Abstract
This study aimed to develop a silk fibroin (SF)-film for the treatment of chronic diabetic wounds. Silk fibroin was purified through a newly developed heating degumming (HD) process and casted on a hydrophobic surface to form SF-films. The process allowed the fabricated film to achieve a 42% increase in transparency and a 32% higher proliferation rate for BALB/3T3 fibroblasts compared to that obtained by conventional alkaline degumming treatment. Fourier transform infrared analysis demonstrated that secondary structure was retained in both HD- and alkaline degumming-derived SF preparations, although the crystallinity of beta-sheet in SF-film after the HD processing was slightly increased. This study also investigated whether conjugating insulin-like growth factor-1 (IGF-1) would promote diabetic wound healing and what the optimal dosage is. Using BALB/3T3 cells grown in hyperglycemic medium as a model, it was demonstrated that the optimal IGF-1 dosage to promote the cell growth was approximately 0.65 pmol. Further analysis of wound healing in a diabetic mouse model indicated that SF-film loaded with 3.25 pmol of IGF-1 showed significantly superior wound closure, a 13% increase at the 13th day after treatment relative to treatment with 65 pmol of free IGF-1. Improvement in diabetic wound healing was exerted synergistically by SF-film and IGF-1, as reflected by parameters including levels of re-epithelialization, epithelial tissue area, and angiogenesis. Finally, IGF-1 increased the epithelial tissue area and micro-vessel formation in a dose-dependent manner in a low dosage range (3.25 pmol) when loaded to SF-films. Together, these results strongly suggest that SF-film produced using HD and loaded with a low dosage of IGF-1 is a promising dressing for diabetic wound therapy.
Highlights
Diabetes mellitus is one of the most prevalent non-communicable diseases, affecting422 million adults in 2014 and causing about 1.5 million deaths in 2012 [1]
These results indicate that silk fibroin (SF)-film loaded with a low dosage (3.25 pmol) of insulin-like growth factor 1 (IGF-1) is a useful dressing for diabetic wound treatment
This study demonstrated that optimization of the Silk fibroin film (SF-film) manufacturing procedure and insulin-like growth factors (IGFs)-1 dosage are essential to prepare a dressing for diabetic wound healing
Summary
Diabetes mellitus is one of the most prevalent non-communicable diseases, affecting. 422 million adults in 2014 and causing about 1.5 million deaths in 2012 [1]. 15% of diabetic patients suffer from chronic wounds or foot ulcers that frequently lead to limb amputation or even death [2,3]. In 2010, approximately 73,000 amputations were performed on diabetic patients with non-healing wounds in the United States [4]. The standard practices in diabetic wound management include surgical debridement, systematical glycemic control, wound off-loading, and dressings [5,6]. Significant efforts have been exerted to improve diabetic wound healing, no satisfactory therapy has been developed far [7]. More research on novel interventions to improve healing of diabetes-associated chronic wounds is urgently required
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