The analgesic hybrid of dermorphin/substance P and analog of enkephalin improve wound healing in streptozotocin‐induced diabetic rats

Abstract

The purpose of this study was to investigate the effect of the peptide analgesic hybrid compounds: AWL3106 analog of dermorphin and substance P (7‐11), and biphalin enkephalin analog on wound healing in streptozotocin‐induced diabetic rats. The diabetes was induced in 6–7 week‐old male Wistar rats by intraperitoneal injection of streptozotocin. After 70 days, the wounds were created on the back of the rats and then, once a day for 21 days, the dressing containing lanolin ointment, 10% of keratin scaffolds, and 1 mM of AWL3106 or biphalin was applied. The wounds histology were analyzed by hematoxylin and eosin staining. The orientation and organization of collagen was analyzed by Masson's trichome staining. The number of macrophages, blood vessels, and fibroblasts were visualized by CD68, CD34, and vimentin immunoreactivity, respectively. Our results demonstrated that the wound area of AWL3106‐ and biphalin‐treated groups was greatly reduced (up to 47% on the 7 day) in comparison with untreated diabetic groups. The immunohistochemical staining of macrophages demonstrated that AWL3106 and biphalin accelerated inflammatory progression and subsequently decreased persistent inflammation. The histological analysis showed that the structure of tissue in the groups under the study was very similar to the one of wound tissue in N‐DM group. The H&E and Masson's trichome staining demonstrated that the orientation and organization of collagen as well as the number and shape of blood vessels were better in 3106‐ and BIF‐treated group than in DM group. In conclusion, the obtained data suggested that our hybrid peptides enhanced wound healing, particularly by accelerating the inflammatory phase and promoted the wound closure.

Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

“…Moreover, several studies have shown that insoluble keratin enhances tissue recovery and promotes macrophages infiltration during the skin repair process in healthy and diabetic animals. The potentially extensive surface allows modification of compounds with antibacterial or analgesic properties, which is an additional advantage [ 20 , 24 , 25 ].…”

Biphalin—A Potent Opioid Agonist—As a Panacea for Opioid System-Dependent Pathophysiological Diseases?

“…For many years, biphalin has continued to be a source of inspiration for many scientists. Every year, at least a few new biphalin analogs have been designed, synthesized, and tested [ 27 , 89 , 90 ], and their non-analgesic properties related to the opioid system are still being discovered and studied [ 42 , 65 , 71 ]. This comprehensive review shows how many areas biphalin has been studied in.…”

“…The stimulating effect of biphalin on wound healing was observed by Muchowska et al in 2020 [ 65 ]. In in vivo experiments, they demonstrated that topically applied biphalin, suspended in lanolin ointment at a 300 µL of 1 mM concentration, accelerated wound closure by about 30% in streptozotocin-induced rats compared to the negative control (streptozotocin-induced diabetic rats without any dressing, DM).…”

The Regenerative Potential of Substance P

“…Inspired by the demonstrated positive influence of SP on wound healing, Muchowska et al wanted to see if such an effect could be found for a related peptide, AWL3106 [ 49 ]. This compound is an analgesic hybrid peptide, whose structure contains fragments coming from an opioid peptide dermorphine and a C-terminal five amino acid sequence of SP.…”