Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

Abstract

A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone.

Nerve Repair Using Decellularized Nerve Grafts in Rat Models. A Review of the Literature

“…In the autograft group, Wang et al (2017b) reported a SFI markedly lower than average at all three time points, with a value of -48 at weeks 2–5, -45 at weeks 6–9, and -40 at weeks 10–15. Zhang et al (2014) reported a much higher SFI and muscle wet weight ratio, with an increase from –32.3 after 2 weeks to –18.7 after 8 weeks and a muscle weight ratio of 89.5% at 8 weeks after surgery. Also, Xiang et al (2017) reported a SFI value higher (-17) compared to the autograft average at 12 weeks.…”

“…There are three main decellularization protocols for the creation of a functional graft: the one described by Sondell et al (1998) and Hudson et al (2004) , and the combined Hudson protocol added with chondroitinase ABC by Krekoski et al (2001) . SP was used in 33% of the studies ( Jia et al, 2012 , 2017 ; Wang et al, 2012 ; Zhang et al, 2014 ; Zheng et al, 2014 ; Zhou et al, 2014 ; Zhu and Weihua, 2014 ; Huang et al, 2015 ; Garcia-Pérez et al, 2017 ; Zhu et al, 2015 , 2017 ); HP was used in 24% ( Saheb-Al-Zamani et al, 2013 ; Gao et al, 2014a ; Hoben et al, 2015 ; Marquardt et al, 2015 ; Kim et al, 2016 ; Tajdaran et al, 2016 ; Yan et al, 2016 ; Cai et al, 2017 ), and a combined HP was used in 12% ( Whitlock et al, 2009 ; Vasudevan et al, 2014 ; Wood et al, 2014 ; Jiang et al, 2016 ). Other studies (6%) used a FTP with or without the addition of chondroitinase ABC as introduced by Krekoski et al (2001 ; Godinho et al, 2013 ; Wang H. et al, 2016 ).…”

“…The electrophysiological parameters (CV, WA, and LP) reported in Figure 2 were compared among studies, obtaining data for the sham controls and AG 2–5 weeks from one study ( Wang H. et al, 2016 ), for AG 6–9 weeks from four studies ( Jia et al, 2012 ; Zhang et al, 2014 ; Wang H. et al, 2016 ; Jia et al, 2017 ), and for AG 10–15 weeks from six studies ( Liu et al, 2011 ; Zhang and Lv, 2013 ; Zheng et al, 2014 ; Huang et al, 2015 ; Jiang et al, 2015 ; Wang H. et al, 2016 ). The low amount of recorded data did not permit to statistically analyze the differences in the results.…”

“…In the case of histomorphometric analyses, several authors reported evaluable data to be analyzed through non-parametric statistical tests, as reported in Figure 3 . Indeed, for the sham controls, five authors reported quantitative parameters ( Jia et al, 2012 , 2017 ; Zhang et al, 2014 ; Wang H. et al, 2016 ; Wang et al, 2017b ). For AG at 6–9 weeks, seven records indicated values for myelin and axon morphology ( Whitlock et al, 2009 ; Jia et al, 2012 ; Zhang et al, 2014 ; Marquardt et al, 2015 ; Tajdaran et al, 2016 ; Cai et al, 2017 ; Jia et al, 2017 ), as well as, fourteen records detailed values for AG at 10–15 weeks ( Whitlock et al, 2009 ; Liu et al, 2011 ; Wang et al, 2012 , 2017b ; Godinho et al, 2013 ; Vasudevan et al, 2014 ; Wood et al, 2014 ; Zheng et al, 2014 ; Zhou et al, 2014 ; Hoben et al, 2015 ; Huang et al, 2015 ; Jiang et al, 2015 ; Kim et al, 2016 ; Wang H. et al, 2016 ).…”

“…In the studies that used the classic decellularization protocols (SP, HP, NP, and FTP), the majority (75.8%) used grafts ranging in length from 10 to 15 mm ( Whitlock et al, 2009 ; Liu et al, 2011 ; Nagao et al, 2011 ; Jia et al, 2012 , 2017 ; Godinho et al, 2013 ; Zhang and Lv, 2013 ; Gao et al, 2014a ; Wood et al, 2014 ; Zhang et al, 2014 ; Zheng et al, 2014 ; Zhou et al, 2014 ; Huang et al, 2015 ; Wakimura et al, 2015 ; Zhu et al, 2015 ; Jiang et al, 2016 ; Kim et al, 2016 ; Kusaba et al, 2016 ; Tajdaran et al, 2016 ; Wang W. et al, 2016 ; Wang et al, 2017b ; Cai et al, 2017 ; Garcia-Pérez et al, 2017 ; Xiang et al, 2017 ). Among the others, only Zhu and Weihua (2014) used a shorter graft (6 mm), while others still used longer grafts: a 20-mm graft in five studies ( Wang et al, 2012 ; Saheb-Al-Zamani et al, 2013 ; Hoben et al, 2015 ; Yan et al, 2016 ; Wang H. et al, 2016 ); a 30-mm graft in two ( Whitlock et al, 2009 ; Marquardt et al, 2015 ); a 35–40 mm graft in two ( Saheb-Al-Zamani et al, 2013 ; Vasudevan et al, 2014 ), and a 60- mm graft in one study ( Saheb-Al-Zamani et al, 2013 ).…”