This study presents the advantages of combining three-dimensional biodegradable scaffolds with the injection bioprinting of hydrogels. This combination takes advantage of the synergic effect of the properties of the various components, namely the very favorable mechanical and structural properties of fiber scaffolds fabricated from polycaprolactone and the targeted injection of a hydrogel cell suspension with a high degree of hydrophilicity. These properties exert a very positive impact in terms of promoting inner cell proliferation and the ability to create compact tissue. The scaffolds were composed of a mixture of microfibers produced via meltblown technology that ensured both an optimal three-dimensional porous structure and sufficient mechanical properties, and electrospun nanofibers that allowed for good cell adhesion. The scaffolds were suitable for combination with injection bioprinting thanks to their mechanical properties, i.e., only one nanofibrous scaffold became deformed during the injection process. A computer numerical-control manipulator featuring a heated printhead that allowed for the exact dosing of the hydrogel cell suspension into the scaffolds was used for the injection bioprinting. The hyaluronan hydrogel created a favorable hydrophilic ambiance following the filling of the fiber structure. Preliminary in vitro testing proved the high potential of this combination with respect to the field of bone tissue engineering. The ideal structural and mechanical properties of the tested material allowed osteoblasts to proliferate into the inner structure of the sample. Further, the tests demonstrated the significant contribution of printed hydrogel-cell suspension to the cell proliferation rate. Thus, the study led to the identification of a suitable hydrogel for osteoblasts.

Department of Nonwovens and Nanofibrous Materials Faculty of Textile Engineering Technical University of Liberec 461 17 Liberec Czech Republic

See more in PubMed

Caddeo S., Boffito M., Sartori S. Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models. Front. Bioeng. Biotechnol. 2017;5:40. doi: 10.3389/fbioe.2017.00040. PubMed DOI PMC

Jirkovec R., Holec P., Hauzerova S., Samkova A., Kalous T., Chvojka J. Preparation of a Composite Scaffold from Polycaprolactone and Hydroxyapatite Particles by Means of Alternating Current Electrospinning. ACS Omega. 2021;6:9234–9242. doi: 10.1021/acsomega.1c00644. PubMed DOI PMC

Khorshidi S., Karkhaneh A. Hydrogel/fiber conductive scaffold for bone tissue engineering. J. Biomed. Mater. Res. Part A. 2017;106:718–724. doi: 10.1002/jbm.a.36282. PubMed DOI

Catros S., Guillotin B., Bačáková M., Fricain J.-C., Guillemot F. Effect of laser energy, substrate film thickness and bioink viscosity on viability of endothelial cells printed by Laser-Assisted Bioprinting. Appl. Surf. Sci. 2011;257:5142–5147. doi: 10.1016/j.apsusc.2010.11.049. DOI

Rider P., Kačarević P.Z., Alkildani S., Retnasingh S., Barbeck M. Bioprinting of tissue engineering scaffolds. J. Tissue Eng. 2018;9 doi: 10.1177/2041731418802090. PubMed DOI PMC

Mironov V., Visconti R.P., Kasyanov V., Forgacs G., Drake C.J., Markwald R.R. Organ printing: Tissue spheroids as building blocks. Biomaterials. 2009;30:2164–2174. doi: 10.1016/j.biomaterials.2008.12.084. PubMed DOI PMC

Corona B.T., Ward C.L., Harrison B.S., Christ G.J. Regenerative medicine: Basic concepts, current status, and future applications. J. Investig. Med. 2010;58:849–858. doi: 10.2310/JIM.0b013e3181efbc61. PubMed DOI

Murphy S.V., Atala A. 3D bioprinting of tissues and organs. Nat. Biotechnol. 2014;32:773–785. doi: 10.1038/nbt.2958. PubMed DOI

Jakab K., Norotte C., Marga F., Murphy K., Vunjak-Novakovic G., Forgacs G. Tissue engineering by self-assembly and bio-printing of living cells. Biofabrication. 2010;2:022001. doi: 10.1088/1758-5082/2/2/022001. PubMed DOI PMC

Murphy S.V., Skardal A., Atala A. Evaluation of hydrogels for bio-printing applications. J. Biomed. Mater. Res. Part A. 2013;101:272–284. doi: 10.1002/jbm.a.34326. PubMed DOI

Peppas N.A., Hilt J.Z., Khademhosseini A., Langer R. Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology. Adv. Mater. 2006;18:1345–1360. doi: 10.1002/adma.200501612. DOI

Jun I., Han H.-S., Edwards J.R., Jeon H. Electrospun Fibrous Scaffolds for Tissue Engineering: Viewpoints on Architecture and Fabrication. Int. J. Mol. Sci. 2018;19:745. doi: 10.3390/ijms19030745. PubMed DOI PMC

Lukáš D., Sarkar A., Martinová L., Vodsed’álková K., Lubasová D., Chaloupek J., Pokorný P., Mikeš P., Chvojka J., Komárek M. Physical principles of electrospinning (Electrospinning as a nano-scale technology of the twenty-first century) Text. Prog. 2009;41:59–140. doi: 10.1080/00405160902904641. DOI

Huang Z.-M., Zhang Y.-Z., Kotaki M., Ramakrishna S. A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos. Sci. Technol. 2003;63:2223–2253. doi: 10.1016/S0266-3538(03)00178-7. DOI

Guceri S., Gogotsi Y.G., Kuznetsov V. Nanoengineered Nanofibrous Materials. Kluwer Academic Publishers; Dordrecht, The Netherland: 2003. pp. 97–106.

Cato T.L., Khan Y. Scaffold in Tissue Engineering. CRC Press; Boca Raton, FL, USA: 2006. Polymer/Calcium Phosphate Scaffolds for Bone Tissue Engineering; pp. 253–282.

Erben J., Pilarova K., Sanetrnik F., Chvojka J., Jencova V., Blazkova L., Havlicek J., Novak O., Mikes P., Prosecka E., et al. The combination of meltblown and electrospinning for bone tissue engineering. Mater. Lett. 2015;143:172–176. doi: 10.1016/j.matlet.2014.12.100. DOI

Erben J., Jencova V., Chvojka J., Blazkova L., Strnadova K., Modrak M., Kostakova E.K. The combination of meltblown technology and electrospinning—The influence of the ratio of micro and nanofibers on cell viability. Mater. Lett. 2016;173:153–157. doi: 10.1016/j.matlet.2016.02.147. DOI

Russell S.J. Handbook of Nonvowens. Woodhead Publishing Limited; Boca Raton, FL, USA: CRC Press LLC; Boca Raton, FL, USA: 2007. pp. 172–185.

Gutarowska B., Michalski A. Antimicrobial activity of filtrating meltblown nonwoven’s with addition of silver ions. Fibres Text. East. Eur. 2009;17:23–28.

Bidault X., Pneau N. Impact of the granularity of a high-explosive material on its shock properties. Res. Rev. J. Mater. Sci. 2017;5 doi: 10.4172/2321-6212-C1-006. DOI

Miranda D.G., Malmonge S.M., Campos D.M., Attik N.G., Grosgogeat B., Gritsch K. A chitosan-hyaluronic acid hydrogel scaffold for periodontal tissue engineering. J. Biomed. Mater. Res. Part B Appl. Biomater. 2016;104:1691–1702. doi: 10.1002/jbm.b.33516. PubMed DOI

Martins J. Master Thesis. Faculty of Engineering of University of Porto; Porto, Portugal: 2014. Development of a Polymeric Matrix based on Hyaluronic Acid and Dextrin Hydrogels for the Expansion of Undifferentiated Mesenchymal Stem Cells.

Hollister S.J. Porous scaffold design for tissue engineering. Nat. Mater. 2005;4:518–524. doi: 10.1038/nmat1421. PubMed DOI

Wei G., Ma P.X. Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering. Biomaterials. 2004;25:4749–4757. doi: 10.1016/j.biomaterials.2003.12.005. PubMed DOI

Fransiska S., Ho M.H., Li C.H., Shih J.L., Hsiao S.W., Thien D.V.H. To enhance protein production from osteoblasts by using micro-patterned surfaces. Biochem. Eng. J. 2013;78:120–127. doi: 10.1016/j.bej.2013.04.025. DOI

Harrington S., Williams J., Rawal S., Ramachandran K., Stehno-Bittel L. Hyaluronic Acid/Collagen Hydrogel as an Alternative to Alginate for Long-Term Immunoprotected Islet Transplantation. Tissue Eng. Part A. 2017;23:1088–1099. doi: 10.1089/ten.tea.2016.0477. PubMed DOI PMC