Polymer Scaffolds with Preferential Parallel Grooves Enhance Nerve Regeneration

Abstract

We have modified the surface topography of poly e-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 mm). 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 mm 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.

Linearized texture of three-dimensional extracellular matrix is mandatory for bladder cancer cell invasion

“…The maintenance of morphological and geometrical features of the ECM of the human bladder is certainly of potential relevance for the design of an innovative biosynthetic scaffold. Indeed, proper 3D geometry of the extracellular environment and an adequate space allocated for cell seeding are needed for cell engraftment and polarization which may eventually lead to vascularization and innervation, as it was recently reported with scaffolds made of synthetic polymers121314.…”

“…In addition to the biochemical signalling provided to cells by ECM proteins, stiffness, topography and geometry of the extracellular space also modulate cell behaviour and phenotype123. Recently, three-dimensional geometry has been reported as an important feature of synthetic scaffolds favoring cell stemness, maintenance and differentiation, nerve regeneration and vascularization11121314. Further evidence of the role of matrix geometry is the fact that a depletion of all integrins does not impede the movement of dendritic cells in 3D matrices15, whereas matrix geometry and the resulting cell confinement were the main parameters regulating cell phenotype and cell behavior161718.…”

Thermally drawn fibers as nerve guidance scaffolds

“…These include drug delivery [18], addition of cellular components [19, 20], electrical stimulation [21, 22], and topography [23]. The latter has been primarily studied in the context of flat lithographically patterned substrates [10, 23–25] limited to macroscopic rolling for experiments in vivo [12]. Consequently, despite the abundance of literature illustrating the growth promoting effects of topographical features [10], nerve guidance channels approved for clinical use remain limited to a simple round geometry [26].…”

Handcrafted Microwire Regenerative Peripheral Nerve Interfaces with Wireless Neural Recording and Stimulation Capabilities

“…PDMS has been widely used as a major material of the implantable devices for both research and clinical purposes [28][29][30][31][32][33], due to its easy fabrication technique and biocompatibility. To achieve translational capabilities, PDMS could be replaced by biodegradable materials, such as PCL, PLGA, and PGA [34][35][36][37][38][39]. After the nerve regeneration, the biodegradable microchannel will be dissolved to give the structures as close to a natural nerve as possible.…”