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The development of bioactive coatings for orthopedic implants has been of great interest in recent years in order to achieve both early- and long-term osseointegration. Numerous bioactive materials have been investigated for this purpose, along with loading coatings with therapeutic agents (active compounds) that are released into the surrounding media in a controlled manner after surgery. This review initially focuses on the importance and usefulness of characterization techniques for bioactive coatings, allowing the detailed evaluation of coating properties and further improvements. Various advanced analytical techniques that have been used to characterize the structure, interactions, and morphology of the designed bioactive coatings are comprehensively described by means of time-of-flight secondary ion mass spectrometry (ToF-SIMS), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), 3D tomography, quartz crystal microbalance (QCM), coating adhesion, and contact angle (CA) measurements. Secondly, the design of controlled-release systems, the determination of drug release kinetics, and recent advances in drug release from bioactive coatings are addressed as the evaluation thereof is crucial for improving the synthesis parameters in designing optimal bioactive coatings.

Various active compounds isolated from natural sources exhibit remarkable benefits, making them attractive for pharmaceutical and biomedical applications, such as antioxidant, antimicrobial, and anti-inflammatory activities, which contribute to the treatment of cardiovascular diseases, neurodegenerative disorders, various types of cancer, diabetes, and obesity. However, their major drawbacks are their reactivity, instability, relatively poor water solubility, and consequently low bioavailability. Synthetic drugs often face similar challenges associated with inadequate solubility or burst release in gastrointestinal media, despite being otherwise a safe and effective option for the treatment of numerous diseases. Therefore, drug-eluting pharmaceutical formulations have been of great importance over the years in efforts to improve the bioavailability of active compounds by increasing their solubility and achieving their controlled release in body media. This review highlights the success of the fabrication of micro- and nanoformulations using environmentally friendly supercritical fluid technologies for the processing and incorporation of active compounds. Several novel approaches, namely micronization to produce micro- and nano-sized particles, supercritical drying to produce aerogels, supercritical foaming, and supercritical solvent impregnation, are described in detail, along with the currently available drug delivery data for these formulations.

The presented study shows the possibility of using bioaerogels, namely neat alginate, pectin, chitosan aerogels, and alginate and pectin aerogels coated with chitosan, as drug delivery systems for esomeprazole. Two different techniques were used for the impregnation of esomeprazole: Supercritical impregnation, and diffusion via ethanol during the sol-gel synthesis. The prepared samples were characterized by employing N2 adsorption-desorption analysis, TGA/DSC, and FTIR. The achieved loadings were satisfactory for all the tested samples and showed to be dependent on the technique used for impregnation. In all cases, higher loadings were achieved when impregnation via diffusion from ethanol was used. Extensive release studies were performed for all impregnated samples. The in vitro dissolution profiles were found to be dependent on the carrier and impregnation method used. Most importantly, in all cases more controlled and delayed release was achieved with the bioaerogels compared to using pure esomeprazole.

The development of drug-eluting bioactive coatings for orthopedic implants has gained increased interest in recent years with an intent to reduce postoperative complications and improve tissue regeneration at the implant interface. Due to the remarkable benefits of natural polyphenolic components, such as antioxidant, antimicrobial, anti-inflammatory, anti-cancer and bioactive activity, and their ubiquitous availability in nature, they are promising candidates for incorporation into bioactive coatings of advanced medical devices in future clinical applications. However, further research is needed to address all challenges. This review aims to highlight the prosperity of natural compounds widely available in nature loaded in implantable devices, summarize the “state of the art” in this field, identify the challenges, and accordingly suggest the optimal preparation methods and characterization.

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