doi: 10.1016/j.biomaterials.2004.01.023. PubMed DOI

Zilla P., Bezuidenhout D., Human P. Prosthetic vascular grafts: Wrong models, wrong questions and no healing. Biomaterials. 2007;28:5009–5027. doi: 10.1016/j.biomaterials.2007.07.017. PubMed DOI

Cassady A.I., Hidzir N.M., Grøndahl L. Enhancing expanded poly(tetrafluoroethylene) (ePTFE) for biomaterials applications. J. Appl. Pol. Sci. 2014;131:15. doi: 10.1002/app.40533. DOI

Liu X., Yuan L., Li D., Tang Z., Wang Y., Chen G., Chen H., Brash J.L. Blood compatible materials: State of the art. J. Mat. Chem. B. 2014;2:5718–5738. doi: 10.1039/C4TB00881B. PubMed DOI

Weber N., Wendel H.P., Ziemer G. Hemocompatibility of heparin-coated surfaces and the role of selective plasma protein adsorption. Biomaterials. 2002;23:429–439. doi: 10.1016/S0142-9612(01)00122-3. PubMed DOI

Biran R., Pond D. Heparin coatings for improving blood compatibility of medical devices. Adv. Drug Deliv. Rev. 2017;112:12–23. doi: 10.1016/j.addr.2016.12.002. PubMed DOI

Feng L., Andrade J.D. Protein adsorption on low temperature isotropic carbon: V. How is it related to its blood compatibility? J. Biomater. Sci. Polym. Ed. 1995;7:439–452. doi: 10.1163/156856295X00445. PubMed DOI

Kannan R.Y., Salacinski H.J., Butler P.E., Hamilton G., Seifalian A.M. Current status of prosthetic bypass grafts: A review. J. Biomed. Mater. Res. Part. B. 2005;74B:570–581. doi: 10.1002/jbm.b.30247. PubMed DOI

Li Q., Ma L., Gao C. Biomaterials for in situ tissue regeneration: Development and perspectives. J. Mat. Chem. B. 2015;3:8921–8938. doi: 10.1039/C5TB01863C. PubMed DOI

Abdulghani S., Mitchell G.R. Biomaterials for in situ tissue regeneration: A review. Biomolecules. 2019;9:750. doi: 10.3390/biom9110750. PubMed DOI PMC

Harding J.L., Reynolds M.M. Combating medical device fouling. Trends Biotech. 2014;32:140–146. doi: 10.1016/j.tibtech.2013.12.004. PubMed DOI

Yu Q., Zhang Y., Wang H., Brash J., Chen H. Antifouling bioactive surfaces. Acta Biomat. 2011;7:1550–1557. doi: 10.1016/j.actbio.2010.12.021. PubMed DOI

Blaszykowski C., Sheikh S., Thompson M. A survey of state-of-the-art surface chemistries to minimize fouling from human and animal biofluids. Biomat. Sci. 2015;3:1335–1370. doi: 10.1039/C5BM00085H. PubMed DOI

Vaisocherová H., Brynda E., Homola J. Functionalizable low-fouling coatings for label-free biosensing in complex biological media: Advances and applications. Anal. Bioanal. Chem. 2015;407:3927–3953. doi: 10.1007/s00216-015-8606-5. PubMed DOI

De Vos W.M., Leermakers F.A.M., Lindhoud S., Prescott S.W. Modeling the structure and antifouling properties of a polymer brush of grafted comb-polymers. Macromolecules. 2011;44:2334–2342. doi: 10.1021/ma1028642. DOI

Gunkel G., Weinhart M., Becherer T., Haag R., Huck W.T.S. Effect of polymer brush architecture on antibiofouling properties. Biomacromolecules. 2011;12:4169–4172. doi: 10.1021/bm200943m. PubMed DOI

Lísalová H., Brynda E., Houska M., Víšová I., Mrkvová K., Song X.C., Gedeonová E., Surman F., Riedel T., Pop-Georgievski O., et al. Ultralow-Fouling Behavior of Biorecognition Coatings Based on Carboxy-Functional Brushes of Zwitterionic Homo- and Copolymers in Blood Plasma: Functionalization Matters. Anal. Chem. 2017;89:3524–3531. doi: 10.1021/acs.analchem.6b04731. PubMed DOI

Vaisocherová H., Jiang S., Yang W., Cheng G., Cao Z., Homola J., Piliarik M., Zhang Z. Ultralow Fouling and Functionalizable Surface Chemistry Based on a Zwitterionic Polymer Enabling Sensitive and Specific Protein Detection in Undiluted Blood Plasma. Anal. Chem. 2008;80:7894–7901. doi: 10.1021/ac8015888. PubMed DOI

Zhang Z., Chen S., Jiang S. Dual-functional biomimetic materials: Nonfouling poly(carboxybetaine) with active functional groups for protein immobilization. Biomacromolecules. 2006;7:3311–3315. doi: 10.1021/bm060750m. PubMed DOI

Rodriguez-Emmenegger C., Brynda E., Riedel T., Houska M., Šubr V., Alles A.B., Hasan E., Gautrot J.E., Huck W.T.S. Polymer brushes showing non-fouling in blood plasma challenge the currently accepted design of protein resistant surfaces. Macromol. Rapid Comm. 2011;32:952–957. doi: 10.1002/marc.201100189. PubMed DOI

Vorobii M., Kostina N.Y., Rahimi K., Grama S., Söder D., Pop-Georgievski O., Sturcova A., Horak D., Grottke O., Singh S., et al. Antifouling Microparticles to Scavenge Lipopolysaccharide from Human Blood Plasma. Biomacromolecules. 2019;20:959–968. doi: 10.1021/acs.biomac.8b01583. PubMed DOI

Rodriguez-Emmenegger C., Kylián O., Houska M., Brynda E., Artemenko A., Kousal J., Alles A.B., Biederman H. Substrate-independent approach for the generation of functional protein resistant surfaces. Biomacromolecules. 2011;12:1058–1066. doi: 10.1021/bm101406m. PubMed DOI

De Los Santos Pereira A., Sheikh S., Blaszykowski C., Pop-Georgievski O., Fedorov K., Thompson M., Rodriguez-Emmenegger C. Antifouling Polymer Brushes Displaying Antithrombogenic Surface Properties. Biomacromolecules. 2016;17:1179–1185. doi: 10.1021/acs.biomac.6b00019. PubMed DOI

Surman F., Riedel T., Bruns M., Kostina N.Y., Sedláková Z., Rodriguez-Emmenegger C. Polymer brushes interfacing blood as a route toward high performance blood contacting devices. Macromol. Biosci. 2015;15:636–646. doi: 10.1002/mabi.201400470. PubMed DOI

Zoppe J.O., Ataman N.C., Mocny P., Wang J., Moraes J., Klok H.-A. Surface-Initiated Controlled Radical Polymerization: State-of-the-Art, Opportunities, and Challenges in Surface and Interface Engineering with Polymer Brushes. Chem. Rev. 2017;117:1105–1318. doi: 10.1021/acs.chemrev.6b00314. PubMed DOI

Pop-Georgievski O., Rodriguez-Emmenegger C., Pereira A.D.L.S., Proks V., Brynda E., Rypáček F. Biomimetic non-fouling surfaces: Extending the concepts. J. Mat. Chem. B. 2013;1:2859–2867. doi: 10.1039/c3tb20346h. PubMed DOI

Joung Y.K., You S.S., Park K.M., Go D.H., Park K.D. In situ forming, metal-adhesive heparin hydrogel surfaces for blood-compatible coating. Colloids Surf. B. 2012;99:102–107. doi: 10.1016/j.colsurfb.2011.10.047. PubMed DOI

Orski S.V., Fries K.H., Sheppard G.R., Locklin J. High density scaffolding of functional polymer brushes: Surface initiated atom transfer radical polymerization of active esters. Langmuir. 2010;26:2136–2143. doi: 10.1021/la902553f. PubMed DOI

Vaisocherová H., Ševců V., Adam P., Špačková B., Hegnerová K., de los Santos Pereira A., Rodriguez-Emmenegger C., Riedel T., Houska M., Brynda E., et al. Functionalized ultra-low fouling carboxy- and hydroxy-functional surface platforms: Functionalization capacity, biorecognition capability and resistance to fouling from undiluted biological media. Biosens. Bioelectron. 2014;51:150–157. doi: 10.1016/j.bios.2013.07.015. PubMed DOI

Choi J., Schattling P., Jochum F.D., Pyun J., Char K., Theato P. Functionalization and patterning of reactive polymer brushes based on surface reversible addition and fragmentation chain transfer polymerization. J. Pol. Sci. Part. A Pol. Chem. 2012;50:4010–4018. doi: 10.1002/pola.26200. DOI

Lowe A.B. Thiol-ene “click” reactions and recent applications in polymer and materials synthesis: A first update. Pol. Chem. 2014;5:4820–4870. doi: 10.1039/C4PY00339J. DOI

Mohammad Mahdi Dadfar S., Sekula-Neuner S., Trouillet V., Hirtz M. A Comparative Study of Thiol-Terminated Surface Modification by Click Reactions: Thiol-yne Coupling versus Thiol-ene Michael Addition. Adv. Mat. Interfaces. 2018;5:1–9.

Proks V., Jaroš J., Pop-Georgievski O., Kučka J., Popelka Š., Dvořák P., Hampl A., Rypáček F. “Click & seed” approach to the biomimetic modification of material surfaces. Macromol. Biosci. 2012;12:1232–1242. PubMed

Parrillo V., de los Santos Pereira A., Riedel T., Rodriguez-Emmenegger C. Catalyst-free “click” functionalization of polymer brushes preserves antifouling properties enabling detection in blood plasma. Anal. Chim. Acta. 2017;971:78–87. doi: 10.1016/j.aca.2017.03.007. PubMed DOI

Poręba R., de Los Santos Pereira A., Pola R., Jiang S., Pop-Georgievski O., Sedláková Z., Schönherr H. “Clickable” and Antifouling Block Copolymer Brushes as a Versatile Platform for Peptide-Specific Cell Attachment. Macromol. Biosci. 2020;20:e1900354. doi: 10.1002/mabi.201900354. PubMed DOI

De Rosa L., Di Stasi R., D’Andrea L.D. Pro-angiogenic peptides in biomedicine. Arch. Biochem. Biophys. 2018;660:72–86. doi: 10.1016/j.abb.2018.10.010. PubMed DOI

Hynes R.O., Zhao Q. The evolution of cell adhesion. J. Cell Biol. 2000;150:89–96. doi: 10.1083/jcb.150.2.F89. PubMed DOI

Psarra E., Foster E., König U., You J., Ueda Y., Eichhorn K.J., Müller M., Stamm M., Revzin A., Uhlmann P. Growth Factor-Bearing Polymer Brushes—Versatile Bioactive Substrates Influencing Cell Response. Biomacromolecules. 2015;16:3530–3542. doi: 10.1021/acs.biomac.5b00967. PubMed DOI

Hsiong S.X., Huebsch N., Fischbach C., Kong H.J., Mooney D.J. Integrin-adhesion ligand bond formation of preosteoblasts and stem cells in three-dimensional RGD presenting matrices. Biomacromolecules. 2008;9:1843–1851. doi: 10.1021/bm8000606. PubMed DOI PMC

Ruoslahti E. Rgd and Other Recognition Sequences for Integrins. Annu. Rev. Cell Dev. Biol. 2002;12:697–715. doi: 10.1146/annurev.cellbio.12.1.697. PubMed DOI

Narasimhan S.K., Sejwal P., Zhu S., Luk Y.Y. Enhanced cell adhesion and mature intracellular structure promoted by squaramide-based RGD mimics on bioinert surfaces. Bioorg. Med. Chem. 2013;21:2210–2216. doi: 10.1016/j.bmc.2013.02.032. PubMed DOI

De los Santos Pereira A., Riedel T., Brynda E., Rodriguez-Emmenegger C. Hierarchical antifouling brushes for biosensing applications. Sens. Actuators B. 2014;202:1313–1321. doi: 10.1016/j.snb.2014.06.075. DOI

Pop-Georgievski O., Zimmermann R., Kotelnikov I., Proks V., Romeis D., Kučka J., Caspari A., Rypáček F., Werner C. Impact of Bioactive Peptide Motifs on Molecular Structure, Charging, and Nonfouling Properties of Poly(ethylene oxide) Brushes. Langmuir. 2018;34:6010–6020. doi: 10.1021/acs.langmuir.8b00441. PubMed DOI

Rodriguez-Emmenegger C., Janel S., de los Santos Pereira A., Bruns M., Lafont F. Quantifying bacterial adhesion on antifouling polymer brushes via single-cell force spectroscopy. Pol. Chem. 2015;6:5740–5751. doi: 10.1039/C5PY00197H. DOI

Jones D.M., Brown A.A., Huck W.T.S. Surface-Initiated Polymerizations in Aqueous Media:  Effect of Initiator Density. Langmuir. 2002;18:1265–1269. doi: 10.1021/la011365f. DOI

Direct and Indirect Biomimetic Peptide Modification of Alginate: Efficiency, Side Reactions, and Cell Response

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