McLeod Karrington A, Di Gregorio Madeleine, Tinney Dylan, Carmichael Justin, Zuanazzi David, Siqueira Walter L, Rizkalla Amin, Hamilton Douglas W
Faculty of Engineering, School of Biomedical Engineering, University of Western Ontario, London, ON N6A 3K7, Canada.
Department of Anatomy and Cell Biology, University of Western Ontario, London, ON N6A 5C1, Canada.
Bioengineering (Basel). 2024 Sep 25;11(10):960. doi: 10.3390/bioengineering11100960.
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 ( < 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.
慢性伤口一直处于促炎状态,因此旨在诱导再上皮化和愈合增殖期的策略是可取的。作为凝集素家族的一员,半乳糖凝集素-3参与巨噬细胞表型和上皮迁移的调节。我们研究了在C57BL/6小鼠全层切除伤口模型中局部递送半乳糖凝集素-3是否能促进皮肤愈合。制备了负载半乳糖凝集素-3的静电纺丝明胶支架,并与半乳糖凝集素-3的局部递送进行比较。静电纺丝明胶/半乳糖凝集素-3支架的平均纤维直径为200 nm,支架孔隙率约为83%,平均孔径为1.15μm。所制备的支架在体外支持真皮成纤维细胞的黏附、基质沉积和增殖。用明胶/半乳糖凝集素-3支架对6 mm全层切除伤口进行体内治疗,对伤口闭合、再上皮化或巨噬细胞表型没有影响,但增加了胶原蛋白的合成。相比之下,在第7天,局部递送半乳糖凝集素-3[6.7μg/mL]与未治疗组和明胶/半乳糖凝集素-3支架相比,显著增加了精氨酸酶-I细胞密度(<0.05)。对半乳糖凝集素-3局部递送浓度增加的初步评估表明,在第7天,半乳糖凝集素-3[12.5μg/mL]以浓度依赖的方式显著增加了上皮迁移和胶原蛋白含量。总之,局部递送半乳糖凝集素-3显示出以浓度依赖方式调节皮肤愈合的潜在疗效。