Amniotic membrane hydrogel as novel injectable platform in combination with metformin for treatment of sciatic nerve injury

Peripheral nerve tissue engineering is a field that uses cells, growth factors and biological scaffold material to provide a nutritional and physical support in the repair of nerve injuries. The specific properties of injectable human amniotic membrane-derived hydrogel including growth factors as well as anti-inflammatory and neuroprotective agents make it an ideal tool for nerve tissue repair, and metformin may also aid in nerve regeneration. The aim of this study was to investigate the effects of hydrogel derived from amniotic membrane (AM) along with metformin (MET) administration in the repair of sciatic nerve injury in male rats. We randomly divided 60 male rats into five groups. A control and four sciatic nerve compression groups including model; hydrogel; metformin and mix which received hydrogel and metformin. The recovery rate was assessed by Sciatic Functional Index (SFI), Static Sciatic Index (SSI) and von-frey test. Conduction velocity of the sciatic nerve was measured by Electrophysiological studies, and histological evaluations were performed 14 days after injury. SFI, SSI, latency time, remyelination rate and the expression of NF-200 and S-100β improved in hydrogel group. Response to mechanical stimulus, myelin density, axonal regeneration, and myelin sheath reconstruction improved in the mix group. The gastrocnemius muscle index was significantly reduced in the experimental groups while collagen fibers increased in these groups. These findings suggest that injection of hydrogel derived from decellularized amniotic membrane into the epineurium can be promoted reconstruction of peripheral nerve injury and improved functional nerve recovery. Also, metformin administration can reinforce the therapeutic effect of the hydrogel.