MDRCBB, Minnesota Dental Research Center for Biomaterials and Biomechanics, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Biomacromolecules. 2020 Dec 14;21(12):4945-4961. doi: 10.1021/acs.biomac.0c01163. Epub 2020 Oct 2.
Bioadhesive membranes with controllable and reversible underwater adhesion are desirable for several biomedical applications ranging from biosensing, drug/therapeutic delivery, and tissue regeneration. Here, we present dual soft mucosal and hard bone/enamel tissue adhesive nanofiber membranes composed of chitosan and pectin derivatives for pH-controlled delivery of antimicrobial peptides (AMPs) in the oral cavity. testing with porcine esophagus (soft mucosal mimic) indicated a 2-fold increase in the mucoadhesion of chitosan membranes with 0.05 wt % oxidized pectin coating, while the uncoated membranes exhibited 3-4-fold stronger adhesion to hydroxyapatite discs (enamel/hard bone mimic) compared to the coated membranes. The former is attributed to a synergistic interaction of surface nanofiber topography, intermolecular hydrogen bonding, and aldehyde-amine chemistry between surface polar groups and mucosal proteins, while the latter may arise from electrostatic interactions between cationic amines (-NH) in chitosan and anionic phosphates (-PO) in hydroxyapatite. Further, the dual hard-soft oral tissue adhesive nanofiber membranes loaded with cationic amphipathic AMPs (D-GL13K and IDR-1018) elicited pH-responsive AMP delivery and antimicrobial action comparable to chlorhexidine (CHX) against oral streptococci. Concurrently, the AMP loaded membranes were cytocompatible to both soft epithelial tissue-derived human oral keratinocytes and hard calvarial murine pre-osteoblast cells. We envision these membranes to function as adhesive gingival grafts and guided bone regeneration (GBR) membranes at the hard-soft tissue interface while simultaneously protecting against oral infections.
具有可控和可重复水下附着的生物粘附膜对于从生物传感、药物/治疗药物输送和组织再生等多个生物医学应用是理想的。在这里，我们提出了由壳聚糖和果胶衍生物组成的双重软粘膜和硬骨/牙釉质组织粘附纳米纤维膜，用于在口腔中 pH 控制抗菌肽（AMP）的递送。用猪食道（软粘膜模拟物）进行的测试表明，具有 0.05wt%氧化果胶涂层的壳聚糖膜的粘膜粘附性增加了 2 倍，而未涂层的膜对羟基磷灰石盘（牙釉质/硬骨模拟物）的粘附力比涂层膜强 3-4 倍。前者归因于表面纳米纤维形貌、分子间氢键以及表面极性基团和粘膜蛋白之间的醛胺化学之间的协同相互作用，而后者可能源于壳聚糖中的阳离子胺（-NH）和羟基磷灰石中的阴离子磷酸盐（-PO）之间的静电相互作用。此外，负载有阳离子两亲性 AMP（D-GL13K 和 IDR-1018）的双重硬软口腔组织粘附纳米纤维膜引起了 pH 响应的 AMP 递送和抗菌作用，可与洗必泰（CHX）相媲美，对抗口腔链球菌。同时，负载 AMP 的膜对软上皮组织衍生的人口腔角质形成细胞和硬颅骨鼠前成骨细胞均具有细胞相容性。我们设想这些膜可以作为硬软组织界面处的粘附性牙龈移植物和引导骨再生（GBR）膜，同时防止口腔感染。
