Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles.
Spinal cord injury results in immediate disruption of neuronal membranes, followed by extensive secondary neurodegenerative processes. A key approach for repairing injured spinal cord is to seal the damaged membranes at an early stage. Here, we show that axonal membranes injured by compression can be effectively repaired using self-assembled monomethoxy poly(ethylene glycol)-poly(d,l-lactic acid) di-block copolymer micelles. Injured spinal tissue incubated with micelles (60 nm diameter) showed rapid restoration of compound action potential and reduced calcium influx into axons for micelle concentrations much lower than the concentrations of polyethylene glycol, a known sealing agent for early-stage spinal cord injury. Intravenously injected micelles effectively recovered locomotor function and reduced the volume and inflammatory response of the lesion in injured rats, without any adverse effects. Our results show that copolymer micelles can interrupt the spread of primary spinal cord injury damage with minimal toxicity.
Shi
Yunzhou
Y
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, USA.
Kim
Sungwon
S
Huff
Terry B
TB
Borgens
Richard B
RB
Park
Kinam
K
Shi
Riyi
R
Cheng
Ji-Xin
JX
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D019344:Lactic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008823:Micelles; D009043:Motor Activity / Q000187:drug effects; D011091:Polyesters; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011108:Polymers / Q000009:adverse effects / Q000627:therapeutic use*; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy*
D008823:Micelles; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide)