文献类型：期刊文献

英文题名：Hemiaminal hydrogel-manganese nanoparticle hybrids boost healing of penetrating orocutaneous fistulas through microenvironmental regulation

作者：Yang, Yuzi[1];Wang, Jing[2,3];Pan, Fen[4,5];Li, Ya[1];Wang, Shuqi[1];Ma, Chunyue[2,3];Wang, Ruohua[1];Pan, Xueyan[1];Cao, Yuanyuan[1];Zhang, Dapeng[1];Li, Yongsheng[1]

机构：[1]East China Univ Sci & Technol, Frontier Sci Ctr Mat Biol & Dynam Chem, Sch Mat Sci & Engn, Minist Educ,Key Lab Ultrafine Mat,Lab Low Dimens M, Shanghai 200237, Peoples R China;[2]Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Natl Clin Res Ctr Oral Dis, Sch Med,Natl Ctr Stomatol,Dept Oral Maxillofacial, Shanghai 200011, Peoples R China;[3]Hainan Western Cent Hosp, Dept Oral & Maxillofacial Surg, Dan Zhou 571700, Peoples R China;[4]Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Sch Med, Dept Clin Lab, Shanghai, Peoples R China;[5]Shanghai Jiao Tong Univ, Inst Pediat Infect Immun & Crit Care Med, Sch Med, Shanghai 200062, Peoples R China

年份：2027

卷号：337

外文期刊名：BIOMATERIALS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001848474200001)】；

基金：This work was financially supported by the National Key Research and Development Program of China (Grant No. 2022YFC2403200), the National Natural Science Foundation of China (Nos. 22305081, 32571562, 52572303, 22472058), Leading Talents in Shanghai in 2018, Shanghai Sailing Program (23YF1408600), the Fundamental Research Funds for the Central Universities in China, Cross-disciplinary Research Fund of Shanghai Ninth People's Hospital (JYJC202314), Natural Sciences Fund in Hainan Province (SQ2024MSXMO324), and Danzhou Science and Technology, Industry and Information Development Bureau Fund (DGXJ[2024]80).

语种：英文

外文关键词：Organic-inorganic hybrid hydrogel; ROS-Responsive degradation; Penetrating orocutaneous fistulas; Immune microenvironment modulation

摘要：Penetrating orocutaneous and oropharyngeal fistulas (POFs) are difficult to treat due to continuous oral muscle movement and saliva leakage, and persistent bacterial infection and inflammation in the oral environment. However, healing biomaterials that can simultaneously block the penetrating wound, exert antibacterial and anti-inflammatory effects and degrade timely to accommodate fistula closure are rarely reported. Here, we report an organic-inorganic hybrid hydrogel termed MPMQb@gel, which exhibits robust mechanical strength, flexibility, and adhesion ability, enabling effective POF blockage. It consists of hemiaminal structure-containing polymeric hydrogel and Mn-polydopamine nanoparticles cross-linked via aldehyde-amine condensation. Triggered by excessive reactive oxygen species (ROS) in the POF microenvironment, MPMQb@gel gradually degrades and releases Mn2+, quercetin (Que), and basic fibroblast growth factor (bFGF) to achieve synergistic antibacterial, anti-inflammatory and pro-healing effects. In a New Zealand rabbit model of severe POF infection, this hybrid hydrogel realized complete POF healing within 12 days with administration every 4 days, markedly faster than commercial iodoform gauze-treated group. RNA sequencing and mechanistic analysis reveal that MPMQb@gel suppresses Th1 and Th17 cell differentiation, inhibit the Th17/IL-17-associated signaling axis and modulate the TLR2/STAT3 pathway to promote a stable immune microenvironment, thereby attenuating the inflammatory response and ultimately promoting POF repair. Collectively, by addressing the critical challenge of reconciling wound contraction with the requirement for durable occlusion through a controllably biodegradable organic-inorganic hybrid hydrogel, this work offers a transformative therapeutic strategy for POFs and penetrating wounds.