Layer-by-Layer Coatings of Collagen–Hyaluronic acid Loaded with an Antibacterial Manuka Honey Bioactive Compound to Fight Metallic Implant Infections

Abstract

Implant-associated severe infections can result in catastrophic implant failures; thus, advanced antibacterial coatings are needed to combat infections. This study focuses on harnessing nature-inspired self-assembly of extracellular matrix (ECM)-like coatings on Ti alloy with a combination of jellyfish-derived collagen (J-COLL) and hyaluronic acid (HA) using our customized automated hybrid layer-by-layer apparatus. To improve the anti-infection efficacy of coatings, we have incorporated a natural antibacterial agent methylglyoxal (MGO, a Manuka honey compound) in optimized multilayer coatings. The obtainment of MGO-loaded multilayer coatings was successfully assessed by profilometry, contact angle, attenuated total reflectance (ATR)-Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. <i>In vitro</i> degradation confirmed the controlled release activity of MGO with a range of concentrations from 0.90 to 2.38 mM up to 21 days. A bacterial cell culture study using <i>Escherichia coli</i> (<i>E. coli</i>) and <i>Staphylococcus epidermidis</i> (<i>S. epidermidis</i>) confirmed that the MGO incorporated within layers 7 and 9 had a favorable effect on preventing bacterial growth and colonization on their surfaces. An <i>in vitro</i> cytocompatibility study confirmed that MGO agents included in the layers did not affect or reduce the cellular functionalities of L929 fibroblasts. In addition, MGO-loaded layers with Immortalized Mesenchymal Stem Cells (Y201 TERT-hMSCs) were found to favor the growth and differentiation of Y201 cells and promote calcium nodule formation. Overall, these surface coatings are promising candidates for delivering antimicrobial activity with bone-inducing functions for future bone tissue engineering applications.