Amine functionalized TiO2 doped mesoporous bioactive glass coated curcumin infused 3d printed poly (L-lactic acid): A promising multifunctional scaffold with enhanced osteogenesis and tumour relapse inhibition characteristics.

The two main clinical problems with post-operative metastatic bone disease are high death rate and a notable local recurrence rate. When diseased bone sections are removed from patients, they suffer from significant bone defects that cannot be repaired on their own, and therefore require a support mechanism via the incorporation of scaffolds. In such cases, multifunctional scaffolds are deemed to be an appropriate option with promising potential as bone substitutes and limit the recurrence of post-operative tumour cells. This can be achieved via constructing a multi-functional scaffold incorporated with therapeutic compounds that helps in the prevention of tumour recurrence and improved surface characteristics for achieving enhanced osteogenesis. In the current work, a multi-functional scaffold is constructed via coating of amine functionalized Titanium dioxide (TiO2) doped mesoporous bioactive glass (MBG) on 3D printed curcumin infused PLA support. The influence of curcumin incorporation towards inhibiting the growth of osteosarcoma cells and surface coating for enhanced osteogenesis of adipose-derived mesenchymal stem cells (AD-MSCs) is investigated. In this study, MBG is doped with TiO2 and surface grafted with amine groups to facilitate coating on 3D printed PLA and curcumin infused PLA surface via EDC-NHS carbodiimide chemistry. As revealed by FESEM analysis, the bioactive coating was observed to induce in-vitro bioactivity on day 1 of SBF treatment. Most importantly, the release of curcumin shows antibacterial activity against gram-positive (∼90 %) and gram-negative bacterial strain (∼85 %) as well as cytotoxicity towards osteosarcoma cells lines (∼ 90 % cell apoptosis observed after 14 days of culture). The TiO2 doped MBG promotes osteogenic differentiation, observed with a significant increase in calcium mineralization (p < 0.0001) and Alkaline phosphatase activity (p < 0.0001) compared to PLA scaffolds via mild release of reactive oxygen species, which facilitates production of antioxidant proteins and ultimately promotes upregulation of early and late osteogenic markers.