Superparamagnetic particle scaffold for regenerating damaged neural tissue

Abstract

The invention generally relates to a method of regenerating a nerve fiber in a damaged neural tissue of a patient, the method comprising the steps of: administering an aqueous formulation comprising superparamagnetic particles to the damaged neural tissue in the patient; applying a magnetic field in an orientation which is parallel to the nerve fiber; using the magnetic field for aligning the superparamagnetic particles; forming one or more aligned chains of the superparamagnetic particles in the magnetic field as a scaffold to guide directional growth of regenerating nerve cells; and reconnecting damaged nerve ends in the damaged neural tissue of the patient.

1 . (canceled) 
     
     
         2 . A method of regenerating a nerve fiber in a damaged neural tissue of a patient, the method comprising:
 (a) administering a formulation of superparamagnetic particles to said damaged neural tissue, wherein the formulation does not comprise a liposome; and   (b) applying a magnetic field to said damaged neural tissue.   
     
     
         3 . The method of  claim 2 , wherein said magnetic field is configured to align said superparamagnetic particles. 
     
     
         4 . The method of  claim 3 , wherein said aligning comprises forming one or more aligned chains of said superparamagnetic particles as a scaffold. 
     
     
         5 . The method of  claim 4 , wherein said scaffold guides directional growth of regenerating nerve cells. 
     
     
         6 . The method of  claim 2 , wherein said superparamagnetic particles comprise a functionalized surface comprising one or more chemical moieties. 
     
     
         7 . The method of  claim 6 , wherein said one or more moieties are selected from the group consisting of: a carbohydrate, a protein, a lipid, a glass, an oligosaccharide, a peptide, a laminin, a biotin, an avidin, a streptavidin, a DNA, a cross-linking agent, a thiol, a sulfide, an oxide, a sulfhydryl, a sulfide, a disulfide, a sulfinyl, a sulfoxide, a sulfonyl, a sulfone, a sulfinic acid, a sulfino, a sulfonic acid, a sulfo, a thioketone, a carbonothioyl, a thial, a primary amine, a secondary amine, a tertiary amine, a carboxylate, a carboxyl, an alkoxy, a hydroperoxy, a peroxy, an alkyl, an alkene, an alkyne, an aryl derivative, a halo group, a hydroxyl, a carbonyl, an aldehyde, an acyl halide, an ester, a carbonate ester, an ether, a hemi-acetal, a hemiketal, a ketal, an orthoester, a methylenedioxy, a cycloalkyl, a heterocyclic, a heteroaryl, an orthocarbonate ester, a carboxamide, a primary ketimine, a secondary ketimine, a primary aldimine, a secondary aldimine, an imide, a nitro, a phosphonic acid, a phosphate, a phosphodiester, a nitrile, an isonitrile, an isocyanate, an antibody, a pharmaceutical excipient, a pH buffer, a cerium oxide nanoparticle, a manganese dioxide nanoparticle, EDTA, EGTA, NTA, HEDTA, a cytokine, and any combination thereof. 
     
     
         8 . The method of  claim 6 , wherein said superparamagnetic particles comprise Janus particles. 
     
     
         9 . The method of  claim 8 , wherein said superparamagnetic particles comprise a first surface functionalized with a first chemical moiety and a second surface functionalized with a second chemical moiety. 
     
     
         10 . The method of  claim 9 , wherein said first chemical moiety comprises a thiol and wherein said second chemical moiety comprises an amine. 
     
     
         11 . The method of  claim 9 , wherein said first chemical moiety comprises a carboxylic acid and wherein said second chemical moiety comprises an amine. 
     
     
         12 . The method of  claim 2 , wherein said formulation further comprises a molecule selected from the group consisting of: a neuronal cell growth factor, a chemotactic factor, a cell proliferation factor, a directional cell growth factor, a neuronal regeneration signaling molecule, a laminin, an inhibitor of glial cell induced scar formation, an inhibitor of astrocyte cell induced scar formation, an inhibitor of oligodendrocyte cell induced scar formation, an inhibitor of astrocyte precursor cell induced scar formation, an inhibitor of oligodendrocyte precursor cell induced scar formation, an inhibitor of 4-sulfation on astrocyte-derived chondroitin sulfate proteoglycan, an inhibitor of chondroitin sulfate proteoglycan phosphacan, an inhibitor of chondroitin sulfate proteoglycan neurocan, a chondroitinase-ABC, an inhibitor of chondroitin sulfate proteoglycan 4, an inhibitor of neuron-glial antigen 2, an antibody to chondroitin sulfate proteoglycan 4, an antibody against neuron-glial antigen 2, an inhibitor of glial cell expression of chondroitin sulfate proteoglycan 4, an inhibitor of glial cell expression of neuron-glial antigen 2, an inhibitor of keratan sulfate synthesis, an inhibitor of glial cell expression of an enzyme involved in keratin sulfate synthesis, an inhibitor of an oligodendritic cell debris origin neuroregeneration inhibiting protein, an inhibitor of a glial cell debris origin neuroregeneration inhibiting protein, an antibody against myelination inhibitory factor NI-35, an antibody against myelination inhibitory factor NOGO, an anti-oxidants, cerium oxide nanoparticles, an amino acid, a phospholipid, a lipid, a vitamin, an anticoagulant, and any combination thereof. 
     
     
         13 . The method of  claim 2 , wherein said damaged neural tissue is in the brain of said patient. 
     
     
         14 . The method of  claim 2 , wherein said damaged neural tissue is in the spinal cord of said patient. 
     
     
         15 . The method of  claim 2 , wherein said damaged neural tissue is in the peripheral nervous system of said patient. 
     
     
         16 . The method of  claim 4 , further comprising a step of stabilizing said one or more aligned chains of said superparamagnetic particles with a cross-linking polymer architecture for locking said one or more aligned chains of said superparamagnetic particles. 
     
     
         17 . The method of  claim 16 , wherein said cross-linking polymer architecture is selected from the group consisting of a cross-linking homopolymer of said superparamagnetic particles, a cross-linking junction controlled branch polymer of said superparamagnetic particles, and a combination thereof. 
     
     
         18 . The method of  claim 16 , wherein said cross-linking polymer architecture is formed using molecules selected from the group consisting of: psoralen, methyl methacrylate, avidin, streptavidin, antibodies, antigens, ligands, biotin, laminin, fluorescein, DNA, DNA origami, DNA dendrimers, aptamers, protein-protein binding, protein-DNA binding, metal ion chelators, His-tags, polyethylene glycol-linkers, agarose, acrylamide, collagen, phase transfer catalysts, and any combination thereof. 
     
     
         19 . The method of  claim 2 , wherein said superparamagnetic particles comprise dimensions selected from the group consisting of: between about 0.5 microns to about 10 microns in diameter, between about 0.1 microns to about 5 microns in diameter, between about 1 micron to about 20 microns in diameter, between about 2 microns to about 40 microns in diameter, between about 3 microns to about 10 microns in diameter, between about 1 micron to about 15 microns in diameter, between about 0.05 microns to about 100 microns in diameter, between about 5 microns to about 500 microns in diameter, and any combination thereof. 
     
     
         20 . The method of  claim 1 , wherein said magnetic field has a strength of between about 1 millitesla (mT) to about 500 mT. 
     
     
         21 . The method of  claim 2 , further comprising placing a healthy section of neural tissue from said patient into an area of said damaged neural tissue of said patient prior to said administering said formulation.