Evaluation of Sustained 3D Growth Factor Gradients for Nerve Repair

Tissuegen, Inc., Dallas TX

Investigators

Abstract

? DESCRIPTION (provided by applicant): TissueGen has developed proprietary technology that allows the release of growth factors from biodegradable fibers. These fibers, commercially available as ELUTE(r) Biodegradable Drug- Loaded fibers (www.tissuegen.com), can be used in microfluidic spaces to form three- dimensional gradients using variable pitch coils. The ELUTE fibers are coiled along the lumen of the microchannels with a variable pitch angle, such that when the pitch angle is small and the fiber coils are very close together the concentration of the neurotrophic factor in the lumen is high, and conversely when the fiber coils are far apart the concentration within the lumen of the microchannel drops. By choosing both the concentration of the appropriate neurotrophic factor in the fiber as well as the rate at which the pitch angle changes we have the ability to dial---in a wide range of concentration gradients. Here, we will take advantage of these growth factor gradients in microchannels to improve peripheral nerve regeneration. The ELUTE fibers can release protein for periods ranging from weeks to several months depending on how the fiber is fabricated. Therefore, the concentration gradient will be maintained within the lumen for prolonged periods. The rate at which the ELUTE fibers release the protein decreases with time, and hence the concentration of growth factor at a particular point within the lumen will likewise decrease with time; however, the slope and shape of the gradient will be maintained as long as the fiber continues to release the protein. In other words, the ratio of the concentration at the high end to the concentration at the low end will remain constant throughout the entire time course of drug release. The first specific aim of this research is to determine an appropriate concentration gradient by investigating various neurotrophic concentrations within the ELUTE fiber as determined by in vitro assays involving explanted dorsal root ganglion (DRG) cells from neonatal rats. After we have verified that a specific gradient concentration within the microchannels eluting a specific gradient induces directional growth of axons from DRGs we will be prepared to move to specific aim 2, which is to create a long gap (4cm) in a rabbit peroneal nerve injury model. The gap will be filled with an appropriate sized ELUTE BNI (or control). The endpoints will include both histological evidence and functional recovery. If successful, this technology can be beneficial to other areas or nerve repair both in the peripheral and central nervous systems.