RESUMO
Microneedles have been used in various applications in biomedical engineering, including drug delivery, biosensing, and vaccine delivery. In this study, we develop a novel protocol to fabricate silk fibroin/off-stoichiometry thiol-ene (OSTE) hybrid microneedle array patches. Silk fibroin, as a natural biomaterial, has been proven to be suitable as a drug carrier. Firstly, drug (we use insulin in this experiment) dissolved in silk fibroin solution is deposited on a microneedle mold and dried thoroughly. After that, silk fibroin needle tips are formed on the OSTE base by replica molding. We investigated the influence of the silk fibroin concentration on the length of silk needle tips and found that the silk concentration had a small influence on the tip length. We also tested the mechanical strength of the microneedles by inserting them into gelatin gel for dummy drug delivery tests. Such composite structures have the potential to increase the delivery efficiency by delivering the whole silk tip into the dermis.
RESUMO
At present, there is an increasing need to mimic the in vivo micro-environment in the culture of cells and tissues in micro-tissue engineering. Concave microwells are becoming increasingly popular since they can provide a micro-environment that is closer to the in vivo environment compared to traditional microwells, which can facilitate the culture of cells and tissues. Here, we will summarize the fabrication methods of concave microwells, as well as their applications in micro-tissue engineering. The fabrication methods of concave microwells include traditional methods, such as lithography and etching, thermal reflow of photoresist, laser ablation, precision-computerized numerical control (CNC) milling, and emerging technologies, such as surface tension methods, the deformation of soft membranes, 3D printing, the molding of microbeads, air bubbles, and frozen droplets. The fabrication of concave microwells is transferring from professional microfabrication labs to common biochemical labs to facilitate their applications and provide convenience for users. Concave microwells have mostly been used in organ-on-a-chip models, including the formation and culture of 3D cell aggregates (spheroids, organoids, and embryoids). Researchers have also used microwells to study the influence of substrate topology on cellular behaviors. We will briefly review their applications in different aspects of micro-tissue engineering and discuss the further applications of concave microwells. We believe that building multiorgan-on-a-chip by 3D cell aggregates of different cell lines will be a popular application of concave microwells, while integrating physiologically relevant molecular analyses with the 3D culture platform will be another popular application in the near future. Furthermore, 3D cell aggregates from these biosystems will find more applications in drug screening and xenogeneic implantation.
