Facile Cell-Friendly Hollow-Core Fiber Diffusion-Limited Photofabrication

Alexander G Savelyev; Anastasia V Sochilina; Roman A Akasov; Anton V Mironov; Alina Yu Kapitannikova; Tatiana N Borodina; Natalya V Sholina; Kirill V Khaydukov; Andrei V Zvyagin; Alla N Generalova; Evgeny V Khaydukov

doi:10.3389/fbioe.2021.783834

Facile Cell-Friendly Hollow-Core Fiber Diffusion-Limited Photofabrication

Front Bioeng Biotechnol. 2021 Dec 3:9:783834. doi: 10.3389/fbioe.2021.783834. eCollection 2021.

Authors

Alexander G Savelyev^{1

2}, Anastasia V Sochilina^{1

3}, Roman A Akasov^{1

2

3}, Anton V Mironov¹, Alina Yu Kapitannikova², Tatiana N Borodina¹, Natalya V Sholina^{1

2}, Kirill V Khaydukov¹, Andrei V Zvyagin^{2

3

4}, Alla N Generalova^{1

3}, Evgeny V Khaydukov^{1

2

3}

Affiliations

¹ Federal Scientific Research Centre "Crystallography and Photonics" Russian Academy of Sciences, Moscow, Russia.
² Center of Biomedical Engineering, Institute of Molecular Medicine, Sechenov University, Moscow, Russia.
³ Shemyakin-Ovchinnikov Institute of Bioorganic Сhemistry RAS, Moscow, Russia.
⁴ MQ Photonics Centre, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, Australia.

Abstract

Bioprinting emerges as a powerful flexible approach for tissue engineering with prospective capability to produce tissue on demand, including biomimetic hollow-core fiber structures. In spite of significance for tissue engineering, hollow-core structures proved difficult to fabricate, with the existing methods limited to multistage, time-consuming, and cumbersome procedures. Here, we report a versatile cell-friendly photopolymerization approach that enables single-step prototyping of hollow-core as well as solid-core hydrogel fibers initially loaded with living cells. This approach was implemented by extruding cell-laden hyaluronic acid glycidyl methacrylate hydrogel directly into aqueous solution containing free radicals generated by continuous blue light photoexcitation of the flavin mononucleotide/triethanolamine photoinitiator. Diffusion of free radicals from the solution to the extruded structure initiated cross-linking of the hydrogel, progressing from the structure surface inwards. Thus, the cross-linked wall is formed and its thickness is limited by penetration of free radicals in the hydrogel volume. After developing in water, the hollow-core fiber is formed with centimeter range of lengths. Amazingly, HaCaT cells embedded in the hydrogel successfully go through the fabrication procedure. The broad size ranges have been demonstrated: from solid core to 6% wall thickness of the outer diameter, which was variable from sub-millimeter to 6 mm, and Young's modulus ∼1.6 ± 0.4 MPa. This new proof-of-concept fibers photofabrication approach opens lucrative opportunities for facile three-dimensional fabrication of hollow-core biostructures with controllable geometry.

Keywords: cell-laden hydrogel; flavin mononucleotide; hollow-core fiber; hyaluronic acid; photofabrication; photopolymerization; radical diffusion; vessel engineering.