Controlled Osteogenic Differentiation of Human Mesenchymal Stem Cells Using Dexamethasone-Loaded Light-Responsive Microgels

Abstract

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.

Rheology Applied to Microgels: Brief (Revision of the) State of the Art

“…These AuNPs’ cores served to stimulate the collapse of the PNIPAM shell when excited with visible light. This visible light generates heat that causes the swelling of PNIPAM [ 48 ]. Regarding hybrid microgels containing magnetic nanoparticles, Rames et al developed a platelet-like stimuli-responsive microgel suspension based on poly(NIPAM-co-AA) that responds to the magnetic field and UV photocuring.…”

“…Within this context microgels are currently being studied for various tissue engineering applications: cartilage, vascular, cardiac, hepatic, and neuronal tissues, among others [ 59 ], as in the aforementioned work of Serpe et al in which they designed light-responsive microgels with potential bone tissue regeneration. These microgels are capable of loading and releasing dexamethasone (DEX), an active compound able to induce human mesenchymal stem cells’ (hMSCs) differentiation into osteoblast [ 48 ]. Another example of the use of microgels for tissue regeneration is the work of Rieder et al on the development of injectable microgels densely packed into a microporous scaffold.…”

A high spatial resolution osteogenic differentiation in human mesenchymal stem cells induced by femtosecond laser

“…With the knowledge advancement, a series of biochemical methods including growth factors and chemical reagents are always applied to induce osteogenic differentiation. Nevertheless, these growth factors are prone to lose their bioactivity and cause undesired effects such as tumorigenesis and inflammation [8,9]. In clinical studies, the delivery of in vitro expanded MSCs combined with biomaterials in various architecture and chemicals to injured sites holds encouraging promise for the bone regeneration [10,11].…”

Triply-responsive OEG-based microgels and hydrogels: regulation of swelling ratio, volume phase transition temperatures and mechanical properties

“…Microgels (MGs) are crosslinked polymer colloid particles that can swell in a thermodynamically good solvent or when the pH approaches the particle pKa [1][2][3][4] . Responsive MGs are "smart" particles, that can respond to external stimuli such as heat 5 , pH 6 , light 7,8 , ionic strength 9 , enzymes 10 , magnetic fields 11,12 and solvent composition 13 . Such smart colloids have potential applications in a range of fields such as drug delivery 14 , catalysis 15,16 , sensors 17 , surface coatings 18 , tissue engineering [19][20][21] and chemical separation 22 .…”