Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (6): 1789-1800.doi: 10.4103/NRR.NRR-D-23-01518

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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

Carina Hromada1, 2, Patrick Heimel2, 3, 4, Markus Kerbl2, 3, 5, László Gál6 , Sylvia Nürnberger2, 3, 7, Barbara Schaedl2, 3, 4, James Ferguson2, 3, Nicole Swiadek2, 3, Xavier Monforte1, 2, Johannes C. Heinzel2, 3, 8, Antal Nógrádi6 , Andreas H. Teuschl-Woller1, 2, §, David Hercher1, 2, 3, *, §   

  1. 1 Department Life Science Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria;  2 Austrian Cluster for Tissue Regeneration, Vienna, Austria;  3 Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Vienna, Austria; 4 University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria;  5 Department of Plastic, Reconstructive and Aesthetic Surgery, Landesklinikum Wiener Neustadt, 2700 Wiener Neustadt, Austria;  6 Department of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary;  7 Medical University of Vienna, Department of Orthopedics and Trauma Surgery, Devision of Trauma Surgery, Vienna, Austria;  8 Department of Hand-, Plastic, Reconstructive and Burn Surgery, BG Unfallklinik Tuebingen, University of Tuebingen, Tuebingen, Germany
  • Online:2025-06-15 Published:2024-11-12
  • Contact: David Hercher, PhD, david.hercher@trauma.lbg.ac.at.
  • Supported by:
    This work was supported by the Lorenz Böhler Fonds, #2/19 (obtained by the Neuroregeneration Group, Ludwig Boltzmann Institute for Traumatology) and the City of Vienna project ImmunTissue, MA23#30-11 (obtained by the Department Life Science Engineering, University of Applied Sciences Technikum Wien).

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Abstract: Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits (tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects (typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk+ tNGCs with the tubes without holes (silk– tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk+ tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk+ group was found compared with autologous nerve transplants and silk– , accompanied by improved axon regeneration at the distal coaptation point compared with the silk– tNGCs at 7 weeks postoperatively. In the 15-mm (critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk+ tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk+ tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.

Key words: axon regeneration, blood vessel, functional recovery, macroporous, nerve lesion, peripheral nerve repair, sciatic nerve, silkbased nerve guidance conduit, vascularization