Effect of filament diameter and extracellular matrix molecule precoating on neurite outgrowth and Schwann cell behavior on multifilament entubulation bridging device in vitro

Abstract

At present there is no clinically effective treatment for injuries or pathological processes that disrupt the continuity of axons in the mature central nervous system. However, a number of studies suggest that a tremendous potential exists for developing biomaterial based therapies. In particular, biomaterials in the form of bridging substrates have been shown to support at least some level of axonal regeneration across the lesion site, but display a limited capacity for directing axons toward their targets. To improve the directionality and outgrowth rate of the axonal regeneration process, filaments and tubes appear promising, but the technology is far from optimized. As a step toward optimization, the influence of filament diameter and various extracellular matrix coatings on nerve regeneration was evaluated in this article using a dorsal root ganglion (DRG) explant model. An increasing pattern of alignment and outgrowth of neurites in the direction parallel the long axis of the packed filament bundles with decreasing filament diameters ranging from supracellular and beyond (500 to 100 mum), cellular (30 mum), down to subcellular size (5 mum) was observed. Such effects became most prominent on filament bundles with individual filament diameters in the range of cellular size and below (5 and 30 mum) where highly directional and robust neuronal outgrowth was achieved. In addition, laminin-coated filaments that approached the size of spinal axons support significantly longer regenerative outgrowth than similarly treated filaments of larger diameter, and exceed outgrowth distance on similarly sized filaments treated with fibronectin. These data suggested the feasibility of using a multifilament entubulation bridging device for supporting directional axonal regeneration.