Biologically inspired approaches to drug delivery for nerve regeneration

Abstract

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.

Hyaluronic acid-based hydrogel enhances neuronal survival in spinal cord slice cultures from postnatal mice

“…This hypothesis is in line with literature describing the effects of other soft matrices on cultured CNS tissue. 2,24–27 Implantation of soft hydrogels into CNS injury cavities has resulted in neuronal ingrowth with reduction of glial scarring. 28…”

“…38 The need for a less invasive method for drug delivery incorporating an appropriate ECM that counteracts tissue injury and scarring has led to the development of scaffolds to be used as drug carriers. 27,39…”

Hyaluronic acid-based hydrogel enhances neuronal survival in spinal cord slice cultures from postnatal mice

“…This hypothesis is in line with literature describing the effects of other soft matrices on cultured CNS tissue. 2,24–27 Implantation of soft hydrogels into CNS injury cavities has resulted in neuronal ingrowth with reduction of glial scarring. 28…”

“…38 The need for a less invasive method for drug delivery incorporating an appropriate ECM that counteracts tissue injury and scarring has led to the development of scaffolds to be used as drug carriers. 27,39…”

Electrospun micro- and nanofiber tubes for functional nervous regeneration in sciatic nerve transections

“…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 ].…”

Facial Paralysis: Research and Future Directions

“…High-efficiency transmission of axons through nerve grafting materials is likely to involve ''smart'' biomaterials, 37 in which both polymeric substances and biologically relevant agents are cleverly combined to create living bioartificial nerve conduits (see Ref. 38 for review). The delivery of a combination of nerve growth-promoting substances, along with inhibitors of inflammation and/or rejection, are likely to be the key to exceeding the regeneration now obtainable through autografts and the most promising commercially available polymer conduits.…”

Hyaluronic acid-based hydrogel enhances neuronal survival in spinal cord slice cultures from postnatal mice

“…This hypothesis is in line with literature describing the effects of other soft matrices on cultured CNS tissue. 2,24–27 Implantation of soft hydrogels into CNS injury cavities has resulted in neuronal ingrowth with reduction of glial scarring. 28…”

“…38 The need for a less invasive method for drug delivery incorporating an appropriate ECM that counteracts tissue injury and scarring has led to the development of scaffolds to be used as drug carriers. 27,39…”

Electrospun micro- and nanofiber tubes for functional nervous regeneration in sciatic nerve transections

“…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 ].…”

Facial Paralysis: Research and Future Directions

“…High-efficiency transmission of axons through nerve grafting materials is likely to involve ''smart'' biomaterials, 37 in which both polymeric substances and biologically relevant agents are cleverly combined to create living bioartificial nerve conduits (see Ref. 38 for review). The delivery of a combination of nerve growth-promoting substances, along with inhibitors of inflammation and/or rejection, are likely to be the key to exceeding the regeneration now obtainable through autografts and the most promising commercially available polymer conduits.…”

Hyaluronic acid-based hydrogel enhances neuronal survival in spinal cord slice cultures from postnatal mice

“…This hypothesis is in line with literature describing the effects of other soft matrices on cultured CNS tissue. 2,24–27 Implantation of soft hydrogels into CNS injury cavities has resulted in neuronal ingrowth with reduction of glial scarring. 28…”

“…38 The need for a less invasive method for drug delivery incorporating an appropriate ECM that counteracts tissue injury and scarring has led to the development of scaffolds to be used as drug carriers. 27,39…”

Electrospun micro- and nanofiber tubes for functional nervous regeneration in sciatic nerve transections

“…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 ].…”

Facial Paralysis: Research and Future Directions

“…High-efficiency transmission of axons through nerve grafting materials is likely to involve ''smart'' biomaterials, 37 in which both polymeric substances and biologically relevant agents are cleverly combined to create living bioartificial nerve conduits (see Ref. 38 for review). The delivery of a combination of nerve growth-promoting substances, along with inhibitors of inflammation and/or rejection, are likely to be the key to exceeding the regeneration now obtainable through autografts and the most promising commercially available polymer conduits.…”