Bone tissue is the second tissue to be replaced. Annually, over four million surgical treatments are performed. Tissue engineering constitutes an alternative to autologous grafts. Its application requires three-dimensional scaffolds, which mimic human body environment. Bone tissue has a highly organized structure and contains mostly inorganic components. The scaffolds of the latest generation should not only be biocompatible but also promote osteoconduction. Poly (lactic acid) nanofibers are commonly used for this purpose; however, they lack bioactivity and do not provide good cell adhesion. Chitosan is a commonly used biopolymer which positively affects osteoblasts' behavior. The aim of this article was to prepare novel hybrid 3D scaffolds containing nanohydroxyapatite capable of cell-response stimulation. The matrixes were successfully obtained by PLA electrospinning and microwave-assisted chitosan crosslinking, followed by doping with three types of metallic nanoparticles (Au, Pt, and TiO2). The products and semi-components were characterized over their physicochemical properties, such as chemical structure, crystallinity, and swelling degree. Nanoparticles' and ready biomaterials' morphologies were investigated by SEM and TEM methods. Finally, the scaffolds were studied over bioactivity on MG-63 and effect on current-stimulated biomineralization. Obtained results confirmed preparation of tunable biomimicking matrixes which may be used as a promising tool for bone-tissue engineering.

Department of Physical Chemistry Faculty of Chemical Engineering and Technology Cracow University of Technology 31 155 Cracow Poland

Faculty of Mining and Geology Technical University of Ostrava; 708 00 Ostrava Czech Republic

See more in PubMed

Turnbull G., Clarke J., Picard F., Riches P., Jia L., Han F., Li B., Shu W. 3D bioactive composite scaffolds for bone tissue engineering. Bioact. Mater. 2018;3:278–314. doi: 10.1016/j.bioactmat.2017.10.001. PubMed DOI PMC

Bhattarai D.P., Aguilar L.E., Park C.H., Kim C.S. A Review on Properties of Natural and Synthetic Based Electrospun Fibrous Materials for Bone Tissue Engineering. Membranes. 2018;8:62. doi: 10.3390/membranes8030062. PubMed DOI PMC

Di Martino A., Liverani L., Rainer A., Salvatore G., Trombetta M., Denaro V. Electrospun scaffolds for bone tissue engineering. Musculoskelet. Surg. 2011;95:69–80. doi: 10.1007/s12306-011-0097-8. PubMed DOI

Khajavi R., Abbasipour M., Bahador A. Electrospun biodegradable nanofibers scaffolds for bone tissue engineering. J. Appl. Polym. Sci. 2016;133:42883. doi: 10.1002/app.42883. DOI

Qu H., Fu H., Hana Z., Sun Y. Biomaterials for bone tissue engineering scaffolds: A review. RSC Adv. 2019;9:26252–26262. doi: 10.1039/C9RA05214C. PubMed DOI PMC

Aslankoohi N., Mondal D., Rizkalla A.S., Mequanint K. Bone Repair and Regenerative Biomaterials: Towards Recapitulating the Microenvironment. Polymers. 2019;11:1437. doi: 10.3390/polym11091437. PubMed DOI PMC

Permyakova E.S., Kiryukhantsev-Korneev P.V., Gudz K.Y., Konopatsky A.S., Polčak J., Zhitnyak I.Y., Gloushankova N.A., Shtansky D.V., Manakhov A.M. Comparison of Different Approaches to Surface Functionalization of Biodegradable Polycaprolactone Scaffolds. Nanomaterials. 2019;9:1769. doi: 10.3390/nano9121769. PubMed DOI PMC

Witzler M., Büchner D., Shoushrah S.H., Babczyk P., Baranova J., Witzleben S., Tobiasch E., Schulze M. Polysaccharide-Based Systems for Targeted Stem Cell Differentiation and Bone Regeneration. Biomolecules. 2019;9:840. doi: 10.3390/biom9120840. PubMed DOI PMC

Fang C.-H., Lin Y.-W., Lin F.-H., Sun J.-S., Chao Y.-H., Lin H.-Y., Chang Z.-C. Biomimetic Synthesis of Nanocrystalline Hydroxyapatite Composites: Therapeutic Potential and Effects on Bone Regeneration. Int. J. Mol. Sci. 2019;20:6002. doi: 10.3390/ijms20236002. PubMed DOI PMC

Xu Z., Wang N., Liu P., Sun Y., Wang Y., Fei F., Zhang S., Zheng J., Han B. Poly(Dopamine) Coating on 3D-Printed Poly-Lactic-Co-Glycolic Acid/β-Tricalcium Phosphate Scaffolds for Bone Tissue Engineering. Molecules. 2019;24:4397. doi: 10.3390/molecules24234397. PubMed DOI PMC

Narayanan G., Vernekar N., Kuyinu E.L., Laurencin C.T. Poly (Lactic Acid)-Based Biomaterials for Orthopaedic Regenerative Engineering. Adv. Drug Deliv. Rev. 2016;107:247–276. doi: 10.1016/j.addr.2016.04.015. PubMed DOI PMC

Rogina A. Electrospinning process: Versatile preparation method for biodegradable and natural polymers and biocomposite systems applied in tissue engineering and drug delivery. Appl. Surf. Sci. 2014;296:221–230. doi: 10.1016/j.apsusc.2014.01.098. DOI

Bhattarai R.S., Bachu R.D., Boddu S.H.S., Bhaduri S. Biomedical Applications of Electrospun Nanofibers: Drug and Nanoparticle Delivery. Pharmaceutics. 2019;11:5. doi: 10.3390/pharmaceutics11010005. PubMed DOI PMC

Cassan D., Becker A., Glasmacher B., Roger Y., Hoffmann A., Gengenbach T.R., Easton C.D., Hänsch R., Menzel H. Blending chitosan-g-poly(caprolactone) with poly(caprolactone) by electrospinning to produce functional fiber mats for tissue engineering applications. J. Appl. Polym. Sci. 2019;94:48650. doi: 10.1002/app.48650. DOI

Yusof M.R., Shamsudin R., Zakaria S., Hamid M.A.A., Yalcinkaya F., Abdullah Y., Yacob N. Fabrication and Characterization of Carboxymethyl Starch/Poly(l-Lactide) Acid/β-Tricalcium Phosphate Composite Nanofibers via Electrospinning. Polymers. 2019;11:1468. doi: 10.3390/polym11091468. PubMed DOI PMC

Chan K.V., Asadian M., Onyshchenko I., Declercq H., Morent R., De Geyter N. Biocompatibility of Cyclopropylamine-Based Plasma Polymers Deposited at Sub-Atmospheric Pressure on Poly (ε-caprolactone) Nanofiber Meshes. Nanomaterials. 2019;9:1215. doi: 10.3390/nano9091215. PubMed DOI PMC

Braghirolli D.I., Steffens D., Pranke P. Electrospinning for regenerative medicine: a review of the main topics. Drug Discov Today. 2014;19:743–753. doi: 10.1016/j.drudis.2014.03.024. PubMed DOI

Niiyama E., Uto K., Lee C.M., Sakura K., Ebara M. Alternating Magnetic Field-Triggered Switchable Nanofiber Mesh for Cancer Thermo-Chemotherapy. Polymers. 2018;10:1018. doi: 10.3390/polym10091018. PubMed DOI PMC

Szentivanyi A.L., Zernetsch H., Menzel H., Glasmacher B. A review of developments in electrospinning technology: New opportunities for the design of artificial tissue structures. Int. J. Artif. Organs. 2011;34:986–997. doi: 10.5301/ijao.5000062. PubMed DOI

Shahidi F., Abuzaytoun R. Chitin, chitosan, and co-products: Chemistry, production, applications, and health effects. Adv. Food Nutr. Res. 2005;49:93–135. PubMed

Dash M., Chiellini F., Ottenbrite R.M., Chiellini E. Chitosan—A versatile semi-synthetic polymer in biomedical applications. Prog. Polym. Sci. 2011;36:981–1014. doi: 10.1016/j.progpolymsci.2011.02.001. DOI

Kean T., Thanou M. Biodegradation, biodistribution and toxicity of chitosan. Adv. Drug Deliv. Rev. 2010;62:3–11. doi: 10.1016/j.addr.2009.09.004. PubMed DOI

LogithKumar R., KeshavNarayan A., Dhivya S., Chawla A., Saravanan S., Selvamurugan N. A review of chitosan and its derivatives in bone tissue engineering. Carbohydr. Polym. 2016;151:172–188. doi: 10.1016/j.carbpol.2016.05.049. PubMed DOI

Saravanan S., Leena R.S., Selvamurugan N. Chitosan based biocomposite scaffolds for bone tissue engineering. Int. J. Biol. Macromol. 2016;93:1354–1365. doi: 10.1016/j.ijbiomac.2016.01.112. PubMed DOI

Fathi-Achachelouei M., Knopf-Marques H., Ribeiro da Silva C.E., Barthès J., Bat E., Tezcanerand A., Vrana N.E. Use of Nanoparticles in Tissue Engineering and Regenerative Medicine. Front. Bioeng. Biotechnol. 2019;7:113. doi: 10.3389/fbioe.2019.00113. PubMed DOI PMC

Khan I., Saeed K., Khan I. Nanoparticles: Properties, applications and toxicities. Arab. J. Chem. 2019;12:908–931. doi: 10.1016/j.arabjc.2017.05.011. DOI

Vieira S., Vial S., Reis R.L., Oliveira J.M. Nanoparticles for bone tissue engineering. Biotechnol. Prog. 2017;33:590–611. doi: 10.1002/btpr.2469. PubMed DOI

AshaRani P.V., Low Kah Mun G., Hande M.P., Valiyaveettil S. Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano. 2009;3:279–290. doi: 10.1021/nn800596w. PubMed DOI

Chithrani B.D., Ghazani A.A., Chan W.C. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 2006;6:662–668. doi: 10.1021/nl052396o. PubMed DOI

Chompoosor A., Saha K., Ghosh P.S., Macarthy D.J., Miranda O.R., Zhu Z.J., Arcaro K.F., Rotello V.M. The role of surface functionality on acute cytotoxicity, ROS generation and DNA damage by cationic gold nanoparticles. Small. 2010;6:2246–2249. doi: 10.1002/smll.201000463. PubMed DOI PMC

Pedone D., Moglianetti M., De Luca E., Giuseppe B., Pompa P.P. Platinum nanoparticles in nanobiomedicine. Chem. Soc. Rev. 2017;46:4951–4975. doi: 10.1039/C7CS00152E. PubMed DOI

Brammer K.S., Frandsen C.J., Jin S. TiO2 nanotubes for bone regeneration. Trends Biotechnol. 2012;30:315–322. doi: 10.1016/j.tibtech.2012.02.005. PubMed DOI

Lee J.-E., Bark C.W., Quy H.V., Seo S.-J., Lim J.-H., Kang S.-A., Lee Y., Lee J.-M., Suh J.-Y., Kim Y.-G. Effects of Enhanced Hydrophilic Titanium Dioxide-Coated Hydroxyapatite on Bone Regeneration in Rabbit Calvarial Defects. Int. J. Mol. Sci. 2018;19:3640. doi: 10.3390/ijms19113640. PubMed DOI PMC

Kumar P. Nano-TiO2 Doped Chitosan Scaffold for the Bone Tissue Engineering Applications. Int. J. Biomater. 2018;2018:6576157. doi: 10.1155/2018/6576157. PubMed DOI PMC

Ikono R., Li N., Pratama N.H., Vibriani A., Yuniarni D.R., Luthfansyah M., Bachtiar B.M., Bachtiar E.W., Mulia K., Nasikin M., et al. Enhanced bone regeneration capability of chitosan sponge coated with TiO2 nanoparticles. Biotechnol. Rep. 2019;24:e00350. doi: 10.1016/j.btre.2019.e00350. PubMed DOI PMC

Guo N., Zhang L., Wang J., Wang S., Zoud Y., Wang X. Novel fabrication of morphology tailored nanostructures with Gelatin/Chitosan Co-polymeric bio-composited hydrogel system to accelerate bone fracture healing and hard tissue nursing care management. Process. Biochem. 2020;90:177–183. doi: 10.1016/j.procbio.2019.11.016. DOI

Santoro M., Shah S.R., Walker J.L., Mikos A.G. Poly(lactic acid) nanofibrous scaffolds for tissue engineering. Adv. Drug Deliv. Rev. 2016;107:206–212. doi: 10.1016/j.addr.2016.04.019. PubMed DOI PMC

Coltelli M.B., Cinelli P., Gigante V., Aliotta L., Morganti P., Panariello L., Lazzeri A. Chitin Nanofibrils in Poly(Lactic Acid) (PLA) Nanocomposites: Dispersion and Thermo-Mechanical Properties. Int. J. Mol. Sci. 2019;20:504. doi: 10.3390/ijms20030504. PubMed DOI PMC

Pautke C., Schieker M., Tischer T., Kolk A., Neth P., Mutschler W., Milz S. Characterization of osteosarcoma cell lines MG-63, Saos-2 and U-2 OS in comparison to human osteoblasts. Anticancer Res. 2004;24:3743–3748. PubMed

Katsanevakis E., Wen X.J., Shi D.L., Zhang N. Biomineralization of Polymer Scaffolds. Key Eng. Mater. 2010;441:269–295. doi: 10.4028/www.scientific.net/KEM.441.269. DOI

Lu H.T., Lu T.W., Chen C.H., Lu K.Y., Mi F.L. Development of nanocomposite scaffolds based on biomineralization of N,O-carboxymethyl chitosan/fucoidan conjugates for bone tissue engineering. Int. J. Biol. Macromol. 2018;120:2335–2345. doi: 10.1016/j.ijbiomac.2018.08.179. PubMed DOI

Feng P., Kong Y., Yu L., Li Y., de Gao C., Peng S., Pan H., Zhao Z., Shuai C. Molybdenum disulfide nanosheets embedded with nanodiamond particles: Co-dispersion nanostructures as reinforcements for polymer scaffolds. Appl. Mater. Today. 2019;17:216–226. doi: 10.1016/j.apmt.2019.08.005. DOI

Shuai C., Yang W., He C., Peng S., Gao C., Yang Y., Qi F., Feng P. A magnetic micro-environment in scaffolds for stimulating bone regeneration. Mater. Des. 2020;185:108275. doi: 10.1016/j.matdes.2019.108275. DOI

Shuai C., Liu G., Yang Y., Yang W., He C., Wang G., Liu Z., Qi F., Peng S. Functionalized BaTiO3 enhances piezoelectric effect towards cell response of bone scaffold. Colloids Surf. B Biointerfaces. 2020;185:110587. doi: 10.1016/j.colsurfb.2019.110587. PubMed DOI

Feng P., Wu P., Gao C., Yang Y., Guo W., Yang W., Shuai C. A Multimaterial Scaffold With Tunable Properties: Toward Bone Tissue Repair. Adv. Sci. 2018;5:1700817. doi: 10.1002/advs.201700817. PubMed DOI PMC

Shuai C., Yu L., Yang W., Peng S., Zhong Y., Feng P. Phosphonic Acid Coupling Agent Modification of HAP Nanoparticles: Interfacial Effects in PLLA/HAP Bone Scaffold. Polymers. 2020;12:199. doi: 10.3390/polym12010199. PubMed DOI PMC