Healing properties of epidermal growth factor and tocotrienol-rich fraction formulation in deep partial-thickness burn wound model
Burns are one of the most devastating injuries in the world, divided into superficial, partial-thickness (superficial or deep partial-thickness) and full-thickness burns. The current treatment of deep partial-thickness burns is mainly focused on preventing wound infections and less attention to t...
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Format: | Thesis |
Language: | English |
Published: |
2017
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Online Access: | http://psasir.upm.edu.my/id/eprint/68341/1/FPSK%28p%29%202018%202%20IR.pdf http://psasir.upm.edu.my/id/eprint/68341/ |
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Summary: | Burns are one of the most devastating injuries in the world, divided into
superficial, partial-thickness (superficial or deep partial-thickness) and
full-thickness burns. The current treatment of deep partial-thickness burns is
mainly focused on preventing wound infections and less attention to the burn
healing process. Therefore, it is imperative to develop medications aimed at
promoting the stage of wound healing. It has been shown that epidermal
growth factor (EGF) can promote the proliferation of various cells and it is
known that tocotrienol-rich fraction (TRF) from palm oil has a strong
antioxidant activity. Thus, a combination of EGF and TRF is included in the
present formulation (EGF+TRF cream), which is expected to accelerate
wound healing and inhibit oxidative stress in the burn. Deep partial-thickness
burn wounds were produced on the dorsal part of Sprague-Dawley rats.
Animals were then randomly divided into six groups: untreated, treated with
Silverdin® cream, base cream, base cream with c% EGF, base cream with 3
% TRF or base cream with c% EGF and 3% TRF, respectively. Creams were
applied once daily for 21 consecutive days. Digital images were captured
daily for macroscopic evaluation. Six animals from each group were sacrificed
on the 3rd, 7th, 11th, 14th and 21st day post-burn, harvesting skin tissues with
the wound for histological, cellular, biochemical and gene expression analysis.
Prior to the research of the EGF+TRF formulation in wound healing, a new
apparatus was designed to create burn wounds. With this device, uniform
deep partial-thickness burn was achieved with a contact temperature of 70°C,
a fixed pressure of 300 g, and duration of 10 seconds. In addition, a novel
histological scoring system was developed to make the evaluation process
more systematic and reproducible. The chronological events in burn healing
were initiated by the recruitment of neutrophils to the wound site on the 3rd day post-burn followed by the up-regulation of tumor necrosis factor-α (TNF-α)
expression and rapid synthesis of collagens to facilitate leukocytes adhesion
and crust attachment. The EGF+TRF treatment preceded this process and on
the 7th day post-burn, wound contraction accelerated and the dermal healing
was sped up by the proliferation of myofibroblasts and augmented expression
of Collagen-1. By down regulation of interleukin 6 (IL-6) and TNF-α
expression on Day 11 post-burn, the EGF+TRF treatment expedited the
wound contraction and entering the re-modelling phase and arriving
epithelialization on Day 14. This formulation was capable of promoting the
recovery of the dermis and attenuate the oxidative stress by down regulating
the expression of IL-6, TNF-α, inducible nitric oxide synthase (iNOS), matrix
metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2),
transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A
(VEGF-A) and Collagen-1. Finally, by Day 21 post-burn, the treatment of
EGF+TRF formulation could advance the restoration of the epidermis and
dermis and cut down the oxidative stress by down regulating the expression
of IL-6 and iNOS. In conclusion, all results from the present study fully
supported the beneficial application of EGF+TRF formulation in the treatment
of deep-partial thickness burn, adhered to the mechanisms of burn healing
process. |
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