Biomedical hydrogel has been widely used as regenerative biomaterials, however, an immune inflammatory response of hydrogel constantly crops up in body due to crosslinking agent, external stimulus or small molecule residues. Here we present a strategy to treat pelvic organ prolapse (POP) by combining both anti-inflammatory and promote tissue regeneration, using drug-loaded hydrogel to reconstruct the pelvic floor and minimize multiple inflammations. Photo-crosslinked gelatin hydrogel (GelMA) loaded with Puerarin (Pue) regulate inflammation by inhibiting the aggregation of neutrophils and eosinophils, simultaneously intervene the matrix regenerating/remodeling via TGF-β/MMPs pathway to repair the fascia of pelvic floor in rabbit models (POP model). The assessment of inflammatory cytokines expression (IL-3, IL-6, TNF-α, TGF-β1) in human uterus fibroblasts (HUVs), and extracellular matrix (ECM) related factors (COL-1, COL-3, MMP2, MMP9) was performed in rabbit. Immune microenvironment was analyzed by immunohistochemistry in rabbit samples. Pue-loaded GelMA (Pue@GelMA) down regulate inflammatory cytokines (IL-3 and IL-6) and matrix metalloproteinase 2/9 (MMP 2/9), and up regulate 1/3 type collagen (COL-1/3) in vitro. In this study, Pue@GelMA was able to regulate immune microenvironment through restricting the aggregation of neutrophils and eosinophils and remodel the distribution of ECM collagen in vivo. In the POP model, Pue@GelMA can effectively inhibits the inflammatory response caused by material implanted and promote fascia regenerate. This Hydrogel drug loading system was considered as an safe and effective method to treat POP without persistent complications, and it can also be applied to other prolapse diseases (e.g., intestinal hernia) or complex diseases treatment.

生物医学水凝胶已被广泛用作再生生物材料，但是，由于交联剂，外部刺激或小分子残基的作用，水凝胶的免疫炎症反应不断在体内出现。在这里，我们提出一种通过结合抗炎和促进组织再生，使用载有药物的水凝胶来重建骨盆底并最大程度减少多种炎症来治疗骨盆器官脱垂（POP）的策略。载有葛根素（Pue）的光交联明胶水凝胶（GelMA）通过抑制嗜中性粒细胞和嗜酸性粒细胞的聚集来调节炎症，同时通过TGF-β/ MMPs途径干预基质的再生/重塑，以修复兔模型中的骨盆底筋膜（ POP模式）。炎性细胞因子表达的评估（IL-3，IL-6，TNF-α，在兔中进行了人类子宫成纤维细胞（HUVs）中的TGF-β1）和细胞外基质（ECM）相关因子（COL-1，COL-3，MMP2，MMP9）的检测。通过免疫组织化学分析兔样品中的免疫微环境。载Pue的GelMA（Pue @ GelMA）下调炎症细胞因子（IL-3和IL-6）和基质金属蛋白酶2/9（MMP 2/9），上调1/3型胶原（COL-1 / 3）体外。在这项研究中，Pue @ GelMA能够通过限制嗜中性粒细胞和嗜酸性粒细胞的聚集并重塑ECM胶原在体内的分布来调节免疫微环境。在POP模型中，Pue @ GelMA可有效抑制植入材料引起的炎症反应并促进筋膜再生。