Chitosan Tubes Prefilled with Aligned Fibrin Nanofiber Hydrogel Enhance Facial Nerve Regeneration in Rabbits

Abstract

Facial nerves are fragile and easily injured, for example, by traffic accidents or operations. Facial nerve injury drastically reduces the quality of life in affected patients, and its treatment presents clinical challenges. A promising therapeutic strategy includes nerve conduits with appropriate fillers capable of guiding nerve regeneration. In this study, a three-dimensional hierarchically aligned fibrin nanofiber hydrogel (AFG) assembled via electrospinning and molecular self-assembly was first used to mimic the architecture of the native fibrin cable, which is similar to the nerve extracellular matrix (ECM). AFG as a substrate in chitosan tubes (CST) was used to bridge a 7 mm-long gap in a rabbit buccal branch facial nerve defect model. The results showed that AFG and CST showed good compatibility to support the adhesion, activity, and proliferation of Schwann cells (SCs). Further morphological, histological, and functional analyses demonstrated that the regenerative outcome of AFG-prefilled CST was close to that of autologous nerve grafts and superior to that of CST alone or CSTs prefilled with random fibrin nanofiber hydrogel (RFG), which indicated that AFG-prefilled CST markedly improved axonal regeneration with enhanced remyelination and functional recovery, thus showing great potential for clinical application for facial nerve regeneration treatments.

Chitosan Tubes Inoculated with Dental Pulp Stem Cells and Stem Cell Factor Enhance Facial Nerve-Vascularized Regeneration in Rabbits

“…Furthermore, tensile tests of chitosan tubes were carried out, and the representative diagrams are shown in Figure 6 E. The stress of four samples was between 7 and 9 MPa, which indicated that the stress of chitosan tubes was relatively stable and the manufacturing method of chitosan tubes was repeatable. The chitosan tube’s mechanical properties analyzed from the tensile test are shown in Figure 6 F. The elastic modulus was 180 ± 40.3 MPa, the tensile strength was 8.6 ± 1.4 MPa, and the breaking elongation was 8.2 ± 1.8%, which was consistent with our previous experimental results 43 and meets the mechanical requirements of nerve conduits. 47 , 48 …”

“…Three observers evaluated the whisker movements separately every three weeks according to grading standards: 0 means no apparent movement; 1 means almost imperceptible movement; 2 means fewer significant autonomous movements; 3 means significant but an asymmetric autonomous movement; and 4 means symmetric autonomous movement. , …”

“…In addition, recent studies demonstrated that the chitosan tube might be used to regenerate face nerves. 43 , 44…”

“…Certainly, the artificial nerve conduit, bridging the two stumps of the defected nerves, provided enough space for nerve regeneration. , The nerve conduit should have some characteristics, such as sufficient transparency, low tissue adhesion, collapse resistance, and high malleability to facilitate the coaptation of nerve stumps and reduce postoperative complications. , Several studies have reported that chitosan potentially interacted with the microenvironment related to nerve regeneration, which improved axonal regeneration and reduced neuroma formation. − The chitosan tube is now commonly employed in the field of peripheral nerve surgery. In addition, recent studies demonstrated that the chitosan tube might be used to regenerate face nerves. , …”

Engineering Complex Anisotropic Scaffolds beyond Simply Uniaxial Alignment for Tissue Engineering

“…[197] Inspired by this finding, Wang's team employed a hierarchically aligned fibrin nanofiber hydrogel (AFG) inserted within chitosan tubes as a nerve graft. [62,190] The AFG can mimic the native fibrin cable as well as the oriented and low-elastic features of the nerve ECM, providing an instructive microenvironment to accelerate neurite regrowth. They further functionalized AFG with self-assembling peptide to carry out synergistic topographical and biochemical cues for peripheral nerve regeneration.…”