Abstract
We have modified the surface topography of poly ɛ-caprolactone (PCL) and polylactic acid (PLA) blended films to improve cell proliferation and to guide the regeneration of peripheral nerves. Films with differing shaped grooves were made using patterned silicon templates, sloped walls (SL), V-shaped (V), and square-shaped (SQ), and compared with nongrooved surfaces with micropits. The solvent cast films were tested in vitro using adult adipose-derived stem cells differentiated to Schwann cell-like cells. Cell attachment, proliferation, and cell orientation were all improved on the grooved surfaces, with SL grooves giving the best results. We present in vivo data on Sprague-Dawley rat sciatic nerve injury with a 10-mm gap, evaluating nerve regeneration at 3 weeks across a polymer nerve conduit modified with intraluminal grooves (SL, V, and SQ) and differing wall thicknesses (70, 100, 120, and 210 μm). The SL-grooved nerve conduit showed a significant improvement over the other topographical-shaped grooves, while increasing the conduit wall thickness saw no positive effect on the biological response of the regenerating nerve. Furthermore, the preferred SL-grooved conduit (C) with 70 μm wall thickness was compared with the current clinical gold standard of autologous nerve graft (Ag) in the rat 10-mm sciatic nerve gap model. At 3 weeks postsurgery, all nerve gaps across both groups were bridged with regenerated nerve fibers. At 16 weeks, features of regenerated axons were comparable between the autograft (Ag) and conduit (C) groups. End organ assessments of muscle weight, electromyography, and skin reinnervation were also similar between the groups. The comparable experimental outcome between conduit and autograft, suggests that the PCL/PLA conduit with inner lumen microstructured grooves could be used as a potential alternative treatment for peripheral nerve repair.
Highlights
Repair of a peripheral nerve gap is a clinical problem for which a bioengineered solution is being sought
We present in vivo data on SpragueDawley rat sciatic nerve injury with a 10-mm gap, evaluating nerve regeneration at 3 weeks across a polymer nerve conduit modified with intraluminal grooves (SL, V, and SQ) and differing wall thicknesses (70, 100, 120, and 210 mm)
We have previously demonstrated that poly e-caprolactone (PCL) films can support adipose-derived stem cells (ASCs), differentiated to a Schwann cell-like phenotype, as a potential tissue-engineered route to nerve repair.[6]
Summary
Repair of a peripheral nerve gap is a clinical problem for which a bioengineered solution is being sought. An effective nerve conduit needs to provide a supportive environment for cellular interactions promoting axonal regeneration across a nerve gap Biodegradable polymers such as poly e-caprolactone (PCL) and polylactic acid (PLA) are promising materials toward development of innovative nerve conduits.[1,2,3] The blend of these polymers has been studied to tailor crucial properties, including mechanical strength and hydrophobicity/hydrophilicity.[4] We have previously reported that ultrathin PCL films and PCL/PLA blended films with a micropitted surface are able to support the attachment and growth of the NG108-15 neuronal cell line and Schwann cells.[5] Schwann cells are key players in nerve regeneration through delivery of neurotrophic factors and extracellular matrix proteins; the absence of Schwann cells in a nerve gap has led to much current work being focused on the use of stem cells to deliver this. The surface and the material properties of the biodegradable polymers could be designed and engineered with specific topographical cues to improve the cellular interaction with the biomaterial and to provide the optimal environment for peripheral nerve regeneration
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