Study On The Role Of New Diagnostic And Therapeutic Integrated Materials In The Repair And Imaging Of Peripheral Nerve Injury

Peripheral nerve injury(PNI)is a worldwide public health problem which is plagued by clinical practice because of its high incidence rate and poor functional recovery.After peripheral nerve trauma and degenerative injury,the functional specificity of nerve tissue determines the proportion of disability and the degree of harm is much higher than that of other tissue injuries.The rapid regeneration and early diagnosis of nerve injury limit the therapeutic effect of peripheral nerve injury at the same time.At present,clinical physical examination and electrophysiological diagnosis are still two main methods to diagnose and monitor peripheral nerve injury.However,these methods are not ideal for timely and accurate evaluation of nerve recovery,which often leads to delayed diagnosis and missed the best operation period.In view of the timeliness and personalized needs of neurotherapy,there is an urgent need for an early,direct and accurate detection method to evaluate the level of nerve regeneration and better judge the repair effect of peripheral nerve.This will not only help to better understand the mechanism of natural nerve regeneration,but also help to provide a visual and controllable intervention environment for the regeneration process.In recent years,the concept of nano therapeutic diagnostics has been paid more and more attention by neuroscientists.It relies on composite nano materials with dual functions of diagnosis and treatment.It can realize image-based navigation therapy and clarify the repair effect in the early stage of treatment.It may also be used to evaluate the biological distribution of therapeutic drugs or specific molecular targets during intervention.Therefore,multifunctional nano diagnosis and treatment integrated materials are potential tools in the field of Neuromedicine.By organically combining several nano treatment technologies and imaging strategies,it is expected to realize early diagnosis,individualized precise treatment and long-term noninvasive monitoring of peripheral nerve injury.Focusing on multiple repair nodes of peripheral nerve regeneration,this paper constructs two new integrated nano platforms for diagnosis and treatment of different types of nerve injuries,and systematically studies their nerve repair effect,intervention mechanism and neuroimaging ability,which are summarized into the following two parts.1.Novel iron oxide nanosphere-Fe3O4@COOH-BDA)promotes the repair of peripheral nerve injury and long-term anterograde tracing research.In this study,we successfully prepared an MRI and Pai dual-mode anterograde nerve Tracer Probe(microsphere)with high spatial resolution and deep tissue penetrationFe3O4@COOH-BDA),which can dynamically describe the process of axon extension through axon internalization and participation in anterograde axoplasmic transport.Through the comparison of in vivo imaging and specific immune results of nerve regeneration after injury,it is confirmed that it realizes the noninvasive in vivo tracking of peripheral nerve injury and regeneration,and has high spatial resolution,penetration depth and rich contrast.At the same time,the introduction of microfluidic microsphere encapsulation technology limits the leakage of tracer,which provides a good visualization of neural anatomy and improves the continuous tracking effect.Different from other imaging methods focusing on the spatial localization of subcellular structures such as myelin sheath,we pay more attention to the macro description of axoplasmic transport,and the relatively long-term observation results may also provide some supplementary information for "regeneration tracking" and longitudinal monitoring of nerve regeneration.2.Exosome encapsulated anti ROS carbon dots(r-cds)-IR@exo Study on the early diagnosis and treatment of diabetic peripheral neuropathy(DPN)rats.This study will further expand the aforementioned method of diagnosis and treatment in the early diagnosis and treatment of diabetic peripheral nerve injury.Aiming at oxidative stress,an important mechanism of DPN,we successfully synthesized carbon dots(R-CDs)with dual functions of blue fluorescence and ROS clearance.In order to realize in vivo imaging diagnosis and improve the internalization and utilization of carbon dots,R-CDs and irdye-800 cw co transfected exosomes(CDS)were constructed by in vitro electroporation-IR@exo)Exosome was labeled with blue / near-infrared light,and nerve targeting peptides hnp401 and CDs were modified on the surface of exosome-IR@exo Sciatic nerve tissue imaging can be performed through blue light channel and saphenous nerve in vivo imaging can be performed through near-infrared light channel.Exosome packaging can effectively improve the nerve internalization rate and prolong the retention time of ir-800.After establishing the animal model of diabetic peripheral neuropathy in rats,the effect of DPN on the nerve injury was preliminarily verified.After 4 weeks of local administration,the apoptosis of DPN cells in the treatment group was significantly reduced,and the number of sensory fibers in the innervation area increased.Compared with DPN injury group,sciatic nerve ultrastructure showed Schwann cell contraction,myelin sheath structure separation and mitochondrial destruction.The treatment group showed the characteristics of more complete Schwann cell morphology,normal appearance of myelin sheath intima and reduced mitochondrial vacuolation.Combined with whole proteomic assay and downstream verification,R-CDs can slow down the nerve damage caused by mitochondrial dysfunction through anti ROS effect,and has the potential to be used as nano drugs for early intervention of DPN.In conclusion,this study focuses on the research pain point of peripheral nerve injury repair and imaging.Taking nano therapeutic diagnostics as the research tool,aiming at the three research dimensions of deep nerve imaging,regulation of nerve regeneration microenvironment and diagnosis and treatment of degenerative nerve diseases,this study has created two new integrated intervention systems for diagnosis and treatment of nerve injury,which are expected to provide new theoretical basis and treatment means for accurate and personalized treatment of peripheral nerve diseases,It is of great significance to improve the repair level of nerve injury.