Electrospun Composites of Chitosan with Cerium Oxide Nanoparticles for Wound Healing Applications: Characterization and Biocompatibility Evaluation In Vitro and In Vivo.

Cerium oxide nanoparticles (CeONPs), as part of tissue regeneration matrices, can protect cells from reactive oxygen species and oxidative stress. In addition, they can influence the properties of the scaffold, including its electrospinnability and mechanical strength. In this work, we prepared electrospun fiber mats from a chitosan and polyethylene oxide blend (CS-PEO) with the addition of ceria nanoparticles (CS-PEO-CeONP). The addition of CeONPs resulted in a smaller fiber diameter and higher swelling compared to CS-PEO fiber mats. CeONP-modified fiber mats also had a higher Young's modulus due to the reinforcing effect of the nanoparticles. Both mats had comparable adhesion and cytocompatibility to mesenchymal stem cells, which had a more rounded morphology on CS-PEO-CeONP compared to elongated cells on the CS-PEO mats. Biocompatibility in an in vivo rat model showed no acute toxicity, no septic or allergic inflammation, and no rough scar tissue formation. The degradation of both mats passed the stage of matrix swelling. CS-PEO-CeONP showed significantly slower biodegradation, with most of the matrix remaining in the tissue after 90 days. The reactive inflammation was aseptic in nature with the involvement of multinucleated foreign-body type giant cells and was significantly reduced by day 90. CeONPs induced the formation of the implant's connective tissue capsule. Thus, the introduction of CeONPs influenced the physicochemical properties and biological activity of CS-PEO nanofiber mats.

Properties of Resorbable Conduits Based on Poly(L-Lactide) Nanofibers and Chitosan Fibers for Peripheral Nerve Regeneration.

New tubular conduits have been developed for the regeneration of peripheral nerves and the repair of defects that are larger than 3 cm. The conduits consist of a combination of poly(L-lactide) nanofibers and chitosan composite fibers with chitin nanofibrils. In vitro studies were conducted to assess the biocompatibility of the conduits using human embryonic bone marrow stromal cells (FetMSCs). The studies revealed good adhesion and differentiation of the cells on the conduits just one day after cultivation. Furthermore, an in vivo study was carried out to evaluate motor-coordination disorders using the sciatic nerve functional index (SFI) assessment. The presence of chitosan monofibers and chitosan composite fibers with chitin nanofibrils in the conduit design increased the regeneration rate of the sciatic nerve, with an SFI value ranging from 76 to 83. The degree of recovery of nerve conduction was measured by the amplitude of M-response, which showed a 46% improvement. The conduit design imitates the oriented architecture of the nerve, facilitates electrical communication between the damaged nerve's ends, and promotes the direction of nerve growth, thereby increasing the regeneration rate.