Abstract
One of the key problems hindering skin repair is the deficiency of dermal vascularization and difficulty of epidermis regeneration, which makes it challenging to fabricate scaffolds that can biologically fulfill the requirements for skin regeneration. To overcome this problem, three-dimensional printing was used to fabricate a gelatin-sulfonated silk composite scaffold that was incorporated with basic fibroblast growth factor 2 (FGF-2) through binding with a sulfonic acid group (SO3) (3DG-SF-SO3-FGF). The efficacy and mechanism by which the 3DG-SF-SO3-FGF scaffolds promote skin regeneration were investigated both within in vitro cell culture and in vivo with a full-thickness skin defect model. The histological results showed that the gelatin-sulfonated silk composite scaffolds promoted granulation, and that incorporation of FGF-2 significantly enhanced the regeneration of skin-like tissues after implantation in rat skin defects for 14 and 28 days. Further investigations demonstrated that 3DG-SF-SO3-FGF scaffolds might stimulate dermal vascularization. These findings thus suggest that incorporation of FGF-2 into the 3D printed scaffolds is a viable strategy for enhancing skin regeneration.
Highlights
One of the key problems hindering skin repair is the deficiency of dermal vascularization and difficulty of epidermis regeneration, which makes it challenging to fabricate scaffolds that can biologically fulfill the requirements for skin regeneration
The peaks around 1658 cm−1 and 1540 cm−1 which are characteristic absorption bands for peptides and proteins, were shifted to 1625 cm−1 and 1520 cm−1, respectively, when treated with the diazonium coupling mixture. These findings indicate the transition from a random coil to a b-sheet structure, which are similar to the results observed in previous studies[28, 30, 31]
Scanning electron microscopy (SEM) showed that both the 3D printed gelatin grid coated by pure Silk fibroin (SF) (3DG-SF, pore size = 100~200 μm) and the 3D printed gelatin grid coated by sulfonated SF (3DG-SF-SO3, pore size = 400~500 μm.) displayed porous structures (Fig. 1C)
Summary
One of the key problems hindering skin repair is the deficiency of dermal vascularization and difficulty of epidermis regeneration, which makes it challenging to fabricate scaffolds that can biologically fulfill the requirements for skin regeneration To overcome this problem, three-dimensional printing was used to fabricate a gelatin-sulfonated silk composite scaffold that was incorporated with basic fibroblast growth factor 2 (FGF-2) through binding with a sulfonic acid group (SO3) (3DG-SF-SO3-FGF). Different types of biomaterials have been employed to fabricate skin substitutes including naturally derived polymers (alginate, gelatin, collagen, chitosan, fibrin and hyaluronic acid), synthetic molecules (polyethylene glycol, PEG) and their cross-linking agents[9, 10] Amongst these materials, gelatin, a form of hydrolyzed collagen, has attracted much attention due to its similarity to human extracellular matrix (ECM) and its amenability for suspending cells within a gel environment at low temperature[11]. Various chemical modifications have been carried out to improve the physical and biological properties of gelatin hydrogels[12, 13]
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