Nanoparticles for growth fator delivery in nerve guidance conduits: An Overview

Injuries of peripheral nervous system (PNS) are a major source of disabilities; the mobility of muscles gets impaired, sensations suffer distortions and can lead to painful neuropathies.^[1] There is a critical nerve gap of around 5 mm length beyond which nerve regeneration does not happen, and in this case the simplest technique after injury to a peripheral nerve is the coaptation of the two ends of the nerve using sutures. The progress in tissue engineering has resulted in the development of artificial nerve constructs that can guide and facilitate the axonal nerve growth, overcoming the issues that autologous tissues were presenting.^[2]

To date, various strategies have been developed; there are four central components that can be tuned in order to achieve a proper peripheral nerve regeneration: (1) the scaffold or substrate, (2) the growth factors, (3) ECM molecules, and (4) the incorporation of cells.^[1]

Peripheral nerve regeneration is a complicated process where Schwann Cells secrete and up-regulate a number of growth factors including nerve growth factor (NGF), leukaemia inhibitory factor (LIF), glial derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), growth-associated protein (GAP-43), brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) which plays a significant role in axon regeneration.^[1]

Several NPs have been developed in order to introduce growth factors into the lumen of the NGCs. Among inorganic NPs silica, gold, zink or silver have been widely used. Also polymeric NPs have been developed to deliver growth factors within the NGC, mainly because of their molecule high loading capability. Biologically derived natural NPs such as the exosomes are in charge of intracellular transfer of macromolecules, which has made them gain attention to deliver growth factors.^[3]

[1]         M. C. Dodla, M. Alvarado-Velez, V. J. Mukhatyar, R. V. Bellamkonda, Princ. Regen. Med. 2019, 1223.

[2]         G. E. Wnek, G. L. Bowlin, Encyclopedia of biomaterials and biomedical engineering; Informa Healthcare USA, 2008.

[3]         C. R. Carvalho, J. Silva-Correia, J. M. Oliveira, R. L. Reis, Adv. Drug Deliv. Rev. 2019.

This work is funded by the R&D Project NanOptoNerv - Nano-accelerated nerve regeneration and optogenetic empowering of neuromuscular functionality, with reference PTDC/NAN-MAT/29936/2017, financed by FCT. J. M. Oliveira would like to thank to FCT for the fund provided under the program Investigador FCT 2015 (IF/01285/2015).