Cold preserved nerve allografts: Changes in basement membrane, viability, immunogenicity, and regeneration

Evans, Peter; Mackinnon, Susan E.; Levi, Allan D.; Wade, J. A.; Hunter, Daniel A.; Nakao, Yasushi; Midha, Rajiv

doi:10.1002/(sici)1097-4598(199811)21:11<1507::aid-mus21>3.0.co;2-w

Cited by 113 publications

(92 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The drawback however was the long processing times (approximately seven weeks) as well as poor mechanical properties of the decellularised graft (Evans et al, 1998). …”

Section: Resultsmentioning

confidence: 99%

Decellularisation and histological characterisation of porcine peripheral nerves

Žilić

Wilshaw

Haycock

2016

Biotech & Bioengineering

View full text Add to dashboard Cite

Peripheral nerve injuries affect a large proportion of the global population, often causing significant morbidity and loss of function. Current treatment strategies include the use of implantable nerve guide conduits (NGC's) to direct regenerating axons between the proximal and distal ends of the nerve gap. However, NGC's are limited in their effectiveness at promoting regeneration Current NGCs are not suitable as substrates for supporting either neuronal or Schwann cell growth, as they lack an architecture similar to that of the native extracellular matrix (ECM) of the nerve. The aim of this study was to create an acellular porcine peripheral nerve using a novel decellularisation protocol, in order to eliminate the immunogenic cellular components of the tissue, while preserving the three‐dimensional histoarchitecture and ECM components. Porcine peripheral nerve (sciatic branches were decellularised using a low concentration (0.1%; w/v) sodium dodecyl sulphate in conjunction with hypotonic buffers and protease inhibitors, and then sterilised using 0.1% (v/v) peracetic acid. Quantitative and qualitative analysis revealed a ≥95% (w/w) reduction in DNA content as well as preservation of the nerve fascicles and connective tissue. Acellular nerves were shown to have retained key ECM components such as collagen, laminin and fibronectin. Slow strain rate to failure testing demonstrated the biomechanical properties of acellular nerves to be comparable to fresh controls. In conclusion, we report the production of a biocompatible, biomechanically functional acellular scaffold, which may have use in peripheral nerve repair. Biotechnol. Bioeng. 2016;113: 2041–2053. © 2016 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals, Inc.

show abstract

“…The drawback however was the long processing times (approximately seven weeks) as well as poor mechanical properties of the decellularised graft (Evans et al, 1998). …”

Section: Resultsmentioning

confidence: 99%

Decellularisation and histological characterisation of porcine peripheral nerves

Žilić

Wilshaw

Haycock

2016

Biotech & Bioengineering

View full text Add to dashboard Cite

show abstract

“…Once harvested, tibial nerves were transferred into the cold preservation solution and vials were sealed, labelled and stored at 4°C (48,49). Seven days later, mice in groups II, IV or VI received these tibial nerve isografts pretreated with cold preservation (15,31).…”

Section: Cold Preservationmentioning

confidence: 99%

“…These investigators have suggested that the release of MAG is dependent on the duration of nerve segment predegeneration and the presence of myelin debris. Indeed, cold preservation of nerve grafts ensures a finite period of nerve graft predegeneration (30,31), and both FK506 and cold preservation significantly decrease myelin debris (15,16).…”

mentioning

confidence: 99%

The effects of cold preservation and subimmunosuppressive doses of FK506 on axonal regeneration in murine peripheral nerve isografts

Myckatyn

Hunter

Mackinnon

2003

Canadian Journal of Plastic Surgery

View full text Add to dashboard Cite

“…These contributions included the following: 1) isolation of the SCs from adult, human nerve tissue; 2) ability to induce division and growth of the cells once isolated with the use of particular mitogens (heregulin b1/forskolin), proving that once manipulated and grown in culture the cells could still perform their basic function of promoting axon regeneration and producing myelin; and 3) confirming the safety of these cells and making sure that they did not produce tumorous growths in vivo. 10,14,15,19,21,23,24,30,31 After this foundation was laid, several studies have shown the ability of SCs to enhance axonal regeneration and improve functional recovery in peripheral nerve injury in mice, rats, and nonhuman primates. 3,20,24,25,34 In this report we present 2 long-segment (7.5-and 5-cm) sciatic nerve injuries where SCs were combined with an autologous nerve construct.…”

mentioning

confidence: 99%

First human experience with autologous Schwann cells to supplement sciatic nerve repair: report of 2 cases with long-term follow-up

Gersey

Burks

Anderson

et al. 2017

FOC

View full text Add to dashboard Cite

OBJECTIVE Long-segment injuries to large peripheral nerves present a challenge to surgeons because insufficient donor tissue limits repair. Multiple supplemental approaches have been investigated, including the use of Schwann cells (SCs). The authors present the first 2 cases using autologous SCs to supplement a peripheral nerve graft repair in humans with long-term follow-up data. METHODS Two patients were enrolled in an FDA-approved trial to assess the safety of using expanded populations of autologous SCs to supplement the repair of long-segment injuries to the sciatic nerve. The mechanism of injury included a boat propeller and a gunshot wound. The SCs were obtained from both the sural nerve and damaged sciatic nerve stump. The SCs were expanded and purified in culture by using heregulin β1 and forskolin. Repair was performed with sural nerve grafts, SCs in suspension, and a Duragen graft to house the construct. Follow-up was 36 and 12 months for the patients in Cases 1 and 2, respectively. RESULTS The patient in Case 1 had a boat propeller injury with complete transection of both sciatic divisions at midthigh. The graft length was approximately 7.5 cm. In the postoperative period the patient regained motor function (Medical Research Council [MRC] Grade 5/5) in the tibial distribution, with partial function in peroneal distribution (MRC Grade 2/5 on dorsiflexion). Partial return of sensory function was also achieved, and neuropathic pain was completely resolved. The patient in Case 2 sustained a gunshot wound to the leg, with partial disruption of the tibial division of the sciatic nerve at the midthigh. The graft length was 5 cm. Postoperatively the patient regained complete motor function of the tibial nerve, with partial return of sensation. Long-term follow-up with both MRI and ultrasound demonstrated nerve graft continuity and the absence of tumor formation at the repair site. CONCLUSIONS Presented here are the first 2 cases in which autologous SCs were used to supplement human peripheral nerve repair in long-segment injury. Both patients had significant improvement in both motor and sensory function with correlative imaging. This study demonstrates preliminary safety and efficacy of SC transplantation for peripheral nerve repair.

show abstract

Cold preserved nerve allografts: Changes in basement membrane, viability, immunogenicity, and regeneration

Cited by 113 publications

References 53 publications

Decellularisation and histological characterisation of porcine peripheral nerves

Decellularisation and histological characterisation of porcine peripheral nerves

The effects of cold preservation and subimmunosuppressive doses of FK506 on axonal regeneration in murine peripheral nerve isografts

First human experience with autologous Schwann cells to supplement sciatic nerve repair: report of 2 cases with long-term follow-up

Contact Info

Product

Resources

About