23.3

Ionic Substitution in Hydroxyapatite

Ionic substitution in hydroxyapatite (HA) has received much attention in the recent

past, as substitution of different ions in HA can modify its physicochemical

characteristics, alter specific biological responses, and therefore help in producing

multifunctional HAs (O’Neill et al. 2018). Even a small extent of ionic substitution

in HA can significantly change its properties such as morphology, particle size,

solubility, porosity, and specific surface area and helps in increasing its ability for

involvement in the natural bone remodeling process. Ionic substitution in HA

presents a key role in the biochemistry of bone, dentin, and enamel (Zhang et al.

2014). Hence, it is very important to unleash the potential of ionic substituted HA for

various biomedical applications like medical implants, tissue engineering, gene

therapies, drug delivery, etc.

Several cationic and anionic substitutions are feasible in HA due to its high

stability and flexible structure. The biocompatibility and bioactivity of synthetic

HA can be enhanced by substitution of particular trace ions like cations (K⁺, Na⁺,

Sr²⁺, Mg²⁺, Ba²⁺, Zn²⁺, Mn²⁺, Pb²⁺, Tb³⁺, Y³⁺, Eu³⁺) and anions (Cl
, F
, CO3

2
,

HPO4

2
, SiO4

4
) within the lattice structure (LeGeros 1991; Norhidayu et al. 2008).

The substitution of physiologically significant ions in HA can affect its chemical and

physical properties like morphology, lattice parameters “a” and “c,” crystallinity,

solubility, thermal stability, and osteoconductivity (Capuccini et al. 2008; Bracci

et al. 2009).

23.3.1 Types of Ionic Substitutions in HA

Several cationic and anionic substitutions can be done in the structure of hydroxy-

apatite (Jiang et al. 2019); however, the extent and type of such ionic substitutions

can be altered.

23.3.1.1 Single-Ion Substitution in HA

One of the efforts in the development of substituted HA is single-ion substitution,

either by a cation or an anion. Cationic substitutions can occur in HA for the calcium

ions, and anionic substitutions can occur in HA for PO4

3
ions or OH
ions.

In the stoichiometric HA, the cationic sites can take up vacancies for a maximum

of 2 sites out of 10 available sites (Rey 1998). Cations smaller than Ca²⁺ such as

Zn²⁺, Mg²⁺, and Mn²⁺ or low concentrations of slightly larger cations with strong

interactions can be accommodated in site Ca (I), while larger cations like K⁺ and Sr²⁺

at high concentrations can be accommodated in site Ca (II) (Boanini et al. 2010).

Potassium (K) has an impact on the biomineralization process (Kannan et al.

2006), and it also exhibits versatile nature in the regulation of biochemical processes.

It can be substituted into HA lattice without significant changes in structural

parameters. Zinc (Zn) is recognized as an important bone mineral, which is compe-

tent in enhancing biomineralization, bone formation, and osteoblast proliferation. It

also incites alkaline phosphatase activity (Ovesen et al. 2001; Hall et al. 1999;

422

S. Kapoor et al.