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3D bio-printed living nerve-like fibers refine the ecological niche for long-distance spinal cord injury regeneration.

ABSTRACT: 3D bioprinting holds great promise toward fabricating biomimetic living constructs in a bottom-up assembly manner. To date, various emergences of living constructs have been bioprinted for in vitro applications, while the conspicuous potential serving for in vivo implantable therapies in spinal cord injury (SCI) has been relatively overlooked. Herein, living nerve-like fibers are prepared via extrusion-based 3D bioprinting for SCI therapy. The living nerve-like fibers are comprised of neural stem cells (NSCs) embedded within a designed hydrogel that mimics the extracellular matrix (ECM), assembled into a highly spatial ordered architecture, similar to densely arranged bundles of the nerve fibers. The pro-neurogenesis ability of these living nerve-like fibers is tested in a 4 mm-long complete transected SCI rat model. Evidence shows that living nerve-like fibers refine the ecological niche of the defect site by immune modulation, angiogenesis, neurogenesis, neural relay formations, and neural circuit remodeling, leading to outstanding functional reconstruction, revealing an evolution process of this living construct after implantation. This effective strategy, based on biomimetic living constructs, opens a new perspective on SCI therapies.

SUBMITTER: Yang J

PROVIDER: S-EPMC9931763 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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3D bio-printed living nerve-like fibers refine the ecological niche for long-distance spinal cord injury regeneration.

Yang Jia J Yang Kaiyuan K Man Weitao W Zheng Jingchuan J Cao Zheng Z Yang Chun-Yi CY Kim Kunkoo K Yang Shuhui S Hou Zhaohui Z Wang Guihuai G Wang Xiumei X

Bioactive materials 20230202

3D bioprinting holds great promise toward fabricating biomimetic living constructs in a bottom-up assembly manner. To date, various emergences of living constructs have been bioprinted for <i>in vitro</i> applications, while the conspicuous potential serving for <i>in vivo</i> implantable therapies in spinal cord injury (SCI) has been relatively overlooked. Herein, living nerve-like fibers are prepared via extrusion-based 3D bioprinting for SCI therapy. The living nerve-like fibers are comprised ...[more]

PMID: 36817821

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Project description:Human umbilical cord-derived mesenchymal stromal cells (UC-MSCs), which can be prepared in advance and are presumed to be advantageous for nerve regeneration, have potential as a cell source for Bio 3D conduits. The purpose of this study was to evaluate the nerve regeneration ability of Bio 3D conduits made from UC-MSCs using a rat sciatic nerve defect model.MethodsA Bio 3D conduit was fabricated using a Bio 3D printer by placing UC-MSC spheroids into thin needles according to predesigned 3D data. The conduit was transplanted to bridge the 5-mm gaps of Lewis rat sciatic nerve, and nerve regeneration was evaluated at 8 weeks (Bio 3D group). Transplantation of autologous nerve segments (autograft) and silicone tubes represented the positive and negative control groups, respectively. In a second experiment, immunological reactions were evaluated in Bio 3D, autograft, and allograft groups by histochemical staining of transplanted segments in Brown Norway rats.ResultsThe mean angle of attack value in the kinematic analysis was significantly better in the Bio 3D group (‒20.1 ± 0.5°) than in the silicone group (‒33.7 ± 1.5°) 8 weeks after surgery. The average diameters of myelinated axons were significantly larger in the Bio 3D group (3.61 ± 0.15 μm) than in the silicone group (3.07 ± 0.12 μm), and the number of myelinated axons was significantly higher in the Bio 3D group (11,201 ± 980) than in the silicone group (8117 ± 646). Histological findings (hematoxylin and eosin [HE] staining and anti-CD3 fluorescent immunostaining) showed that rejection was suppressed in the Bio 3D group compared to the allograft group. Based on macroscopic findings and histological findings (anti-human mitochondrial fluorescent immunostaining), UC-MSCs in the Bio 3D conduit disappeared gradually from week 1 to week 8.ConclusionsThe Bio 3D conduit prepared from UC-MSCs was superior to the silicone tube and achieved comparable nerve regeneration to the autologous (autograft) group. Rejection was suppressed in the Bio 3D group compared to the allograft group. Although this study used a xenograft model, we speculate that rejection was low due to the characteristics of UC-MSCs. UC-MSCs are a useful cell source for Bio 3D conduits.

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3D bio-printed living nerve-like fibers refine the ecological niche for long-distance spinal cord injury regeneration.

Publications

3D bio-printed living nerve-like fibers refine the ecological niche for long-distance spinal cord injury regeneration.

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