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

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 (−PO4 3–) 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.

Facilitating GL13K Peptide Grafting on Polyetheretherketone via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide: Surface Properties and Antibacterial Activity

“…In the solution phase, most of the antibacterial studies have focused on the minimum inhibition concentrations of GL13K [ 21 , 22 , 23 ] to estimate the quantitative information. To fabricate a porous polymer structure, the GL13K peptide was mixed into mineralized collagen scaffolds [ 24 ] or a pectin-coated chitosan nanofiber membrane [ 25 ]. In addition, this AMP was coated on titanium (Ti) substrates to investigate its antibacterial activities and biofilm resistance [ 19 , 26 , 27 , 28 ].…”

Recent advances in biofunctional guided bone regeneration materials for repairing defective alveolar and maxillofacial bone: A review

“…Boda et al manufactured a bilayer membrane containing a chitosan nanofiber layer for hard tissue, and antimicrobial peptides (AMP) incorporating an oxidized pectin-coated chitosan nanofiber layer as a mucoadhesive [33] . The oxidized pectin coating adhered with adhesion proteins by hydrogen bonding and interaction between the aldehyde groups of the oxidized pectin and the amino groups of adhesion protein to enhance the affinity between the membrane and mucosa.…”

pH-Responsive Chitosan/Alginate Polyelectrolyte Complexes on Electrospun PLGA Nanofibers for Controlled Drug Release

“…Such stimuli include pH, temperature, light, and electrical and magnetic fields [ 1 , 2 , 3 , 4 ]. “Smart” responsive nanofibers have found applications for biomedical purposes as scaffolds for tissue engineering, drug delivery systems, biosensors, and wound dressings [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. When considering drug delivery, pH responsiveness has been widely investigated, especially for the design of systems providing a targeted and controlled release of active pharmaceutical ingredients.…”