Nerve capping techniques have been introduced as a promising treatment modality for the treatment of painful neuroma with varied outcomes; however, its exact mechanism is still unknown. RhoA is one of the members of the RAS superfamily of GTPases that operate as molecular switches and plays an important role in peripheral nerve regeneration. Our aim was to investigate the structural and morphologic mechanisms by which the nerve capping technique prevents the formation of painful neuromas after neuroectomy. We also hoped to provide a theoretical basis for this treatment approach. An aligned nanofiber conduit was used for the capping procedure and the sciatic nerve of Sprague-Dawley rats was selected as the animal model. Behavioral analysis, extent of neuroma formation, histological assessment, expressions of pain markers of substance P and c-fos, molecular biological changes as well as ultrastructural features were investigated and compared with the findings in a no-capping control group. The formation of traumatic neuromas was significantly inhibited in the capping group with relatively “normal” structural and morphological features and no occurrence of autotomy and significantly lower expression of pain markers compared to the no-capping group. The gene expression of RhoA was consistently in a higher level in the capping group within 8 weeks after surgery. This study shows that capping technique will alter the regeneration state of transected nerves and reduce painful neuroma formation, indicating a promising approach for the treatment of painful neuroma. The initiation of the “regenerative brake” induced by structural as well as morphological improvements in the severed nerve is theorized to be most likely a key mechanism for the capping technique in the prevention of painful neuroma formation.

Our findings indicate that the aligned nanofiber conduit is a promising biomaterial for the nerve capping technique, and new treatment strategies using aligned nanofiber conduits may be developed for the management of painful amputated neuromas.

ObjectiveTo evaluate the effect of hemodynamic remodeling on the survival status of the arterialized venous flaps (AVFs) and investigate the mechanism of this procedure.Materials and MethodsTwo 7 x 9 cm skin flaps in each rabbit (n=36) were designed symmetrically in the abdomen. The thoracoepigastric pedicle and one femoral artery were used as vascular sources. Four groups were included: Composite skin grafts group and arterial perfusion group were designed in one rabbit; AVF group and hemodynamic remodeling group by ligation of the thoracoepigastric vein in the middle were outlined in another rabbit. Flap viability, status of vascular perfusion and microvasculature, levels of epidermal metabolite and water content in each group were assessed.ResultsHighly congested veins and simple trunk veins were found using angiography in the AVF group; while a fairly uniform staining and plenty of small vessels were observed in the hemodynamic remodeling group. The metabolite levels of the remodeling group are comparable with those in the arterial perfusion group. There was no statistically significant difference in the percentage of flap survival between the arterial perfusion group and hemodynamic remodeling group; however, significant difference was seen between the AVF group and the hemodynamic remodeling group.ConclusionsUnder the integrated perfusion mode, the AVFs are in an over-perfusion and non-physiological hemodynamic state, resulting in unreliability and unpredictability in flap survival; under the separated perfusion mode produced by remodeling, a physiological-like circulation will be created and therefore, better flap survival can be expected.