Controlling the Spatiotemporal Release of Nerve Growth Factor by Chitosan/Polycaprolactone Conduits for Use in Peripheral Nerve Regeneration

Abstract

Tubular polymeric structures have been recognized in the treatment of peripheral nerves as comparable to autologous grafting. The best therapeutic outcomes are obtained with conduits releasing therapeutic molecules. In this study, a new approach for the incorporation of biologically active agent-loaded microspheres into the structure of chitosan/polycaprolactone conduits was developed. The support of a polycaprolactone helix formed by 3D melt extrusion was coated with dopamine in order to adsorb nerve growth factor-loaded microspheres. The complex analysis of the influence of process factors on the coverage efficiency of polycaprolactone helix by nerve grow factor-loaded microspheres was analyzed. Thus, the PCL helix characterized with the highest adsorption of microspheres was subjected to nerve growth factor release studies, and finally incorporated into chitosan hydrogel deposit through the process of electrophoretic deposition. It was demonstrated by chemical and physical tests that the chitosan/polycaprolactone conduit meets the requirements imposed on peripheral nerve implants, particularly mimicking mechanical properties of surrounding soft tissue. Moreover, the conduit may support regrowing nerves for a prolonged period, as its structure and integrity persist upon incubation in lysozyme-contained PBS solution up to 28 days at body temperature. In vitro cytocompatibility toward mHippoE-18 embryonic hippocampal cells of the chitosan/polycaprolactone conduit was proven. Most importantly, the developed conduits stimulate axonal growth and support monocyte activation, the latter is advantageous especially at early stages of nerve regeneration. It was demonstrated that, through the described approach for controlling spatiotemporal release of nerve growth factors, these biocompatible structures adjusted to the specific peripheral nerve injury case can be manufactured.

Combining PLGA microspheres loaded with Liver X receptor agonist GW3965 with a chitosan nerve conduit can promote the healing and regeneration of the wounded sciatic nerve

“…29,30 On the other hand, there is optimism for the treatment of peripheral nerve damage with the creation of artificial nerve conduits. In recent years, researchers have focused designing nerve conduits with more complex structures, such as luminal filling techniques, 13 microgrooves, and multichannels. 31 These advancements aim to provide a conducive environment for nerve regeneration by incorporating intracavicular filling materials.…”

“…The success of nerve repair relies on creating an optimal regenerative microenvironment 12 . Within the nerve conduit, an ideal intracavitary microenvironment should encompass crucial factors for nerve regeneration, including immune response modulation, angiogenesis promotion, and signaling molecule regulation 12,13 . By providing these components, the artificial nerve conduit aims to facilitate nerve regeneration and functional recovery.…”

3D Gradient and Linearly Aligned Magnetic Microcapsules in Nerve Guidance Conduits with Remotely Spatiotemporally Controlled Release to Enhance Peripheral Nerve Repair

“…People threatened by PNI endure long-term physiological disabilities accompanied by a low quality of life. Recent trends in the development of NGCs highlight the buildup of topography nerve guidance or the spatiotemporally controlled delivery of bioactives can improve nerve regeneration. − However, currently, the challenge relies on the pathfinding of a cost-effective and simple method to create a remotely controllable 3D gradient drug delivery system in NGCs. With this as the target, this study is targeted to design a facile method that permits quick buildup of a linearly aligned and 3D gradient arrangement of microscale drug carriers in hydrogel NGCs.…”

Dextran Methacrylate Reactions with Hydroxyl Radicals and Hydrated Electrons in Water: A Kinetic Study Using Pulse Radiolysis

“…While handling and deoxygenating highly viscous, concentrated polysaccharide solutions may be difficult, it has been subsequently proved that CMC can be radiation-cross-linked or even in dilute solutions when certain conditions are met [ 20 ]. Other examples demonstrate additive-free radiation cross-linking of chitin and chitosan derivatives [ 21 , 22 ], leading to the formation of materials to be used in the field of regenerative medicine [ 23 , 24 , 25 , 26 ].…”