# Biodegradable and Biocompatible Systems Based on Hydroxapatite Nanoparticles
## 4 Functional HAp Biocomposites through Modification/Encapsulation Techniques
### Hydroxyapatite as Non-Viral Gene Delivery System
Thus, the DNA secondary structure was well preserved on the (001) surface of HAp (Figure 12a) and even an attractive binding energy was determined. In contrast, repulsive interactions that led to DNA desorption were evaluated for the (010; OH\({}^{-}\)) surface. Finally, an attractive interaction that resulted in deformation of the double helix was observed for the (010; Ca\({}^{2+}\)) surface (Figure 12b) [127]. The acknowledge of the mechanism involved in the dissolution of HAp particles in acidic environments has been recently clarified [128; 129] shedding light on the potential application of HAp as vehicle for gene delivery. Mechanism of dissolution in acid conditions of HAp nanoparticles encapsulating double-stranded DNA has recently been investigated at the atomistic level using computer simulations [130]. Results indicated a polynuclear decalcification mechanism with significant transfer processes, from the surface to the internal regions of the particle. Highly remarkable is the finding that biomineralization was highly effective to DNA protection, a feature with positive implications in biomedical fields. HAp protection of DNA may have had a very significant role on how DNA survived through mass extinction events, a concept that has recently been formulated and specifically the term of \"hydroxyolites\" has been introduced to appoint these particles with a protective function [131]. Uncontrolled DNA release from damaged cell nucleus together with calcium and phosphate ions  
Figure 11: **(a)** TEM micrograph showing HAp-DNA nanocapsules. Red arrows point out capsules with a clearly distinctive contrast indicative of the encapsulated DNA in their inner part; **(b)** UV-vis absorption spectra of the aqueous solution/dispersion of HAp-DNA nanocrystals, sample digested with deoxyribonuclease to eliminate adsorbed DNA (black trace), corresponding samples after being dissolved in an acid medium (red trace), and DNA in aqueous solution (blue trace). Reproduced with permission from [126], Royal Society of Chemistry, 2013.  
that are also available in cells can initiate a biomineralization process that preserves DNA from further physical or chemical aggressions. Therefore, DNA was not degraded, denatured or modified, despite being an extremely fragile molecule. Genetic information could be transferred to next generations when there were conditions that are more favorable. HAp nanostructures have also been prepared using phages as template [132; 133]. Phages were reported to be able to develop novel nanostructures and biomaterials but also to provide advantages in biomedicine that include molecular targeting, gene delivery and tissue regeneration [134]. Filamentous bacteriophages are genetically modifiable supramacromolecules constituted by a protein shell that is encoded by the DNA located in the core. Phages have a morphology that can mimic collagen fibrils and therefore they can be employed to arrange HAp nanocrystals into the extracellular matrix (ECM). For example, positively charged calcium ions could promote the self-assembly of negatively charged phages [132] or alternatively phages displaying a cationic peptide on their surface can be linked to phosphate ions [135]. Figure 12: Snapshots showing the double helix of DNA adsorbed at the (001) (**a**) and (010; Ca\({}^{2+}\)) (**b**) surfaces of the HAp hexagonal unit cell with \(P6_{3}/m\) geometry (\(a=b=0.9421\) nm, \(c=0.6881\) nm) at the beginning (**left**) and the end (**right**) of the 15 ns isothermal-isobaric ensemble (NPT) molecular dynamic simulations. Reproduced with permission from [127], Royal Society of Chemistry, 2014.