Nano-textured self-assembled aligned collagen hydrogels promote directional neurite guidance and overcome inhibition by myelin associated glycoprotein

Abstract

The UCD community has made this article openly available. Please share how this access benefits you. Your story matters! (@ucd_oa) Some rights reserved. For more information, please see the item record link above. TitleNano-textured self-assembled aligned collagen hydrogels promote directional neurite guidance and overcome inhibition by myelin associated glycoprotein The development of nerve guidance conduits is constantly evolving as the need arises for therapies for spinal cord injury. In addition to providing a path for regrowing axons to reconnect with their appropriate targets, the structural and biochemical cues provided by these conduits should be permissive for directional neurite outgrowth and be protective against inhibition in the vicinity of the injury site. Here, we adapted the use of iso-electric focusing to drive the alignment of supramolecular fibrils into self-assembled collagen hydrogels ($300 mm diameter), and tested those hydrogels for the ability to direct and enhance the migration of neurites. Structural characterization revealed anisotropic alignment of nanofibrillar aggregates ($20 nm diameter), arranged in micron-scale bundles ($1 to 2 mm diameter) similar to the hierarchical size scales observed in native tissues. Neurite outgrowth extended bidirectionally along the axes of aligned hydrogels. Furthermore, it was shown that, as opposed to poly-D-lysine, neurite outgrowth on aligned hydrogels is not inhibited in the presence of myelin-associated glycoprotein (p > 0.05). These results highlight for the first time a structural and biochemical role for iso-electrically aligned collagen hydrogels in controlling neuronal growth, and indicate that the short-term signaling associated with these hydrogels can be used in adjunct therapy following injury to the spinal cord.

The past, present and future in scaffold-based tendon treatments

“…Of significant importance are in vitro data that have been obtained using these materials. When their potential for spinal cord injuries was assessed, it became apparent that such materials not only promote directional neurite guidance, but also overcome inhibition by myelin associated glycoprotein [366]. In a tendon setting, these collagen fibres have been shown to promote bidirectional alignment and migration of tendon derived cells and to differentiate human BMSCs towards tenogenic lineage, even in the absence of biological signals [367,368].…”

A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery

“…Similarly, by optimizing the release kinetics of neurotrophic factors delivery (using new biomaterial technologies) the disadvantage of their limited halflives may be overcome [94][95][96]. New emerging delivery approaches being developed in our own laboratory include the use of biological collagen/fibrin microspheres, microfibres and hydrogels, as well as synthetic polymeric carriers for the creation of a sustained system for viable growth factor delivery [97][98][99].…”

Electromechanical properties of dried tendon and isoelectrically focused collagen hydrogels

“…Previous studies have demonstrated the potential of collagenous scaffolds [8] and hydrogels [9] for tissue engineering applications [10]. The ability to assemble collagenous scaffolds in vitro with the same structure and properties as natural collagenous tissue would be of significant importance for studying cell-matrix interactions as well as for developing compatible engineered tissues.…”

“…Rat tail tendon is an excellent tissue for studying collagen as it consists primarily of type I collagen, with only a small volume of proteoglycan, in which the fibrils have a high degree of alignment along the tendon axis [39]. Similarly, iso-electric focusing has been shown induce the conformational alignment of collagen monomers, which then assemble into hierarchical structures (nano-and micro-fibrils) that co-align along axis of the hydrogels [9].…”

“…Numerous approaches to assemble fibrillar collagen structures have been implemented, including hydrodynamic flow in the presence of potassium [11,12], magnetic field alignment [13], dip-pen lithography [14], chemical nanopatterning [15], microfluidics [16], and atomic force microscopy (AFM) manipulation [17]. Recent attempts to align collagen by electrochemical processes have demonstrated successful alignment of anisotropically-oriented collagen monomers [9,18]. In addition to advantages such as increased mechanical stability [19], aligned collagenous tissues have been shown to influence cell alignment and growth [20].…”