Silk Fibroin Microspheres Based On Microfluidic Technology And Applications In Biomedicine

Silk Fibroin(SF)is an important part of natural silk fibroin,with excellent mechanical properties,biocompatibility and adjustable degradability.SF microspheres are easy to take orally and inject,and widely applied in delivering cells,drugs,growth factors and genes,so it is an important research direction based on silk fibroin materials.Microfluidic has been a hotspot in recent years because of its ability to accurately control size,uniformity,morphology,structure and chemical composition.In this paper,a self-built microfluidic platform was used to prepare silk fibroin microspheres by two different systems(oleic acid,soybean oil)with controllable size range(10-400 μm)and good monodispersity.It was found that the microspheres prepared by the soybean oil system showed a more uniform size and a higher β-sheets content(48.78±0.54%),which were applied in the field of controlled and sustained drug release and 3D cells culture:The limitations of traditional anti-cancer drug delivery methods mainly include the sudden release of the drug,systemic distribution and the need for frequent intravenous administration.To solve these problems,we combined photothermal responsive nanoparticles polydopamine(PDA)with silk fibroin to prepare functionalized silk fibroin microspheres(CMs).The addition of PDA can increase the β-sheet,especially β-crystal contents in CMs.Using doxorubicin hydrochloride as a model drug,the calculated drug load was 7.5%,and the effective encapsulation rate reached 91.6%.The synthetic drug-loaded composite microspheres(CMs-DOX)had an excellent sustained-release effect,and shown a specific response release in an acidic environment of pH5.5 in drug release study.And under near-infrared light irradiation,it showed a stepped trend release,and the cumulative release reached 56%after 14 days,which was about 20%more than the non-light irradiation group,which was conducive to the realization of on-demand drug delivery.The in vitro antitumor experiment proved that CMs-DOX,which integrated photothermal therapy and chemotherapy,had a significant anti-tumor effect.It was found that SF microspheres not only have excellent cell compatibility,but also provide a three-dimensional space for their growth.In this work,we combined silk fibroin with gelatin(SFMA-GelMA)as composite hydrogel microspheres with a diameter in the range of 200-280μm,good biocompatibility,and adjustable biodegradation rate by microfluidics in the field of 3D cells culture.The composite material made up for the lack of cell adhesion sites of a single silk fibroin material and the poor mechanical properties of a single gelatin material,which degrades quickly.It was shown that SFMA-GelMA composite hydrogel microspheres,as a scaffold for 3D cells culture,not only imitated the physiological space environment for cell proliferation,and provided enough space for cells proliferation,but also showed the ability to induce osteogenic differentiation of MC3T3-E1 cells,which was expected to be used in bone tissue engineering.