Chitosan is known for its specific antibacterial mechanism and biodegradability, while polyphenols are known for their antioxidant and anti-inflammatory properties: coupling these properties on a surface for bone contact, such as hydroxyapatite, is of great interest. The system developed here allows the combination of hydroxyapatite, chitosan, and polyphenol properties in the same multifunctional biomaterial in order to modulate the host response after implantation. Crosslinked chitosan is used in this research to create a stable coating on hydroxyapatite, and then it is functionalized for a smart release of the polyphenols. The release is higher in inflammatory conditions and lower in physiological conditions. The properties of the coated and functionalized samples are characterized on the as-prepared samples and after the samples are immersed (for 24 h) in solutions, which simulate the inflammatory and physiological conditions. Characterization is performed in order to confirm the presence of polyphenols grafted within the chitosan coating, the stability of grafting as a function of pH, the morphology of the coating and distribution of polyphenols on the surface, and the redox reactivity and radical scavenging activity of the functionalized coating. All the results are in line with previous results, which show a successful coating with chitosan and functionalization with polyphenols. Moreover, the polyphenols have a different release kinetics that is faster in a simulated inflammatory environment compared to that in the physiological environment. Even after the release tests, a fraction of polyphenols are still bound on the surface, maintaining the antioxidant and radical scavenging activity for a longer time. An electrostatic bond occurs between the negative-charged polar groups of polyphenols (carboxyls and/or phenols) and the positive amide groups of the chitosan coating, and the substitution of the crosslinker by the polyphenols occurs during the functionalization process.

Functionalization of medical devices with biomolecules is a key strategy to control implant outcomes, for instance, polyphenols can produce fast osseointegration and reduce both the infection risk and inflammatory response. This paper is designed to evaluate the role of calcium ions and surface features in surface functionalization with a red pomace extract. An in-depth investigation of the binding mechanism between surfaces and polyphenols was also performed. A smooth Ti6Al4V alloy was used as a control substrate and compared with a bioactive and nanotextured chemical-treated Ti6Al4V alloy. Solutions with and without the addition of calcium ions were used for functionalization. The results showed that polyphenols were adsorbed in all cases, but in a larger amount in the presence of calcium ions. The functionalized surfaces were hydrophilic (contact angles in the range of 45–15°) and had isoelectric points at pH 2.8–3.1. The acidic hydroxyl groups on the chemically treated titanium alloy favored the chemisorption of complex compounds of flavonoids and condensed tannins with calcium ions, through a bridging mechanism, and made desorption sensitive to pH. On the smooth surface, the absence of reactive functional groups led to a lower amount of adsorbed molecules and a physisorption mechanism. Selective physisorption of phenolic acids was supposed to be predominant on the smooth surface in the presence of calcium ions in the solution.