3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats

Stem Cell Research & Therapy, 2021 · DOI: https://doi.org/10.1186/s13287-021-02315-8 · Published: June 8, 2021

Regenerative Medicine Neurology Biomedical

Simple Explanation

Peripheral nerve injuries are a significant clinical problem. This study explores a novel approach to enhance nerve regeneration using 3D-printed nerve guidance conduits (NGCs). These conduits are combined with canine adipose-tissue-derived mesenchymal stromal cells (AdMSCs) to promote nerve repair after sciatic nerve injury in rats. The researchers fabricated 3D-printed polycaprolactone (PCL)-NGCs and populated them with canine AdMSCs embedded in a heterologous fibrin biopolymer. The multi-functionalized NGCs were then implanted into rats with a 12-mm sciatic nerve gap. The study compared the effectiveness of these multi-functionalized NGCs against autografts and empty PCL-NGCs. The results showed that the multi-functionalized NGCs improved functional motor and electrophysiological recovery compared to empty PCL-NGCs, indicating enhanced nerve regeneration. This approach supports a trophic microenvironment, fostering a pro-regenerative state after critical sciatic nerve injury.

Study Duration

12 weeks

Participants

Female Wistar rats (Rattus novergicus) with weights in the range of 200–300 g

Evidence Level

Not specified

Key Findings

1
Nerve guidance conduits multi-functionalized with canine AdMSCs improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks.
2
Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group.
3
Canine AdMSCs embedded in HFB survived for 30 days after transplantation into the NGC and were co-localized with BDNF and GDNF.

Research Summary

This study investigates the use of 3D-printed nerve guidance conduits (NGCs) multi-functionalized with canine adipose-tissue-derived mesenchymal stromal cells (AdMSCs) embedded in heterologous fibrin biopolymer (HFB) to promote neuroregeneration after sciatic nerve injury in rats. The multi-functionalized NGCs improved functional motor and electrophysiological recovery compared to empty PCL-NGCs, demonstrating a shift towards a pro-regenerative state mediated by neurotrophic factors. The approach supports the trophic microenvironment, leading to enhanced nerve regeneration and functional recovery, suggesting its potential as a therapeutic strategy for peripheral nerve injuries.

Practical Implications

Therapeutic Potential

The multi-functionalized NGCs could serve as a promising therapeutic approach for treating peripheral nerve injuries, offering an alternative to autografts.

Clinical Translation

The use of canine AdMSCs and 3D-printed NGCs demonstrates a translational potential for clinical applications in both veterinary and human medicine.

Customizable Scaffolds

3D printing allows for the creation of customizable nerve guidance conduits, tailored to specific injury sizes and anatomical requirements, enhancing treatment efficacy.

Study Limitations

1
The results were not significantly different than those obtained using autografts.
2
Further studies are necessary to overcome the autograft technique analyzing several geometric parameters with 3D printing.
3
The study focuses on a specific nerve injury model in rats, limiting the generalizability of the findings to other types of nerve injuries or species.

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