We previously developed an injectable levan-based hydrogel as a temporary dermal filler. However, the longevity and collagen stimulation effect of the levan-based hydrogel were limited. Herein, we prepared hydroxyapatite (HAp)-embedded levan composite hydrogel as a long-acting dermal filler for enhancing in vivo collagen production and anti-wrinkle efficacy. HAp amount (0.1–5 wt%) in the levan hydrogel was optimized for stability, safety, and efficacy. Increasing the HAp amount decreased the in vitro stability and elastic modulus, but the composite hydrogel structure was still maintained. Furthermore, the composite hydrogel showed improved cell proliferation stimulation compared to the bare levan hydrogel in human dermal fibroblast cells. In vivo stability of the composite hydrogel was enhanced in contrast to the in vitro result, showing stable residence of the composite hydrogels with 0.5 or 1 wt% HAp over 8 weeks. Moreover, the excellent anti-wrinkle efficacy of composite hydrogel with 1 wt% HAp was maintained during 8 weeks and it showed the highest collagen production. Thus, HAp-embedded levan composite hydrogel showed potential as a dermal filler with easy injectability, biocompatibility, and long-acting anti-wrinkle efficacy.

我们之前开发了一种可注射的基于左聚糖的水凝胶作为临时皮肤填充剂。然而，基于左聚糖的水凝胶的寿命和胶原刺激作用是有限的。在此，我们制备了羟基磷灰石 (HAp) 嵌入的果聚糖复合水凝胶作为长效真皮填充剂，用于增强体内胶原蛋白的生成和抗皱功效。左旋水凝胶中的 HAp 量（0.1-5 wt%）针对稳定性、安全性和有效性进行了优化。增加 HAp 量会降低体外稳定性和弹性模量，但复合水凝胶结构仍保持不变。此外，与人真皮成纤维细胞中的裸左聚糖水凝胶相比，复合水凝胶显示出改善的细胞增殖刺激。体内与体外结果相比，复合水凝胶的稳定性得到增强，表明复合水凝胶与 0.5 或 1 重量％的 HAp 可在 8 周内稳定停留。此外，含有 1 wt% HAp 的复合水凝胶的优异抗皱功效在 8 周内得以保持，并显示出最高的胶原蛋白产量。因此，嵌入 HAp 的果聚糖复合水凝胶显示出作为皮肤填充剂的潜力，具有易于注射、生物相容性和长效抗皱功效。