DNA-Based Hydrogels for Peripheral Nerve Repair
Abstract
Every year, thousands of returning wounded Soldiers and Veterans undergo treatment or surgery for temporary or permanent disabilities caused by peripheral nerve injuries (PNIs). Peripheral nerves are responsible for transmitting information from the brain to the organs and regulate vital functions like breathing and heartbeat. Therefore, damage to these nerves can have severe consequences for the health of wounded Service Members that extend beyond the injury itself. PNIs generally result from combat-sustained traumatic injuries, such as blast injuries, but are also common consequences of toxin exposure, burn pit exposure, or infections by pathogens that might occur on the battlefield. PNIs affect patients across all ages and health conditions and currently represent one of the most challenging problems faced by the military health system. The steady improvement in Warfighters’ protective gear has drastically reduced combat fatalities, with the vital organs being most efficiently protected; however, simultaneously, more Soldiers and Veterans are returning from battle with greater incidence of PNIs, mainly in the lower and upper limbs that are less protected than the head and the torso. Because severe PNIs do not spontaneously heal efficiently, the need for nerve transplants and/or other surgical reconnection of the severed nerves is required. However, despite being of one of the most common injuries treated in the military health system, there is currently no treatment or procedure that enables fast and complete recovery of patients after PNIs. Often patients have to undergo multiple long and complex surgical procedures that have a very limited success rate. Because of this lack of efficient therapeutic strategies, many of these patients will experience lifelong symptoms such as chronic pain, weakness, and limb paralysis, which drastically affect their quality of life. There is an unmet need for tissue engineering solutions that enable fast regeneration of peripheral nerves in desired locations only. To solve this unmet need, here we propose to design and assess the efficacy of a novel class of hydrogel-based biomaterials that could be used to provide the physical and biological support to neurons that is necessary to promote their growth and facilitate peripheral nerve repair. Although engineered biomaterials are not new in the treatment of PNIs, our strategy could change the way these hydrogels are currently designed and manufactured. The innovation of our solution derives from the use of DNA nanotechnology tools that allow us to use DNA as a building block for these hydrogels. The extraordinary flexibility and strength of DNA as a biomaterial will allow us to tune the mechanical and electrical properties to match those of the native nerve tissue with unprecedented precision, providing the most realistic environment possible for the nerve cells that is ideally conducive to PN repair. In addition, the pre-assembled DNA skeleton will help guide the conjugation of molecules that promote tissue repair. The DNA skeleton will be further reinforced with conductive polymers to provide conductivity to the hydrogel, which is a critical features of peripheral nerve tissues. Pending demonstration of success in this simple in vitro proof-of-principle study, we will pursue additional efforts to improve the formulation and the stability of our DNA-based hydrogel to support animal models of PNIs. We will particularly focus our efforts on incorporating this hydrogel formulation in hollow nerve guidance conduit that could be used to reconnect the two nerve stumps of a dissected peripheral nerve. The results obtained in this project will be foundational to our long-term efforts to acquire U.S. Food and Drug Administration approval for a novel tissue engineering candidate to treat peripheral nerve injuries. Moreover, if our strategy is successful, it will serve as proof of principle for the application of this novel and versatile scaff
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310037
Entities
People
- Rémi Veneziano
Organizations
- George Mason University
- United States Army