The Emergence of Novel Grafting Strategies for Peripheral Nerves

?The field of peripheral nerve repair has evolved significantly over the years, incorporating both traditional surgical techniques and innovative approaches from tissue engineering and regenerative medicine. Autografts, particularly nerve autografts, have been a cornerstone in managing peripheral nerve injuries, especially those occurring in the upper extremities. The efficacy of nerve autografts in restoring function has been well-documented, with outcomes being most favourable when the procedure is performed without tension and promptly following the injury, as highlighted in studies by Matejcík in 2002 and Kalomiri in 1994. These autografts, however, are not devoid of challenges. Donor site morbidity and the limited availability of suitable donor nerves are significant concerns, as discussed by Pabari in 2014 and Sinis in 2009, which can complicate the decision-making process in clinical practice.

Muscle autografts present an alternative modality, as evidenced by Norris in 1988, demonstrating their successful application in the repair of digital nerves. This suggests a broader spectrum of autologous tissue sources for nerve repair, albeit with inherent limitations similar to those of nerve autografts, including the availability of donor tissue and potential donor site morbidity.

In scenarios where autografts are not viable, due to the extent of the injury or limitations in donor tissue, nerve allograft transplantation emerges as a potential solution. Siemionow's 2007 research into allograft transplantation underscores the expanding therapeutic options for nerve repair. However, this approach raises considerations related to immunogenicity and the need for immunosuppression, which can limit its applicability.

The advent of tissue engineering techniques has introduced novel solutions to the challenges of peripheral nerve repair. The development and application of nerve conduits, as discussed by Carriel in 2014, represent a promising direction. These conduits aim to provide a supportive framework for nerve regeneration, potentially overcoming the limitations of autografts and allografts. However, optimising these bioengineered solutions requires further research, particularly in terms of material biocompatibility, degradation rates, and the integration of growth factors or stem cells to enhance regenerative outcomes.

Evidence synthesis

The synthesis of the provided insights highlights the current landscape and challenges in peripheral nerve repair. Artificial nerve conduits have been identified as a viable alternative to traditional autologous nerve grafting, particularly for repairing short peripheral nerve defects. Despite their emergence, artificial conduits have not yet achieved clinical outcomes that surpass those of autologous nerve grafts. This limitation underscores the importance of a comprehensive understanding of the biological processes underlying peripheral nerve regeneration. Such knowledge is crucial for developing nerve conduits that closely mimic the properties of autologous nerve grafts, thereby enhancing their effectiveness in clinical applications.

Current literature reviews and research summaries in this area have focused on assessing the available nerve conduits, identifying the factors that influence their efficacy, and pinpointing directions for future research that could address existing gaps. Notably, outcomes have been shown to be more favourable in upper limb reconstructions, with the timing between the injury and surgery being a critical factor for success. This is especially true for younger patients, where a shorter delay in treatment correlates with improved recovery.

Innovative approaches have demonstrated significant potential, such as using coaxial autografts from frozen and thawed skeletal muscle for repairing injured digital nerves. These methods have yielded excellent recovery levels and may offer considerable advantages over traditional nerve grafts or cable grafts, especially in the context of large peripheral nerve injuries.

The review underscores the complexity of managing nerve defects surgically, prompting the exploration of alternatives to autologous nerve transplantation. This exploration is driven by the side effects associated with traditional grafting methods. Tubulisation techniques, leveraging various materials, emerge as a promising direction, focusing on balancing the benefits and drawbacks of different conduit materials.

The relationship between patient age, the timing of grafting following an injury, and the outcomes of nerve grafting in the upper extremity has been highlighted. Specifically, grafting without tension is emphasised as superior to neurorrhaphy under tension, as it facilitates better axonal growth and nerve recovery.

Limitations in the availability of autologous nerves for grafting, especially for large nerve defects, necessitate the consideration of alternatives such as cadaveric nerve allografts. While these allografts offer an unlimited source of graft material, the challenge of immune rejection remains, necessitating strategies to minimise or prevent rejection while promoting nerve regeneration.

The review concludes with an overview of the surgical techniques available for treating peripheral nerve defects, including direct repair, autografting, allografting, decellularized allografts, and the use of nerve conduits. Among these, nerve conduits, particularly those from the novel peripheral nerve tissue engineering generation, show promising experimental results. This indicates a continued need for innovation and research to develop optimal treatment methods to enhance patient outcomes following peripheral nerve injuries.

List of the most common nerve autografts used in peripheral nerve repair:

• Sural Nerve: This sensory nerve running along the outside of the calf is the most frequently used donor nerve due to its length and minimal resulting sensory loss after harvesting.
• Medial Antebrachial Cutaneous Nerve: A sensory nerve from the inner forearm, it offers a good option for smaller nerve gaps.
• Lateral Antebrachial Cutaneous Nerve: Another sensory nerve from the forearm, providing a similar alternative to the medial antebrachial cutaneous nerve.
• Superficial Radial Nerve: A sensory nerve on the back of the forearm and hand, used less commonly due to the potential for some sensory loss in the hand.
• Posterior Interosseous Nerve (PIN): Primarily a motor nerve in the forearm, its terminal sensory branches can be used as autografts. However, harvesting PIN branches comes with a small risk of motor weakness.

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Important Considerations:

• The choice of donor nerve depends on the size of the nerve gap, the surgeon's preference, and the need to minimise donor site morbidity for the patient.
• Nerve autografts are generally the preferred option for peripheral nerve repair, but limitations like donor site morbidity and nerve availability must be carefully weighed.

This technique offers several advantages:

• Superior regeneration:?Autografts provide a biological scaffold containing Schwann cells, promoting nerve fibre regrowth and functional recovery [1, 2].
• Minimal immunologic rejection:?Tissue harvested from the patient minimises the risk of immunological reactions [2].
• Good functional outcomes:?Studies have shown positive results with nerve autografts, primarily when performed without tension and shortly after injury [1, 2].

However, surgeons must also consider the limitations of nerve autografts:

• Donor site morbidity:?Harvesting a nerve can cause numbness or weakness in the donor area [3, 4].
• Limited donor availability:?The size and location of the injured nerve determine the available donor sites, potentially restricting graft size [3, 4].

Considering Alternatives

When nerve autografts are not ideal, surgeons can explore alternative options:

• Muscle grafts:?Muscle grafts have succeeded for digital nerve repair [5].
• Nerve allografts:?Cadaveric nerve grafts offer an alternative source of tissue, but carry a risk of rejection [6].
• Nerve conduits:?These engineered tubes provide a guidance structure for nerve regeneration. While promising, further research is needed to optimize their effectiveness [7].

Conclusion

Nerve autografts remain the preferred choice for repairing peripheral nerve injuries in the upper extremities due to their excellent support for nerve regeneration and minimal immunological issues. However, donor site limitations and morbidity necessitate careful consideration of all options. Surgeons should be familiar with alternative techniques like muscle grafts, nerve allografts, and nerve conduits to create a personalised treatment plan for each patient.

References

Carriel, V. ictor, Alaminos, M., Garz\’ on, I., Campos, A., & Cornelissen, M. (2014). Tissue engineering of the peripheral nervous system. Expert Review of Neurotherapeutics, 14(3), 301–318.

Kalomiri, D. E., Soucacos, P. N., & Beris, A. E. (1994). Nerve grafting in peripheral nerve microsurgery of the upper extremity. Microsurgery, 15(7), 506–511.

Matej??\’ k, V. (2002). Peripheral nerve reconstruction by autograft. Injury, 33(7), 627–631.

N. Sinis, A. Kraus, N. Papagiannoulis, F. Werdin, J. Schittenhelm, R. Meyermann, M. Haerle, S. Geuna, & H. Schaller. (2009). Concepts and developments in peripheral nerve surgery. Clinical Neuropathology.

Norris, R., Glasby, M., Gattuso, J., & Bowden, R. (1988). Peripheral nerve repair in humans using muscle autografts. A new technique. The Journal of Bone and Joint Surgery. British Volume, 70-B(4), 530–533.

Pabari, A., Lloyd-Hughes, H., Seifalian, A. M., & Mosahebi, A. (2014). Nerve Conduits for Peripheral Nerve Surgery. Plastic & Reconstructive Surgery, 133(6), 1420–1430.

Siemionow, M., & Sonmez, E. (2007). Nerve Allograft Transplantation: A Review. Journal of Reconstructive Microsurgery, 23(8), 511–520.

Trehan, S. K., Model, Z., & Lee, S. K. (2016). Nerve Repair and Nerve Grafting. Hand Clinics, 32(2), 119–125.

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