The application of hollow nerve conduits in the repair of peripheral nerve defects is effected by inferior recovery, and nerve extension is hampered by the scar tissue generated during the repair process. In this study, the filler in hollow nerve conduit, chitosan/oxidized hydroxyethyl cellulose (CS/OHEC) hydrogel loaded asiaticoside liposome and the conductive reduced graphene oxide (rGO) were developed and used to reform the microenvironment for peripheral nerve regeneration. The physiochemical properties of CS/OHEC/rGO/asiaticoside liposome hydrogel were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and compressive modulus, porosity, swelling ratio, degradation and conductivity. In addition, the asiaticoside release profiles in vitro were investigated. The hydrogel had a continuous porous network structure with pore size distribution in the range of 50–250 μm. The majority of the hydrogels had porosities above 70%, and a compressive modulus of 0.45 MPa. The weight loss rate of hydrogel reached 76.14 ± 4.45% within 8 weeks. The conductivity of the hydrogel was 5.27 ± 0.42 × 10 − 4 S/cm. The hydrogel was non-toxic and suitable for adhesion and proliferation of nerve cells in vitro. In addition, the application of electrical stimulation after the addition of rGO can promote the differentiation and proliferation of nerve cells, accelerating nerve regeneration. The asiaticoside released from the hydrogel had a significant inhibitory effect on the growth and collagen secretion of fibroblasts, eliminating scars for regenerative nerves, which can promote the function recovery of defected peripheral nerve. Together, these positive results indicate that the hydrogel would be a promising candidate for peripheral nerve regeneration.
Asiaticoside is a natural compound possessing diverse pharmacological effects with great potential for clinical use. However, the low solubility and oil-water partition coefficient of asiaticoside lead to reduced effect and limited application. This study aims to construct a porous microsphere for the sustained release of asiaticoside to improve its absorption and enhance the therapeutic effects. Parameters of the formulations, including the drug to polymer ratio , solvent amounts of the inner and external phases, the stirring speed for preparation, and the drug entrapment efficiency were investigated and optimized. Particle size, morphology, pores structure, and Fourier transform infrared spectrum of the microsphere were characterized. The release kinetics and cellular uptake profiles of the asiaticoside-microspheres were examined. The therapeutic effects of asiaticoside-microspheres on wound healing and skin appendages regeneration were investigated in vitro & in vivo . Results showed that the optimized asiaticoside-microspheres possess spherical spongy structure with cylindrical holes. Asiaticoside can be loaded in the microsphere with high efficiency and released with sustained manner. The cellular uptake of asiaticoside from the microspheres was increased with 9.1 folds higher than that of free solution. Asiaticoside-microspheres expressed the strong promotion in the proliferation, migration of keratinocytes and wound scratching healing in vitro . More importantly, they significantly accelerated the re-epithelization, collagen synthesis and pro-angiogenesis in the rat full-skin wound healing. Porous microsphere was shown a novel carrier for the sustained delivery of poorly soluble asiaticoside, with absorption and therapeutic effects improved. Asiaticoside-microsphere is a promising topical preparation with excellent regenerative effects for the wound therapy.
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