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  4. 3D bioprinted dynamic bioactive living construct enhances mechanotransduction-assisted rapid neural network self-organization for spinal cord injury repair

3D bioprinted dynamic bioactive living construct enhances mechanotransduction-assisted rapid neural network self-organization for spinal cord injury repair

Bioactive Materials, 2025 · DOI: https://doi.org/10.1016/j.bioactmat.2024.12.028 · Published: December 27, 2024

Spinal Cord InjuryRegenerative MedicineBiomedical

Simple Explanation

This study introduces a novel approach to spinal cord injury (SCI) repair using a 3D bioprinted living construct. This construct is designed to mimic the natural environment of neural stem cells (NSCs) and promote their differentiation and organization into functional neural networks. The bioink used in the 3D bioprinting process is dynamic and bioactive, meaning it can adapt to the needs of the cells and provide instructive biochemical cues. These cues guide the NSCs to become specific types of neural cells and form connections with each other. The effectiveness of this approach was tested in a rat model of complete spinal cord injury, where the 3D bioprinted construct led to significant motor and sensory function recovery. This suggests that the precise design of cell-instructive bioinks is critical for the success of 3D bioprinted living constructs in neural regeneration.

Study Duration
12 weeks
Participants
90 female SD rats
Evidence Level
Not specified

Key Findings

  • 1
    The dynamic properties of the 3D bioprinted living fibers alleviate mechanical confinement on NSCs, enhancing their mechanosensing, spreading, migration, and matrix remodeling.
  • 2
    The inclusion of N-cadherin-mimicking and BDNF-mimicking peptides enhances cells' ability to sense and respond to mechanical and neurotrophic cues.
  • 3
    The 3D bioprinted construct facilitates mechanotransduction-assisted self-organization into a functional substitute with a developed neural network, achieving remarkable motor and sensory function recovery in SCI rats.

Research Summary

This study developed a 3D bioprinted dynamic living construct that modulates encapsulated NSCs to self-organize into a functional neural network for spinal cord injury repair. The ECM-mimicking bioink, featuring reversible Schiff-base bonds, stable covalent bonds, and bioactive motifs, offers microscopic dynamicity, enhanced cell-adaptability, excellent bioprintability, and cell-instructive properties. In vivo results demonstrated that the 3D bioprinted construct refined the immune microenvironment, remodeled the neurotrophic niche, and reconstructed functional neural circuits, effectively promoting motor and sensory function recovery.

Practical Implications

Advanced Bioink Design

The research highlights the significance of adaptable dynamic biomechanics and instructive biochemical cues in designing functionalized bioinks, directly impacting the effectiveness of 3D bioprinted constructs in tissue regeneration.

SCI Therapeutic Strategy

The GHP@NSC construct offers a promising therapeutic strategy for SCI repair by facilitating functional development of a self-organized neural network within the 3D bioprinted construct.

Clinical Translation Potential

The developed 3D bioprinted living construct offers a potential avenue for clinical translation in treating spinal cord injuries and other neurological disorders.

Study Limitations

  • 1
    Long-term stability of the implanted construct.
  • 2
    Integration with the host tissue.
  • 3
    Potential immune responses to the implanted materials.

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