Regenerating Bone via Multifunctional Coatings: The Blending of Cell Integration and Bacterial Inhibition Properties on the Surface of Biomaterials

Abstract

In dentistry and orthopedics, it is well accepted that implant fixation is a major goal. However, an emerging concern is bacterial infection. Infection of metallic implants can be catastrophic and significantly reduce patient quality of life. Accordingly, in this work, we focus on multifunctional coatings to simultaneously address and mitigate both these problems. We have developed a tailor-made peptide-based chemical platform that integrates the well-known RGD cell adhesive sequence and the lactoferrin-derived LF1-11 antimicrobial peptide. The platform was covalently grafted on titanium via silanization and the functionalization process characterized by contact angle, XPS, and QCM-D. The presence of the platform statistically improved the adhesion, proliferation and mineralization of osteoblast-like cells compared to control surfaces. At the same time, colonization by representative bacterial strains was significantly reduced on the surfaces. Furthermore, the biological potency of the multifunctional platform was verified in a co-culture in vitro model. Our findings demonstrate that this multifunctional approach can be useful to functionalize biomaterials to both improve cell integration and reduce the risk of bacterial infection.

Multifunctional Coatings and Nanotopographies: Toward Cell Instructive and Antibacterial Implants

“…In the first place, it is becoming evident that the biological evaluation of the osteoconductive and antibacterial potential of any new multifunctional surface will require the use of eukaryotic cell–bacteria cocultures, as the results obtained with the individual cell types may greatly differ from the more realistic, competitive scenario. In a recent study, we showed that bacteria directly inhibited the capacity of osteoblastic cells to spread and proliferate . This study indicates that bacteria and cells not only race for the surface, but “fight for it,” and makes us postulate that the interactions between these two cell types and the biomaterial surface are better referred to as “the fight for the surface.” However, the mechanisms governing these interactions are not well understood, as the majority of current methods focus on the “finish line,” but do not monitor the dynamic process of competition for the surface.…”

“…Using this platform we recently combined the RGD sequence with LF1‐11, an AMP derived from lactoferrin that showed excellent antibacterial properties on Ti surfaces . Such approach very effectively improved OB adhesion, proliferation, and mineralization, and inhibited S. aureus and S. sanguinis attachment and biofilm progression ( Figure ) . Importantly, the bifunctional molecule was also effective in a coculture scenario in which the surfaces were exposed to bacterial suspensions (preinfective condition) for 2 h before seeding OB‐like cells.…”

“…SS: S. sanguinis ; SA: S. aureus . Adapted with permission . Copyright 2017, American Chemical Society.…”

Current Advances in Immunomodulatory Biomaterials for Bone Regeneration

“…A number of studies have been carried out focusing on bone implant modification with bioactive molecules with antimicrobial and anti‐inflammation ability such as antibiotics, metal ions, peptides, vaccines, hydrogels, and heparin via coating or immobilization chemistry. [62b,131,152,154,157–159] First, the most promising antimicrobial molecules are antibiotics. To enhance the efficacy of antibiotics, local delivery using immobilization methods has been widely investigated.…”

“…Silver nanoparticles have been widely used for antimicrobial activity in various fields, in which silver ions break through the bacterial cell wall and disrupt the respiration in mitochondria, attaching to the DNA to stop cell replication. [62b,152] In addition, various types of antimicrobial peptides (AMPs) derived from many proteins have been utilized, and novel applications in both physical immobilization of AMPs on the surface and chemical conjugation of AMPs have been widely investigated …”