Dual Oral Tissue Adhesive Nanofiber Membranes for pH-Responsive Delivery of Antimicrobial Peptides

Sunil Kumar Boda, Nicholas G. Fischer, Zhou Ye, Conrado Aparicio

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

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. Ex vivo 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 (-NH3+) in chitosan and anionic phosphates (-PO43-) 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.

Original languageEnglish (US)
Pages (from-to)4945-4961
Number of pages17
JournalBiomacromolecules
Volume21
Issue number12
DOIs
StatePublished - Dec 14 2020

Bibliographical note

Funding Information:
The authors thank Dr. Wei Shen, Department of Biomedical Engineering, and Dr. Changquan Calvin Sun, School of Pharmacy, University of Minnesota, for sharing their electrospinning unit and texture analyzer, respectively. The authors also thank Dr. Alex Fok and Mr. Antonio Olivares for helping with the design of the fixtures and access to adhesion tests. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. Portions of this work were also conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nano Coordinated Infrastructure Network, Award Number NNCI - 1542202. Research reported in this publication was supported by the National Institute of Dental & Craniofacial Research of the National Institutes of Health (award number R01DE026117 to C.A. and T90DE0227232 to N.G.F.) and the National Center for Advancing Translational Sciences (Translational Research Development Program-TRDP award to Z.Y. from award number UL1TR002494). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2020 American Chemical Society. All rights reserved.

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