Dual growth factor-immobilized microspheres for tissue reinnervation:<i>in vitro</i>and preliminary<i>in vivo</i>studies

Kim, Tae Ho; Oh, Se Heang; An, Dan Bi; Lee, Ji Youl; Lee, Jin Ho

doi:10.1080/09205063.2015.1008882

Cited by 5 publications

(2 citation statements)

References 67 publications

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“…This could be due to a very low quantity of growth factors bound to the surface by weak interactions, the degradation of NGF and BDNF because they were not established (Lam et al, 2001). These findings are supported by Kim et al who found that microspheres loaded with heparin bound significantly more bFGF and NGF than microspheres without heparin (Kim et al, 2015). Moreover, Johnson et al also incorporated heparin into hydrogels to stabilise both NGF and BDNF (Johnson et al, 2015).…”

Section: Discussionmentioning

confidence: 87%

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

2021

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Peripheral nerve injury is an important cause of disability, that can hinder significantly sensory and motor function. The clinical gold standard for peripheral nerve repair is the use of autografts, nevertheless, this method has limitations such as donor site morbidity. An emerging alternative to autografts are nerve guide conduits, which are used to entubulate the severed nerve and provide guidance for the directed regeneration of the nerve tissue. These nerve guide conduits are less effective than autografts, and to enhance their performance the incorporation of neurotrophins can be considered. To enable optimal nerve regeneration, it is important to continuously stimulate neurite outgrowth by designing a delivery system for the sustained delivery of neurotrophins. The aim of this study was to develop a novel bioactive surface on electrospun fibres to supply a sustained release of heparin bound NGF or BDNF electrostatically immobilised onto an amine functionalized surface to encourage neurite outgrowth and Schwann cell migration. The bioactive surface was characterised by XPS analysis and ELISA. To assess the effect of the bioactive surface on electrospun fibres, primary chick embryo dorsal root ganglia were used, and neurite outgrowth and Schwann cell migration were measured. Our results showed a significant improvement regarding nerve regeneration, with the growth of neurites of up to 3 mm in 7 days, accompanied by Schwann cells. We hypothesize that the physical guidance provided by the fibres along the sustained delivery of NGF or BDNF created a stimulatory environment for nerve regeneration. Our results were achieved by immobilising relatively low concentrations of neurotrophins (1 ng/ml), which provides a promising, low-cost, and scalable method to improve current nerve guide conduits.

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Section: Discussionmentioning

confidence: 87%

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

2021

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“…The individual effect of bFGF and NGF has been validated in our prior studies [33,84]. Studies have indicated that co-administration of NGF and bFGF together could synergistically promote tissue reinnervation and neural differentiation, compared with bFGF and NGF alone [85,86]. In this study, we evaluated the effectiveness of dual GF administration for the first time in peripheral nerve injuries, and focused on showing how HP hydrogel can augment this therapy strategy.…”

Section: Discussionmentioning

confidence: 91%

Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats

et al. 2018

Biomaterials

190

140

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Peripheral nerve injury (PNI) is a major burden to society with limited therapeutic options, and novel biomaterials have great potential for shifting the current paradigm of treatment. With a rising prevalence of chronic illnesses such as diabetes mellitus (DM), treatment of PNI is further complicated, and only few studies have proposed therapies suitable for peripheral nerve regeneration in DM. To provide a supportive environment to restore structure and/or function of nerves in DM, we developed a novel thermo-sensitive heparin-poloxamer (HP) hydrogel co-delivered with basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) in diabetic rats with sciatic nerve crush injury. The delivery vehicle not only had a good affinity for large amounts of growth factors (GFs), but also controlled their release in a steady fashion, preventing degradation in vitro. In vivo, compared with HP hydrogel alone or direct GFs administration, GFs-HP hydrogel treatment is more effective at facilitating Schwann cell (SC) proliferation, leading to an increased expression of nerve associated structural proteins, enhanced axonal regeneration and remyelination, and improved recovery of motor function (all p<0.05). Our mechanistic investigation also revealed that these neuroprotective and neuroregenerative effects of the GFs-HP hydrogel may be associated with activations of phosphatidylinositol 3 kinase and protein kinase B (PI3K/Akt), janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways. Our work provides a promising therapy option for peripheral nerve regeneration in patients with DM.

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Growth Factor Immobilization to Synthetic Hydrogels: Bioactive bFGF‐Functionalized Polyisocyanide Hydrogels

van Velthoven,

Gudde,

Arendsen

et al. 2023

Adv Healthcare Materials

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With its involvement in cell proliferation, migration and differentiation basic fibroblast growth factor (bFGF) has great potential for tissue engineering purposes. So far, however, clinical translation of soluble bFGF‐based therapies is unsuccessful, because the required effective doses are often supraphysiological, which may cause adverse effects. An effective solution is growth factor immobilization, whereby bFGF retains its bioactivity at increased efficacy. Studied carriers include films, solid scaffolds and particles, as well as natural and synthetic hydrogels. However, these synthetic hydrogels poorly resemble characteristics of the native extracellular matrix (ECM). In this work, bFGF is covalently conjugated to the synthetic, but highly biocompatible, polyisocyanide‐based hydrogel (PIC‐bFGF), which closely mimics the architecture and mechanical properties of the ECM. The growth factor conjugation protocol is straightforward and readily extrapolated to other growth factors or proteins. The PIC‐bFGF hydrogel shows a prolonged bioactivity up to four weeks although no clear effects on the ECM metabolism were observed. Beyond the future potential of the PIC‐bFGF hydrogel towards various tissue engineering applications, this work underlines that simple biological conjugation procedures are a powerful strategy to induce additional bioactivity in 3D synthetic cell culture matrices.This article is protected by copyright. All rights reserved

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Dual growth factor-immobilized microspheres for tissue reinnervation:in vitroand preliminaryin vivostudies

Cited by 5 publications

References 67 publications

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

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

Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats

Growth Factor Immobilization to Synthetic Hydrogels: Bioactive bFGF‐Functionalized Polyisocyanide Hydrogels

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