In Situ Fabrication of Nerve Growth Factor Encapsulated Chitosan Nanoparticles in Oxidized Bacterial Nanocellulose for Rat Sciatic Nerve Regeneration

Abstract

Autograft is currently the gold standard in the clinical treatment of peripheral nerve injury (PNI), which, however, is limited by the availability of a donor nerve and secondary injuries. Nerve guidance conduits (NGC) provide a suitable microenvironment to promote the regeneration of injured nerves, which could be the substitutes for autografts. In this study, nerve growth factor (NGF) encapsulated chitosan nanoparticles (CSNPs) were first constructed in situ in an oxidized bacterial cellulose (OBC) conduit using the ion gel method after the introduction of a CS/NGF solution under pressure to enable a sustainable release of NGF. A novel NGF@CSNPs/OBC nanocomposite with antibacterial activity, biodegradability, and porous microstructure was successfully developed. In vitro experiments showed that the nanocomposite promoted the adhesion and proliferation of Schwann cells. When the nanocomposite was applied as NGC to repair the sciatic nerve defect of rats, a successful repair of the 10 mm nerve defect was observed after 4 weeks. At week 9, the diameter, morphology, histology, and functional recovery of the regenerated nerve was comparable to the autografts, indicating that the NGC effectively promoted the regeneration and function recovery of the nerve. In summary, the NGF@CSNPs/OBC as a novel NGC provides great potential in the treatment of PNI.

Nanocellulosics in Transient Technology

“…124 Recent years have seen advancements in nerve tissue engineering, and various methods are emerging such as nerve guide conduit (NGC), which mitigates the incursion of scar tissue, and offers an alternative to autologous transplants. 125 Materials employed in NGCs are required to meet basic safety regulations and demonstrate efficiency. Moreover, requirements such as biocompatibility, biodegradability, mechanical robustness, and so on, are critical for repairing peripheral nerve injury (PNI).…”

“…Recent years have seen advancements in nerve tissue engineering, and various methods are emerging such as nerve guide conduit (NGC), which mitigates the incursion of scar tissue, and offers an alternative to autologous transplants . Materials employed in NGCs are required to meet basic safety regulations and demonstrate efficiency.…”

“…Materials employed in NGCs are required to meet basic safety regulations and demonstrate efficiency. Moreover, requirements such as biocompatibility, biodegradability, mechanical robustness, and so on, are critical for repairing peripheral nerve injury (PNI) . Nanocellulosics such as BNCs have demonstrated capacity as green­(er) scaffolding materials of choice that meets the requirements for fabricating NGCs, compatible with living cells with no hematological and histological toxicity on living tissues .…”

“…Moreover, requirements such as biocompatibility, biodegradability, mechanical robustness, and so on, are critical for repairing peripheral nerve injury (PNI) . Nanocellulosics such as BNCs have demonstrated capacity as green­(er) scaffolding materials of choice that meets the requirements for fabricating NGCs, compatible with living cells with no hematological and histological toxicity on living tissues . By integrating chitosan nanoparticles (CSNPs) into a BNC matrix using an ionic gelation technique and with no cross-linking agents or dispersants (that is, eco-design), a composite CSNPs-BNC with impressive antibacterial activity capable of promoting the adhesion and proliferation of Schwann cells, with high biocompatibility and impressive in vitro and in vivo conclusions toward a sustainable NGC conduit is reported .…”

Applications of Chitosan in Surgical and Post-Surgical Materials

“…However, it must be kept in mind that the degree of acetylation of chitosan can influence the mechanical properties and degradation time of the conduit and, consequently, the regeneration process [78,80]. Nerve-guiding conduits could help overcome problems of donor nerve availability and secondary injuries associated with autograft, which is the treatment of choice for peripheral nerve injuries [81]. Along these lines, in 2015, the FDA approved a chitosan-based nerve conduit under the tradename Reaxon ® Nerve Guide for bridging gaps of up to 26 mm in peripheral nerves [82].…”