Collagen/β‐TCP nerve guidance conduits promote facial nerve regeneration in mini‐swine and the underlying biological mechanism: A pilot in vivo study

Abstract

This study aimed to evaluate the efficiency of new nerve guidance conduits (NGCs) in bridging facial nerve gaps, and investigate the underlying biological mechanisms implicated in the regeneration process. A collagen/β-TCP conduit was prepared and applied to a facial nerve gap in a mini-swine model. Functional recovery and axonal regeneration were further evaluated by electrophysiological and histological examinations at 3 months after surgery. Furthermore, the global transcriptomic profiles of regenerated and normal tissues were analyzed by gene microarray to identify the differentially expressed genes at day three and seven, postoperatively. Subsequently, associated biological processes were analyzed by gene ontology (GO) enrichment analysis. The electrophysiological examination and morphological analysis revealed that significant nerve regeneration effects were achieved in the Col/β-TCP group (p < 0.05). Transcriptional analysis revealed that at day three post-surgery, the majority of overexpressed genes were associated with inflammatory, immune and stimuli response, accompanied by angiogenesis, while at day seven, the majority of overexpressed genes were associated with cell, tissue and organ regeneration and development, synaptic transmission, neurogenesis, and neuronal differentiation, as well as the WNT, MAPK/ERK, and JAK/STAT signaling pathways. In conclusion, the present results suggest that collagen/ β-TCP NGCs provide a promising tubular micro-environment for nerve regeneration.

Porous Organic Materials in Tissue Engineering: Recent Advances and Applications for Severed Facial Nerve Injury Repair

“…For a new bioengineering technology to be developed to meet clinical needs, preclinical studies are necessary. The animal models for preclinical studies of facial nerve injury repair include rodents, rabbits, and miniature pigs [36,37], among which rodents and rabbits are widely used because of their relatively low operation difficulty. The facial nerve distribution of these experimental animals is similar to that of humans.…”

“…During the development process of facial nerve conduits, more preclinical studies were conducted in the experimental animal model of sciatic nerve injury, and there was still a dearth of research on the repair of facial nerve injury [36,126]. The complexity of the facial nerve's anatomical structure, along with its limited exposure and small operating space, poses challenges in terms of establishing the defect model.…”

3D Printing of Bioinspired Biomaterials for Tissue Regeneration

“…In addition, the studies demonstrated that the collagen in biomaterials would significantly stimulate the adhesion and proliferation of neural stem cells. [61][62][63] Imitating the composition of neural tissue to construct the biomaterials containing the pluripotent stem cellderived cells and collagen may be a future direction to regenerate neural tissue.…”

Repairing whole facial nerve defects with xenogeneic acellular nerve grafts in rhesus monkeys

“…Furthermore, the facial mimetic muscles of beagles are small and thin, making it difficult to perform electromyographical tests. Previous studies have indicated that minipigs and monkeys may be appropriate animal models for preclinical research regarding peripheral nerve injury and repair, although these models are associated with substantial costs and ethical circumspection (Satoda, 1987;Hontanilla et al, 2006;Lu et al, 2015;Aycart et al, 2015;Zhang et al, 2019;Milner et al, 2020). The buccal division of the facial nerve in minipigs is sufficiently thick, straight, and long that it can be used to bridge the defect of a single branch of the facial nerve.…”