Insulin complexed with cyclodextrins stimulates epithelialization and neovascularization of skin wound healing in rats

Besson, Jean Carlos Fernando; Hernandes, Luzmarina; Campos, Jéssica Men de; Morikawa, Karina Amélia; Bersani-Amado, Ciomar Aparecida; Matioli, Graciette

doi:10.1016/j.injury.2017.08.046

Cited by 29 publications

(13 citation statements)

References 24 publications

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“…When the skin is injured, keratinocytes at the wound edge receive signals to suppress differentiation and promote proliferation and migration in order to enable reepithelialization [19,20]. During the proliferative phase of wound healing, it is important to promote keratinocyte migration to the wound site; thus, proliferation ability is essential.…”

Section: Discussionmentioning

confidence: 99%

The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

Mi¹,

Liu²,

Liu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Antimicrobial peptides are effective promoters of wound healing but are susceptible to degradation. In this study, we replaced the GIGDP unit on the N-terminal of the endogenous human antimicrobial peptide hBD-2 with APKAM to produce A-hBD-2 and analyzed the effect on wound healing both in vitro and in vivo. Methods: The effects of A-hBD-2 and hBD-2 on cytotoxicity and proliferation in keratinocytes were assessed by Cell Counting Kit-8 assay. The structural stability and antimicrobial activity of hBD-2 and A-hBD-2 were evaluated against Staphylococcus aureus. RNA and proteins levels were evaluated by real-time PCR and western blotting, respectively. Cell migration was evaluated using a transwell assay. Cell cycle analysis was performed by flow cytometry. Wound healing was assessed in Sprague-Dawley rats. Epidermal thickness was evaluated by hematoxylin and eosin staining. Results: We found that hBD-2 exhibited cytotoxicity at high concentrations and decreased the structural stability in the presence of high sodium chloride concentrations. A-hBD-2 exhibited increased structural stability and antimicrobial activity, and had lower cytotoxicity in keratinocytes. A-hBD-2 increased the migration and proliferation of keratinocytes via phosphorylation of EGFR and STAT3 and suppressed terminal differentiation of keratinocytes. We also found that A-hBD-2 elicited mobilization of intracellular Ca²⁺ and stimulated keratinocytes to produce pro- and anti-inflammatory cytokines and chemokines via phospholipase C activation. Furthermore, A-hBD-2 promoted wound healing in vivo. Conclusion: Our data suggest that A-hBD-2 may be a promising candidate therapy for wound healing.

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Section: Discussionmentioning

confidence: 99%

The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

Mi¹,

Liu²,

Liu³

et al. 2018

Cell Physiol Biochem

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“…In addition, Besson et al (2017) explored the effect of insulin (50U) complexed with cyclodextrins on excisional skin wounds. 29 The highest concentration of serum insulin was detected at four and seven days in wounds treated with the complex, whereas serum insulin was not detected in wounds treated with insulin gel. The insulin and complexed gels significantly stimulated the proliferation of keratinocytes after four days of treatment; however, this effect kept at seven days only in wounds treated with complexed gels.…”

Section: Animal Studiesmentioning

confidence: 92%

<p>Effects of Topical Insulin on Wound Healing: A Review of Animal and Human Evidences</p>

Wang

2020

DMSO

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Wound healing is a complex biological process that repairs damaged tissues and restores skin integrity. Insulin, a potent factor of wound healing, has been reported for nearly a century to induce rapid recovery of various wounds, as shown by numerous human and animal studies. Although many studies have addressed the healing effect of systemic insulin on burn wound, only few have investigated the efficacy of topical insulin. Thus, this study aimed to review evidence of the effects of topical insulin on wound healing, including on diabetic and non-diabetic wounds. The presented animal and clinical studies support that topical insulin improves wound healing through several mechanisms without causing side effects. Additionally, various wound dressings accelerate the wound healing with controlled and sustained delivery of bioactive insulin. Therefore, topical insulin has been appreciated in field of wound healing, and further studies are needed to improve our understanding of the role of insulin in the healing of various wounds.

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“…[42] Hydroxypropy-beta-cyclodextrin complexed with insulin allowed a more constant and prolonged drug a release ( Figure 1) and thus improvement of the re-epithelialization process, matrix remodeling, neovascularization, and inflammatory response modulation. [43] CD-modified sacran hydrogel films also confirmed the potential of these systems for wound healing applications by improving wound closure, probably due to its higher moisturizing properties compared to those of the sacranhydrogel films without CDs. Results showed that sacran, a novel megamolecular polysaccharide, could enhance the skin barrier function during the wound healing process and mediate the production of cytokines (such as IL-5 and TNF-α) and thus, influence the anti-inflammatory activity.…”

Section: Cyclodextrinsmentioning

confidence: 60%

“…[ 42 ] Hydroxypropy‐beta‐cyclodextrin complexed with insulin allowed a more constant and prolonged drug a release (Figure 1) and thus improvement of the re‐epithelialization process, matrix remodeling, neovascularization, and inflammatory response modulation. [ 43 ]…”

Section: Nanomaterials In Wound Healingmentioning

confidence: 99%

Nanomaterials in wound healing: From material sciences to wound healing applications

et al. 2020

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An increasing number of innovative therapies have emerged in the field of wound healing. Nanostructured systems have been used to improve wound healing at different stages. The drug itself may be formulated at a nanoscale such that it can function as its own "carrier" or nanomaterials may be used as drug delivery vehicles. The present work covers the latest advancements on innovative nano-based organic and inorganic materials. These novel drug delivery systems possess high stability, large surface area and tunable compositions and have demonstrated their wound-healing properties using in vitro and in vivo models. Key areas in the development of new systems for wound care are the assessment of biological compatibility, the evaluation of anti-microbial activity and the in vivo efficacy assessment using full-thickness skin models. Due to the multifactorial nature of chronic wound occurrence robust models should support the investigation of new materials in order to elucidate mechanisms involved in the sequence of physiologic processes that take place at wound healing. Although several nanoparticles have been successfully tested both in vitro and in vivo, researchers are still investigating the approaches to implementing large scale production of nanotechnological platforms to wound healing treatments.

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Insulin complexed with cyclodextrins stimulates epithelialization and neovascularization of skin wound healing in rats

Cited by 29 publications

References 24 publications

The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

<p>Effects of Topical Insulin on Wound Healing: A Review of Animal and Human Evidences</p>

Nanomaterials in wound healing: From material sciences to wound healing applications

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