Peripheral nerve injuries (PNIs) are among the most relevant problems in modern neurosurgery and traumatology. Damage to peripheral nerves (PNs) is accompanied by the development of motor, sensory, and trophic disorders, which significantly impair patients’ quality of life and may result in prolonged or complete loss of work capacity. The “gold standard” for the treatment of PNIs is autologous nerve grafting; however, its use is limited by the shortage of donor material, surgical invasiveness, and the development of complications at the donor site.
Natural and synthetic biodegradable polymers, including chitosan, collagen, and alginate, are used for the fabrication of NCs, as they provide favorable conditions for cell proliferation and migration. A promising approach is the development of electrically conductive tissue-engineered conduits using polymer matrices and nanomaterials, in particular fullerene C60 and zinc oxide (ZnO) nanoparticles (NPs). The present dissertation is devoted to the investigation of the efficacy of novel electrically conductive NCs based on polymer matrices and nanomaterials for peripheral nerve regeneration.
To achieve the stated objective, composite materials were synthesized and their physicochemical characteristics were investigated at the Bionanocomposite Research Laboratory of Sumy State University. The samples were divided into groups according to their composition: Alg/Gel/PANI (a biopolymer matrix composed of alginate (Alg) and gelatin (Gel), incorporating polyaniline (PANI)); ZnO/Alg/Gel/PANI (an alginate-gelatin biopolymer matrix incorporating polyaniline (PANI) and zinc oxide (ZnO) nanoparticles); and C60/Alg/Gel/PANI (an alginate-gelatin biopolymer matrix incorporating polyaniline (PANI) and fullerene C60 nanoparticles). Experimental animal studies were performed using an in vivo rat model, with six animals for each type of conduit during two study periods—10 days and 15 weeks—to investigate the effects of inorganic ZnO nanoparticles and fullerene C60 on the composition of electrically conductive conduits in PNI and the mechanisms underlying nerve regeneration.
Modification of the alginate-gelatin matrix with ZnO nanoparticles, fullerene C60, and polyaniline (PANI) substantially affected its structural, mechanical, and functional characteristics. The NCs exhibited a highly porous microarchitecture with pore sizes ranging from 27 to 130 μm, a microscale-rough surface, adequate hydrophilicity, structural stability, and the ability to provide prolonged diffusion and retention of biologically active substances.
The results of the functional study demonstrated that all types of NCs—Alg/Gel/PANI, C60/Alg/Gel/PANI, and ZnO/Alg/Gel/PANI—provided gradual recovery of sciatic nerve (SN) function following injury. At the early stage (day 10), all groups demonstrated marked limb paresis and moderate functional recovery, with SFI values ranging from 49.6 to 56.6, without statistically significant differences between the groups. After 15 weeks, animals in all groups showed substantial improvement in motor coordination, normalization of gait, and recovery of limb function toward the preoperative level.
The architectural characteristics of SN tissue following implantation of different types of NCs were investigated. The type of conduit substantially influenced the pattern of SN regeneration and the severity of degenerative and inflammatory changes. Regenerative processes were observed in all groups, including macrophage activation, clearance of myelin degradation products from the endoneurium, and formation of Bands of Büngner, which guide the growth of regenerating axons.
Ultrastructural examination demonstrated that the pattern of peripheral nerve regeneration was substantially dependent on the type of implanted NC. In the Alg/Gel/PANI group, pronounced degenerative and dystrophic changes predominated, accompanied by hyperactive collagen formation and the development of a massive connective tissue scar. The C60/Alg/Gel/PANI NC provided the most favorable conditions for neural tissue regeneration, characterized by moderate degenerative changes, preservation of axoplasmic structure, and a substantial number of newly formed unmyelinated nerve fibers. In the ZnO/Alg/Gel/PANI group, signs of incomplete myelination, thinning of the myelin sheaths, and partial vacuolization of axoplasmic mitochondria were observed.
The scientifically substantiated findings expand current knowledge regarding the effects of nanomodified electrically conductive biomaterials on peripheral nerve regeneration and provide further insight into the relationship between NC structure, their physicochemical properties, and the effectiveness of neuroregeneration. The obtained results may be used in the development of novel biodegradable implants for reconstructive neurosurgery and regenerative medicine.
