The future role biomaterials may play in spinal cord injury: The Ryan Gilbert Lab

The Gilbert lab specializes in developing translational biomaterials to aid in spinal cord repair. Their laboratory is developing biomaterials to guide axonal and cellular migration through an injury site, as well as, locally deliver therapeutics.

Research
•Biomaterials for Cell Guidance
•Hydrogels in Neural Application
•Hydrogels to Promote Cell Adhesion
•Schwann Cell Growth on Electrospun Fibers
•Electrospun Fiber Density in Axon Motility and Cell Migration

Biomaterials for Cell Guidance – Chris Rivet

The cellular response to biomaterial implants in the injured spinal cord is unique in that the material itself may play a role in both physical and physiological guidance. Currently, the paradigm for biomaterial implants is centered on physical guidance where scaffolds contain either uniaxial channels or aligned porosity. The presence of these attributes enhances regeneration across the lesion site while attempting to limit aberrant sprouting. Although results from these systems indicate regenerative capabilities, they do not take into account secondary devices that may enhance the implant’s performance, namely inflammatory modulation. Astrocytes and macrophages, among other cell types, are an integral part of the injury process and their response may either accentuate or attenuate the subsequent injury severity.

Previously, we were able to demonstrate that electrospun fibers produce a substrate for neural guidance. The topography of the electrospun substrate produces an environment favorable to adhesion. There are many cellular processes that are adhesion dependent, and therefore tailoring materials to the specific requirements of a cellular population may provide an additional method of guidance, through intracellular mechanisms. As the interrelations between cellular types within spinal cord injury are being discovered, the ability to guide inflammatory response by the inherent material properties becomes possible. The use of biomaterials for spinal cord injury in our laboratory is centered on not only physical guidance mechanisms to direct axonal growth, but also to investigate the effects of the material on the adjacent cellular population in attempt to elicit a favorable response.

Hydrogels in Neural Application – Jon Zuidema

The inhibitory environment following CNS injury has been proposed as one of the important factors leading to CNS regeneration failure. Along this line, hydrogels are being developed to fill and replace the growth inhibitory environment with a growth permissive one. Previously, a polysaccharide hydrogel blend was developed that was suitable for drug delivery outside of the lesion site. The goal of the current work is to produce several new polysaccharide hydrogel blends that would have an increased ability to promote regeneration after CNS injury and could be injected directly into the injury site. Also, nanoparticles are being developed to incorporate into the hydrogels to allow for prolonged release of therapeutics following CNS injury. Combining these two engineering strategies could have important implications in the search for a clinically translatable therapy for CNS injuries.

Hydrogels in Neural Application – Chris McKay

The post injury spinal cord is a very complicated and turbulent area, undergoing a series of secondary post injury mechanisms that make regeneration a difficult task. While hydrogels have been widely used as injectable materials for spinal cord regeneration, little research has been performed that determines the effect of the act of injection itself on the surrounding tissue. What research has been done has given rise to the idea that the act of injection itself may be detrimental to the regeneration of neural tissue and may increase secondary post-injury tissue damage.

We seek to develop materials and techniques that will allow for the manipulation of the nature of the post-injury environment to create hydrogels that will gel in-situ, with the hope of reducing intraspinal pressure and reducing the impact of secondary injury mechanisms. The goal is to create hydrogels that mimic the mechanical properties of native spinal tissue, on which neural cells have shown capacity for regeneration, and take advantage of cerebrospinal fluid composition to allow for in-situ gel formation for axonal guidance and regeneration.

The ability of a material to degrade in a proper time frame is of great importance when considering its use for an in-vivo biomaterial scaffold. Various methods have been developed for controlled degradation depending on the material used ranging from simple passive diffusion to enzymatic release form a secondary polymer structure. However, none of these methods take into account the degree of cell growth that has occurred. We are seeking to develop a method, to be used with the hydrogel described above, that will allow for cell attachment to the scaffold to direct enzymatic release and thus degradation of the scaffold. This will couple neural regeneration with the degradation of the scaffold material, effectively allowing the cells themselves to determine when the scaffold is no longer needed for regeneration.

Hydrogels to Promote Cell Adhesion – Chris Johnson

Fibrin is the main constituent in blood-clots during wound healing in vivo. Fibrin has long been a successful biomaterial because itis natural, non-toxic, and has a method of degradation in vivo. Fibrin gels provide a scaffold with adjustable mechanical properties, but the scaffold does not promote cell adhesion as vigorously as less mechanically stable polymers, such as chitin.

Chitin is a biopolymer found in the exoskeleton of crustaceans, mollusks, and the cell walls of fungi. Behind cellulose, it is the second most biologically synthesized polymer. Chitinis a good candidate for a cell promoting biomaterial because it is biocompatible, biodegradable, and non-toxic, andit has been shown to have remarkable antibacterial properties. Unfortunately, chitin is relatively insoluble, so most research uses its close derivative, chitosan, which is easier to work with but still exhibits nearly all of the same properties.

The goal of our current research is to determine how chitosan and fibrin interact, in an effort to design a fibrin-chitosan hydrogel with tunable mechanical properties and improved cell supporting capabilities.

Schwann Cell Growth on Electrospun Fibers – Stephen Quallich

Schwann cells play an important role in nerve regeneration and understanding their behavior in response to different electrospun scaffolds will aid in creating an ideal substrate for neural guidance. To better understand the response of Schwann cell migration to electrospun fibers and an electrical field, we will be examining their growth on parallel and perpendicularly aligned electrospun fibers with varying fiber density with and without the application on an electric field. Previously, our group has examined how varying the diameter of aligned electrospun fibers has affected neurite outgrowth and Schwann cell migration; this project will further break down the interaction between Schwann cells, electrospun fibers, and the effects on an electric field.

Electrospun Fiber Density in Axon Motility and Cell Migration – Nicholas Zaccor

Understanding the cellular response to implanted biomaterials is a crucial step in the process of finding cures and solutions to different injury types. Injuries to the spinal cord present a number of unique issues that the materials have to overcome. One of the most important issues is the distinct lack of extracellular matrix cues to provide direction for new healthy neural and glial cells.

This study will utilize a variety of polymeric scaffolds fabricated from electrospun fibers to investigate cellular response to different density topographies. Dorsal root ganglion cells will be used to model glial and neural cells response to these different density organizations. The same fibers will be doped with a common integrin-laminin binding domain to assess the activity of integrin complexes in the process of axonal outgrowth and cellular migration. The purpose of this experiment is to show how topographical cues and protein cues similar to the ECM can be used to promote cell growth through an injury site. The tests will both characterize and improve upon the electrospun fiber scaffolds used by the Gilbert lab to be used for regeneration of neurons through nerve gaps and lesions due to spinal cord injury.

Ryan J. Gilbert, Ph.D.
Ryan J. Gilbert C.V. Assistant Professor
2135 Biotechnology and Interdisciplinary Studies Building

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