口腔疾病防治2026，Vol.34Issue(6)：529-540,12.DOI:10.12016/j.issn.2096-1456.202550506
噬菌体/白细胞介素-4脂质体复合材料预防小鼠上颌扩弓后复发
Phage/interleukin-4 liposome composite prevents relapse after maxillary expansion in mice
摘要
Abstract
Objective To explore the efficacy of a novel injectable hydrogel(GelMA/P11/IL4@LIP)loaded with P11 bacteriophages and interleukin-4(IL-4)liposomes(LIP)in preventing relapse after maxillary expansion in mice,providing experimental evidence for its clinical application.Methods This study was approved by the experimental animal ethics committee of our hospital.First,15 7-week-old C57BL/6 mice were used to establish a maxillary expan-sion model and divided into 5 groups(3 mice in each group):a control group,post expansion day 3 group(PED3 group),post expansion day 7 group(PED7 group),retention for 14 days group(RET group),and relapse for 7 days group(REL group).The mice in each group were sacrificed at their designated time points(day 0,3,7,21,28),and their maxilla and anterior cranial regions were collected.Bone parameters and the inter-crestal distance(ICD)of maxillary incisor mesial alveolar ridge were measured using micro-computed tomography(micro-CT).Histological staining was performed to evaluate bone formation and resorption,while immunohistochemistry(IHC)was performed for macrophage markers(CD86 and CD206),mesenchymal stem cell markers(glioma-associated oncogene homolog 1[Gli1]),and osteogenic markers(Runt-related transcription factor 2[Runx2]and Osterix[OSX]).Next,GelMA/P11/IL4@LIP was synthesized and administered to mouse models of maxillary expansion.A total of 24 7-week-old C57BL/6 mice were divided into 4 groups(6 mice in each group):a blank control group,GelMA group,GelMA/P11 group,and GelMA/P11/IL4@LIP group.All mice underwent palatal expansion.On PED7,the expanders of all 24 mice were cemented with resin to initi-ate the 14-day retention period.On day 1 of the retention phase,the mice in each group received injections of saline,GelMA,GelMA/P11,or GelMA/P11/IL4@LIP at the midpalatal suture.After the 14-day retention period,three mice in each group were randomly selected and sacrificed,while the other three had their expanders removed and underwent a 7-day relapse before being sacrificed on day 28(REL).Micro-CT,histological staining,and IHC were performed to evaluate the preventive effect of GelMA/P11/IL4@LIP on post-expansion relapse.Results The mice maxillary expan-sion model exhibited a decreased ICD at REL compared to RET in micro-CT analysis(P=0.008).IHC analysis demon-strated prolonged M1 macrophage infiltration,scarce Gli1+mesenchymal stem cells,and insufficient expression of osteo-genic markers(RUNX2 and OSX)(P<0.001).Compared to the blank control and GelMA groups,GelMA/P11/IL4@LIP hydrogel injection in the midpalatal suture led to increased ICD at REL,promoted the timely M2 polarization of macro-phages,recruited Gli1+mesenchymal stem cells,and upregulated the expression of RUNX2 and OSX(P<0.05).Con-clusion The mechanism of relapse after maxillary expansion involves the persistent infiltration of M1 macrophages,as well as the inadequate recruitment and insufficient osteogenic differentiation of MSCs in the midpalatal suture.The GelMA/P11/IL4@LIP composite enhanced orofacial mesenchymal stem cell recruitment and promoted the M2 polariza-tion of macrophages,thereby enhancing osteogenesis in the midpalatal suture and preventing post-expansion relapse.关键词
间充质干细胞/巨噬细胞/噬菌体/噬菌体展示技术/白细胞介素-4/上颌扩弓/上颌横向发育不足/免疫调节Key words
mesenchymal stem cells/macrophages/phage/phage display techniques/interleukin-4/maxil-lary expansion/maxillary transverse deficiency/immunomodulation分类
医药卫生引用本文复制引用
李睿智,刘偌景,汪兴明,蒲曦鸣,尹星,邹淑娟..噬菌体/白细胞介素-4脂质体复合材料预防小鼠上颌扩弓后复发[J].口腔疾病防治,2026,34(6):529-540,12.基金项目
国家自然科学基金面上项目(82271017) （82271017）
四川省科技计划项目重点研发项目(2022YFS0117) （2022YFS0117）
爱齐科研专项基金项目(AQKY22-1-2 （）
AQKY22-2-6) This study was supported by the grants from National Natural Science Foundation of China(No.82271017) （No.82271017）
Sichuan Provincial Department of Science and Technology Applied Basic Research(No.2022YFS0117) （No.2022YFS0117）
Align Technology Re-search Program(No.AQKY22-1-2 and No.AQKY22-2-6). （No.AQKY22-1-2 and No.AQKY22-2-6）
