Biomimetic surface delivery of NGF and BDNF to enhance neurite outgrowth

Abstract

Treatment for peripheral nerve injuries includes the use of autografts and nerve guide conduits (NGCs). However, outcomes are limited, and full recovery is rarely achieved. The use of nerve scaffolds as a platform to surface immobilize neurotrophic factors and deliver locally is a promising approach to support neurite and nerve outgrowth after injury. We report on a bioactive surface using functional amine groups, to which heparin binds electrostatically. X‐ray photoelectron spectroscopy analysis was used to characterize the presence of nitrogen and sulfur. Nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) were bound by electrostatic interaction to heparin, and the release profile evaluated by enzyme‐linked immunosorbent assay, which showed that ca. 1% of NGF was released from each of the bioactive surface within 7 days. Furthermore, each surface showed a maximum release of 97% of BDNF. Neurotrophin release on neurite outgrowth was evaluated by primary dorsal root ganglion with a maximum neurite growth response in vitro of 1,075 µm detected for surfaces immobilized with NGF at 1 ng/ml. In summary, the study reports on the design and construction of a biomimetic platform to deliver NGF and BDNF using physiologically low concentrations of neurotrophin. The platform is directly applicable and scalable for improving the regenerative ability of existing NGCs and scaffolds.

Bioactive 3D Scaffolds for the Delivery of NGF and BDNF to Improve Nerve Regeneration

“…Interestingly, the amount of sulphur detected by the survey scan was 0.2 at %, this confirms the electrostatic binding of heparin to the surface. The amount of sulphur on the surface is in line with our previously reported surface concentration of allylamine-heparin coating in tissue culture plastic (Sandoval-Castellanos et al, 2020). Additionally, this is also in line with the figure reported of 0.5 at %S on the surface by layer-by-layer deposition of polyethyleneheparin on a polylactic acid surface (Gigliobianco et al, 2015).…”

“…In comparison to our previous work (Sandoval-Castellanos et al, 2020), adding the bioactive surface NH 2 + + Heparin + Immobilised NGF/BDNF onto PCL electrospun scaffolds significantly stimulated neurite outgrowth and Schwann cell migration. This might be due to the combination of two elements: 1) topographical cues (PCL electrospun scaffold) as these encourage enhanced neurite outgrowth (Kim et al, 2008); and 2) chemical cues (bioactive surface) as it is known that by adjusting the surface properties, cell behaviour, such as adhesion, proliferation, and migration, is enhanced (Ren et al, 2015;Min et al, 2021).…”

“…Previously, we showed how a bioactive surface, which was used as a delivery system of growth factors, was fabricated by using electrostatic interactions (Crawford-Corrie et al, 2017;Sandoval-Castellanos et al, 2020). Furthermore, we demonstrated that bioactive surfaces composed of NH 2 + + Heparin + Immobilised NGF, NH 2 + + Heparin + Immobilised BDNF, and NH 2 + + Heparin + Immobilised NGF plus BDNF encouraged neurite outgrowth of chick embryo dorsal root ganglia (DRG) on 2D surfaces (Sandoval-Castellanos et al, 2020).…”

3D Printed Personalized Nerve Guide Conduits for Precision Repair of Peripheral Nerve Defects

“…In contrast, 3D printing allows preparing implants that closely match the nerve defects. [ 96 ] In addition, biological cues, such as bacteria, [ 97 ] SCs, [ 98 ] stem cells, [ 99 ] and NTFs, [ 100 ] can be co‐printed with biomaterials into multifunctional NGCs and promote axon elongation and myelination.…”

Neurorepair and Regeneration of the Brain: A Decade of Bioscaffolds and Engineered Microtissue

“…Rats receiving collagen/chitosan scaffold/FGF group presented improved nerve fibers tract regeneration in magnetic resonance imaging. Sandoval-Castellanos et al (2020) developed a platform to increase neurite extension using heparin binding-functional amine groups. NGF and BDNF were bound to heparin by electrostatic interaction.…”