A cross-linked coating loaded with antimicrobial peptides for corrosion control, early antibacterial, and sequential osteogenic promotion on a magnesium alloy as orthopedic implants

Abstract

Magnesium (Mg)-based alloys have been recognized as desirable biodegradable materials for orthopedic implants. However, their clinical application has been limited by rapid degradation rates, insufficient antibacterial and osteogenic-promotion properties. Herein, a MgF₂ priming layer was first constructed on AZ31 surface. Then, dopamine and polyphenols (EGCG) were cross-linked onto this AZ31-F surface to promote osteogenesis and further enhance corrosion protection, followed by chemical grafting of antimicrobial peptides (AMPs) via Michael-addition and Schiff-base reaction to confer antibacterial properties. In vitro electrochemical corrosion tests showed that i_corr of AZ31-FE/AMPs (4.36×10^-7 A/cm²) is two orders of magnitude lower than that of AZ31 (4.17×10^-5 A/cm²). In vitro immersion degradation showed that AZ31-FE/AMPs exhibited the lowest hydrogen release (2.38 mL) after 400 h immersion with the lowest hydrogen evolution rate among them. Further, AZ31-FE/AMPs displayed inhibitory effects against S. aureus and E. coil in the initial stage and even after 7 days immersion in PBS (antibacterial rate > 85 %). AZ31-FE/AMPs promoted ALP secretion and calcium nodule formation in MC3T3-E1 cells. Transcriptome sequencing results indicated that osteogenic promotion mechanism of AZ31-FE/AMPs in MC3T3-E1 may involve the PI3K-Akt signalling pathway. Further, AZ31-FE/AMPs enhanced new bone formation when implanted in a rat femoral bone defect model. This coating strategy addresses initial antibacterial and later osteogenesis needs based on the corrosion control, which is crucial for the surface design of Mg-based implants. STATEMENT OF SIGNIFICANCE: It is critical for magnesium-based orthopedic implants to achieve sequential functions in the bone repair process while controlling an appropriate degradation rate. A MgF₂ priming layer/phenolic-amine grafted AMPs (antimicrobial peptides) duplex coating was constructed on AZ31 surface in this study. The MgF₂ layer provided a basic corrosion protection to magnesium substrate, and dopamine and polyphenols (EGCG) were then cross-linked to the MgF₂ pretreated AZ31 to promote osteogenesis and enhance corrosion resistance, followed by chemical grafting of AMPs to confer antibacterial property. This strategy effectively meets the initial need for infection resistance and later osteogenic promotion on the basis of controlling the substrate corrosion rate, thus holding significant implications for the surface design of magnesium-based implants.

Keywords: Antibacterial; Corrosion control; Mg alloy; Orthopedic implant; Osteogenic promotion.