Mesoporous bioactive glasses (MBGs) have been widely studied as bone regeneration systems, due to their bioactivity and ability to store and release therapeutic agents with specific biological functions. The incorporation of these nanomaterials into a thermosensitive hydrogel (TSH), in which a solution undergoes a sol-gel transition under physiological conditions, represents a promising approach to design multifunctional devices able to deliver selected molecules to pathological sites. In fact, this system can perfectly fit the defect cavity shape prior to the complete gelation, and acts as a carrier for therapeutic agents prolonged release in situ. This challenging concept is the underlying idea of the MOZART project, whose objective was to develop a library of MBGs containing different therapeutic ions and drugs, to be used as a new, smart platform technology for highly targeted therapies to enhance bone healing. The aim of this work is to investigate the bone regeneration potential of MBGs containing strontium ions (pro-osteogenic) and incorporated into thermosensitive poly(etherurethane)(PEU) based on Poloxamer407. In order to further increase the pro-osteogenic response, MBGs were also loaded with N-acetylcysteine (NAC).

MBGs containing 2%mol of Sr²⁺ were prepared by an aerosol-assisted spray-drying method and NAC was loaded post-synthesis via an incipient wetness method. The PEU hydrogel (SHP407) was synthesized via a two-step procedure in nitrogen atmosphere. Particles were characterized (FE-SEM, N₂ adsorption-desorption analysis, TGA, DSC, FT-IR and XRD) and then incorporated into the hydrogel. The hybrid systems rheological properties and stability in aqueous environment at 37°C, and its ability to co-release Sr²⁺ and NAC were analysed. After preliminary biological in vitro tests, a proof-of-concept rodent study was run to assess the ability of the resulting formulation as bone healing device. X-ray at 2 and 4-weeks post-surgery and µCT-analysis were used to evaluate the healing results in a rat osteotomy model of biologically impaired healing. Then, bones were processed for histological evaluation.

Preliminary in vivo results demonstrated that incorporation of MBGs into a TSH is a promising strategy to design a multifunctional injectable formulation for in situ and sustained delivery of pro-osteogenic species enhancing bone regeneration.

Promising work on bioactive glasses (BAGs) in bone defect regeneration has led to their clinical implementation. However, the effects of the ionic dissolution products of different types and the physical interaction modalities of BAGs on the behavior and function of mesenchymal stromal cells (MSCs) of human patients have not received sufficient attention. Recently, we showed that the in vitro response of hMSC to micron-sized, monodispersed BAGs is dependent on dosage, composition, and mode of interaction¹. Two commercially available and widely used types of BAGs, namely the silicate BAGs 45S5 and 1393, were used to study hMSC cell behavior. Interestingly, exposure to 1393 BAG resulted in superior metabolic activity, proliferation, and cell spreading compared to 45S5 BAG in similar dosage, suggesting that additional cellular functions could also be differentially modulated by both glasses¹. In the context of bone regeneration, the hMSCs’ potential to secrete angiogenic factors as well as deposit mineralized matrix upon exposure to BAG dissolution products was investigated in the present study. Aside from dose-dependent effects of both glasses, 45S5 BAG induced a significant pro-angiogenic response, demonstrated by robust tube formation in HUVECs in the presence of MSC conditioned media. 1393 BAG, on the other hand, stimulated osteogenesis by upregulating osteogenic gene expression and mineralized matrix deposition. Based on these results, combining the pro-angiogenic 45S5 BAG and the pro-osteogenic 1393 BAG might be an attractive strategy to target the multiple processes underlying bone regeneration. These results highlight how different BAGs can be utilized to promote MSC-mediated bone regeneration.