Biofunctionalized PEDOT-coated microfibers for the treatment of spinal cord injury

被引:43
作者
Alves-Sampaio, Alexandra [1 ]
Garcia-Rama, Concepcion [1 ]
Collazos-Castro, Jorge E. [1 ]
机构
[1] Hosp Nacl Paraplej SESCAM, Neural Repair & Biomat Lab, Finca La Peraleda S-N, Toledo 45071, Spain
关键词
Microfibers; PEDOT; Functionalization; Spinal cord injury; Axonal; Regeneration; CONDUCTING POLYMERS; GROWTH-FACTOR; INTRASPINAL MICROSTIMULATION; ELECTRICAL-STIMULATION; NEURITE OUTGROWTH; AXONAL DIEBACK; SCAR FORMATION; IN-VITRO; TISSUE; REGENERATION;
D O I
10.1016/j.biomaterials.2016.02.037
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
PoIy(3, 4-ethylenedioxythiophene)-coated carbon microfibers (PEDOT-MFs) hold promise for developing advanced neuroprostheses and neural repair devices. We investigated the chronic cellular responses to PEDOT-MFs implanted into the uninjured and the transected rat spinal cord, and compared the effects of polymer surface biofunctionalization with covalently attached polylysine (PLL) or a multimolecular complex of PLL, heparin, basic fibroblast growth factor (bFGF), and fibronectin. An alginate gel was used to facilitate microfiber implantation and reduce connective tissue scarring after spinal cord injury (SCI). PLL/heparin/bFGF/fibronectin-functionalized PEDOT-MFs showed excellent integration within the uninjured and injured spinal cord, frequently establishing contact with neuronal somas, axons, dendrites and glial cells, accompanied by very little or absent scarring response. On the contrary, non-functionalized and PLL-functionalized microfibers provoked inflammation and fibrosis with loss of neural elements in the surrounding tissue. Within the lesion, the PEDOT-MFs by themselves facilitated longitudinal alignment of migratory cells and growing axons, and their modification with PLL/heparin/bFGF/fibronectin promoted tissue healing, enhancing blood vessel formation and axonal regeneration without increasing inflammation. These results support the incorporation of biofunctionalized electro-conducting microfibers in neuro electronic interfaces and lesion-bridging systems for the treatment of SCI. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:98 / 113
页数:16
相关论文
共 80 条
[1]   Conducting-polymer nanotubes for controlled drug release [J].
Abidian, MR ;
Kim, DH ;
Martin, DC .
ADVANCED MATERIALS, 2006, 18 (04) :405-+
[2]   Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans [J].
Angeli, Claudia A. ;
Edgerton, V. Reggie ;
Gerasimenko, Yury P. ;
Harkema, Susan J. .
BRAIN, 2014, 137 :1394-1409
[3]   Toxicity evaluation of PEDOT/biomolecular composites intended for neural communication electrodes [J].
Asplund, M. ;
Thaning, E. ;
Lundberg, J. ;
Sandberg-Nordqvist, A. C. ;
Kostyszyn, B. ;
Inganas, O. ;
von Holst, H. .
BIOMEDICAL MATERIALS, 2009, 4 (04)
[4]   The surface immobilization of the neural adhesion molecule L1 on neural probes and its effect on neuronal density and gliosis at the probe/tissue interface [J].
Azemi, Erdrin ;
Lagenaur, Carl F. ;
Cui, Xinyan T. .
BIOMATERIALS, 2011, 32 (03) :681-692
[5]   The biological and electrical trade-offs related to the thickness of conducting polymers for neural applications [J].
Baek, Sungchul ;
Green, Rylie A. ;
Poole-Warren, Laura A. .
ACTA BIOMATERIALIA, 2014, 10 (07) :3048-3058
[6]   Intraspinal microstimulation for the recovery of function following spinal cord injury [J].
Bamford, Jeremy A. ;
Mushahwar, Vivian K. .
BRAIN MACHINE INTERFACES: IMPLICATIONS FOR SCIENCE, CLINICAL PRACTICE AND SOCIETY, 2011, 194 :227-239
[7]   The effects of intraspinal microstimulation on spinal cord tissue in the rat [J].
Bamford, Jeremy A. ;
Todd, Kathryn G. ;
Mushahwar, Vivian K. .
BIOMATERIALS, 2010, 31 (21) :5552-5563
[8]  
Bunge R P, 1997, Adv Neurol, V72, P305
[9]   Adult NG2+Cells Are Permissive to Neurite Outgrowth and Stabilize Sensory Axons during Macrophage-Induced Axonal Dieback after Spinal Cord Injury [J].
Busch, Sarah A. ;
Horn, Kevin P. ;
Cuascut, Fernando X. ;
Hawthorne, Alicia L. ;
Bai, Lianhua ;
Miller, Robert H. ;
Silver, Jerry .
JOURNAL OF NEUROSCIENCE, 2010, 30 (01) :255-265
[10]   Chronic Electrical Stimulation of the Intact Corticospinal System after Unilateral Injury Restores Skilled Locomotor Control and Promotes Spinal Axon Outgrowth [J].
Carmel, Jason B. ;
Berrol, Lauren J. ;
Brus-Ramer, Marcel ;
Martin, John H. .
JOURNAL OF NEUROSCIENCE, 2010, 30 (32) :10918-10926