Bone tissue engineering has attracted great interest in the last few years, as the frequency of tissue-damaging or degenerative diseases has increased exponentially. To obtain an ideal treatment solution, researchers have focused on the development of optimum biomaterials to be applied for the enhancement of bioactivity and the regeneration process, which are necessary to support the proper healing process of osseous tissues. In this regard, hydroxyapatite (HA) has been the most widely used material in the biomedical field due to its great biocompatibility and similarity with the native apatite from the human bone. However, HA still presents some deficiencies related to its mechanical properties, which are essential for HA to be applied in load-bearing applications. Bioactivity is another vital property of HA and is necessary to further improve regeneration and antibacterial activity. These drawbacks can be solved by doping the material with trace elements, adapting the properties of the material, and, finally, sustaining bone regeneration without the occurrence of implant failure. Considering these aspects, in this review, we have presented some general information about HA properties, synthesis methods, applications, and the necessity for the addition of doping ions into its structure. Also, we have presented their influence on the properties of HA, as well as the latest applications of doped materials in the biomedical field.

In recent years, the number of people needing bone replacements for the treatment of defects caused by chronic diseases or accidents has continuously increased. To solve these problems, tissue engineering has gained significant attention in the biomedical field, by focusing on the development of suitable materials that improve osseointegration and biologic activity. In this direction, the development of an ideal material that provides good osseointegration, increased antimicrobial activity and preserves good mechanical properties has been the main challenge. Currently, bone tissue engineering focuses on the development of materials with tailorable properties, by combining polymers and ceramics to meet the necessary complex requirements. This study presents the main polymers applied in tissue engineering, considering their advantages and drawbacks. Considering the potential disadvantages of polymers, improving the applicability of the material and the combination with a ceramic material is the optimum pathway to increase the mechanical stability and mineralization process. Thus, ceramic materials obtained from natural sources (e.g., hydroxyapatite) are preferred to improve bioactivity, due to their similarity to the native hydroxyapatite found in the composition of human bone.

One of the main challenges in hydroxyapatite research is to develop cost-effective synthesis methods that consistently produce materials closely resembling natural bone, while maintaining high biocompatibility, phase purity, and mechanical stability for biomedical applications. Traditional synthetic techniques frequently fail to provide desirable mechanical characteristics and antibacterial activity, necessitating the development of novel strategies based on natural precursors and selective ion doping. The present study aims to explore the possibility of synthesizing hydroxyapatite through the co-precipitation method, followed by a microwave-assisted hydrothermal maturation process. The main CaO sources selected for this study are eggshells and mussel shells. Cu²⁺ and Sr²⁺ ions were added into the hydroxyapatite structure at concentrations of 1% and 5% to investigate their potential for biomedical applications. Furthermore, the morpho-structural and biological properties have been investigated. Results demonstrated the success of hydroxyapatite synthesis and ion incorporation into its chemical structure. Moreover, HAp samples exhibited significant antimicrobial properties, especially the samples doped with 5% Cu and Sr. Additionally, all samples presented good biological activity on MC3T3-E1 osteoblast cells, demonstrating good cellular viability of all samples. Therefore, by correlating the results, it could be concluded that the undoped and doped hydroxyapatite samples are suitable biomaterials to be further applied in orthopedic applications.