No abstract

Stimuli-responsive polymers (SRPs) are capable of changing their solubility, conformation, and volume in response to external stimuli. Here, we detail how SRPs can be used for sensing and actuation, and focus on the response mechanism.

Human mesenchymal stem cells (hMSCs), which have the ability to differentiate into osteoblasts, show promise for bone tissue engineering and bone defect treatment. While there are a number of approaches currently available to accomplish this, e.g., utilizing biodegradable materials loaded with the synthetic glucocorticoid osteogenic inducer dexamethasone (DEX), there are still many disadvantages with the current technologies. Here, we generated light-responsive microgels that we showed are capable of loading and releasing DEX in a light-triggered fashion, with the released DEX being able to induce hMSC differentiation into osteoblasts. Specifically, light-responsive poly­(N-isopropylacrylamide-co-nitrobenzyl methacrylate) (pNIPAm-co-NBMA) microgels were synthesized via free radical precipitation polymerization and their size, morphology, and chemical composition were characterized. We then went on to show that the microgels could be loaded with DEX (via what we think are hydrophobic interactions) and released upon exposure to UV light. We went on to show that the DEX released from the microgels was still capable of inducing osteogenic differentiation of hMSCs using an alamarBlue assay and normalized alkaline phosphatase (ALP) activity assay. We also investigated how hMSC differentiation was impacted by intermittent DEX released from UV-exposed microgels. Finally, we confirmed that the microgels themselves were not cytotoxic to hMSCs. Taken together, the DEX-loaded light-responsive microgels reported here may find a use for niche clinical applications, e.g., bone tissue repair.

Stretchable poly(N-isopropylacrylamide)-co-acrylic acid (pNIPAm-co-10% AAc) microgel-based reservoir devices were fabricated and used to control the release rate of the small molecule model drug tris(4-(dimethylamino)phenyl)methylium chloride (crystal violet, CV) to solution by varying the Au layer thickness coating the microgels and device elongation. Specifically, we showed that CV could be loaded into the microgel layer of the devices via electrostatic interactions at pH 6.5, and the release could be triggered upon exposure to a pH 3.0 solution, which breaks the microgel−CV electrostatic interactions. We demonstrated that the rate of release could be increased by decreasing the Au layer thickness coating microgels and by stretching, that is, thin Au and high elongation promoted the relatively fast release of CV from the device. We found that the Au overlayer thickness (and porosity) dominated the observed release rate profiles when the device was not stretched (or at low elongation), while elongation-induced cracks dominated the release rate at high elongation. We also showed that the CV release kinetics could transition from low ("off") to high ("on"), which enhanced when the devices are stretched. This behavior could be exploited in the future for autonomous release systems that release small molecules when stretched by natural processes, for example, movement of joints and muscles.