Biopolymer-nanotube nerve guidance conduit drug delivery for peripheral nerve regeneration:In vivo structural and functional assessment  

作　　者：Ohan S.Manoukian Swetha Rudraiah Michael R.Arul Jenna M.Bartley Jiana T.Baker Xiaojun Yu Sangamesh G.Kumbar 

机构地区：[1]Department of Biomedical Engineering,University of Connecticut,Storrs,CT,USA [2]Department of Orthopedic Surgery,University of Connecticut Health,Farmington,CT,USA [3]Department of Pharmaceutical Sciences,University of Saint Joseph,Hartford,CT,USA [4]Department of Immunology,Center on Aging,University of Connecticut Health,Farmington,CT,USA [5]Department of Biomedical Engineering,Stevens Institute of Technology,Hoboken,NJ,USA

出　　处：《Bioactive Materials》2021年第9期2881-2893,共13页生物活性材料（英文）

基　　金：The authors acknowledge funding support from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health(R01EB020640);Department of Defense through the Peer Reviewed Orthopaedic Research Program under Award No.[W81XWH-13-1-0320];Ohan S.Manoukian is the recipient of the National Science Foundation(NSF)Graduate Research Fellowship(Grant No.DGE-1747453).

摘　　要：Peripheral nerve injuries account for roughly 3%of all trauma patients with over 900,000 repair procedures annually in the US.Of all extremity peripheral nerve injuries,51%require nerve repair with a transected gap.The current gold-standard treatment for peripheral nerve injuries,autograft repair,has several shortcomings.Engineered constructs are currently only suitable for short gaps or small diameter nerves.Here,we investigate novel nerve guidance conduits with aligned microchannel porosity that deliver sustained-release of neurogenic 4-aminopyridine(4-AP)for peripheral nerve regeneration in a critical-size(15 mm)rat sciatic nerve transection model.The results of functional walking track analysis,morphometric evaluations of myelin development,and histological assessments of various markers confirmed the equivalency of our drug-conduit with autograft controls.Repaired nerves showed formation of thick myelin,presence of S100 and neurofilament markers,and promising functional recovery.The conduit’s aligned microchannel architecture may play a vital role in physically guiding axons for distal target reinnervation,while the sustained release of 4-AP may increase nerve conduction,and in turn synaptic neurotransmitter release and upregulation of critical Schwann cell neurotrophic factors.Overall,our nerve construct design facilitates efficient and efficacious peripheral nerve regeneration via a drug delivery system that is feasible for clinical applications.

关 键 词：Peripheral nerve regeneration Nerve guidance conduit Sciatic nerve transection Small-molecule drug delivery Neurotrophic factor Functional recovery 

分 类 号：TB383[一般工业技术—材料科学与工程]