A Red Blood Cell Drug Carrier Specifically Binding To Collagen For Spinal Cord Injury Repair

Spinal cord injury(SCI),a disorder of central nervous system,which usually accompanied by a large loss of sensory and muscle function.And after the injury,the production of a large number of inhibitory molecules and the deposition of glial scars lead to a local inhibitory microenvironment Due to the complex microenvironment formed after SCI,there is no effective treatment currently and regeneration of severe SCI is still regarded as one of the most challenging problems in clinical research.To date,therapeutic strategys for SCI mainly focus on a combinations of scaffold materials and seed cells or active molecules.Previous studies have shown that paclitaxel(PTX)could prevent the formation of axon retraction bulbs,decrease axonal degeneration,and improve behaviors in rat spinal cord injury model.And it is a identify reliable agent for directing neuronal differentiation of neural stem cells effectively into neurons.However,the functional molecule has a short half-life,in addition,the primary challenges with active molecules in combination with scaffold for spinal cord injury repair in vivo is the rapid clearance through cerebrospinal fluid flow,resulting in premature release of therapeutics,with loss in the control of delivery and maintain an effective therapeutic concentration in situ,which is conducive to limited improvement in functional recovery.In this study,we established a PTX-loaded erythrocyte system that can specifically bind to collagen,which aimed to achieve maintained locally concentration and sustained release of drugs.Moreover,to verify the role of locally enrichment and sustained release in vivo,a model of completely transecting the rat spinal cord for 4mm was created and following immediately implanted.Scanning electron microscopy and flow cytometry showed that the addition of functional peptides(PEP)allowed the PTX-loaded erythrocyte to specifically bind to the collagen scaffold.Moreover,the release of paclitaxel in vitro was about 70.77%within 48 hours,indicating an effect of prolonging drug release.At week 12 post-surgery,immunohistochemistry method was used to evaluate the nerve regeneration in the leision site.The results showed that the group assembleing with functional peptide can effectively induce neurons regeneration in the injury site compared with the other experimental groups.In addition,it also has a potential to enhance axonal regeneration and reduce scar formation after SCI.During the observation period,the motor functional recovery of SCI animals was evaluated by Basso-Beattie-Bresnahan(BBB)scoring once per week.The scoring results revealed that animals in that group showed better behavior function recovery.In conclusion,the collagen binding PTX-loaded erythrocyte system,achieved successful encapsulation and prolonged release of paclitaxel,and specifically anchord drug-loaded erythrocytes on scaffold materials through PEP to maintain the concentration of drugs locally,which ultimately improved the recovery of behavioral function after spinal cord injury in rats and improved the quality of repair.Our work may provide a new approach to the treatment of spinal cord injury with a combination of molecules and scaffold materials,as well as a viable potential treatment strategy.