Abstract
BackgroundLL-37 peptide is a member of the human cathelicidin family, and has been shown to promote the healing of pressure ulcers. However, the low stability of this peptide within the wound environment limits its clinical use. Chitosan (CS) hydrogel is commonly used as a base material for wound dressing material.MethodsCS hydrogel (2.5% w/v) was encapsulated with LL-37. Cytotoxicity of the product was examined in cultured NIH3T3 fibroblasts. Effects on immune response was examined by measuring tumor necrosis factor-α (TNF-α) release from RAW 264.7 macrophages upon exposure to lipopolysaccharides. Antibacterial activity was assessed using Staphylococcus aureus. Potential effect on pressure ulcers was examined using a mouse model. Briefly, adult male C57BL/6 mice were subjected to skin pressure using magnets under a 12/12 h schedule for 21 days. Mice were randomized to receive naked LL-37 (20 μg), chitosan gel containing 20-μg LL-37 (LL-37/CS hydrogel) or hydrogel alone under the ulcer bed (n = 6). A group of mice receiving no intervention was also included as a control.ResultsLL-37/CS hydrogel did not affect NIH3T3 cell viability. At a concentration of 1–5 μg/ml, LL-37/CS inhibited TNF-α release from macrophage. At 5 μg/ml, LL-37/CS inhibited the growth of Staphylococcus aureus. The area of the pressure ulcers was significantly lower in mice receiving LL-37/CS hydrogel in comparison to all other 3 groups on days 11 (84.24% ± 0.25%), 13 (56.22% ± 3.91%) and 15 (48.12% ± 0.28%). Histological examination on days 15 and 21 showed increased epithelial thickness and density of newly-formed capillary with naked LL-37 and more so with LL-37/CS. The expression of key macromolecules in the process of angiogenesis (i.e., hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A)) in wound tissue was increased at both the mRNA and protein levels.ConclusionChitosan hydrogel encapsulated with LL-37 is biocompatible and could promote the healing of pressure ulcers.
Highlights
LL-37 peptide is a member of the human cathelicidin family, and has been shown to promote the healing of pressure ulcers
The encapsulation efficiency of LL-37 within CS hydrogels was 86.16% ± 2.61% (Fig. 1c) when LL-37 was loaded at 5 μg per mg CS hydrogel
We show that the mechanism of LL-37 induction of VEGF-A production is regulated by Hypoxia-inducible factor-1α (HIF-1α)
Summary
LL-37 peptide is a member of the human cathelicidin family, and has been shown to promote the healing of pressure ulcers. Known as pressure ulcers, are common in bed-ridden patients, and associated with poor quality of life as well as high medical care costs [1, 2]. Pressure injuries have been associated with poor prognosis and higher mortality in some patients [3]. In clinical wound care and nursing specialties, the development of effective treatments for deep tissue pressure injuries is urgently required. Inflammatory responses and reductions in capillary density caused by ischemia/reperfusion are the main factors that affect deep tissue injury healing [4, 5]. There are limited therapeutic drugs that can achieve these desirable effects; there is an urgent requirement for the development of new, effective means to satisfy the unmet clinical need for the treatment of deep tissue injuries
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