Manufacturing methods, properties, and potential applications in bone tissue regeneration of hydroxyapatite-chitosan biocomposites: A review

Hydroxyapatite (HA) and chitosan (CS) biopolymer are the major materials investigated for biomedical purposes. Both of these components play an important role in the orthopedic field as bone substitutes or drug release systems. Used separately, the hydroxyapatite is quite fragile, while CS mechanical strength is very weak. Therefore, a combination of HA and CS polymer is used, which provides excellent mechanical performance with high biocompatibility and biomimetic capacity. Moreover, the porous structure and reactivity of the hydroxyapatite-chitosan (HA-CS) composite allow their application not only as a bone repair but also as a drug delivery system providing controlled drug release directly to the bone site. These features make biomimetic HA-CS composite a subject of interest for many researchers. Through this review, we provide the important recent achievements in the development of HA-CS composites, focusing on manufacturing techniques, conventional and novel three-dimensional bioprinting technology, and physicochemical and biological properties. The drug delivery properties and the most relevant biomedical applications of the HA-CS composite scaffolds are also presented. Finally, alternative approaches are proposed to develop HA composites with the aim to improve their physicochemical, mechanical, and biological properties.