# Mini-Review: Potential of Diatom-Derived Silica for Biomedical Applications
## 6 Silica for Biomedical Applications: Bottlenecks  
Among the weak aspects of the production of biosilica-based devices, it is worth mentioning that diatom frustules require strong treatments that are usually based on toxic and/or dangerous chemicals [26; 70; 73; 101]. Furthermore, the accuracy of the purification protocols should be the highest possible in case the biosilica-based material is to be used for biomedical purposes. Besides, experiments based on living culture manipulations are often carried out under axenic conditions [87; 89], which requires very careful maintenance to keep the strains bacteria-free and, in case of contamination, highly meticulous protocols to remove bacteria need also to be applied [102].  
Another drawback of using biosilica for biomedical purposes is the low degradation rate of this material. Although biosilica is known to be less stable than crystalline silica and its dissolution rate can be further enhanced by specific physico-chemical manipulations [103], it can still persist for long periods within organs with limited blood supply [104], which may lead to detrimental health consequences. Some authors do not consider biosilica degradation as a real problem, since the silicic acid (i.e., the main product of silica degradation) is naturally found in human tissues and can be easily excreted from the kidneys [105; 106].  
However, the employment of diatom-based biosilica for biomedical purposes has not been approved yet by the Food and Drug Administration (FDA), and neither by other safety governmental agencies. The approval of diatom-based biosilica for biomedical purposes is mandatory to follow up all the studies which foresee the development of biosilica-based devices for biomedical purposes. The FDA considers amorphous silica less toxic than crystalline forms and silicates as generally recognized as safe (GRAS) materials [57; 107], and established that they can be included in oral delivery ingredients in amounts up to 1500 mg per day [103]. Some diatom-derived sources of silicon can be treated, indeed, to reach the food grade and can be used for nutraceuticall purposes. Currently, diatomic of certain \"purity levels\" is considered as a food additive and is permitted as animal feed ([[https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=573.340](https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=573.340)]([https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=573.340](https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=573.340)), accessed date: 22 March 2021), as inert carrier or anticaking agent, and as additive for pharmaceutical preparations. Unfortunately, the use of diatomic for biomedical applications has not been approved yet.  
The recognition of diatomic as a suitable biomaterial for medical and pharmaceutical purposes by the FDA is, indeed, mandatory to pave the way to industrial applications of diatomic-based materials, which have proven to be successful for drug delivery [74], through genetic engineering [108; 109] and for regenerative medicine [26].