# Biodegradable and Biocompatible Systems Based on Hydroxapatite Nanoparticles
## 4 Functional HAp Biocomposites through Modification/Encapsulation Techniques
### Antimicrobial Scaffolds Based on HAp
These nanocomposites were obtained from a one-step solvothermal process and utilized for the construction of inorganic paper through a simple vacuum-filtration procedure. The amount and particle size of silver nanoparticles clearly increased with higher concentrations of silver nitrate (i.e., particle sizes of 4.5, 12.5, 22.5 and 27.5 nm with silver content of 0.174, 0.921, 2.25 and 5.19 wt % could be achieved, respectively). Copper and zinc substitution for Ca in HAp structures can be easily performed using solid state interaction, ion-exchange procedure or sorption process [85]. Relatively high amounts of incorporated ions can give rise to a clear bactericide effect; especially when copper is incorporated [85]. Thus, Ca\({}_{10-x}\)Cu\({}_{x}\)(PO\({}_{4}\))\({}_{6}\)(OH)\({}_{2}\) (\(x\) = 0.05-2.0) was obtained by a co-precipitation method and the antibacterial ratio against _S. aureus_ was found to reach a value of 98% when \(x\) was only 0.2 [86]. The content of Cu\({}^{2+}\) and Zn\({}^{2+}\) in the solid samples logically depended on the concentration of the additives in the initial solutions, being the morphologies of particles approximately spherical with sizes in the range 10-20 nm. Modification of HAp Nanoparticles and Doping with Fluorescent and Magnetic Ions for Imaging Applications  
Lanthanide ion doped nHAp particles have been considered as highly promising fluorescent bioprobes for cell imaging applications [87; 88; 89]. Control of size and morphology of nHAp is extremely important since inevitably influences the imaging quality. To this end, hydrothermal synthetic routes based on a liquid-solid-solution strategy have been employed [90]. Usually, hydroxyl groups of the HAp lattice are substituted by fluoride ions in order to avoid that the excited state of lanthanide ions was quenched by hydroxyls. The resulting fluoride substituted HAp nanorods (FAp) have a hydrophobic surface, making difficult their dispersion in aqueous media and hindering biomedical applications [91; 92]. Different surface modifications have been proposed to overcome this limitation and therefore commercially available amphiphilic polymers have been employed. These can establish hydrophobic interactions between the hydrophobic segments of polymers and the alkyl chain of coated HAp nanomaterials while keeping their polar groups in contact with the aqueous medium [93; 94]. Diblock synthetic polymers derived from stearyl methacrylate (SMA) and poly(ethylene glycol) methacrylate (PEGMA) have been effectively employed as amphiphilic copolymers. FAp particles previously coated with oleic acid and doped with Eu\({}^{3+}\) were able to interact with the diblock copolymer giving rise to stable particles in aqueous solution that kept fluorescent properties (Figure 6) [95]. Phosphor nanoparticles with a crystalline matrix doped with lanthanide ions (e.g., Yb\({}^{3+}\), Er\({}^{3+}\), and Nd\({}^{3+}\)) can act as upconversion fluorophores that are able to convert low energy photons, usually near-infrared region (NIR), to higher energy visible emissions. It should be pointed out that NIR imaging appears as an excellent strategy for visualizing morphological details in tissues because this technique causes a minimum damage while having an innate low auto-fluorescence. It is therefore an ideal imaging technique that makes it possible to attain a deep tissue penetration, high sensitivity and both high spatial and temporal resolution [96]. Figure 5: TEM micrographs of HAp nanowires with (**right**) and without (**left**) Ag nanoparticles prepared by one-step solvothermal method at 180 \({}^{\circ}\)C. Reproduced with permission from [84], John Wiley & Sons, Inc., 2016. Potential biomedical applications (e.g., imaging, sensors and theranostic systems) of polymeric luminescent nanomaterials based on dyes with aggregation-induced emission (AIE) have been recently reviewed by [PERSON] et al. [97]. AIE is a distinctive fluorescence phenomenon characterized by a strong emission when molecules aggregate instead of remaining in solution.