Biomimetic surface delivery of NGF and BDNF to enhance neurite outgrowth

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...

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Veröffentlicht in:Biotechnology and bioengineering 2020-10, Vol.117 (10), p.3124-3135
Hauptverfasser: Sandoval‐Castellanos, Ana M., Claeyssens, Frederik, Haycock, John W.
Format: Artikel
Sprache:eng
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Zusammenfassung: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. Biomaterial surfaces immobilized with nerve growth factor (NGF; 1 ng/ml) stimulate neurite outgrowth. Biomimetic surfaces were fabricated using positively charged amine groups to which heparin was bound electrostatically. NGF and brain‐derived neurotrophic factor (BDNF) were immobilized to heparin electrostatically. Both neurotrophins stimulated neurite outgrowth from primary dorsal root ganglion (DRG) neuronal cells after 7 days of culture, with maximum responses from NGF surfaces preloaded at 1 ng/ml.
ISSN:0006-3592
1097-0290
DOI:10.1002/bit.27466