Non-receptor protein kinases FAK and Src play crucial roles in regulating cellular adhesions, growth, migration and differentiation. However, it remains unclear how the activity of FAK and Src is regulated during the differentiation process from mesenchymal stem cells (MSCs) to bone cells. In this study, we used genetically encoded FAK and Src biosensors based on fluorescence resonance energy transfer (FRET) to monitor the FAK and Src activity in live cells during the differentiation process. The results revealed that the FAK activity increased after the induction of differentiation, which peaked around 20–27 days after induction. Meanwhile, the Src activity decreased continuously for 27 days after induction. Therefore, the results showed significant and differential changes of FAK and Src activity upon induction. This opposite trend between FAK and Src activation suggests novel and un-coupled Src/FAK functions during the osteoblastic differentiation process. These results should provide important information for the biochemical signals during the differentiation process of stem cells toward bone cells, which will advance our understanding of bone repair and tissue engineering.

Professor Shu Chien is a world-renowned leader and founder of Bioengineering. In particular, he has made seminal contributions to advancing our systematic and insightful understanding of how cells perceive their physical/mechanical environment and coordinate cellular functions. In this review, as part of a tribute to Prof. Shu Chien's scientific achievement, we summarize the research progress in understanding the physiology of bone cells interacting with different mechanical/physical environments during bone tissue regeneration/repair. We first introduce the cellular composition of the bone tissue and the mechanism of the physiological bone regeneration/repair process. We then describe the properties and development of biomaterials for bone tissue engineering, followed by the highlighting of research progresses on the cellular response to mechanical environmental cues. Finally, several latest advancements in bone tissue regeneration and remaining challenges in the field are discussed for future research directions.

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The intact function of the salivary glands is of utmost importance for oral health. During radiotherapy in patients with head and neck tumors, the salivary glands can be damaged, causing the composition of saliva to change. This leads to xerostomia, which is a primary contributor to oral mucositis. Medications used for protective or palliative treatment often show poor efficacy as radiation-induced changes in the physico-chemical properties of saliva are not well understood. To improve treatment options, this study aimed to carefully examine unstimulated whole saliva of patients receiving radiation therapy and compare it with healthy unstimulated whole saliva. To this end, the pH, osmolality, electrical conductivity, buffer capacity, the whole protein and mucin concentrations, and the viscoelastic and adhesive properties were investigated. Moreover, hyaluronic acid was examined as a potential candidate for a saliva replacement fluid. The results showed that the pH of radiation-induced saliva shifted from neutral to acidic, the osmolality increased and the viscoelastic properties changed due to a disruption of the mucin network and a change in water secretion from the salivary glands. By adopting an aqueous 0.25% hyaluronic acid formulation regarding the lost properties, similar adhesion characteristics as in healthy, unstimulated saliva could be achieved.

The therapeutic effect of common ocular drug delivery systems is often limited because tear fluid, protective biological barriers, and the blink reflex prevent drugs from reaching their target. Combining nanodrug delivery systems with contact lenses is one approach to increase the precorneal residence time and thus the drug concentration in the eye. Hence, the aim of this study was to selectively print itraconazole (ITZ) nanocrystals on commercially available 1 day soft hydrogel contact lenses using inkjet printing. For this, ITZ nanocrystals stabilized with Poloxamer 407 were prepared and optimized via wet media milling. After careful characterization, the nanocrystals were printed into vials, the printing process was adjusted, and the characteristics of the nanoformulation after printing were investigated. Finally, nanocrystals were printed onto hydrogel contact lenses. By performing a concise design of experiments (DoE), stable nanocrystals with a size of approximately 200 nm, a narrow particle size distribution, a negative surface charge, and an almost spherical shape were obtained. Compared to the bulk material, the apparent solubility was significantly increased and no changes in the solid-state behavior occurred. It was further demonstrated that inkjet printing did not affect the characteristics of the nanocrystals. Multiple layers of the ITZ nanoformulation were printed on soft hydrogel 1 day contact lenses, and a dual drug release profile was obtained in simulated tear fluid. These results clearly show that printing on contact lenses is a promising application for ophthalmic drug delivery.

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