Improved Diabetic Wound Healing by EGF Encapsulation in Gelatin-Alginate Coacervates

Abstract

Topical imageplication of epidermal growth fctor (EGF) has been used to accelerate diabetic foot ulcers but with limited efficacy. In this study, we selected a complex coacervate (EGF-Coa) composed of the low molecular weight gelatin type A and sodium alginate as a novel delivery system for EGF, based on encapsulation efficiency and protection of EGF from protease. EGF-Coa enhanced in vitro migration of keratinocytes and accelerated wound healing in streptozotocin-induced diabetic mice with increased granulation and re-epithelialization. While diabetic wound sites without treatment showed downward growth of hyperproliferative epidermis along the wound edges with poor matrix formation, EGF-Coa treatment recovered horizontal migration of epidermis over the newly deposited dermal matrix. EGF-Coa treatment also resulted in reduced levels of proinflammatory cytokines IL-1, IL-6, and THF-α. Freeze-dried coacervates packaged in aluminum pouches were stable for up to 4 months at 4 and 25 °C in terms of appearance, purity by RP-HPLC, and in vitro release profiles. There were significant physical and chemical changes in relative humidity above 33% or at 37 °C, suggesting the requirement for moisture-proof packaging and cold chain storage for long term stability. We propose low molecular weight gelatin type A and sodium alginate (LWGA-SA) coacervates as a novel EGF delivery system with enhanced efficacy for chronic wounds.

Gelatin-Alginate Coacervates Optimized by DOE to Improve Delivery of bFGF for Wound Healing

“…Instead, EGF encapsulation was possible with the coacervates of low-molecular-weight Type A gelatin (LWGA) and SA [10]. EGF in LWGA-SA coacervates was protected from trypsin digestion, showing enhanced activity in diabetic wound healing compared with EGF in a solution or a physical mixture of LWGA and SA [11]. Major factors governing the coacervation process include the temperature, the pH of the reaction medium, the polymer ratio, the molecular weight, the total concentration, and charge densities [12].…”

Wound-Healing Potential of Cucurbita moschata Duchesne Fruit Peel Extract in a Rat Model of Excision Wound Repair

“…Nowadays, the fabrication and administration of novel delivery systems have also paved the road in wound healing. In this line, using the encapsulation of epidermal growth factor in gelatin-alginate coacervates could significantly reduce the wound area by suppressing inflammatory cytokines (e.g., IL-1, IL-6, and TNF- α ) [ 35 ].…”

Synergistic Effect of Biomaterial and Stem Cell for Skin Tissue Engineering in Cutaneous Wound Healing: A Concise Review

“…They play a prominent role in cell migration into the wound area, promote epithelialization, initiate angiogenesis, and stimulate matrix formation followed by remodeling the wounded area [ 11 ]. Epidermal growth factor (EGF) [ 41 ], basic fibroblast growth factor (bFGF) [ 39 ], transforming growth factor-beta (TGFβ 3 ) [ 40 ], platelet-derived growth factor (PDGF) [ 42 ], and vascular endothelial growth factor (VEGF) [ 43 ] are some of the GFs that contribute to the wound-healing process. EGF secreted by platelets, macrophages, and fibroblasts plays an important role in epithelialization and stimulates growth of keratinocytes [ 44 ].…”

“…EGF secreted by platelets, macrophages, and fibroblasts plays an important role in epithelialization and stimulates growth of keratinocytes [ 44 ]. In an in vivo study conducted by Jeong et al (2020) on healing diabetic mice wounds, EGF encapsulation in gelatine-alginate coacervates showed improved wound healing capacity via enhanced granulated tissue formation and cell migration and re-epithelialization [ 41 ]. According to Li et al (2018) and Xu et al (2020), genetically modified TGFβ 3 and PDGF combined with synthetic biomaterial both accelerated in vivo wound repair in a rabbit and mice model, respectively, but through specific mechanisms.…”