Hou Wenyi, Lin Zhaoyi, Chen Xinling, Sun Yu, Lin Yao, Peng Mengran, Zhou Feng, Jiang Huamin, Li Yan, Zheng Yue
Department of Dermato-Venerology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China.
School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China.
Mater Today Bio. 2025 Jul 29;34:102150. doi: 10.1016/j.mtbio.2025.102150. eCollection 2025 Oct.
There have been various interventions for photoaging skin, such as retinoic acid treatment and laser therapy. However, more precise, secure, and effective technologies and materials were still need to be explored. Cathepsin D (CTSD) repairs the epidermal barrier in chronic photodamaged skin through increasing TGase-1 expression and activity. Cathepsin K (CTSK) affects the metabolism of skin elastic fibers. Therefore, gelatin/alginate composite hydrogel microspheres loaded with CTSD or CTSK were fabricated. The microspheres with an average size of 79.8 ± 30.4 μm were stable in PBS (pH 7.4) for 5 days and then disintegrated . 0.1 mg/mL of microspheres continuously released 12-13 ng/mL CTSD or CTSK for the first three consecutive days. , the microspheres were almost completed degraded on day 7 after the subcutaneous injection. The biosafety and efficacy of CTSD- and CTSK- microspheres were confirmed and . They reduced ROS and inhibited the degradation of skin collagen and elastic fibers by upregulating Nrf2 and downregulating MMP-1 and MMP-3, which reversed photodamage of skin induced by UV. In conclusion, the gelatin/alginate composite microspheres loaded with CTSD or CTSK showed a great potential for chronic photodamaged skin.
针对光老化皮肤已有多种干预措施，如维甲酸治疗和激光疗法。然而，仍需要探索更精确、安全且有效的技术和材料。组织蛋白酶D（CTSD）通过增加转谷氨酰胺酶-1（TGase-1）的表达和活性来修复慢性光损伤皮肤的表皮屏障。组织蛋白酶K（CTSK）影响皮肤弹性纤维的代谢。因此，制备了负载CTSD或CTSK的明胶/海藻酸盐复合水凝胶微球。平均尺寸为79.8±30.4μm的微球在pH 7.4的磷酸盐缓冲液（PBS）中稳定5天，然后分解。0.1mg/mL的微球在连续三天内持续释放12 - 13ng/mL的CTSD或CTSK。皮下注射后第7天，微球几乎完全降解。CTSD和CTSK微球的生物安全性和有效性得到了证实。它们通过上调Nrf2和下调基质金属蛋白酶-1（MMP-1）和基质金属蛋白酶-3（MMP-3）来减少活性氧（ROS）并抑制皮肤胶原蛋白和弹性纤维的降解，从而逆转紫外线诱导的皮肤光损伤。总之，负载CTSD或CTSK的明胶/海藻酸盐复合微球在慢性光损伤皮肤方面显示出巨大潜力。
