Coaxial Electrospun Metronidazole Loaded Core/Shell Nanofiber Membranes For Guided Tissue Regeneration

Guided tissue regeneration technology has become a standard procedure for periodontal tissue regeneration therapy. However, infection is the major reason for GTR failure in clinical applications. Although systemic administration of antibiotics is effective, high oral doses are necessary to obtain effective concentrations in the gingival fluid without systemic side effects. Besides, long-term usage of antibiotics may lead to the development of resistant bacterial strains. The drawbacks have led researchers worldwide to focus on the development of drug loaded GTRM with the function of localized delivery of antibiotics directly at the diseased site to realize controlled release in accordance with the therapeutic purpose and the pharmacological or biological properties. with an aim of developing a biologically mimetic guided tissue regeneration (GTR) membrane with an anti-inflammatory function for periodontal disease, the coaxial electrospinning technique was conducted to fabricate anti-inflammatory-loaded core/shell nanofibers coated with a layer of natural polymer for purpose of controlled release.The drug release behavior was affected by many factors, such as drug loading, fibers’morphology, the compatibility between drug and polymer matrix, and the shell material’s hydrophilicity. In this study, synthetic PCL was selected as the core material for its good biocompatibility and mechanical property. MNA was selected as drug model for its ability of inhibit anerobic bacteria colonized during GTR infection. The hydrophilic gelatin and the hydrophobic zein was separately selected as shell material to investigate the effect of hydrophilicity to the drug release behavior.Different types of MNA-loaded nanofibers was fabricated and displayed a uniform bead-free round morphology with core/shell structure by mean of scanning electron microscopy (SEM) and transmission electron microscopy (TEM). X-ray diffraction and differential scanning calorimetry verified that MNA presents an amorphous state in all nanofibers with MNA content below 20 wt%. In vitro drug release results showed that with the encapsulation of shell material, MNA released from the nanofiber membranes with biphasic release profile over a period of 4 days via a diffusion mechanism without initial burst release, and the encapsulation of hydrophobic zein is superior to delay the drug release. The released MNA remained antibacterial activity and inhibited the colonization of anaerobic bacteria. All the membranes showed good biocompatibility, and the surface natural polymer could enhance cell attachment and proliferation. Thus, the MNA loaded core/shell nanofiber membrane can be considered as a promising candidate for anti-inflammatory GTR membrane.