Qiuning Lin

Uncontrollable bleeding is a major problem in surgical procedures and after major trauma. Existing hemostatic agents poorly control hemorrhaging from traumatic arterial and cardiac wounds because of their weak adhesion to wet and mobile tissues. Here we design a photo-reactive adhesive that mimics the extracellular matrix (ECM) composition. This biomacromolecule-based matrix hydrogel can undergo rapid gelling and fixation to adhere and seal bleeding arteries and cardiac walls after UV light irradiation. These repairs can withstand up to 290 mm Hg blood pressure, significantly higher than blood pressures in most clinical settings (systolic BP 60-160 mm Hg). Most importantly, the hydrogel can stop high-pressure bleeding from pig carotid arteries with 4~ 5 mm-long incision wounds and from pig hearts with 6 mm diameter cardiac penetration holes. Treated pigs survived after hemostatic treatments with this hydrogel, which is well-tolerated and appears to offer significant clinical advantage as a traumatic wound sealant.

The regeneration of articular cartilage, which scarcely shows innate self-healing ability, is a great challenge in clinical treatment. Stem cell-derived exosomes (SC-Exos), an important type of extracellular nanovesicle, exhibit great potential for cartilage regeneration to replace stem cell-based therapy. Cartilage regeneration often takes a relatively long time and there is currently no effective administration method to durably retain exosomes at cartilage defect sites to effectively exert their reparative effect. Therefore, in this study, we exploited a photoinduced imine crosslinking hydrogel glue, which presents excellent operation ability, biocompatibility and most importantly, cartilage-integration, as an exosome scaffold to prepare an acellular tissue patch (EHG) for cartilage regeneration. It was found that EHG can retain SC-Exos and positively regulate both chondrocytes and hBMSCs in vitro. Furthermore, EHG can integrate with native cartilage matrix and promote cell deposition at cartilage defect sites, finally resulting in the promotion of cartilage defect repair. The EHG tissue patch therefore provides a novel, cell-free scaffold material for wound repair.

An excellent mesoporous silica nanoparticle (MSN) based drug deliver system (DDS) was reported for regulated anticancer drug release upon the irradiation of either one- or two-photon excitation. In this system, the coumarin grafted on MSN acted as both the "phototrigger" for the drug release and fluorescence group for cell luminescence imaging. External light manipulations such as changing irradiation wavelength, intensity, and time can regulate the release of the anticancer drug precisely. Biological studies in vitro suggest that the drug carrier can effectively deliver the anticancer drug into intracellular environs and, hence, promote the drug action to kill the cancer cells upon irradiation. We envision that the good biocompatibility, cellular uptake property, and efficient photoregulated drug release will be of great benefit to future controlled release in vivo biomedical applications.

Phototrigger‐controlled drug‐release devices (PDDs) can be conveniently manipulated by light to obtain on‐demand release patterns, thereby affording an improved therapeutic efficacy. However, no example of the PDDs has been demonstrated beyond the cellular level to date. By loading 7‐amino‐coumarin derivative caged anticancer drug chlorambucil to yolk–shell structured nanocages possessing upconversion nanophosphors (UCNPs) as moveable core and silica as mesoporous shell, a near‐infrared (NIR)‐regulated PDD is successfully created. In vitro experiments demonstrate that drug release from the PDD could be triggered by continuous‐wave 980 nm light in a controlled pattern. The PDD could be taken up by cancer cells and release the drug to kill cancer cells upon NIR irradiation. Further in vivo studies demonstrate that the PDD can effectively response the NIR stimuli in living tissue. This is the first example of successful NIR‐regulated drug release in living animal model. Such achievement resolves the problem of low tissue penetration depth for traditional PDDs by adopting UCNPs as an NIR light switcher, which gives impetus to practical applications.