A Novel Gold Calreticulin Nanocomposite Based on Chitosan for Wound Healing in a Diabetic Mice Model

Abstract

The development of new nanomaterials to promote wound healing is rising, because of their topical administration and easy functionalization with molecules that can improve and accelerate the process of healing. A nanocomposite of gold nanoparticles (AuNPs) functionalized with calreticulin was synthetized and evaluated. The ability of the nanocomposite to promote proliferation and migration was determined in vitro, and in vivo wound healing was evaluated using a mice model of diabetes established with streptozotocin (STZ). In vitro, the nanocomposite not affect the cell viability and the expression of proliferating cell nuclear antigen (PCNA). Moreover, the nanocomposite promotes the clonogenicity of keratinocytes, endothelial cells, and fibroblasts, and accelerates fibroblast migration. In vivo, mice treated with the nanocomposite presented significantly faster wound healing. The histological evaluation showed re-epithelization and the formation of granular tissue, as well as an increase of collagen deposition. Therefore, these results confirm the utility of AuNPs–calreticulin nanocomposites as potential treatment for wound healing of diabetic ulcers.

Efficacy of alginate‐and chitosan‐based scaffolds on the healing of diabetic skin wounds in animal experimental models and cell studies: A systematic review

“…The articles were excluded because of study design, study topic (not diabetic wound), human studies, or studies not report wound healing as outcome measurements. Finally, 29 21,24‐51 studies that evaluated the effect of chitosan or alginate on diabetic wound healing were included. Figure 1 illustrated the trial selection process.…”

“…Table 1 presented the descriptive characteristics of the included articles. Overall, there were 23 trials 21,24‐30,32‐46 on chitosan, three trials on alginate, 31,47,48 and three trials on the combination of alginate and chitosan 49‐51 . The animal studies were conducted from 2002 and 2019.…”

“…Twenty‐three studies had insufficient information about how randomization was carried out in the experiment group and control group or provided inadequate report on the assignment of samples 21,24‐26,28‐37,42,44‐48,50,51 . Five studies did not give information about the randomization 27,38‐41 . All the included studies provided baseline characteristics including sex, age, the weight of the subjects, and wound area.…”

“…Only one trial provided sufficient reports on allocation concealment 47 . Four trials reported a nonrandom approach when housing the animals within the facility 27,30,31,38 . Four studies did not describe all measures used for random housing 16,30,31,38 .…”

“…Of included studies, eight studies reported the effect of chitosan‐based scaffolds on wound healing in cell studies 21,24,25,27‐31 . Escherichia coli , Pseudomonas aeruginosa , Bacillus subtilis , and Staphylococcus aureus 24,28 were used in the in vitro studies to examine the antibacterial activities of chitosan.…”