Vascularized Denervated Muscle Targets and Funnel Conduits for Surgical Prevention/Treatment of Symptomatic Neuromas
Abstract
Any time a nerve is injured and not repaired, a neuroma will form on the end of the proximal nerve stump. Neuromas are aggregates of free nerve endings regenerating from the proximal nerve stump without a target to reinnervate. Neuromas often cause severe, debilitating pain that is difficult to treat. Among the many causes of nerve injury resulting in neuroma formation, extremity amputation is particularly problematic, given that multiple large caliber nerves are necessarily transected, and the proximal nerve stumps are then left in discontinuity. As a result, amputees tend to suffer from severe, intractable neuroma pain, with estimates of prevalence ranging from 25% to 75%. Residual limb pain following amputation often limits prosthetic use and can have profound effects on functional status, activities of daily living, and overall quality of life. Post-amputation neuroma pain is a major problem affecting both the military and civilian populations that is expected to worsen as extremity amputations become more common, largely driven by the increased prevalence of peripheral vascular disease. In 2005, there were 1.6 million Americans with limb loss, and that number is expected to double by 2050. The prevalence of traumatic limb loss in the military has also increased as a result of the recent and ongoing conflicts in Iraq and Afghanistan. A total of 1,718 United States Service members sustained one or more combat-related extremity amputations between 2001 and 2017. This unfortunate trend has largely been driven by an increased exposure to improvised explosive devices (IEDs) along with advances in personal protective equipment (PPE) that have increased the chances of survival, but leave the extremities vulnerable to serious injury, particularly from upward-directed blast forces. Neuroma pain is very difficult to control with medications. There are many different surgical strategies, but they all have significant limitations. With this in mind, we seek to introduce two novel strategies to address this difficult problem: (1) vascularized denervated muscle targets (VDMTs) offer a novel surgical approach that has the potential to provide superior outcomes by combining the benefits of previously described approaches while also avoiding their pitfalls; (2) funnel conduit with chondroitin sulfate proteoglycan (CSPG)- incorporated nanofiber hydrogel composite (NHC) matrix offers a novel bioengineered device intended to improve treatment outcomes of targeted motor reinnervation (TMR), one of the more promising contemporary approaches to treat TMR. In the proposed studies, we aim to develop and test VDMTs and funnel conduits with CSPG-incorporated NHC in translational rodent studies, confirm the hypothesized benefits in treating and preventing neuroma formation, and in doing so advance these novel and highly translatable solutions towards clinical application. As a surgical approach, VDMTs will be quickly adopted into clinical practice if efficacy can be demonstrated in robust preclinical studies, which in turn will lead to rigorous clinical studies to confirm efficacy and superiority over the current approaches. The funnel conduit with CSPG-incorporated NHC is derived from well-developed components that have demonstrated ideal properties for this new purpose in prior collaborative endeavors by the lead investigators. The device is composed of materials currently used in FDA-approved products, and the manufacturing method is easily scalable. The study team has demonstrated success in commercializing bioengineered products for clinical use. These factors taken together will facilitate rapid clinical translation. The approaches we seek to introduce have the potential to offer profound benefits to Warfighters suffering from painful neuromas as a result of extremity amputation or isolated nerve injury. By alleviating their severe, chronic neuroma pain, they will experience dramatic improvement in quality of life.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110172
Entities
People
- Sami Tuffaha
Organizations
- Johns Hopkins University
- United States Army