Abstract:Nerve guidance conduits (NGCs) are FDA-approved devices used to bridge gaps across severed nerve cables and help direct axons sprouting from the proximal end toward the distal stump. In this paper we present the development of a novel electrically conductive, biodegradable NGC made from a polypyrrole-block-polycaprolactone (PPy-PCL) copolymer material laminated with poly(lactic-co-glycolic acid) (PLGA). The PPy-PCL has a bulk conductivity ranging 10–20 S/cm and loses 40 wt% after 7 months under physiologic con… Show more
“…Electrical stimulation can be further integrated into the scaffold by choosing a conductive base material. Polypyrrole (PPy) is biocompatible, biodegradable, as well as electrically conductive, so NGCs augmented with PPy can support electrical stimulation (Nguyen et al, 2014). When DRGs on PPy-modified flat scaffolds were stimulated with an electric field, neurite extension was enhanced by 13% in a DC EF, and 21% in an alternating current (AC) EF.…”
Section: Application Of Electric Fields To Manipulate Neurite Extensionmentioning
As they differentiate from neuroblasts, nascent neurons become highly polarized and elongate. Neurons extend and elaborate fine and fragile cellular extensions that form circuits enabling long-distance communication and signal integration within the body. While other organ systems are developing, projections of differentiating neurons find paths to distant targets. Subsequent post-developmental neuronal damage is catastrophic because the cues for reinnervation are no longer active. Advances in biomaterials are enabling fabrication of micro-environments that encourage neuronal regrowth and restoration of function by recreating these developmental cues. This mini-review considers new materials that employ topographical, chemical, electrical, and/or mechanical cues for use in neuronal repair. Manipulating and integrating these elements in different combinations will generate new technologies to enhance neural repair.
“…Electrical stimulation can be further integrated into the scaffold by choosing a conductive base material. Polypyrrole (PPy) is biocompatible, biodegradable, as well as electrically conductive, so NGCs augmented with PPy can support electrical stimulation (Nguyen et al, 2014). When DRGs on PPy-modified flat scaffolds were stimulated with an electric field, neurite extension was enhanced by 13% in a DC EF, and 21% in an alternating current (AC) EF.…”
Section: Application Of Electric Fields To Manipulate Neurite Extensionmentioning
As they differentiate from neuroblasts, nascent neurons become highly polarized and elongate. Neurons extend and elaborate fine and fragile cellular extensions that form circuits enabling long-distance communication and signal integration within the body. While other organ systems are developing, projections of differentiating neurons find paths to distant targets. Subsequent post-developmental neuronal damage is catastrophic because the cues for reinnervation are no longer active. Advances in biomaterials are enabling fabrication of micro-environments that encourage neuronal regrowth and restoration of function by recreating these developmental cues. This mini-review considers new materials that employ topographical, chemical, electrical, and/or mechanical cues for use in neuronal repair. Manipulating and integrating these elements in different combinations will generate new technologies to enhance neural repair.
“…112 The use of PPY derived scaffold materials in neural tissue engineering is extensive. 13–19, 68, 113–115 In addition, PPY scaffolds have been also used for bone, 116, 117 liver, 118 and cardiac tissue engineering. 119 …”
Section: Conductive Polymers For Nerve Growth Conduitsmentioning
Treatment of large peripheral nerve damages ranges from the use of an autologous nerve graft to a synthetic nerve growth conduit. Biological grafts, in spite of many merits, show several limitations in terms of availability and donor site morbidity, and outcomes are suboptimal due to fascicle mismatch, scarring, and fibrosis. Tissue engineered nerve graft substitutes utilize polymeric conduits in conjunction with cues both chemical and physical, cells alone and or in combination. The chemical and physical cues delivered through polymeric conduits play an important role and drive tissue regeneration. Electrical stimulation (ES) has been applied toward the repair and regeneration of various tissues such as muscle, tendon, nerve, and articular tissue both in laboratory and clinical settings. The underlying mechanisms that regulate cellular activities such as cell adhesion, proliferation, cell migration, protein production, and tissue regeneration following ES is not fully understood. Polymeric constructs that can carry the electrical stimulation along the length of the scaffold have been developed and characterized for possible nerve regeneration applications. We discuss the use of electrically conductive polymers and associated cell interaction, biocompatibility, tissue regeneration, and recent basic research for nerve regeneration. In conclusion, a multifunctional combinatorial device comprised of biomaterial, structural, functional, cellular, and molecular aspects may be the best way forward for effective peripheral nerve regeneration.
“…The ideal NGC should not only bridge gaps across severed nerve defects but also stimulate axons sprouting from the proximal end toward the distal stump (Nguyen et al, 2014). Poly (l-lactic acid-co-ε-caprolactone) (PLCL) is a nontoxic, biodegradable and synthetic co-polymer of poly (L-lactic acid) (PLLA) and poly (ε-caprolactone) (PCL; Jin et al, 2009).…”
Electrospinning and electric stimulation (ES) are both promising methods to support neuron adhesion and guide extension of neurons for nerve regeneration. Concurrently, all studies focus on either electrospinning for conduits material or ES in vitro study to accelerate nerve regeneration; few work on the combined use of these two strategies or ES in vivo study. Therefore, this study aimed to investigate the abilities of direct current ES through electrospinning conductive polymer composites composed of polypyrrole and Poly (l-lactic acid-co-ε-caprolactone) (PPY/PLCL) in peripheral nerve regeneration. PPY/PLCL composite conduits were synthesized by polymerizing pyrrole coated electrospun PLCL scaffolds. Morphologies and chemical compositions were characterized by scanning electron microscope and attenuated total reflection fourier transform infrared (ATR-FTIR) microscope. Rat pheochromocytoma 12 (PC12) cells and dorsal root ganglia (DRG) cells cultured on PPY/PLCL scaffolds were stimulated with 100 mV/cm for 4 h per day. The median neurite length and cell viability were measured in PC-12 cells. The levels of brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) were analyzed in DRG cells. In rats, 15 mm gaps of sciatic nerves were bridged using an autograft, non-stimulated PPY/PLCL conduit and PPY/PLCL conduit stimulated with 100 mV potential, respectively. A 100 mV potential direct current ES was applied for 1 h per day at 1, 3, 5 and 7 days post-implantation. The PPY/PLCL conduits with ES showed a similar performance compared with the autograft group, and significantly better than the non-stimulated PPY/PLCL conduit group. These promising results show that the PPY/PLCL conductive conduits’ combined use with ES has great potential for peripheral nerve regeneration.
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