Arch Hand Microsurg.  2019 Sep;24(3):273-284. 10.12790/ahm.2019.24.3.273.

The Effect of Cryopreservation of Allograft Nerve on the Recovery of Motor Function

• Choi SS
• Park I
• Hyun JK
• Jung JU
• Kim JP

• KMID: 2456253
• DOI: http://doi.org/10.12790/ahm.2019.24.3.273

Abstract

PURPOSE
Peripheral nerve allograft can be an acceptable alternative, but it has not yet become clinically useful because of immune response to foreign tissue. With significant advances in the research and tissue engineering, various alternatives to nerve autograft including synthetic nerve conduit and decellularization have been used, but their therapeutic effects were not satisfactory. The purpose of this study was to confirm the effectiveness of cryopreservation of the allograft nerve as a useful nerve-graft substitute.
METHODS
A total of 39 Sprague-Dawley rats (recipient) and 13 Lewis rats (donor) weighing 200 g to 300 g were used in this study. Animals were randomly divided 3 groups and received ipsilateral sciatic nerve graft: autograft (group 1), allograft (group 2), and cryopreserved nerve allograft (group 3), Nerve regeneration was evaluated at sixteen weeks on the basis of the animal weight, ankle contracture angle, compound muscle action potential, isometric tetanic muscle force, wet muscle weight of the tibialis anterior muscle, and the histomorphometry.
RESULTS
Cryopreserved nerve allograft (group 3) showed superior motor recovery than allograft group (group 2), which was comparable to those of autograft (group 1).
CONCLUSION
Pretreatment of nerve allograft using cryopreservation decreased rejection caused by immune response of the donor and improved motor nerve recovery. In clinical perspective, use of a pretreated nerve allograft can be an alternative to the autograft.

Keyword

Nerve; Allograft; Autograft; Cryopreservation; Decellularizations

MeSH Terms

Action Potentials
Allografts*
Animals
Ankle
Autografts
Contracture
Cryopreservation*
Humans
Nerve Regeneration
Peripheral Nerves
Rats
Rats, Sprague-Dawley
Sciatic Nerve
Therapeutic Uses
Tissue Donors
Tissue Engineering
Transplants
Therapeutic Uses

Figure

• 

  Fig. 1. Experimental procedure.

• 

  Fig. 2. Measurement of the ankle contracture angle.

• 

  Fig. 3. Compound muscle action pot.

• 

  Fig. 4. (A) Isometric tetanic muscle force. (B) Data output from LabVIEW.

• 

  Fig. 5. Tibialis anterior muscle of nonoperative side (superior), operative side (inferior).

• 

  Fig. 6. Toluidine blue stain.

• 

  Fig. 7. Comparison of weight gain (%). *p<0.05.

• 

  Fig. 8. Comparison of the recovery rate of the ankle contracture angle compared to nonoperative side.

• 

  Fig. 9. Comparison of the rate of compound muscle action potential (CMAP) compared to nonoperative side. *p<0.05.

• 

  Fig. 10. Comparison of the rate of isometric tetanic muscle force compared to nonoperative side. *p<0.05.

• 

  Fig. 11. Comparison of the histomorphometry. *p<0.05.

• 

  Fig. 12. Comparison of the rate of the tibialis anterior muscle weight compared to nonoperative side. *p<0.05.

Reference

1.Griffin JW., Hogan MV., Chhabra AB., Deal DN. Peripheral nerve repair and reconstruction. J Bone Joint Surg Am. 2013. 95:2144–51.

2.Mackinnon SE., Doolabh VB., Novak CB., Trulock EP. Clinical outcome following nerve allograft transplantation. Plast Reconstr Surg. 2001. 107:1419–29.

3.Sahakyants T., Lee JY., Friedrich PF., Bishop AT., Shin AY. Return of motor function after repair of a 3-cm gap in a rabbit peroneal nerve: a comparison of autograft, collagen conduit, and conduit filled with collagen-GAG matrix. J Bone Joint Surg Am. 2013. 95:1952–8.

4.Isaacs J., Browne T. Overcoming short gaps in peripheral nerve repair: conduits and human acellular nerve allograft. Hand (N Y). 2014. 9:131–7.

5.Moore AM., Ray WZ., Chenard KE., Tung T., Mackinnon SE. Nerve allotransplantation as it pertains to composite tissue transplantation. Hand (N Y). 2009. 4:239–44.

6.Zhong H., Chen B., Lu S., Zhao M., Guo Y., Hou S. Nerve regeneration and functional recovery after a sciatic nerve gap is repaired by an acellular nerve allograft made through chemical extraction in canines. J Reconstr Microsurg. 2007. 23:479–87.

7.Rinker B., Vyas KS. Clinical applications of autografts, conduits, and allografts in repair of nerve defects in the hand: current guidelines. Clin Plast Surg. 2014. 41:533–50.

8.Karabekmez FE., Duymaz A., Moran SL. Early clinical outcomes with the use of decellularized nerve allograft for repair of sensory defects within the hand. Hand (N Y). 2009. 4:245–9.

9.Squintani G., Bonetti B., Paolin A, et al. Nerve regeneration across cryopreserved allografts from cadaveric donors: a novel approach for peripheral nerve reconstruction. J Neurosurg. 2013. 119:907–13.

10.Evans PJ., Mackinnon SE., Levi AD, et al. Cold preserved nerve allografts: changes in basement membrane, viability, immunogenicity, and regeneration. Muscle Nerve. 1998. 21:1507–22.

11.Marmor L. The repair of peripheral nerves by irradiated homografts. Clin Orthop Relat Res. 1964. 34:161–9.

12.Wang MS., Zeleny-Pooley M., Gold BG. Comparative dose-dependence study of FK506 and cyclosporin A on the rate of axonal regeneration in the rat sciatic nerve. J Pharmacol Exp Ther. 1997. 282:1084–93.

13.Shin RH., Friedrich PF., Crum BA., Bishop AT., Shin AY. Treatment of a segmental nerve defect in the rat with use of bioabsorbable synthetic nerve conduits: a comparison of commercially available conduits. J Bone Joint Surg Am. 2009. 91:2194–204.

14.Giusti G., Willems WF., Kremer T., Friedrich PF., Bishop AT., Shin AY. Return of motor function after segmental nerve loss in a rat model: comparison of autogenous nerve graft, collagen conduit, and processed allograft (AxoGen). J Bone Joint Surg Am. 2012. 94:410–7.

15.Brenner MJ., Lowe JB 3rd., Fox IK, et al. Effects of Schwann cells and donor antigen on long-nerve allograft regeneration. Microsurgery. 2005. 25:61–70.

16.Zalewski AA., Azzam NA., Azzam RN. The loss of re-generated host axons in nerve allografts after stopping immunosuppression with cyclosporin A is related to immune effects on allogeneic Schwann cells. Exp Neurol. 1995. 133:189–97.

17.Levi AD., Evans PJ., Mackinnon SE., Bunge RP. Cold stor-age of peripheral nerves: an in vitro assay of cell viability and function. Glia. 1994. 10:121–31.

18.Hare GM., Evans PJ., Mackinnon SE., Wade JA., Young AJ., Hay JB. Phenotypic analysis of migrant, efferent lym-phocytes after implantation of cold preserved, peripheral nerve allografts. J Neuroimmunol. 1995. 56:9–16.

19.Atchabahian A., Mackinnon SE., Hunter DA. Cold pres-ervation of nerve grafts decreases expression of ICAM-1 and class II MHC antigens. J Reconstr Microsurg. 1999. 15:307–11.

20.Rustemeyer J., Dicke U. Allografting combined with systemic FK506 produces greater functional recovery than conduit implantation in a rat model of sciatic nerve injury. J Reconstr Microsurg. 2010. 26:123–9.

21.Doolabh VB., Mackinnon SE. FK506 accelerates functional recovery following nerve grafting in a rat model. Plast Reconstr Surg. 1999. 103:1928–36.

22.Fansa H., Keilhoff G., Altmann S., Plogmeier K., Wolf G., Schneider W. The effect of the immunosuppressant FK 506 on peripheral nerve regeneration following nerve grafting. J Hand Surg Br. 1999. 24:38–42.

23.Udina E., Gold BG., Navarro X. Comparison of continuous and discontinuous FK506 administration on autograft or allograft repair of sciatic nerve resection. Muscle Nerve. 2004. 29:812–22.

24.Fox IK., Jaramillo A., Hunter DA., Rickman SR., Mohana-kumar T., Mackinnon SE. Prolonged cold-preservation of nerve allografts. Muscle Nerve. 2005. 31:59–69.

25.Fansa H., Lassner F., Kook PH., Keilhoff G., Schneider W. Cryopreservation of peripheral nerve grafts. Muscle Nerve. 2000. 23:1227–33.

26.Hundepool CA., Nijhuis TH., Kotsougiani D., Friedrich PF., Bishop AT., Shin AY. Optimizing decellularization techniques to create a new nerve allograft: an in vitro study using rodent nerve segments. Neurosurg Focus. 2017. 42:E4.

27.Deslivia MF., Lee HJ., Adikrishna A., Jeon IH. Decellularized nerves for upper limb nerve reconstruction: a system-atic review of functional outcomes. J Reconstr Microsurg. 2015. 31:660–7.

28.Sridharan R., Reilly RB., Buckley CT. Decellularized grafts with axially aligned channels for peripheral nerve regeneration. J Mech Behav Biomed Mater. 2015. 41:124–35.

29.Houschyar KS., Momeni A., Pyles MN, et al. The role of current techniques and concepts in peripheral nerve repair. Plast Surg Int. 2016. 2016:4175293.