Abstract
Hypertrophic scarring (HS) has been considered as a great concern for patients and a challenging problem for clinicians as it can be cosmetically disfiguring and functionally debilitating. In this study, Ginsenoside Rg3/Poly(l-lactide) (G-Rg3/PLLA) electrospun fibrous scaffolds covering on the full-thickness skin excisions location was designed to suppress the hypertrophic scar formation in vivo. SEM and XRD results indicated that the crystal G-Rg3 carried in PLLA electrospun fibers was in amorphous state, which facilitates the solubility of G-Rg3 in the PLLA electrospun fibrous scaffolds, and solubility of G-Rg3 in PBS is increased from 3.2 µg/ml for pure G-Rg3 powders to 19.4 µg/ml for incorporated in PLLA-10% fibers. The released G-Rg3 content in the physiological medium could be further altered from 324 to 3445 µg in a 40-day release period by adjusting the G-Rg3 incorporation amount in PLLA electrospun fibers. In vitro results demonstrated that electrospun G-Rg3/PLLA fibrous scaffold could significantly inhibit fibroblast cell growth and proliferation. In vivo results confirmed that the G-Rg3/PLLA electrospun fibrous scaffold showed significant improvements in terms of dermis layer thickness, fibroblast proliferation, collagen fibers and microvessels, revealing that the incorporation of the G-Rg3 in the fibers prevented the HS formation. The above results demonstrate the potential use of G-Rg3/PLLA electrospun fibrous scaffolds to rapidly minimize fibroblast growth and restore the structural and functional properties of wounded skin for patients with deep trauma, severe burn injury, and surgical incision.
Highlights
Hypertrophic scarring (HS) is a dermal fibroproliferative disorder that often occurs following deep trauma, severe burn injury, and surgical incision [1], and is a great concern for patients and a challenging problem for clinicians [2]
It can be seen that there are no beads in the fibrous structure and the fibers are uniform in size, randomly interconnected
The drug entrapment did not significantly affect the porosity of electrospun PLLA fibrous scaffolds, since there is no significant difference in the porosity among PLLA fibrous scaffolds (64.5%) and Ginsenoside Rg3 (G-Rg3)/PLLA fibrous scaffolds (64.1%–70.1%)
Summary
Hypertrophic scarring (HS) is a dermal fibroproliferative disorder that often occurs following deep trauma, severe burn injury, and surgical incision [1], and is a great concern for patients and a challenging problem for clinicians [2]. HS is normally characterized by proliferation of dermal tissue with excessive deposition of fibroblast-derived extracellular matrix proteins, especially collagen, by excessive neovascularization, persistent inflammation, and fibrosis [3]. Some studies have shown that HS growth can be inhibited by reducing the growth of scar fibroblast proliferation or inducing apoptosis of fibroblasts to reduce collagen synthesis and secretion [4,5]. Selective inhibition of excessive proliferation of fibroblasts in early proliferative phase of HS is a promising new method for treating HS. G-Rg3 was found to be able to induce apoptosis of human hypertrophic scar fibroblasts [10,11]. We speculate that G-Rg3 may be applied on the injury tissue for preventing or reducing HS formation
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