Galectin-3/Gelatin Electrospun Scaffolds Modulate Collagen Synthesis in Skin Healing but Do Not Improve Wound Closure Kinetics

Abstract

Chronic wounds remain trapped in a pro-inflammatory state, with strategies targeted at inducing re-epithelialization and the proliferative phase of healing desirable. As a member of the lectin family, galectin-3 is implicated in the regulation of macrophage phenotype and epithelial migration. We investigated if local delivery of galectin-3 enhanced skin healing in a full-thickness excisional C57BL/6 mouse model. An electrospun gelatin scaffold loaded with galectin-3 was developed and compared to topical delivery of galectin-3. Electrospun gelatin/galectin-3 scaffolds had an average fiber diameter of 200 nm, with 83% scaffold porosity approximately and an average pore diameter of 1.15 μm. The developed scaffolds supported dermal fibroblast adhesion, matrix deposition, and proliferation in vitro. In vivo treatment of 6 mm full-thickness excisional wounds with gelatin/galectin-3 scaffolds did not influence wound closure, re-epithelialization, or macrophage phenotypes, but increased collagen synthesis. In comparison, topical delivery of galectin-3 [6.7 µg/mL] significantly increased arginase-I cell density at day 7 versus untreated and gelatin/galectin-3 scaffolds (p < 0.05). A preliminary assessment of increasing the concentration of topical galectin-3 demonstrated that at day 7, galectin-3 [12.5 µg/mL] significantly increased both epithelial migration and collagen content in a concentration-dependent manner. In conclusion, local delivery of galectin 3 shows potential efficacy in modulating skin healing in a concentration-dependent manner.

Keywords

• wound chronicity
• macrophage
• keratinocytes
• lectins
• matricellular proteins
• arginase-I