Design of silver containing mesoporous bioactive glass-embedded polycaprolactone substrates with antimicrobial and bone regenerative properties

Objectives: The aim of the present study was to design, produce and characterize composite substrates consisting of different formulations of poly(epsilon-caprolactone) (PCL), as a polymer matrix, and silver-containing mesoporous bioactive glasses (Ag-MBGs) with improved properties for bone tissue engineering.Methods: Ag-MBGs were synthesized by an evaporation-induced self-assembly process. Different polymer-to-particles weight ratios were considered (90/10, 80/20, 70/30 wt%). PCL/Ag-MBGs composites substrates were manufactured by melting and molding technique. The effect of Ag-MBGs embedded in the polymer matrix was investigated by morphological (field emission scanning electron microscopy (FE-SEM), SEM and contact angle measurement), structural/functional (small punch and tensile tests), antimicrobial, and in vitro biological analyses.Results: The obtained results highlighted that the inclusion of 10% by weight of Ag-MBGs improved the punching performances as well as the tensile Young's modulus (from 350.3 +/- 32.0 MPa for PCL to 473.5 +/- 41.0 MPa), without negatively altering the tensile strength of the neat PCL. Indeed, small punch test findings indicated that, over a threshold concentration (10% by weight), the Ag-MBGs acted as "weak points", rather than reinforcement, because the mechanical properties of the composite substrates decreased. The bacterial growth monitoring showed a clear antimicrobial effect against both Gram-negative and Gram-positive, confirmed by reduced cell viability registered after 24 h (2 x105 CFU/mL for P. aeruginosa and 2.3 x105 CFU/mL for S. aureus). The results were confirmed in terms of adhesion and adherent growth, reduced at day 3 on PCL samples with 10% of Ag/ MBGs. Furthermore, this formulation induced a significant inhibition zone (21 mm for P. aeruginosa, 23 mm for S. aureus). In vitro biological assays confirmed that all formulations of PCL/Ag-MBGs supported periodontal ligament stem cells' viability and differentiation over time. Particularly, substrates with Ag-MBGs at a concentration of 10% and 20% by weight of Ag-MBGs provided higher values of the percentage of Alamar Blue reduction meanwhile, the highest Ag-MBGs concentration induced a higher expression of alkaline phosphatase activity.Significance: Ag-MBGs proved to be suitable candidates as filler at a specific threshold concentration (10% by weight), considering a compromise among physicochemical, antimicrobial, and pro-regenerative features. These findings provide useful data for the design and development of improved biomaterials with optimized properties, suggesting a potential application in maxillofacial bone and/or periodontal tissue repair.