Chitosan hydrogel encapsulated with LL-37 peptide promotes deep tissue injury healing in a mouse model

Abstract

Background LL-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. Methods CS 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. Results LL-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. Conclusion Chitosan hydrogel encapsulated with LL-37 is biocompatible and could promote the healing of pressure ulcers.

Chitosan and Cellulose-Based Hydrogels for Wound Management

“…Yang et al developed chitosan hydrogels loaded with LL-37 peptide for the treatment of pressure ulcer. The hydrogel at a concentration of 5 μg/mL was effective against S. aureus [ 112 ]. In vivo studies on animal models revealed high epithelial thickness and newly-formed capillary at day 15 and 21.…”

“…The hydrogels exhibited excellent cytocompatibility and were non-cytotoxic in vitro. The expression of VEGF in the wound treated with the hydrogel was high at day 14, showing the correlation of HIF-1α with VEGF protein expression which indicates that HIF-1α promotes angiogenesis in deep tissue injuries [ 112 ].…”

Obstruction of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice

“…In addition to angiogenesis, the wound contraction that mainly results from fibroblasts is also an important phase during wound repair after skin damage [ 26 , 28 ] . It has been accepted that efficient wound contraction is greatly beneficial for accelerating wound healing.…”

Wound healing center establishment and new technology application in improving the wound healing quality in China

“…New concepts emphasize that the wound healing speed and quality could be accelerated and improved by using advanced techniques and new methods. The new dressings play a key role not just in covering the wounds, but also in accelerating wound healing [ 11 , 12 ]. In some new wound care units or centers in China, some comprehensive methods were used to treat different kinds of chronic skin wounds.…”

“…The wound healing rate was increased by 10% for chronic skin ulcers. Biomaterials, such as collagen and artificial dermal materials, are also used in managing chronic skin ulcers [ 14 , 15 ]. These biomaterials help in reconstructing the dermis after deep and extensive debridement in skin wounds, especially for severe infection skin wounds, diabetic foot (over Wagner classification 3) and radiating chronic skin wounds.…”