Relevance and Recent Developments of Chitosan in Peripheral Nerve Surgery

Abstract

Developments in tissue engineering yield biomaterials with different supporting strategies to promote nerve regeneration. One promising material is the naturally occurring chitin derivate chitosan. Chitosan has become increasingly important in various tissue engineering approaches for peripheral nerve reconstruction, as it has demonstrated its potential to interact with regeneration associated cells and the neural microenvironment, leading to improved axonal regeneration and less neuroma formation. Moreover, the physiological properties of its polysaccharide structure provide safe biodegradation behavior in the absence of negative side effects or toxic metabolites. Beneficial interactions with Schwann cells (SC), inducing differentiation of mesenchymal stromal cells to SC-like cells or creating supportive conditions during axonal recovery are only a small part of the effects of chitosan. As a result, an extensive body of literature addresses a variety of experimental strategies for the different types of nerve lesions. The different concepts include chitosan nanofibers, hydrogels, hollow nerve tubes, nerve conduits with an inner chitosan layer as well as hybrid architectures containing collagen or polyglycolic acid nerve conduits. Furthermore, various cell seeding concepts have been introduced in the preclinical setting. First translational concepts with hollow tubes following nerve surgery already transferred the promising experimental approach into clinical practice. However, conclusive analyses of the available data and the proposed impact on the recovery process following nerve surgery are currently lacking. This review aims to give an overview on the physiologic properties of chitosan, to evaluate its effect on peripheral nerve regeneration and discuss the future translation into clinical practice.

Advances in the repair of segmental nerve injuries and trends in reconstruction

“…However, these conduits are generally similar in their principles and features, as they are biodegradable through various mechanisms and promote regeneration by means of first the formation of endogenous ECM within the empty tube structure. Extensive reviews of the wide range of conduit material properties are available …”

“…As the body of work on experimental alternatives is substantial, this section will highlight specific recent areas that show promise for translation. For a more comprehensive review of bioengineered nerve graft alternatives, see Pfister et al, Boecker et al, and Kornfeld et al…”

Fibroblasts Colonizing Nerve Conduits Express High Levels of Soluble Neuregulin1, a Factor Promoting Schwann Cell Dedifferentiation

“…A promising biomaterial widely used for peripheral nerve regeneration and recently approved for clinical use is chitosan, a polysaccharide of natural origins [10][11][12]. It is a highly versatile biomaterial, indeed it has been tested in several forms, such as hydrogels, films, or conduits used to repair nerve gap [13].…”

Restoration of Neurological Function Following Peripheral Nerve Trauma

“…Axon regeneration is extensive through conduits composed of fibrin [145,153], hydrogel tubes [154], alginate/chitosan polyelectrolyte [155][156][157], poly epsilon-caprolactone [158,159], polyglycolic acid [160], poly(lactic-co-glycolic acid) or silk-based [161][162][163][164]. Conduits composed of decellularized human umbilical artery [165] and muscles [166] are also effective in promoting axon regeneration across nerve gaps.…”