Biodegradable nanofibers are extensively employed in different areas of biology and medicine, particularly in tissue engineering. The electrospun polycaprolactone (PCL) nanofibers are attracting growing interest due to their good mechanical properties and a low-cost structure similar to the extracellular matrix. However, the unmodified PCL nanofibers exhibit an inert surface, hindering cell adhesion and negatively affecting their further fate. The employment of PCL nanofibrous scaffolds for wound healing requires a certain modification of the PCL surface. In this work, the morphology of PCL nanofibers is optimized by the careful tuning of electrospinning parameters. It is shown that the modification of the PCL nanofibers with the COOH plasma polymers and the subsequent binding of NH2 groups of protein molecules is a rather simple and technologically accessible procedure allowing the adhesion, early spreading, and growth of human fibroblasts to be boosted. The behavior of fibroblasts on the modified PCL surface was found to be very different when compared to the previously studied cultivation of mesenchymal stem cells on the PCL nanofibrous meshes. It is demonstrated by X-ray photoelectron spectroscopy (XPS) that the freeze-thawed platelet-rich plasma (PRP) immobilization can be performed via covalent and non-covalent bonding and that it does not affect biological activity. The covalently bound components of PRP considerably reduce the fibroblast apoptosis and increase the cell proliferation in comparison to the unmodified PCL nanofibers or the PCL nanofibers with non-covalent bonding of PRP. The reported research findings reveal the potential of PCL matrices for application in tissue engineering, while the plasma modification with COOH groups and their subsequent covalent binding with proteins expand this potential even further. The use of such matrices with covalently immobilized PRP for wound healing leads to prolonged biological activity of the immobilized molecules and protects these biomolecules from the aggressive media of the wound.

CEITEC Central European Institute of Technology Masaryk University Kamenice 5 625 00 Brno Czech Republic

Institute of Biochemistry ⁻ subdivision of the FRC FTM 2 Timakova str 630117 Novosibirsk Russia

Laboratory of Inorganic Nanomaterials National University of Science and Technology MISiS Leninsky pr 4 119049 Moscow Russia

Physics and Materials Science Research Unit Laboratory for the Physics of Advanced Materials University of Luxembourg 162a avenue de la Faïencerie L 1511 Luxembourg Luxembourg

Scientific Institute of Clinical and Experimental Lymphology Branch of the ICG SB RAS 2 Timakova str 630060 Novosibirsk Russia

Zobrazit více v PubMed

Lev-Tov H., Li C.-S., Dahle S., Isseroff R.R. Cellular versus acellular matrix devices in treatment of diabetic foot ulcers: Study protocol for a comparative efficacy randomized controlled trial. Trials. 2013;14:8. doi: 10.1186/1745-6215-14-8. PubMed DOI PMC

Watt S.M., Pleat J.M. Stem cells, niches and scaffolds: Applications to burns and wound care. Adv. Drug Deliv. Rev. 2018;123:82–106. doi: 10.1016/j.addr.2017.10.012. PubMed DOI

Dickinson L.E., Gerecht S. Engineered Biopolymeric Scaffolds for Chronic Wound Healing. Front. Physiol. 2016;7:623. doi: 10.3389/fphys.2016.00341. PubMed DOI PMC

Chaudhari A.A., Vig K., Baganizi D.R., Sahu R., Dixit S., Dennis V., Singh S.R., Pillai S.R., Hardy J.G. Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review. Int. J. Mol. Sci. 2016;17:1974. doi: 10.3390/ijms17121974. PubMed DOI PMC

Manakhov A., Kedroňová E., Medalová J., Černochová P., Obrusník A., Michlíček M., Shtansky D.V., Zajíčková L. Carboxyl-anhydride and amine plasma coating of PCL nanofibers to improve their bioactivity. Mater. Des. 2017;132:257–265. doi: 10.1016/j.matdes.2017.06.057. DOI

Al-Enizi A.M., Zagho M.M., Elzatahry A.A. Polymer-Based Electrospun Nanofibers for Biomedical Applications. Nanomaterials. 2018;8:259. doi: 10.3390/nano8040259. PubMed DOI PMC

Phan L.T., Yoon S.M., Moon M.-W. Plasma-Based Nanostructuring of Polymers: A Review. Polymers. 2017;9:417. doi: 10.3390/polym9090417. PubMed DOI PMC

Ivanova A.A., Syromotina D.S., Shkarina S.N., Shkarin R., Cecilia A., Weinhardt V., Baumbach T., Saveleva M.S., Gorin D.A., Douglas T.E.L., et al. Effect of low-temperature plasma treatment of electrospun polycaprolactone fibrous scaffolds on calcium carbonate mineralisation. RSC Adv. 2018;8:39106–39114. doi: 10.1039/C8RA07386D. PubMed DOI PMC

Permyakova E.S., Polčák J., Slukin P.V., Ignatov S.G., Gloushankova N.A., Zajíčková L., Shtansky D.V., Manakhov A. Antibacterial biocompatible PCL nanofibers modified by COOH-anhydride plasma polymers and gentamicin immobilization. Mater. Des. 2018;153:60–70. doi: 10.1016/j.matdes.2018.05.002. DOI

Savelyeva M.S., Abalymov A.A., Lyubun G.P., Vidyasheva I.V., Yashchenok A.M., Douglas T.E.L., Gorin D.A., Parakhonskiy B.V. Vaterite coatings on electrospun polymeric fibers for biomedical applications. J. Biomed. Mater. Res. Part A. 2017;105:94–103. doi: 10.1002/jbm.a.35870. PubMed DOI

Saveleva M., Ivanov A., Kurtukova M., Atkin V., Ivanova A., Lyubun G., Martyukova A., Cherevko E., Sargsyan A., Fedonnikov A., et al. Hybrid PCL/CaCO3 scaffolds with capabilities of carrying biologically active molecules: Synthesis, loading and in vivo applications. Mater. Sci. Eng. C. 2018;85:57–67. doi: 10.1016/j.msec.2017.12.019. PubMed DOI

Chen C.-H., Chen S.-H., Kuo C.-Y., Li M.-L., Chen J.-P. Response of Dermal Fibroblasts to Biochemical and Physical Cues in Aligned Polycaprolactone/Silk Fibroin Nanofiber Scaffolds for Application in Tendon Tissue Engineering. Nanomaterials. 2017;7:219. doi: 10.3390/nano7080219. PubMed DOI PMC

Kiran A.S.K., Kumar T.S., Sanghavi R., Doble M., Ramakrishna S. Antibacterial and Bioactive Surface Modifications of Titanium Implants by PCL/TiO2 Nanocomposite Coatings. Nanomaterials. 2018;8:860. doi: 10.3390/nano8100860. PubMed DOI PMC

Bereiter-hahn J., Luck M., Mdebach T., Stelzer H.K., Voth M. Spreading of trypsinized cells: Cytoskeletal dynamics and energy requirements. J. Cell Sci. 1990;96:171–188. PubMed

Cuvelier D., Théry M., Chu Y.-S., Dufour S., Thiery J.-P., Bornens M., Nassoy P., Mahadevan L. The Universal Dynamics of Cell Spreading. Curr. Boil. 2007;17:694–699. doi: 10.1016/j.cub.2007.02.058. PubMed DOI

Tvorogova A., Saidova A., Smirnova T., Vorobjev I. Dynamic microtubules drive fibroblast spreading. Boil. Open. 2018;7:bio038968. doi: 10.1242/bio.038968. PubMed DOI PMC

Pollard T.D., Borisy G.G. Cellular Motility Driven by Assembly and Disassembly of Actin Filaments. Cell. 2003;113:549. doi: 10.1016/S0092-8674(03)00357-X. PubMed DOI

McGrath J.L. Cell Spreading: The Power to Simplify. Curr. Boil. 2007;17:R357–R358. doi: 10.1016/j.cub.2007.03.057. PubMed DOI

Olsen B.R. Matrix Molecules and Their Ligands. 4th ed. Elsevier; Amsterdam, The Netherlands: 2014.

Bershadsky A.D., Balaban N.Q., Geiger B. Adhesion-Dependent Cell Mechanosensitivity. Annu. Cell Dev. Boil. 2003;19:677–695. doi: 10.1146/annurev.cellbio.19.111301.153011. PubMed DOI

Pelham R.J., Jr., Wang Y. Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc. Natl. Acad. Sci. USA. 1997;94:13661–13665. PubMed PMC

Zhou G., Liu S., Ma Y., Xu W., Meng W., Lin X., Wang W., Wang S., Zhang J. Innovative biodegradable poly(L-lactide)/collagen/hydroxyapatite composite fibrous scaffolds promote osteoblastic proliferation and differentiation. Int. J. Nanomed. 2017;12:7577–7588. doi: 10.2147/IJN.S146679. PubMed DOI PMC

Kiran S., Nune K.C., Misra R.D.K. The significance of grafting collagen on polycaprolactone composite scaffolds: Processing-structure-functional property relationship. J. Biomed. Mater. A. 2015;103:2919–2931. doi: 10.1002/jbm.a.35431. PubMed DOI

Daelemans L., Steyaert I., Schoolaert E., Goudenhooft C., Rahier H., De Clerck K. Nanostructured Hydrogels by Blend Electrospinning of Polycaprolactone/Gelatin Nanofibers. Nanomaterials. 2018;8:551. doi: 10.3390/nano8070551. PubMed DOI PMC

Lin S.J., Jee S.H., Hsaio W.C., Lee S.J., Young T.H. Formation of melanocyte spheroids on the chitosan-coated surface. Biomaterials. 2005;26:1413–1422. doi: 10.1016/j.biomaterials.2004.05.002. PubMed DOI

Salević A., Prieto C., Cabedo L., Nedović V., Lagaron J.M. Physicochemical, Antioxidant and Antimicrobial Properties of Electrospun Poly(ε-caprolactone) Films Containing a Solid Dispersion of Sage (Salvia officinalis L.) Extract. Nanomaterials. 2019;9:270. doi: 10.3390/nano9020270. PubMed DOI PMC

DeFrates K., Moore R., Lin G., Hu X., Beachley V., Borgesi J., Mulderig T. Protein-Based Fiber Materials in Medicine: A Review. Nanomaterials. 2018;8:457. doi: 10.3390/nano8070457. PubMed DOI PMC

Zardi L., Cecconi C., Barbieri O., Carnemolla B., Picca M., Santi L. Concentration of Fibronectin in Plasma of Tumor-bearing Mice and Synthesis by Ehrlich Ascites Tumor Cells. Cancer Res. 1979;39:3774–3777. PubMed

Sottile J., Hocking D.C., Schwartz M. Fibronectin Polymerization Regulates the Composition and Stability of Extracellular Matrix Fibrils and Cell-Matrix Adhesions. Mol. Boil. Cell. 2002;13:3546–3559. doi: 10.1091/mbc.e02-01-0048. PubMed DOI PMC

Sottile J., Hocking D.C., Swiatek P.J. Fibronectin matrix assembly enhances adhesion-dependent cell growth. J. Cell Sci. 1998;111:2933–2943. PubMed

Agrawal A.A. Evolution, current status and advances in application of platelet concentrate in periodontics and implantology. World J. Clin. Cases. 2017;5:159–171. doi: 10.12998/wjcc.v5.i5.159. PubMed DOI PMC

Guszczyn T., Surażyński A., Zaręba I., Rysiak E., Popko J., Pałka J. Differential effect of platelet-rich plasma fractions on β 1-integrin signaling, collagen biosynthesis, and prolidase activity in human skin fibroblasts. Drug Des. Dev. Ther. 2017;11:1849–1857. doi: 10.2147/DDDT.S135949. PubMed DOI PMC

Chen B., Ding J., Zhang W., Zhou G., Cao Y., Liu W. Tissue Engineering of Tendons: A Comparison of Muscle-Derived Cells, Tenocytes, and Dermal Fibroblasts as Cell Sources. Plast. Reconstr. Surg. 2016;137:536e–544e. doi: 10.1097/01.prs.0000479980.83169.31. PubMed DOI

Li J., Chen M., Wei X., Hao Y., Wang J. Evaluation of 3D-Printed Polycaprolactone Scaffolds Coated with Freeze-Dried Platelet-Rich Plasma for Bone Regeneration. Materials. 2017;10:831. doi: 10.3390/ma10070831. PubMed DOI PMC

Beamson G., Briggs D. High Resolution XPS of Organic Polymers. John Wiley & Sons; Chichester, UK: 1992.

Liverani L., Boccaccini A.R., Armentano I. Versatile Production of Poly(Epsilon-Caprolactone) Fibers by Electrospinning Using Benign Solvents. Nanomaterials. 2016;6:75. doi: 10.3390/nano6040075. PubMed DOI PMC

Lee K., Kim H.Y., Bang H., Jung Y., Lee S. The change of bead morphology formed on electrospun polystyrene fibers. Polymer. 2003;44:4029–4034. doi: 10.1016/S0032-3861(03)00345-8. DOI

Pillay V., Dott C., Choonara Y.E., Tyagi C., Tomar L., Kumar P., Du Toit L.C., Ndesendo V.M.K. A Review of the Effect of Processing Variables on the Fabrication of Electrospun Nanofibers for Drug Delivery Applications. J. Nanomater. 2013;2013:1–22. doi: 10.1155/2013/789289. DOI

Netti M.V., Netti P.A. Engineering Cell Instructive Materials To Control Cell Fate and Functions through Material Cues and Surface Patterning. Acs Appl. Mater. Interfaces. 2016;8:14896–14908. PubMed

Solovieva A., Miroshnichenko S., Kovalskii A., Permyakova E., Popov Z., Dvořáková E., Kiryukhantsev-Korneev P., Obrosov A., Polčak J., Zajíčková L., et al. Immobilization of Platelet-Rich Plasma onto COOH Plasma-Coated PCL Nanofibers Boost Viability and Proliferation of Human Mesenchymal Stem Cells. Polymer. 2017;9:736. doi: 10.3390/polym9120736. PubMed DOI PMC

Eggenhofer E., Luk F., Dahlke M.H., Hoogduijn M.J. The Life and Fate of Mesenchymal Stem Cells. Front. Immunol. 2014;5:5. doi: 10.3389/fimmu.2014.00148. PubMed DOI PMC

Chen L., Tredget E.E., Wu P.Y.G., Wu Y. Paracrine Factors of Mesenchymal Stem Cells Recruit Macrophages and Endothelial Lineage Cells and Enhance Wound Healing. PLoS ONE. 2008;3:e1886. doi: 10.1371/journal.pone.0001886. PubMed DOI PMC

Gharaibeh B., Lavasani M., Cummins J.H., Huard J. Terminal differentiation is not a major determinant for the success of stem cell therapy—Cross-talk between muscle-derived stem cells and host cells. Stem Cell Ther. 2011;2:31. doi: 10.1186/scrt72. PubMed DOI PMC

Chiarugi P., Giannoni E. Anoikis: A necessary death program for anchorage-dependent cells. Biochem. Pharm. 2008;76:1352–1364. doi: 10.1016/j.bcp.2008.07.023. PubMed DOI

Lefort C.T., Wojciechowski K., Hocking D.C. N-cadherin Cell-Cell Adhesion Complexes Are Regulated by Fibronectin Matrix Assembly. J. Biol. Chem. 2011;286:3149–3160. doi: 10.1074/jbc.M110.115733. PubMed DOI PMC

Brennan J.R., Hocking D.C. Cooperative effects of fibronectin matrix assembly and initial cell–substrate adhesion strength in cellular self-assembly. Acta Biomater. 2016;32:198–209. doi: 10.1016/j.actbio.2015.12.032. PubMed DOI PMC

Sousa S.R., Moradas-Ferreira P., Barbosa M.A., Sousa S. TiO2 type influences fibronectin adsorption. J. Mater. Sci. Mater. Med. 2005;16:1173–1178. doi: 10.1007/s10856-005-4725-4. PubMed DOI

Advances in Electrospun Hybrid Nanofibers for Biomedical Applications

The Effect of the Controlled Release of Platelet Lysate from PVA Nanomats on Keratinocytes, Endothelial Cells and Fibroblasts

Well-Blended PCL/PEO Electrospun Nanofibers with Functional Properties Enhanced by Plasma Processing

Comparison of Different Approaches to Surface Functionalization of Biodegradable Polycaprolactone Scaffolds