Use of Engineered Nervous Tissue Constructs to Repair Extensive Nerve Injury Each year approximately 360,000 people in the United States suffer a peripheral nerve injury, which is a leading source of lifelong disability. While a primary strategy to repair major peripheral nerve injury is to bridge the damage with autologous nerve grafts, producing nerves of sufficient length and number has posed a significant challenge. The so called """"""""gold standard"""""""" in peripheral nerve graft repair (i.e. the autologous nerve graft) is limited by the time consuming harvesting of donor nerves and complications arising from the harvesting surgery. In addition, most alternative methods currently used for nerve graft repair (e.g., synthetic tubes) are limited in the length that they can span to promote repair and are typically used for gaps of less than 2 or 3 cm. Here, we propose to utilize a novel tissue engineering technique to create transplantable nervous tissue constructs for major peripheral nerve repair. The key of this procedure is to use a specially designed microstepper motor system to produce continuous mechanical tension on axons spanning two populations of neurons in culture. As our central hypothesis, we propose that engineered living nervous tissue constructs will promote recovery after major peripheral nerve injury by providing a living labeled pathway to guide host axons from the proximal nerve stump across large nerve lesions to reinnervate the target tissue. In addition to providing a pathway through the injured gap, we also propose that axons from the construct will grow into both the proximal and distal nerve stumps. In the first part of this proposal, we will repair acute extensive acute nerve injury in an animal model using our novel living engineered nervous tissue constructs. In the second part of this study, we will attempt major reconstruction of brachial plexus injury in rodents, spanning the forelimb from the vertebrae to the paw using our living nervous tissue constructs. We will directly compare the outcome of animals receiving the nervous tissue construct containing the elongated dorsal root ganglion cell cultures with groups receiving conventional autologous nerve reconstruction (reverse autologous graft), repair with a synthetic tube alone (material substrate control), no repair (no treatment control), immunosuppression control (receiving daily cyclosporine A injection) and physical rehabilitation control. In the third part of this study, we will assess the immunogenicity of our nervous tissue construct. We will investigate the hypothesis that the lack of MHC I expression in our elongated DRG neurons is the main reason that immunorejection does not occur in transplanted hosts. If successful, our novel tissue engineered nerve construct could revolutionize methods for major nerve reconstruction by providing laboratory grown 'off-the-shelf'living nerves ready for transplant in patients with extensive peripheral nerve injuries.
In this study we propose to use a fundamentally novel tissue engineering technique to create nerve constructs for repair of extensive nerve injury in an animal model. If successful, our findings could benefit patients with devastating nerve injuries by providing laboratory grown 'off-the-shelf'living nerves ready for transplant.
|Lyon, Kristopher A; Huang, Jason H (2018) Bevacizumab as an adjuvant therapy for glioblastoma in elderly patients: the facts. Transl Cancer Res 7:S802-S805|
|Nizamutdinov, Damir; Stock, Eileen M; Dandashi, Jad A et al. (2018) Prognostication of Survival Outcomes in Patients Diagnosed with Glioblastoma. World Neurosurg 109:e67-e74|
|Sulhan, Suraj; Lyon, Kristopher A; Shapiro, Lee A et al. (2018) Neuroinflammation and blood-brain barrier disruption following traumatic brain injury: Pathophysiology and potential therapeutic targets. J Neurosci Res :|
|Wang, Fushun; Pan, Fang; Shapiro, Lee A et al. (2017) Stress Induced Neuroplasticity and Mental Disorders. Neural Plast 2017:9634501|
|Lantrip, Crystal; Huang, Jason H (2017) Cognitive Control of Emotion in Older Adults: A Review. Clin Psychiatry (Wilmington) 3:|
|Berman, Marvin H; Halper, James P; Nichols, Trent W et al. (2017) Photobiomodulation with Near Infrared Light Helmet in a Pilot, Placebo Controlled Clinical Trial in Dementia Patients Testing Memory and Cognition. J Neurol Neurosci 8:|
|Wang, Fushun; Wang, Xiaowei; Shapiro, Lee A et al. (2017) NKCC1 up-regulation contributes to early post-traumatic seizures and increased post-traumatic seizure susceptibility. Brain Struct Funct 222:1543-1556|
|Wu, Qiuqian; Huang, Jason H (2017) Intervertebral Disc Aging, Degeneration, and Associated Potential Molecular Mechanisms. J Head Neck Spine Surg 1:|
|Wang, Fushun; Yuan, Tifei; Pereira Jr, Alfredo et al. (2016) Glial Cells and Synaptic Plasticity. Neural Plast 2016:5042902|
|Konda, Sneha; Dayawansa, Samantha; Huang, Jason H (2016) The Evolution and Challenge of the Zika virus and its Uncharted Territory in the Neurological Realm. J Neuroinfect Dis 7:|
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