Chitosan-film enhanced chitosan nerve guides for long-distance regeneration of peripheral nerves

Abstract

Biosynthetic nerve grafts are developed in order to complement or replace autologous nerve grafts for peripheral nerve reconstruction. Artificial nerve guides currently approved for clinical use are not widely applied in reconstructive surgery as they still have limitations especially when it comes to critical distance repair. Here we report a comprehensive analysis of fine-tuned chitosan nerve guides (CNGs) enhanced by introduction of a longitudinal chitosan film to reconstruct critical length 15 mm sciatic nerve defects in adult healthy Wistar or diabetic Goto-Kakizaki rats. Short and long term investigations demonstrated that the CNGs enhanced by the guiding structure of the introduced chitosan film significantly improved functional and morphological results of nerve regeneration in comparison to simple hollow CNGs. Importantly, this was detectable both in healthy and in diabetic rats (short term) and the regeneration outcome almost reached the outcome after autologous nerve grafting (long term). Hollow CNGs provide properties likely leading to a wider clinical acceptance than other artificial nerve guides and their performance can be increased by simple introduction of a chitosan film with the same advantageous properties. Therefore, the chitosan film enhanced CNGs represent a new generation medical device for peripheral nerve reconstruction.

Reflex‐based grasping, skilled forelimb reaching, and electrodiagnostic evaluation for comprehensive analysis of functional recovery—The 7‐mm rat median nerve gap repair model revisited

“…Series of 40 blind‐coded cross‐sections (7 μm) were prepared. Hematoxylin and eosin staining (HE) was applied to selected sections and consecutive sections were double stained for neurofilament (NF200) (Meyer et al., 2016) and myelin basic protein (MBP). Briefly, sections were incubated in blocking solution (3% milk powder (Bio Magermilch Pulver, Heirler Cenovis GmbH, Germany) and 0.5% triton X‐100 (Roche Diagnostics GmbH, Germany) in PBS) prior to incubation with the following antibodies one after the other: (i) primary rabbit α‐NF200 antibody (against phosphorylated NFeH, N4142, 1:500, Sigma‐Aldrich GmbH, Germany, RRID:AB_477272, +4°C overnight), (ii) Alexa 488‐conjugated secondary goat α‐rabbit antibody (A11034, 1:1,000, Invitrogen AG, Germany, 1 hr at room temperature (RT)), (iii) mouse α‐MBP antibody (SMI94, 1:200, Covance Antibody Products, Germany, RRID:AB_510039, +4°C overnight), and (iv) Alexa 555‐conjugated secondary goat α‐mouse antibody (A21422, 1:1,000, Invitrogen AG, 1 hr at RT).…”

“…Usage of ANGs, however, leads to considerable donor side morbidity. Therefore, autologous muscle‐in‐vein grafts (MVGs), leading only to minor donor side morbidity (Manoli, Schulz, Stahl, Jaminet, & Schaller, 2014), represent promising alternative digital nerve grafts (Manoli, Schulz, et al., 2014; Marcoccio & Vigasio, 2010; Tos, Battiston, Ciclamini, Geuna, & Artiaco, 2012) as do several clinically approved biodegradable nerve guidance conduits (NGCs) (Bertleff, Meek, & Nicolai, 2005; Donoghoe, Rosson, & Dellon, 2007; Lohmeyer, Siemers, Machens, & Mailander, 2009; Meyer et al., 2016). …”

Schwannoma of the hypoglossal nerve: Review of the literature based on an illustrative case

“…In these cases, in order to limit morbidity, reconstruction by direct nerve repair with epineurial microsutures or nervous grafts may be performed. In addition to these procedures, there are novel and upcoming techniques using biocompatible scaffolds that may help in the reconstruction of the transected nerve (32)(33)(34)(35)(36).…”

Peripheral Nerve Reconstruction Using Enriched Chitosan Conduits

“…In vitro, it has been shown that chitosan membranes are a suitable substrate for survival and orientation of Schwann cell growth as well as survival and differentiation of neuronal cells [31,32]. In vivo, studies showed that chitosan tubes can efficiently bridge peripheral nerve defects [33][34][35][36].…”