Nerve Growth Factor Biodelivery: A Limiting Step in Moving Toward Extensive Clinical Application?

Alastra, Giuseppe; Aloe, Luigi; Baldassarro, Vito Antonio; Calzà, Laura; Cescatti, Maura; Duskey, Jason Thomas; Focarete, Maria Letizia; Giacomini, Daria; Giardino, Luciana; Giraldi, Valentina; Lorenzini, Luca; Moretti, Marzia; Parmeggiani, Irene; Sannia, Michele; Tosi, Giovanni

doi:10.3389/fnins.2021.695592

Cited by 25 publications

(14 citation statements)

References 146 publications

(166 reference statements)

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“…Precedents for NGF delivery using hydrogels and scaffolds [ 40 ] imply the potential to engineer recombinant silks as substrates for NGF sequestration and delivery. To specifically test for both the accessibility and NGF‐binding competence of the N B motifs in the N B Silk, as implied through the surface localization and observation of dynamics of the N B motifs over MD simulations, steady‐state intrinsic Trp fluorescence spectroscopy was used.…”

Section: Resultsmentioning

confidence: 99%

Nerve Growth Factor‐Binding Engineered Silk Films Promote Neuronal Attachment and Neurite Outgrowth

Baker

Akher

et al. 2022

Adv Funct Materials

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Spider silks have outstanding potential as biomaterials due to their soughtafter mechanical properties and low immunogenicity. The toughest spider silk is aciniform silk, which is used by spiders to wrap prey and produce egg sacs. A variety of recombinant aciniform silk constructs are now been developed, including hybrid silks with domains from multiple spider silk proteins fused together. In this study, an engineered aciniform silk construct, termed N B Silk, fused both N-and C-terminally to heptapeptide motifs that bind the neurotrophic factor and nerve growth factor-β (NGF) is introduced. N B Silk is shown to be amenable to casting into robust films that remain intact while sequestering and maintaining bioactive NGF at the film surface for at least 7 days. These films support cell survival while enhancing differentiation and neurite density and outgrowth in neuron-like PC12 cells, with elevation of signaling through both the mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) signaling pathways. Strikingly, preloading of N B Silk films with NGF enhances neuritogenesis even over conditions where cells are grown with NGF supplementation in the culture medium. N B Silk scaffolds, thus, warrant future development and evaluation as biomaterials for nerve regeneration.

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Section: Resultsmentioning

confidence: 99%

Nerve Growth Factor‐Binding Engineered Silk Films Promote Neuronal Attachment and Neurite Outgrowth

Baker

Akher

et al. 2022

Adv Funct Materials

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“…Their clinical application is not only limited by the side effect but also the routes of administration and variable bioactivity (52). Alternative approaches, such as small molecule mimetics, topical application and biomaterial-assisted delivery (54), are being developed and may bring a new outlook to the decade-old treatment strategy with neurotrophic factors. Another potential treatment strategy is to stimulate the endogenous overexpression of the neurotrophic factors in a more natural, physiological manner (52).…”

Section: Discussionmentioning

confidence: 99%

Skin keratinocyte-derived SIRT1 and BDNF modulate mechanical allodynia in mouse models of diabetic neuropathy

OʼBrien

Niehaus

Remark

et al. 2023

Preprint

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Diabetic neuropathy (DN) is a debilitating disorder characterized by mechanical allodynia and sensory loss. It has traditionally been considered a small-fiber neuropathy, defined by the loss of free nerve endings in the epidermis. Free nerve endings, however, are nociceptors which may not be the only sensor for mechanical pain. To investigate the role of mechanoreceptors, specifically Meissner corpuscles, in the development of diabetic mechanical allodynia, our study focused on the keratinocyte-secreted brain-derived neurotrophic factor (BDNF) and its transcriptional regulator sirtuin 1 (SIRT1). Wild-type DN mice demonstrated decreased SIRT1 deacetylase activity, leading to a decrease in BDNF expression and Meissner corpuscle densities in foot skin. Epidermal SIRT1 knockout (KO) mice developed exacerbated DN phenotypes including severe mechanical allodynia, markedly reduced Meissner corpuscles, and subcutaneous A-beta axon degeneration. Among the major skin-derived neurotrophic factors, only BDNF was down-regulated in epidermal SIRT1 KO mice. With similar KO phenotypes, epidermal BDNF appeared to belong to the same pathway as SIRT1 in modulating diabetic mechanical allodynia. Furthermore, mice overexpressing epidermal SIRT1 showed BDNF up-regulation and improved DN phenotypes, supporting an important role of epidermal SIRT1 and BDNF in skin sensory apparatus regeneration and functional recovery in the setting of diabetes.

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“…At the same time, surgery often includes craniotomy and cranioplasty, calling for the need to develop biocompatible materials that can substitute physiological tissues and promote recovery [ 43 , 44 ]. Both of these issues have been under investigation in recent years, leading to the design and formulation of biocompatible scaffolds that allow the prolonged release of therapeutics, along with the promotion of tissue curing [ 45 , 46 ]. In fact, many scaffolds have been developed, using different materials and production techniques ( Table S2 ).…”

Section: Pathologies Of the Central And Peripheral Nervous System And...mentioning

confidence: 99%

Hyaluronic Acid Scaffolds for Loco-Regional Therapy in Nervous System Related Disorders

Djoudi

Molina-Peña²,

Ferreira³

et al. 2022

IJMS

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Hyaluronic acid (HA) is a Glycosaminoglycan made of disaccharide units containing N-acetyl-D-glucosamine and glucuronic acid. Its molecular mass can reach 10 MDa and its physiological properties depend on its polymeric property, polyelectrolyte feature and viscous nature. HA is a ubiquitous compound found in almost all biological tissues and fluids. So far, HA grades are produced by biotechnology processes, while in the human organism it is a major component of the extracellular matrix (ECM) in brain tissue, synovial fluid, vitreous humor, cartilage and skin. Indeed, HA is capable of forming hydrogels, polymer crosslinked networks that are very hygroscopic. Based on these considerations, we propose an overview of HA-based scaffolds developed for brain cancer treatment, central and peripheral nervous systems, discuss their relevance and identify the most successful developed systems.

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Nerve Growth Factor Biodelivery: A Limiting Step in Moving Toward Extensive Clinical Application?

Cited by 25 publications

References 146 publications

Nerve Growth Factor‐Binding Engineered Silk Films Promote Neuronal Attachment and Neurite Outgrowth

Nerve Growth Factor‐Binding Engineered Silk Films Promote Neuronal Attachment and Neurite Outgrowth

Skin keratinocyte-derived SIRT1 and BDNF modulate mechanical allodynia in mouse models of diabetic neuropathy

Hyaluronic Acid Scaffolds for Loco-Regional Therapy in Nervous System Related Disorders

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