Design of barrier coatings on kink-resistant peripheral nerve conduits

Abstract

Here, we report on the design of braided peripheral nerve conduits with barrier coatings. Braiding of extruded polymer fibers generates nerve conduits with excellent mechanical properties, high flexibility, and significant kink-resistance. However, braiding also results in variable levels of porosity in the conduit wall, which can lead to the infiltration of fibrous tissue into the interior of the conduit. This problem can be controlled by the application of secondary barrier coatings. Using a critical size defect in a rat sciatic nerve model, the importance of controlling the porosity of the nerve conduit walls was explored. Braided conduits without barrier coatings allowed cellular infiltration that limited nerve recovery. Several types of secondary barrier coatings were tested in animal studies, including (1) electrospinning a layer of polymer fibers onto the surface of the conduit and (2) coating the conduit with a cross-linked hyaluronic acid-based hydrogel. Sixteen weeks after implantation, hyaluronic acid-coated conduits had higher axonal density, displayed higher muscle weight, and better electrophysiological signal recovery than uncoated conduits or conduits having an electrospun layer of polymer fibers. This study indicates that braiding is a promising method of fabrication to improve the mechanical properties of peripheral nerve conduits and demonstrates the need to control the porosity of the conduit wall to optimize functional nerve recovery.

Additive manufactured biodegradable poly(glycerol sebacate methacrylate) nerve guidance conduits

“…This issue was overcome by using laser cutting post-production, creating precisely designed highly reproducible conduits. The NGCs were elastic in nature, and when bent did not fracture or kink, making them easier to handle surgically than previously studied stiff polyethylene glycol (PEG) conduits, which exhibited a stiffness of 470 MPa as compared to 3.2 MPa for the PGSm NGCs in this study [31].I ti s reported that kinking of NGC's may occlude the conduit lumen, hindering axonal regeneration, particularly with larger gap injuries [40]. It is therefore advantageous for a conduit to flex with body movements before kinking.…”

Fibrin glue as a stabilization strategy in peripheral nerve repair when using porous nerve guidance conduits

“…Braiding introduces porosity in the nerve conduit wall [8, 17, 53–55]. Gao et al showed that braided nerve conduits made of filaments of poly(L-lactide-co-glycolide) (PLGA) were highly porous (pore size between 50–100 µm) [54].…”

“…Braided conduits were fabricated using previously published procedures [8]. Briefly, E1001(1k) powder was melt-extruded into 80–110 µm diameter fibers on a Randcastle microextruder (Cedar Grove, NJ).…”

“…It is known that the conduit wall porosity can impact nerve re-growth [7, 8]. Numerous studies have investigated conduit porosity in the context of peripheral nerve regeneration and reported contradictory results [9–11].…”

“…Clements et al applied electrospun fiber mats made from tyrosine-derived polycarbonates, with hyaluronic acid (HA) hydrogel coating, to the conduit walls to reduce the pore size of braided conduits. They demonstrated that only the HA hydrogel barrier coatings, but not the electrospun fiber coatings, were effective in controlling the pore size of the conduits leading to improved functional nerve recovery in vivo [8]. …”