A cell-free SHED lysate-hydrogel system for oral ulcer healing with anti-inflammatory and pro-angiogenic effects

作者：Na Dong, Chen Zhang, Qiao Zhang, Shisan Bao, Yunfan Hu, Haichao Xu, Peng Dai, Caiyan Li, Shengcun Li, Pin Wu, Jin Xu, Xiaojun Cai, Zhouguang Wang, Lihua Luo · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03597-3 · 被引用次数：16 · 研究领域：Proteoglycans and glycosaminoglycans research、Mesenchymal stem cell research、Salivary Gland Disorders and Functions

Oral ulcer (OU) is one of the most common mucosal diseases, yet current drug treatments yield unsatisfactory outcomes. Persistent inflammatory responses and insufficient angiogenesis are the two major obstacles to OU healing. Recently, stem cell-based therapies, particularly mesenchymal stem cells (MSCs), have shown great regenerative potential through their anti-inflammatory and proangiogenic properties in OU treatment. However, they still face challenges, such as low cell survival rates, uncontrolled differentiation, and immune rejection. Meanwhile, a humid and highly dynamic oral environment degrades and dilutes biological drugs via saliva, thereby reducing their bioavailability during OU repair. To address these limitations, we developed an injectable fibrinogen/thrombin (FT) hydrogel encapsulating cell lysate (CL) derived from the stem cells of human exfoliated deciduous teeth (SHEDs). The SHED-derived CL retained the therapeutic properties of SHEDs while eliminating risks associated with cell transplantation. The FT hydrogel exhibited excellent biocompatibility, controlled CL release, and strong adhesion to oral wounds (> 24 h). In vitro, the FT/CL hydrogel polarized macrophages toward the anti-inflammatory M2 phenotype (upregulating CD206 and Arg1 expression) and suppressed pro-inflammatory M1 markers (iNOS and TNF-α) secretion. It also significantly enhanced tube formation, with a 2.5-fold increase in luminal length and 3.7-fold increase in the number of tubes compare...