Nuciferine-loaded chitosan hydrogel-integrated 3D-printed polylactic acid scaffolds for bone tissue engineering: A combinatorial approach.

Critical-sized bone defects resulting from severe trauma and open fractures cannot spontaneously heal and require surgical intervention. Limitations of traditional bone grafting include immune rejection and demand-over-supply issues leading to the development of novel tissue-engineered scaffolds. Nuciferine (NF), a plant-derived alkaloid, has excellent therapeutic properties, but its osteogenic potential is yet to be reported. Furthermore, the bioavailability of NF is obstructed due to its hydrophobicity, requiring an efficient drug delivery system, such as chitosan (CS) hydrogel. We designed and fabricated polylactic acid (PLA) scaffolds via 3D printing and integrated them with NF-containing CS hydrogel to obtain the porous biocomposite scaffolds (PLA/CS-NF). The fabricated scaffolds were subjected to in vitro physicochemical characterization, cytotoxicity assays, and osteogenic evaluation studies. Scanning electron microscopic studies revealed uniform pore size distribution on PLA/CS-NF scaffolds. An in vitro drug release study showed a sustained and prolonged release of NF. The cyto-friendly nature of NF in PLA/CS-NF scaffolds towards mouse mesenchymal stem cells (mMSCs) was observed. Also, cellular and molecular level studies signified the osteogenic potential of NF in PLA/CS-NF scaffolds on mMSCs. These results indicate that the PLA/CS-NF scaffolds could promote new bone formation and have potential applications in bone tissue engineering.

Antiproliferative and Apoptotic Effects of pH-Responsive Veratric Acid-Loaded Polydopamine Nanoparticles in Human Triple Negative Breast Cancer Cells.

Veratric acid (VA) is plant-derived phenolic acid known for its therapeutic potential, but its anticancer effect on highly invasive triple-negative breast cancer (TNBC) is yet to be evaluated. Polydopamine nanoparticles (nPDAs) were chosen as the drug carrier to overcome VA's hydrophobic nature and ensure a sustained release of VA. We prepared pH-sensitive nano-formulations of VA-loaded nPDAs and subjected them to physicochemical characterization and in vitro drug release studies, followed by cell viability and apoptotic assays on TNBC cells (MDA-MB-231 cells). The SEM and zeta analysis revealed spherical nPDAs were uniform size distribution and good colloidal stability. In vitro drug release from VA-nPDAs was sustained, prolonged and pH-sensitive, which could benefit tumor cell targeting. MTT and cell viability assays showed that VA-nPDAs (IC50=17.6 µM) are more antiproliferative towards MDA-MB-231 cells than free VA (IC50=437.89 µM). The induction of early and late apoptosis by VA-nPDAs in the cancer cells was identified using annexin V and dead cell assay. Thus, the pH response and sustained release of VA from nPDAs showed the potential to enter the cell, inhibit cell proliferation, and induce apoptosis in human breast cancer cells, indicating the anticancer potential of VA.