Development of Tissue Engineered Neuromuscular Interfaces from GalSafe Neurons.

从 GalSafe 神经元开发组织工程神经肌肉接口。

• 批准号: 10385405
• 负责人: Kritika Katiyar
• 金额: $ 25.04万
• 依托单位: AXONOVA MEDICAL, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-15 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10385405
• 关键词: Address; Afferent Neurons; Animals; Architecture; Autologous Transplantation; Axon; Axotomy; Biological Assay; Biological Products; Biomass; Bungarotoxins; Caliber; Carbohydrates; Cell Differentiation process; Cell Survival; Cells; Chronic; Clinic; Clinical; Clinical Trials; Control Groups; Cyclic GMP; Defect; Development; Distal; Embryo; Engineering; Environment; Enzyme-Linked Immunosorbent Assay; FDA approved; Family suidae; Functional Regeneration; Galactosidase; Genetic Engineering; Harvest; Human; Hydrogels; Immune response; Implant; In Vitro; Induced pluripotent stem cell derived neurons; Injectable; Injury; Label; Laboratories; Lactate Dehydrogenase; Lesion; Licensing; Maintenance; Medical; Modeling; Motor; Motor Neurons; Multiple Trauma; Muscle; Muscle Cells; Muscle function; Natural regeneration; Nerve; Nervous system structure; Neuromuscular Junction; Neurons; Operative Surgical Procedures; Organ; Outcome; Patients; Pennsylvania; Peripheral nerve injury; Phase; Play; Population; Process; Protocols documentation; Proxy; Quality of life; Rattus; Recovery; Recovery of Function; Risk; Rodent; Schwann Cells; Sensory; Site; Small Business Innovation Research Grant; Source; Spinal Cord; Structure; Synaptophysin; Techniques; Testing; Time; Tissue Engineering; Tissue Transplantation; Tissues; Trauma; Tumorigenicity; Universities; axon regeneration; biofabrication; clinical practice; design; efficacy study; experience; human stem cells; immunocytochemistry; implantation; in vivo; in vivo evaluation; injury and repair; limb injury; manufacturing process; meetings; minimally invasive; nerve damage; nerve injury; nerve repair; nerve supply; neural network; neuromuscular; peroneal nerve; phase 2 study; porcine model; pre-clinical; preclinical safety; preservation; product development; programs; regenerative; reinnervation; repair strategy; repaired; safety study; standard of care

PROJECT SUMMARY Major peripheral nerve injury (PNI) is classified as an injury with a long defect (≥3cm) or occurring proximally, requiring long regenerative distances of the host nerve to distal structures (distal nerve, target muscle, etc.). These features result in minimal, if any, functional regeneration as the distal nerve and muscle often degenerate before the host nerve is able to reinnervate these structures due to inherently slow regeneration rates. Since current standard clinical practices delay repairing nerve injuries until the patient (in cases of polytrauma) or the injury site is stabilized, functional recovery is often extremely limited. In order to maintain the innervation capability of nerves and muscles following injury, the team at Axonova Medical has developed a proxy for these degenerating axons to maintain or “babysit” the distal structures until the host axons are able to reinnervate the distal targets. This product, the tissue engineered neuromuscular interface (TE-NMI), consists of axon tracts spanning a discrete population of neurons within a hydrogel column. Notably, the diameter of TE-NMIs is designed to be on the scale of micrometers, making them easily injectable to facilitate incorporation into current standard of care practices in the clinic. In pre-clinical rodent studies, TE-NMIs have been seen to extend axons into distal structures post implantation, resulting in babysitting of distal nerve and muscle, therefore keeping it receptive to eventual host axon reinnervation. Previously, laboratory-grade TE-NMIs have been fabricated using primary rat and porcine neurons as well as human induced pluripotent stem cell (iPSC)-derived neurons. In this study, a clinical product will be developed and characterized using GalSafe® neurons as the starting biomass. GalSafe® tissue is an FDA-approved xenogeneic source produced by Revivicor, Inc. Revivicor has genetically engineered swine to produce tissue lacking a carbohydrate, known as -galactosidase, that is known to play a key role in eliciting an immune response in humans. GalSafe® neurons are harvested from the spinal cords of GalSafe® swine embryo, and is the chosen biomass for Axonova’s other product, tissue engineered nerve grafts (TENGs). For this proposal, initial characterization and a preliminary in vivo study to determine the efficacy of TE-NMIs to promote recovery in a chronic axotomy model in swine will be carried out. Successful execution of these studies will accelerate preclinical safety and efficacy studies and will be incorporated in Axonova’s IND application. Overall, TE-NMIs hold promise in transforming the field of nerve repair by significantly increasing the clinical window for PNI repair.

项目总结