# Mini-Review: Potential of Diatom-Derived Silica for Biomedical Applications
## 7 Future Perspectives  
In the present review, we report studies from different research groups aimed at assessing the effectiveness of diatom-derived silica for biomedical applications. Previous studies clearly demonstrated that diatom biosilica could be suitable as a drug carrier, as a scaffold for regenerative medicine, and for in vivo enzyme immobilization. We summarized the main benefits and disadvantages associated with the use of this biomaterial, and, in our opinion, the advantages outweigh the drawbacks. Future research should ascertain long-term compatibility of biosilica with biological systems, and should search for cost-effective and environmentally friendly techniques for biosilica production. The employment of silica-based diatom cell walls for biotechnological applications implies that naturally abundant fossil sources (e.g., diatomic) can be considered as a viable and cost-efficient alternative to synthetic silica, which requires time-consuming and hazardous methods for its production. Overall, fossil biosilica sources can be used as heavy metal sorbents, food-grade additives, fertilizers or biosensors. In contrast, living diatom-derived biosilica appears to be more suitable than biosilica of fossil origin for biomedical applications such as drug carriers. Specifically, drugs need to be released from the carrier at constant and known rates, and for this purpose the size, shape, and porosity of biosilica particles should vary as little as possible. Biosilica derived from monospecific cultures has, indeed, a regular and predictable structure compared to fossil sources that typically encompass a given morphological diversity, leading to heterogeneity in the frustule size, shape and porosity. A recent device for biosilica production from living cultures has been patented [110] and paves the way to the exploitation of diatoms. With respect to other biological silica sources, such as sponges and Radiolaria, diatoms can be easily cultured in the laboratory, and are ubiquitous and highly abundant in the marine environment. Moreover, silica structures from diatoms generally have smaller dimensions than protozoan shells and sponge spicules, which can reach 2 mm in length [74]. The reduced particle size is, for us, advantageous in drug delivery systems to enhance degradability, and for avoiding or limiting pulverization pre-treatments. In our opinion, treatments for the depigmentation and elimination of collagen (in which spicules are enveloped) can render the process of sponge-derived silica even more difficult than the typical techniques for frustule purification [111; 112]. Other non-biological silica sources, such as fly ash derived from power plants, may be used in lieu of fossil diatom-derived sources. Similarly to diatomic, this alternative source is disposable and abundant in the natural environment, and its effectiveness as a raw material for carbon sequestration [113] and as a biofertilizer [114] has already been demonstrated. Nevertheless, in our opinion, the high heterogeneity of fly ash (structural features vary according to the power plant and the combustion processes), and the presence of metals and other impurities makes it more suitable for bioremediation and land fertilization purposes, rather than biomedical applications. To improve the economic viability of massive diatom culturing for biosilica production, other fractions of algal biomass could also be exploited. Diatoms can be used, indeed, as photosynthetic biorefineries [115] for a number of industrial processes, and the exploitation of both the inorganic and organic fractions of the algal biomass can contribute to minimisewaste production. A possible route for the complete exploitation of diatom biomass is shown in Figure 3. The extraction of the biochemical components from microalgal biomass does not affect the structure and the integrity of silica frustules, which can remain unaltered also in the presence of acidic conditions.