Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats  

作　　者：Justin C.Burrell Suradip Das Franco A.Laimo Kritika S.Katiyar Kevin D.Browne Robert B.Shultz Vishal J.Tien Phuong T.Vu Dmitriy Petrov Zarina SAli Joseph M.Rosen D.Kacy Cullen 

机构地区：[1]Center for Brain Injury&Repair,Department of Neurosurgery,Perelman School of Medicine,University of Pennsylvania,Philadelphia,PA,USA [2]Department of Bioengineering,School of Engineering&Applied Science,University of Pennsylvania,Philadelphia,PA,USA [3]Center for Neurotrauma,Neurodegeneration&Restoration,Corporal Michael J.Crescenz Veterans Affairs Medical Center,Philadelphia,PA,19104,USA [4]Axonova Medical,LLC,Philadelphia,PA,USA [5]Dartmouth-Hitchcock Medical Center,Division of Plastic Surgery,Dartmouth College,Lebanon,NH,USA

出　　处：《Bioactive Materials》2022年第12期339-353,共15页生物活性材料（英文）

基　　金：The authors would like to thank Elizabeth Boyle for technical support.Financial support provided by the U.S.Department of Defense[CDMRP/JPC8-CRMRP W81XWH-16-1-0796(Cullen)&CDMRP/PRORP W81XWH-19-1-0867(Cullen&Das)];the Department of Veterans Affairs[BLR&D Merit Review I01-BX003748(Cullen)];the National Institutes of Health[R44-NS108869(Katiyar&Cullen);T32-EB005583(Shultz),TL1-TR001880(Burrell)];the Center for Undergraduate Research and Fellowships at the University of Pennsylvania.Opinions,interpretations,conclusions and recommendations are those of the author(s)and are not necessarily endorsed by the Department of Defense,the Department of Veterans Affairs,or the National Institutes of Health.

摘　　要：Nerve injury requiring surgical repair often results in poor functional recovery due to the inability of host axons to re-grow long distances and reform meaningful connections with the target muscle. While surgeons can re-route local axon fascicles to the target muscle, there are no technologies to provide an exogenous source of axons without sacrificing healthy nerves. Accordingly, we have developed tissue engineered neuromuscular interfaces (TE-NMIs) as the first injectable microtissue containing motor and sensory neurons in an anatomically-inspired architecture. TE-NMIs provide axon tracts that are intended to integrate with denervated distal structures and preserve regenerative capacity during prolonged periods without host innervation. Following implant, we found that TE-NMI axons promoted Schwann cell maintenance, integrated with distal muscle, and preserved an evoked muscle response out to 20-weeks post nerve transection in absence of innervation from host axons. By repopulating the distal sheath with exogenous axons, TE-NMIs also enabled putative delayed fusion with proximal host axons, a phenomenon previously not achievable in delayed repair scenarios due to distal axon degeneration. Here, we found immediate electrophysiological recovery after fusion with proximal host axons and improved axon maturation and muscle reinnervation at 24-weeks post-transection (4-weeks following delayed nerve fusion). These findings show that TE-NMIs provide the potential to improve functional recovery following delayed nerve repair.

关 键 词：Nerve regeneration Neuromuscular injury Muscle preservation Tissue engineering Microtissue Axon fusion 

分 类 号：R741[医药卫生—神经病学与精神病学]