Radially Aligned, Electrospun Nanofibers as Dural Substitutes for Wound Closure and Tissue Regeneration Applications

Abstract

This paper reports the fabrication of scaffolds consisting of radially aligned poly(ε-caprolactone) nanofibers by utilizing a collector comprised of a central point electrode and a peripheral ring electrode. This novel class of scaffolds was able to present nanoscale topographic cues to cultured cells, directing and enhancing their migration from the periphery to the center. We also established that such scaffolds could induce faster cellular migration and population than nonwoven mats consisting of random nanofibers. Dural fibroblast cells cultured on these two types of scaffolds were found to express type I collagen, the main extracellular matrix component in dural mater. The type I collagen exhibited a high degree of organization on the scaffolds of radially aligned fibers and a haphazard distribution on the scaffolds of random fibers. Taken together, the scaffolds based on radially aligned, electrospun nanofibers show great potential as artificial dural substitutes and may be particularly useful as biomedical patches or grafts to induce wound closure and/or tissue regeneration. Keywordselectrospinning; aligned nanofibers; dural substitutes; wound closure Dura mater is a membranous connective tissue located at the outermost of the three layers of the meninges surrounding the brain and spinal cord, which covers and supports the dural sinuses and carries blood from the brain towards the heart. 1 Dural substitutes are often needed after a neurosurgical procedure to expand or replace the resected dura mater. 2 Although a lot of efforts have been made, the challenge to develop a suitable dural substitute has been met with limited success. 3 Autografts (e.g., fascia lata, temporalis fascia, and pericranium) are preferred because they do not provoke severe inflammatory or immunologic reactions, but they are limited by potential drawbacks such as difficulty in achieving a watertight closure, formation of scar tissue, insufficiently accessible graft materials to close large dural defects, and additional incisions for harvesting the graft. 4,5 Allografts and xenografts are often associated with adverse effects such as graft dissolution, encapsulation, foreign body reaction, scarring, and adhesion formation. Lyophilized human * Address correspondence to: xia@biomed.wustl.edu. † These two authors contributed equally to this work. NIH Public AccessAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2011 September 28.Published in final edited form as: ACS Nano. 2010 September 28; 4(9): 5027-5036. doi:10.1021/nn101554u. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript dura mater as a dural substitute has also been clarified as a source of Creutzfeldt-Jakob disease. 6,7 In terms of materials, nonabsorbable synthetic polymers, such as silicone and expanded polytetrafluoroethylene (ePTFE), often cause serious complications. These may include induction of granulation tissue formation due to their chronic stimulation of the surrounding tissues and long-term foreign body reactions. [8]...

A facile route for controlled alignment of carbon nanotube-reinforced, electrospun nanofibers using slotted collector plates

“…Another approach was developed by Chvojka et al [22] who produced PVA nano yarns using a special saw-like collector, by twisting electrospun PVA nanofibers and introduced a simple analysis of the field strength that causes the prevailing unidirectional fiber deposition between neighbouring lamellae of a special saw-like collector. Few groups have also worked on producing aligned fibers by using collector plates of special designs [23][24][25]. But, it is difficult to understand how the electric field behaves in each of these types of collector designs.…”

Electrospun Nanofibers for Regenerative Medicine

“…[68] As a demonstration, we have recently shown that dural fibroblasts could cover the entire scaffold with a radial alignment at a faster speed relative to a scaffold made of random nanofibers. [69] A number of methods have been developed for controlling the alignment of electrospun nanofibers. These methods can be categorized into three major categories depending on the type of forces involved ( Fig.…”

“…Since cells tend to migrate along the fibers, cells seeded around the periphery of a radially aligned scaffold would follow the nanofibers and migrate inward to cover the whole scaffold at a speed faster than if they were seeded on a scaffold made of random nanofibers. [69] Another useful type of alignment can be found in scaffolds that contain arrays of microwells. These scaffolds can be fabricated using an array of metallic beads as the collector (Fig.…”

“…An increase in the proportion of neurons and neural precursor cells and a decrease in the proportion of astrocytes was found for aligned nanofibers compared to random nanofibers. [69] Neural guidance conduits (NGCs) with variations in both fiber organization and composition can be easily constructed by rolling and sealing non-woven mats of nanofibers. Leong and coworkers demonstrated that NGCs composed of axially aligned fibers were able to improve peripheral nerve regeneration across a 15-mm nerve defect compared with NGCs consisting of random or circumferentially aligned fibers.…”

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

“…2c). 222 In the subsequent studies, they generated microisland arrays of nanofibers with uniaxially aligned nanofibers in between (Fig. 2d) 223 and demonstrated that the nanoscale topographical guidance promoted skin cell migration in vitro and reepithelialization in vivo.…”