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.
Highlights
Ramakrishna, 2016; Mcgregor & English, 2019)
Using primary chick embryo dorsal root ganglion (DRG), enhanced neurite outgrowth was observed when cultured on neurotrophin‐enriched surfaces compared to control surfaces tissue culture plastic (TCP), NH2+, and NH2+ + heparin with soluble growth factors
When DRGs were cultured on surfaces immobilized with Nerve growth factor (NGF) plus brain‐derived neurotrophic factor (BDNF) (Figure 3c), neurite outgrowth was longest for 100‐ng/ml surfaces
Summary
Ramakrishna, 2016; Mcgregor & English, 2019). Autografting is a standard clinical approach to treat regeneration of completely. Development of bioactive surfaces in direct contact with regenerating axons will target the delivery of neurotrophic factors more precisely, with direct stimulation for neurite outgrowth. We have developed a glycosaminoglycan surface platform for growth factor delivery using heparin, through transient charge attraction of negative functional groups and local release (WO 2017/ 017425 A1, 2017). For this particular study, we employed a commercial source of amine functionalized surfaces that arose directly from this prior study (Robinson et al, 2012). Investigation of a neurotrophin delivery platform is logical to explore for neurite outgrowth by the immobilized of NGFs onto NH2+ + heparin surfaces for local and sustained release. Using primary chick embryo dorsal root ganglion (DRG), enhanced neurite outgrowth was observed when cultured on neurotrophin‐enriched surfaces compared to control surfaces tissue culture plastic (TCP), NH2+, and NH2+ + heparin with soluble growth factors
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