Diabetic foot ulcers (DFUs) that are not effectively treated could lead to partial or complete lower limb amputations. The lack of connective tissue growth factor (CTGF) and insulin-like growth factor (IGF-I) in DFUs results in limited matrix deposition and poor tissue repair. To enhance growth factor (GF) availability in DFUs, heparin (HN)-mimetic alginate sulfate/polycaprolactone (AlgSulf/PCL) double emulsion nanoparticles (NPs) with high affinity and sustained release of CTGF and IGF-I were synthesized. The NPs size, encapsulation efficiency (EE), cytotoxicity, cellular uptake and wound healing capacity in immortalized primary human adult epidermal cells (HaCaT) were assessed. The sonication time and amplitude used for NPs synthesis enabled the production of particles with a minimum of 236 ± 25 nm diameter. Treatment of HaCaT cells with up to 50 μg mL⁻¹ of NPs showed no cytotoxic effects after 72 h. The highest bovine serum albumin EE (94.6 %, P = 0.028) and lowest burst release were attained with AlgSulf/PCL. Moreover, cells treated with AlgSulf/CTGF (250 ng mL⁻¹) exhibited the most rapid wound closure compared to controls while maintaining fibronectin synthesis. Double-emulsion NPs based on HN-mimetic AlgSulf represent a novel approach which can significantly enhance diabetic wound healing and can be expanded for applications requiring the delivery of other HN-binding GFs.

未得到有效治疗的糖尿病足溃疡 (DFU) 可能导致部分或完全下肢截肢。DFU 中缺乏结缔组织生长因子 (CTGF) 和胰岛素样生长因子 (IGF-I) 导致基质沉积有限和组织修复不良。为了提高 DFU 中生长因子 (GF) 的可用性，合成了具有高亲和力和持续释放 CTGF 和 IGF-I 的肝素 (HN)-模拟海藻酸盐硫酸盐/聚己内酯 (AlgSulf/PCL) 双乳液纳米颗粒 (NPs)。评估了永生化原代成人表皮细胞 (HaCaT) 中 NP 的大小、封装效率 (EE)、细胞毒性、细胞摄取和伤口愈合能力。用于 NPs 合成的超声处理时间和振幅能够生产最小直径为 236 ± 25 nm 的粒子。^-1的 NPs 在 72 小时后没有表现出细胞毒性作用。使用 AlgSulf/PCL 获得最高的牛血清白蛋白 EE（94.6%，P = 0.028）和最低的突释。此外，与对照相比，用AlgSulf/CTGF (250 ng mL ^-1 )处理的细胞表现出最快的伤口闭合，同时保持纤连蛋白合成。基于 HN 模拟 AlgSulf 的双乳液 NPs 代表了一种新方法，可以显着增强糖尿病伤口愈合，并且可以扩展到需要传递其他 HN 结合 GF 的应用。