Mesoporous Bioactive Glasses Incorporated into an Injectable Thermosensitive Hydrogel for Sustained Co-Release of Sr2+ Ions and N-Acetylcysteine

Abstract

An injectable delivery platform for promoting delayed bone healing has been developed by combining a thermosensitive polyurethane-based hydrogel with strontium-substituted mesoporous bioactive glasses (MBG_Sr) for the long-term and localized co-delivery of pro-osteogenic Sr2+ ions and an osteogenesis-enhancing molecule, N-Acetylcysteine (NAC). The incorporation of MBG_Sr microparticles, with a final concentration of 20 mg/mL, did not alter the overall properties of the thermosensitive hydrogel, in terms of sol-to-gel transition at a physiological-like temperature, gelation time, injectability and stability in aqueous environment at 37 °C. In particular, the hydrogel formulations (15% w/v polymer concentration) showed fast gelation in physiological conditions (1 mL underwent complete sol-to-gel transition within 3–5 min at 37 °C) and injectability in a wide range of temperatures (5–37 °C) through different needles (inner diameter in the range 0.4–1.6 mm). In addition, the MBG_Sr embedded into the hydrogel retained their full biocompatibility, and the released concentration of Sr2+ ions were effective in promoting the overexpression of pro-osteogenic genes from SAOS2 osteoblast-like cells. Finally, when incorporated into the hydrogel, the MBG_Sr loaded with NAC maintained their release properties, showing a sustained ion/drug co-delivery along 7 days, at variance with the MBG particles as such, showing a strong burst release in the first hours of soaking.

The role of N-acetylcysteine in osteogenic microenvironment for bone tissue engineering

“…Mesoporous bioactive glass with the structured mesoporous architecture enables the incorporation of various drugs and biomolecules, making it an innovative material in bone tissue engineering ( Vallet-Regi and Salinas, 2021 ). The combination of NAC with strontium-doped mesoporous bioactive glass and thermosensitive polyurethane hydrogel efficiently enhances osteogenic factor expression in precursor cells ( Pontremoli et al, 2022 ). Furthermore, NAC can be integrated into nanoparticles, nanofibers, and other nanomaterials to create nano-engineered composite materials.…”

Mesoporous Materials Make Hydrogels More Powerful in Biomedicine

“…Incorporation with mesoporous bioactive glasses is considered a promising way to improve the physicochemical stability and mechanical properties of the hydrogels in hard tissue engineering [ 80 , 81 , 82 ]. At the same time, the combined mesoporous bioactive glass can optimize the drug delivery and release performance of hydrogels, improving the efficacy of loaded drugs [ 48 , 83 ]. A naringin or calcitonin gene-related peptide co-printed into the mesoporous bioactive glass/sodium alginate/gelatin hydrogels displayed a steady sustained release behavior for up to 21 days without an initial burst release and promoted MG-63 cell proliferation and osteogenesis-related gene expression [ 84 ].…”

Development of Dipeptide N–acetyl–L–cysteine Loaded Nanostructured Carriers Based on Inorganic Layered Hydroxides

“…NAC has effective antioxidant properties and, consequently, a strong capability to be used in treatments related to the generation of free radicals and as a food supplement. This drug has therapeutic potential for the treatment of other diseases such as Alzheimer’s [ 6 ], type-2 diabetes [ 7 ], type-1 diabetes [ 8 ], gestational diabetes mellitus [ 9 ], diseases related to psychiatric disorders [ 10 ], neurodegenerative diseases [ 11 ], inhibition and induced death of lung cancer cells [ 12 ], HIV-associated tuberculosis [ 13 ], and bone regeneration approaches [ 14 , 15 ]. NAC is considered helpful in the nutraceutical control of RNA viruses such as influenza and coronavirus and has been investigated as an adjuvant to the prevention and therapy of COVID-19 [ 16 , 17 , 18 ] and post-COVID-19 pulmonary fibrosis [ 19 ].…”