Background: Cranial nerve palsies are a rare but severe cause of strabismus and amblyopia in children, typically resulting in significant vision loss. Current treatment options are limited, consisting mainly of transposition procedures that limit the range of ocular rotation necessary for peripheral gaze. However, recent advancements in polymer science have introduced the development of hydrogels with muscle-like hierarchical nano/micro-architecture, offering a promising avenue for treatment of cranial nerve palsies. 

Purpose: To develop a biocompatible hydrogel that mimics the mechanical characteristics of human extraocular muscles (EOM), including high strength, fatigue resistance, and elasticity. This hydrogel will serve as a substitute for paralyzed EOMs, aiming to realign the eyes and preserve contralateral movement for the treatment of cranial nerve palsies. 

Methods: Hierarchically-structured anisotropic polyvinyl (PVA) hydrogel samples were crosslinked with varying concentrations of glutaraldehyde and a thiol + vinyl silane-based reaction to replicate the stress-strain behavior of porcine and rabbit EOMs. 1,000 cycles of tensile testing at 200% stretch was conducted to assess the hydrogel’s durability. The hydrogel was cultured with orbital fibroblasts to evaluate both its biocompatibility and elastic integrity in the presence of fibroblast proliferation. To simulate cranial nerve palsy, the left lateral rectus muscle in a rabbit was extirpated. The hydrogel was then implanted into the rabbit’s orbital wall and sutured to the lateral rectus insertion point to function as an abducting force. 

Results: Preliminary findings suggest that a PVA hydrogel, crosslinked through a 1.8% weight thiol-silane + vinyl-silane reaction, best replicated the mechanical behaviors of the rabbit extraocular muscle master curve. Tensile stress testing conducted at 200% stretch demonstrated sustained mechanical stability in the hydrogels. Confocal microscopic images revealed minimal cell toxicity and maintained elastic modulus even in the presence of fibroblast proliferation. Following lateral rectus extirpation, hydrogel implantation led to an improvement in ocular alignment from esotropia to relative exotropia. Additionally, the hydrogel permitted partial horizontal movement, which closely resembled the speed and angle of rotation observed in the control eye.

Conclusions: The synthetic hydrogel emulates the mechanical properties of human extraocular muscle, demonstrates biocompatibility, and improves ocular alignment while maintaining partial contralateral movement. This proposed hydrogel offers a potential replacement for denervated extraocular muscles for the treatment of cranial nerve palsies.