Additive-lathe 3D bioprinting of bilayered nerve conduits incorporated with supportive cells

Jingyi Liu; Bin Zhang; Liang Li; Jun Yin; Jianzhong Fu

doi:10.1016/j.bioactmat.2020.08.010

Additive-lathe 3D bioprinting of bilayered nerve conduits incorporated with supportive cells

Bioact Mater. 2020 Aug 19;6(1):219-229. doi: 10.1016/j.bioactmat.2020.08.010. eCollection 2021 Jan.

Authors

Jingyi Liu^{1

2}, Bin Zhang¹, Liang Li³, Jun Yin^{1

2}, Jianzhong Fu^{1

2}

Affiliations

¹ The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310028, China.
² Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310028, China.
³ Department of Orthopedics, No. 906 Hospital of People's Liberation Army, Ningbo, 315040, China.

Abstract

Nerve conduits have been identified as one of the most promising treatments for peripheral nerve injuries, yet it remains unsolved how to develop ideal nerve conduits with both appropriate biological and mechanical properties. Existing nerve conduits must make trade-offs between mechanical strength and biocompatibility. Here, we propose a multi-nozzle additive-lathe 3D bioprinting technology to fabricate a bilayered nerve conduit. The materials for printing consisted of gelatin methacrylate (GelMA)-based inner layer, which was cellularized with bone marrow mesenchymal stem cells (BMSCs) and GelMA/poly(ethylene glycol) diacrylate (PEGDA)-based outer layer. The high viability and extensive morphological spreading of BMSCs encapsulated in the inner layer was achieved by adjusting the degree of methacryloyl substitution and the concentration of GelMA. Strong mechanical performance of the outer layer was obtained by the addition of PEGDA. The performance of the bilayered nerve conduits was assessed using in vitro culture of PC12 cells. The cell density of PC12 cells attached to cellularized bilayered nerve conduits was more than 4 times of that on acellular bilayered nerve conduits. The proliferation rate of PC12 cells attached to cellularized bilayered nerve conduits was over 9 times higher than that on acellular bilayered nerve conduits. These results demonstrate the additive-lathe 3D bioprinting of BMSCs embedded bilayered nerve conduits holds great potential in facilitating peripheral nerve repair.

Keywords: Additive-lathe 3D bioprinting; Gelatin methacrylate; Mesenchymal stem cells; Nerve conduit; Neuron outgrowth.