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.

The role of aligned polymer fiber-based constructs in the bridging of long peripheral nerve gaps

“…Topographical cues involving grooves and fibers have been previously demonstrated to cause Schwann cell alignment and subsequent neurite extension in vitro [13][14][15], and some studies have used magnetically aligned collagen filaments [16], microbraided polymer fibers [3], or micron-scale filaments to promote nerve regeneration [17,18]. In this study, the quantitative comparison of both DRG outgrowth in vitro and nerve regeneration in vivo on two different polymer surface topographies (i.e., aligned and randomly oriented fiber films, but with identical material and fabrication process) clearly provides key insights into the importance of the structural cues (i.e., alignment) for promoting nerve regeneration.…”

The effect of the alignment of electrospun fibrous scaffolds on Schwann cell maturation

“…They demonstrated that the alignment of smooth muscle cells significantly differed only when the half pitch of the nanogratings was changed from 350nm to 2μm. Wen and Tresco [39] studied the effects of polypropylene filament diameter on neurite outgrowth and Schwann cell migration distance. They demonstrated that both neurite outgrowth and Schwann cell migration distance were significantly decreased as the diameters of the filament increased by two orders of magnitude, from 5μm to 200μm.…”

Long-Term Survival and Integration of Transplanted Engineered Nervous Tissue Constructs Promotes Peripheral Nerve Regeneration

“…For instance, longitudinally aligned polymer fibers confer a directional bias for neurite outgrowth based on specific geometrical attributes. 24,25 Moreover, our nervous tissue constructs may recapitulate an axonal regeneration process that occurs in damaged nerves that are not completely transected, where regenerating axons follow the path of intact axons. Additionally, this form of regeneration may not be dependent upon cellular infiltration, proliferation, or organization, and thus may occur more expeditiously than that reliant upon SC columnar alignment and matrix deposition.…”