树枝状聚合物交联的γ-聚谷氨酸/海藻酸钠海绵：增强止血和持续抗炎活性用于鼻窦炎术后治疗

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中文摘要

鼻窦炎常需功能性内镜鼻窦手术（FESS），但术后出血和持续炎症仍是关键挑战。本研究开发了一种多功能复合海绵（GSPB），以γ-聚谷氨酸（γ-PGA）和海藻酸钠（SA）为基质，以第3代聚酰胺胺（PAMAM）树枝状聚合物（G3）同时作为交联剂和布地奈德（Bud）增溶剂。通过EDC/NHS介导的交联和冷冻干燥制备，GSPB表现出多孔结构、平衡的压缩模量41.95 ± 3.50 kPa，以及优异的循环压缩抗疲劳性（50次压缩循环后应力衰减率仅为8.98%）。它还表现出对水和血液的快速吸收，并在21天内完全生物降解。同时，G3将Bud的水溶性提高12.5倍，从而实现长期持续药物递送。体外研究证实了优异的生物相容性、强效止血功效和抗炎活性。使用鼻出血和急性鼻窦炎模型的体内实验表明，与商业明胶海绵和Nasopore相比，GSPB实现了更快的止血和更少的失血。它还有效抑制黏膜炎症、减少胶原沉积并抑制杯状细胞增生，且无全身毒性，这通过小鼠血清生化、血常规和主要器官H&E组织学染色得到验证。作为一种整合止血和抗炎活性的可生物降解支架，GSPB为鼻窦炎术后护理提供了一种新颖且有前景的解决方案，具有显著的临床转化潜力。

英文摘要

Sinusitis often requires functional endoscopic sinus surgery (FESS), but postoperative bleeding and persistent inflammation remain critical challenges. This study developed a multifunctional composite sponge (GSPB) using γ-polyglutamic acid (γ-PGA) and sodium alginate (SA) as the matrix, with Generation 3 polyamidoamine (PAMAM) dendrimer (G3) serving as both cross-linkers and budesonide (Bud) solubilizers. Fabricated via EDC/NHS-mediated cross-linking and freeze-drying, GSPB exhibited a porous structure, a balanced compressive modulus of 41.95 ± 3.50 kPa, and excellent cyclic compression fatigue resistance (stress attenuation rate of only 8.98% after 50 compression cycles). It also showed rapid absorption toward water and blood, alongside full biodegradability within 21 days. Meanwhile, G3 elevates the aqueous solubility of Bud by 12.5 times, thereby achieving long-term sustained drug delivery. In vitro studies confirmed excellent biocompatibility, potent hemostatic efficacy, and anti-inflammatory activity. In vivo experiments using nasal bleeding and acute sinusitis models demonstrated that GSPB achieved faster hemostasis with less blood loss than commercial gelatin sponges and Nasopore. It also effectively suppressed mucosal inflammation, reduced collagen deposition, and inhibited goblet cell hyperplasia without systemic toxicity, verified by serum biochemistry, routine blood tests, and major organ H&E histological staining in mice. As a biodegradable scaffold integrating hemostasis and anti-inflammatory activity, GSPB provides a novel and promising solution for post-sinusitis surgery care, with significant clinical translational potential.