Neutrophils are essential effector cells for mediating rapid host defense and their insufficiency arising from therapy-induced side-effects, termed neutropenia, can lead to immunodeficiency-associated complications. In autologous hematopoietic stem cell transplantation (HSCT), neutropenia is a complication that limits therapeutic efficacy. Here, we report the development and in vivo evaluation of an injectable, biodegradable hyaluronic acid (HA)-based scaffold, termed HA cryogel, with myeloid responsive degradation behavior. In mouse models of immune deficiency, we show that the infiltration of functional myeloid-lineage cells, specifically neutrophils, is essential to mediate HA cryogel degradation. Post-HSCT neutropenia in recipient mice delayed degradation of HA cryogels by up to 3 weeks. We harnessed the neutrophil-responsive degradation to sustain the release of granulocyte colony stimulating factor (G-CSF) from HA cryogels. Sustained release of G-CSF from HA cryogels enhanced post-HSCT neutrophil recovery, comparable to pegylated G-CSF, which, in turn, accelerated cryogel degradation. HA cryogels are a potential approach for enhancing neutrophils and concurrently assessing immune recovery in neutropenic hosts.

中文翻译：

---

用于增强中性粒细胞再生的免疫响应性可生物降解支架

中性粒细胞是介导快速宿主防御的重要效应细胞，治疗引起的副作用（称为中性粒细胞减少症）引起的它们的不足可导致免疫缺陷相关并发症。在自体造血干细胞移植 (HSCT) 中，中性粒细胞减少症是一种限制治疗效果的并发症。在这里，我们报告了一种可注射的、可生物降解的透明质酸 (HA) 支架（称为 HA 冷冻凝胶）的开发和体内评估，该支架具有骨髓响应性降解行为。在免疫缺陷的小鼠模型中，我们发现功能性骨髓系细胞，特别是中性粒细胞的浸润对于介导 HA 冷冻凝胶降解至关重要。受体小鼠的 HSCT 后中性粒细胞减少延迟 HA 冷冻凝胶的降解长达 3 周。我们利用中性粒细胞反应性降解来维持 HA 冷冻凝胶中粒细胞集落刺激因子 (G-CSF) 的释放。从 HA 冷冻凝胶中持续释放 G-CSF 增强了 HSCT 后中性粒细胞的恢复，与聚乙二醇化 G-CSF 相当，这反过来又加速了冷冻凝胶的降解。HA 冷冻凝胶是增强中性粒细胞和同时评估中性粒细胞减少宿主免疫恢复的潜在方法。