Abstract
Chitosan is a resorbable cationic polysaccharide known for its biodegradability and electrostatic and self-aggregation properties. Chitosan has been shown to influence Schwann cell proliferation, reduce scarring, support axon growth, and provide superior peripheral nerve regenerative outcomes compared to nerve injuries without chitosan. This article reviews preclinical studies to collectively determine whether the presence of chitosan enhances neuroregenerative outcomes following nerve injury as compared to settings without chitosan. The most consistent outcome measure reported across studies was functional analysis, followed by histomorphometry. Most animal studies showed no significant differences in functional recovery, electrophysiology metrics, and histomorphometry parameters between chitosan-based conduit repairs, reconstruction using autografts, or direct nerve repairs. A subset of studies reported superior outcomes with chitosan conduits for nerve reconstruction, while others indicated inferior results compared to conventional repair. The two human studies focused on digital nerve repair with sensory gaps ≤ 26 mm and demonstrated significantly improved 2-point discrimination at 6 months and equivalent function by 12 months with chitosan conduits compared to standard direct repair. The introduction of chitosan into nerve repair and reconstructions provides a potentially beneficial biological augmentation to the nerve microenvironment that enhances cellular, electrophysiological, and functional outcomes. However, heterogeneous approaches to functional, electrodiagnostic, and histological assessments in addition to varying control groups create a significant deficiency in understanding the true utility of chitosan-based devices within the field of nerve regeneration. Further needs for standardization in the study and comparison of biomaterials for effective clinical translation is needed. Nonetheless, this study highlights papers that are effective in achieving a strong propensity towards the utility of chitosan within biomaterial development for nerve reconstruction.
Impact Statement
This review investigating the use of chitosan-based devices as compared to repairs and reconstructions without chitosan in preclinical and clinical studies found greater neuroregenerative outcomes in the presence of chitosan compared to environments without chitosan in some studies. However, with the heterogeneity of postimplantation assessments and varying control groups, comparisons within and across studies remains difficult. With the growing availability of chitosan-based devices for clinical use, this study provides insights into the potential benefits of chitosan but also the shortcomings of current research and need for more rigorous approaches to determine true impact of chitosan and other novel biomaterials.
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