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

Abstract

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.

Keratin Biomaterials in Skin Wound Healing, an Old Player in Modern Medicine: A Mini Review

“…It should be mentioned that lots of studies describe the application of a soluble fraction of keratin as a wound dressing [3,91,92]. However, in the literature, we can find only a few studies that described the insoluble fractions of keratins in wound treatment [7,10,93]. Moreover, the basic wound dressing can be modified with antimicrobial compounds, such as silver nanoparticles (AgNP), antibiotics, or other substances, that can improve the recovery of injured tissues and prevent secondary infection [10,23].…”

“…In a subsequent study, Konop et al [93] modified keratin biomaterial (base dressing FKDP) with opioid peptide-casomorphin and examined in vitro and in vivo in diabetic mice model of full-thickness wound model. They showed that casomorphin slowly releases from the wound dressing.…”

“…All studies performed by Konop et al [7,8,10,93] showed the possibility of applying an insoluble fraction of keratin biomaterial as a wound dressing. Moreover, due to heterogeneous surfaces, it is possible to incorporate compounds with antimicrobial or analgesic properties.…”

Dual-Drug Loaded Biomimetic Chitosan-Collagen Hybrid Nanocomposite Scaffolds for Ameliorating Potential Tissue Regeneration in Diabetic Wounds

“…DWs are hard to repair and tend to become chronic or stalled. The wound bed microenvironment of a chronic or halted wound differs significantly from that of an acute or healing wound, with the high inflammatory intermediaries and proteases levels (8, 9). These wounds will still be in the inflammatory phase, marked by a constant influx of neutrophils and the production of cytotoxic enzymes, reactive oxygen species (ROS), and inflammatory mediators that cause tissue damage.…”

Acute Skin Wounds Treated with Mesenchymal Stem Cells and Biopolymer Compositions Alone and in Combination: Evaluation of Agent Efficacy and Analysis of Healing Mechanisms

“…Added to this is the trend of increased life expectancy, and hence comorbidity, which is accompanied by a growing prevalence of chronic trophic ulcers of various etiologies that are becoming an acute clinical problem [4][5][6]. Despite the constantly increasing number of drugs and methods used to treat wounds, the problem of effective regeneration has not yet been resolved [5][6][7][8][9][10][11][12]. The results of meta-analyses and systematic reviews of the effectiveness of different agents and methods used to treat wounds demonstrate the lack of a uniform and effective approach, as well as a limited choice of drugs for use in wound treatment [13][14][15][16].…”