Biologically inspired approaches to drug delivery for nerve regeneration

ArticleinExpert opinion on biological therapy 6(11):1105-11 · December 2006with15 Reads
DOI: 10.1517/14712598.6.11.1105 · Source: PubMed
As the biological processes governing nerve regeneration have become elucidated over the past decades, interest has developed in manipulating these processes to improve nerve regeneration. Drug delivery to the regenerating nerve has the potential for major clinical applications in neurodegenerative diseases, spinal cord injury and peripheral nerve injury or sacrifice. This article reviews the evolution of the field of drug delivery to the regenerating nerve, from simple local applications of neurotrophic agents in solution and osmotic pump delivery, to the existing approaches involving novel biomaterials and genetically manipulated cell populations. A discussion of the various known nerve growth-promoting agents, and the chemical considerations involved in their delivery, is included. A perspective on the role of tissue engineering approaches for nerve regeneration in the future is offered.
    • "Various injury models have been used to study different aspects of injury and regenerative capacity. Contusion, hemisection , and complete transection are the most common models (Hadlock and Sundback, 2006; Zhang et al., 2005 ). While each of the models has reproducible effects, it is more difficult in the contusion and hemisection models to determine if recovery is due to sparing and compensatory sprouting or new regeneration. "
    [Show abstract] [Hide abstract] ABSTRACT: Biomaterial scaffold architecture has not been investigated as a tunable source of influence on spinal cord regeneration. This study compared regeneration in a transected spinal cord within various designed-macro-architecture scaffolds to determine if these architectures alone could enhance regeneration. Three-dimensional (3-D) designs were created and molds were built on a 3-D printer. Salt-leached porous poly(epsilon-caprolactone) was cast in five different macro-architectures: cylinder, tube, channel, open-path with core, and open-path without core. The two open-path designs were created in this experiment to compare different supportive aspects of architecture provided by scaffolds and their influence on regeneration. Rats received T8 transections and implanted scaffolds for 1 and 3 months. Overall morphology and orientation of sections were characterized by H&E, luxol fast blue, and cresyl violet staining. Borders between intact gray matter and non-regenerated defect were observed from GFAP immunolabeling. Nerve fibers and regenerating axons were identified with Tuj-1 immunolabeling. The open-path designs allowed extension of myelinated fibers along the length of the defect both exterior to and inside the scaffolds and maintained their original defect length up to 3 months. In contrast, the cylinder, tube, and channel implants had a doubling of defect length from secondary damage and large scar and cyst formation with no neural tissue bridging. The open-path scaffold architectures enhanced spinal cord regeneration compared to the three other designs without the use of biological factors.
    Full-text · Article · Sep 2008
    • "By quantifying nervous tissue regeneration (morphometric analyses) and animal functional recovery (neural tracers and evoked action potentials), our work has proved that multi-scaled electrospun nerve conduits are promising bioabsorbable scaffolds for stimulating and guiding peripheral nerve functional regeneration in rat models of sciatic nerve transection. Our detailed analysis of various aspects of nerve regeneration shows how microfibrous and nanofibrous prosthesis do not produce mechanical stress-related nervous degenerations and, on the other hand, favour a functional and effective nervous regeneration that could be further ameliorated via complementary strategies like hydrogels for drug delivery [48], electrical stimulation [49] and techniques adopted in clinics, such as physiotherapy [50]. "
    [Show abstract] [Hide abstract] ABSTRACT: Although many nerve prostheses have been proposed in recent years, in the case of consistent loss of nervous tissue peripheral nerve injury is still a traumatic pathology that may impair patient's movements by interrupting his motor-sensory pathways. In the last few decades tissue engineering has opened the door to new approaches;: however most of them make use of rigid channel guides that may cause cell loss due to the lack of physiological local stresses exerted over the nervous tissue during patient's movement. Electrospinning technique makes it possible to spin microfiber and nanofiber flexible tubular scaffolds composed of a number of natural and synthetic components, showing high porosity and remarkable surface/volume ratio. In this study we used electrospun tubes made of biodegradable polymers (a blend of PLGA/PCL) to regenerate a 10-mm nerve gap in a rat sciatic nerve in vivo. Experimental groups comprise lesioned animals (control group) and lesioned animals subjected to guide conduits implantated at the severed nerve stumps, where the tubular scaffolds are filled with saline solution. Four months after surgery, sciatic nerves failed to reconnect the two stumps of transected nerves in the control animal group. In most of the treated animals the electrospun tubes induced nervous regeneration and functional reconnection of the two severed sciatic nerve tracts. Myelination and collagen IV deposition have been detected in concurrence with regenerated fibers. No significant inflammatory response has been found. Neural tracers revealed the re-establishment of functional neuronal connections and evoked potential results showed the reinnervation of the target muscles in the majority of the treated animals. Corroborating previous works, this study indicates that electrospun tubes, with no additional biological coating or drug loading treatment, are promising scaffolds for functional nervous regeneration. They can be knitted in meshes and various frames depending on the cytoarchitecture of the tissue to be regenerated. The versatility of this technique gives room for further scaffold improvements, like tuning the mechanical properties of the tubular structure or providing biomimetic functionalization. Moreover, these guidance conduits can be loaded with various fillers like collagen, fibrin, or self-assembling peptide gels or loaded with neurotrophic factors and seeded with cells. Electrospun scaffolds can also be synthesized in different micro-architectures to regenerate lesions in other tissues like skin and bone.
    Full-text · Article · Feb 2008
  • [Show abstract] [Hide abstract] ABSTRACT: Fibrous mats via electrospinning have been widely applied in tissue engineering. In this work, nanofibers were prepared via electrospinning from polymer with different content of carboxyl groups. A natural material, collagen, was then immobilized onto the nanofiber surface by N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)/N-Hydroxysuccinimide (NHS) activation process. It was found that the immobilization degree of collagen could be facilely modulated. The obtained collagen-modified nanofibers were used for neural stem cells culture, and unmodified nanofibers were used as a control. Results indicated that the modification of collagen could enhance the attachment and viability of the cultured neural stem cells.
    Article · Mar 2008
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