# Biodegradable and Biocompatible Systems Based on Hydroxapatite Nanoparticles
## 4 Functional HAp Biocomposites through Modification/Encapsulation Techniques  
### Antimicrobial Scaffolds Based on HAp  
Microorganisms can grow and survive for long periods of time into material surfaces developing biofilms through several common steps (e.g., reversible and irreversible attachments, maturation and dispersion [69; 70]). The problem of biofilm formation is enhanced in hospital environments, being high the risk associated to the development of chronic infections and surgical site infections (SSI) [71; 72]. In fact, approximately the 50% of infections acquired in hospitals are associated to implants [73], a problem that is expected to increase as consequence of their continuously increasing consume. Therefore, it is important to produce HAp nanoparticles with antibacterial properties, independently of using a matrix that could also display such activity. Although incorporation of antibiotics was firstly considered, other preventive solutions are being developed because the increasing resistance of microorganisms towards antibiotics [74; 75]. Today, one of the best and simplest methods to provide HAp with antibacterial properties consists on the incorporation of silver ions, which can inhibit the bacterial growth according to different mechanisms (e.g., disruption of cell membrane due to positive charges, deactivation of enzymes by binding to their thiol groups, inhibition of phosphate uptake, modification of DNA structure, and production of reactive oxygen compounds [76; 77; 78; 79]). Some caution should be taken into account when silver ions are incorporated into the scaffold since a cytotoxic effect could be derived as a consequence of a high load or even of a fast and local release. Ions can be incorporated by a simple and highly effective co-precipitation process (addition of a phosphate precursor over a mixture of calcium and silver precursors) and by ion exchange processes that should render a higher silver concentration on the HAp surface [80; 81; 82]. In any case, a compromise between the bactericide effect and the derived cytotoxicity should be taken into account, being reported as optimal a silver content of 0.5 wt % for samples prepared by co-precipitation. Properties and biological response depend on the preparation method and, logically, an immediate but not sustainable effect could be expected for samples obtained by ion-exchange. In this case, a greater toxicity due to a local high concentration of released ions could be expected. Few works have been reported concerning systems that incorporate nHAp particles loaded with antibiotics. A biosensorable composite of calcium sulfate and nHAp particles was studied considering its antibiotic release properties and biocompatibility. This composite showed excellent properties regarding resorption, biocompatibility and release of gentamicin and vancomycin as model studied antibiotics. The release of gentamicin and vancomycin was 94.7% and 96.3% after 10 days of exposure to phosphate-buffered saline (PBS) medium, respectively. The concentrations of released gentamicin and vancomycin exceed 100-fold and 10-fold the minimal inhibition concentrations (MICs) of susceptible _Staphylococcus aureus_ within the first 24 h and for three and four days, respectively. Furthermore, it was probed that substitution of calcium sulfate by HAp decreased the inherent cytotoxicity of the sulfate [83]. Silver nanoparticles (AgNPs) possess excellent bactericide activity but applications are limited by their strong tendency to aggregate, which decreases their antimicrobial activity. This feature can be avoided by the fabrication of particles having AgNPs immobilized on their surface. One-dimensional nanowires appear an ideal morphology for supporting AgNPs due to unique properties such as ability to organize into three-dimensional networks that form porous macrostructures. In this way, free-standing inorganic films with bactericide activity have been prepared from ultralong hydroxyapatite nanowires (Figure 5) [84].