"Title: Electrospun silica nanofibres as multifunctional substrate for drug delivery and tissue regeneration
Introduction: Over the last two decades, electrospun nanofibres were demonstrated to be interesting material applicable in regenerative medicine and drug delivery, possessing number of unique properties including high specific surface area, high porosity and small pore size. Properties such as chemical and mechanical stability, biocompatibility and degradation kinetics then depend on chemical composition, crosslinking or possibly functionalization. While polymer nanofibres may exhibit serious disadvantages including swelling in moist environment and during degradation or low surface functionality or limited bioactivity, inorganic nanofibres represent a family of nanofibres unlimited by these factors and potent for medical applications. Silica nanofibres, being member of this family, combine traditional properties of nanofibres based on their structure and advantages of inorganic bioactive material. The aim of this paper is to outline properties and performance of silica nanofibres as biocompatible, biodegradable, and easy to modify high performance material for regenerative medicine and drug delivery.
Methodology: Silica nanofibres were prepared by sol-gel method and needle-less electrospinning, which led to formation of nanofibrous matrix of 5 – 30 g/m2 and mean fibre diameter 180 – 850 nm depending on the spinning conditions. Biocompatibility was tested in vitro on several model cell lines including 3T3-A31 fibroblasts, Hacat keratinocytes, Vero cells and HepG2 hepatocyte-like cells in compliance to ISO 10993-5. Biodegradation of silica nanofibres was evaluated in vitro under simulated conditions (37 °C, SBF). Silica release into the SBF was measured using ICP-MS. Impact of degradation on the surface morphology was evaluated by electron microscopy (SEM). Surface availability for functionalization and its impact on relevant properties was tested by APTES aminosilane silanization.
Results: Silica nanofibres, obtained by electrospinning, were confirmed to promote multitissue biocompatibility in vitro. Fast degradation under simulated conditions in vitro was observed with surface erosion appearing after 24 hours in simulated body fluid (SBF) with limited swelling and sustained integrity of the nanofibrous matrix. Silica released upon degradation in form of orthosilicic acid, was confirmed to have a beneficial impact on cellular proliferation in vitro, which is known effect provided silica nanomaterials in general. Successful grafting of –NH2 amino group by silanization of surface silanol group was confirmed without relevant impact on the fibre morphology or integrity. Positive impact of the silanization process on biocompatibility was verified.
Conclusion: The electrospun silica nanofibres were confirmed as biocompatible and bioactive nanomaterial with capacity to promote tissues regeneration through its degradation products. Moreover, the unique degradation mechanism reminiscent of Stöber silica degradation mechanism was revealed. The high specific surface available for surface functionalization, can be applied in drug and bioactive molecules delivery in wound healing and tissue regeneration."