Biologically inspired approaches to drug delivery for nerve regeneration

Massachusetts Eye and Ear Infirmary and Harvard Medical School, Division of Facial Plastic and Reconstructive Surgery, 243 Charles St, Boston, MA 02114, USA.
Expert opinion on biological therapy (Impact Factor: 3.74). 12/2006; 6(11):1105-11. 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.

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    • "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]. "
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    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.
    BMC Biotechnology 02/2008; 8(1):39. DOI:10.1186/1472-6750-8-39 · 2.03 Impact Factor
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    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.
    Journal of Materials Science Materials in Medicine 03/2008; 19(2):847-54. DOI:10.1007/s10856-007-3087-5 · 2.59 Impact Factor
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    ABSTRACT: Facial paralysis has fascinated physicians through the centuries. Management of the condition has evolved extensively over the past 50 years, relying largely upon neural repair techniques and static techniques prior to the 1940s, followed by heavy emphasis on regional muscle transfer by the 1970s. With the advent of the operating microscope and the development of microinstrumentation, in the mid-1970s free tissue transfer became technically feasible, and new techniques quickly ensued that introduced functioning muscle as a viable and valuable option in the management of the paralyzed face. These techniques have been subject to continual refinement to improve their reliability and reduce morbidity. In the modern era of evidence-based medicine, the field of facial nerve management has expanded exponentially with critical questions that will help future facial reanimation surgeons refine the approach for patients with acute and long-standing facial paralysis. This article will discuss current research areas with respect to assessment and management of the facial nerve patient, as well as future surgical outcomes. We will also present the state of both clinical research and contemporary basic science issues relevant to facial nerve disorders.
    Facial Plastic Surgery 06/2008; 24(2):260-7. DOI:10.1055/s-2008-1075842 · 0.64 Impact Factor
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