Anti-inflammatory Drug-loaded Electrospun Scaffolds Aimed at Modulating Inflammation in Chronic Skin Wounds

Detamornrat, Usanee (2020) Anti-inflammatory Drug-loaded Electrospun Scaffolds Aimed at Modulating Inflammation in Chronic Skin Wounds. PhD thesis, University of Nottingham.

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The prolonged inflammation in chronic wounds is one of the key factors that delays the healing of wounds. During the inflammation phase, neutrophils and macrophages release TNF-α and IL-1β to induce the production or expression of pro-inflammatory mediators: prostaglandin E2 (PGE2), matrix metalloproteinases (MMPs) and nitric oxide (NO). Herein the medicated electrospun scaffolds were developed and aimed to provide a fibrous structure that mimics the architecture of natural extracellular matrix (ECM) to support cell proliferation. In addition, the scaffolds were also designed to deliver anti-inflammatory drugs to inhibit the production/expression of the pro-inflammatory mediators.

The anti-inflammatory effect of ibuprofen sodium (IBU Na) was related to the inhibition of cyclooxygenase (COX) enzymes and PGE2 production. IBU Na was incorporated into PLGA electrospun scaffolds (at 1, 2, and 5 % w/w). SEM images have confirmed that all scaffolds consisted of smooth rounded microfibres. IBU Na was found to have a great impact on the properties of PLGA scaffolds—higher contents of IBU Na led to the decreases in ultimate tensile strength and Young’s modulus of the scaffolds. Moreover, IBU Na was found to accelerate the scaffold degradation. ToF-SIMS revealed that most IBU Na was located on the surfaces of the fibres, which can explain the rapid burst release profile of IBU Na in PBS. Higher metabolic activity of cells was observed, implying that PLGA-IBU Na scaffolds could support the proliferation of mouse fibroblasts.

Doxycycline hydrochloride (DOX HCl) is an analogue in tetracycline family. It exhibits anti-inflammatory effect via the inhibition of MMPs. In this case, PCL was selected as the polymer for fabricating DOX HCl-loaded scaffolds (at 1, 2 and 5% w/w). PCL-DOX HCl scaffolds consisted of nano-sized fibres with smooth surface and rounded morphology. DOX HCl enhanced the ultimate tensile strength and Young’s modulus of the scaffolds. The scaffolds remained their fibrous integrity over 90-day incubation in PBS. The scaffolds supported the adhesion and proliferation of primary human dermal fibroblasts.

Apart from conventional scaffold fabrication, this work shows that coaxial electrospun scaffold can also be fabricated. The structure of the scaffold’s fibres constituted of PCL shell and PLGA core. DOX HCl and IBU Na were loaded into PCL shell at 1% w/w and PLGA core at 5% w/w, respectively. Even though the incorporated drugs in the scaffolds increased the ultimate tensile strength of the scaffolds, they unfortunately speeded up the process of scaffold degradation. The release of DOX HCl and IBU Na from the scaffolds were rapid in PBS. This is due to the deposition of these two drugs at the surfaces of fibres. The coaxial scaffolds could also support the proliferation of primary human dermal fibroblasts.

The efficacy testing was carried out to assess the ability of the scaffolds to inhibit the production/expression of pro-inflammatory mediators stimulated by TNF-α and IL-1β. Unfortunately, the significant increase in the productions of PGE2 and nitrite in primary human dermal fibroblasts induced by the cytokines were not achieved. This was due to the presence of basic fibroblast growth factor (bFGF) in cell culture media. On the other hand, the expression of MMP-1 enzyme was successfully induced by TNF-α and IL-1β. The results demonstrated that PCL-DOX HCl scaffolds could inhibit the cytokine-induced MMP-1 expression in a dose dependent manner. The coaxial PCL-DOX HCl 1%/PLGA-IBU Na 5% scaffolds also showed an inhibiting effect on the cytokine-induced MMP-1 expression, which corresponded to the presence of IBU Na in the scaffolds not DOX HCl.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Buttery, Lee
Rose, Felicity
Keywords: electrospun scaffolds, wounds, surgical dressings, wound healing, inflammation, tissue engineering
Subjects: R Medicine > R Medicine (General) > R855 Medical technology. Biomedical engineering. Electronics
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 60048
Depositing User: Detamornrat, Usanee
Date Deposited: 05 Oct 2023 14:41
Last Modified: 05 Oct 2023 14:41

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