Recent Advances in Polymeric Drug Delivery Systems for Peripheral Nerve Regeneration

Abstract

When a traumatic event causes complete denervation, muscle functional recovery is highly compromised. A possible solution to this issue is the implantation of a biodegradable polymeric tubular scaffold, providing a biomimetic environment to support the nerve regeneration process. However, in the case of consistent peripheral nerve damage, the regeneration capabilities are poor. Hence, a crucial challenge in this field is the development of biodegradable micro- nanostructured polymeric carriers for controlled and sustained release of molecules to enhance nerve regeneration. The aim of these systems is to favor the cellular processes that support nerve regeneration to increase the functional recovery outcome. Drug delivery systems (DDSs) are interesting solutions in the nerve regeneration framework, due to the possibility of specifically targeting the active principle within the site of interest, maximizing its therapeutical efficacy. The scope of this review is to highlight the recent advances regarding the study of biodegradable polymeric DDS for nerve regeneration and to discuss their potential to enhance regenerative performance in those clinical scenarios characterized by severe nerve damage.

Beyond the limiting gap length: peripheral nerve regeneration through implantable nerve guidance conduits

“…Among the discussed manufacturing techniques, unidirectional freezing and electrospinning have the highest benefit-cost ratio given that they can mimic the nerve environment with an anisotropic nanofibrillar structure, and tunable porous morphology, which favor nutrient exchange, and subsequently axonal elongation. 246 A wide variety of materials can be processed with these techniques and their relative simplicity and versatility can ensure industrial scalability. Among the reviewed examples, natural-based materials such as COL, chitosan and silk-fibroin represent the best solution for nerve regeneration.…”

“…Accordingly, various sustained delivery strategies have been proposed in recent years and reviewed in ref. 255. Therefore, it is understood that the enhancement of nerve regeneration beyond the LGL is a very complex issue, with a fervent debate in the scientific community.…”

Nano-pulling stimulates axon regeneration in dorsal root ganglia by inducing stabilization of axonal microtubules and activation of local translation

“…The use of nanotechnology in nerve regeneration therapy has gained increasing interest. The main uses include the production of biomaterials (natural or synthetic) for the development of scaffolds and nerve guidance conduits ( Gerth et al, 2015 ; Sarker et al, 2018 ), or for implementing smart drug delivery ( Tajdaran et al, 2019 ; Bianchini et al, 2023 ). Of these, MNPs have been effectively used for the delivery of growth factors, such as nerve growth factor (NGF) ( Ziv-Polat et al, 2014 ; Zuidema et al, 2015 ; Giannaccini et al, 2017 ; Marcus et al, 2018 ), brain-derived neurotrophic factor (BDNF) ( Pilakka-Kanthikeel et al, 2013 ; Wise et al, 2016 ), glial cell line-derived neurotrophic factor (GDNF) ( Ziv-Polat et al, 2014 ), vascular endothelial growth factor (VEGF) ( Giannaccini et al, 2017 ) to promote nerve survival and neurite regeneration ( Zuidema et al, 2015 ; Wise et al, 2016 ; Giannaccini et al, 2017 ).…”

Surface Eroding Methacrylic Anhydride Copolymers and Model Drug Release

“…As such, drug delivery systems have been intensively researched over the decades to find solutions such as extendedrelease or drug encapsulation. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] However, the field is limited by the number of biodegradable polymers and the subsequent degradation rates and mechanisms. Conventional biocompatible polymers such as poly(lactic acid), poly(glycolic acid), and chitosan undergo bulk erosion mechanisms.…”