Different approaches to develop engineered scaffolds for periodontal tissues regeneration have been proposed. In this review, innovations in stem cell technology and scaffolds engineering focused primarily on Periodontal Ligament (PDL) regeneration are discussed and analyzed based on results from pre-clinical in vivo studies and clinical trials. Most of those developments include the use of polymeric materials with different patterning and surface nanotopography and printing of complex and sophisticated multiphasic composite scaffolds with different compartments to accomodate for the different periodontal tissues’ architecture. Despite the increased effort in producing these scaffolds and their undoubtable efficiency to guide and support tissue regeneration, appropriate source of cells is also needed to provide new tissue formation and various biological and mechanochemical cues from the Extraccellular Matrix (ECM) to provide biophysical stimuli for cell growth and differentiation. Cell sheet engineering is a novel promising technique that allows obtaining cells in a sheet format while preserving ECM components. The right combination of those factors has not been discovered yet and efforts are still needed to ameliorate regenerative outcomes towards the functional organisation of the developed tissues.

Background: Artemisia absinthium (A. absinthium), commonly known as absinthe, is a perennial plant with distinctive broad ovate pointed leaves of a silvery-gray color, reaching a height of 1.5 m. The utilization of this herb as a source of natural compounds and as the primary ingredient in the alcoholic beverage absinthe has recently seen a resurgence following a period of prohibition. This study investigates the biological effects of A. absinthium extract on healthy human periodontal ligament stem cells (hPDLSCs) and the human tongue squamous carcinoma cell line (HSC-3). Methods: A. absinthium element characterization was performed using High-Performance Liquid Chromatography (HPLC) and the Folin method. Alizarin assays evaluated the osteogenic capacity of human periodontal ligament cells (hPDLSCs) while CCK-8 and MTT determined the cytotoxicity of the extract against HSC-3 and hPDLSCs. Results: High artemisinin levels were detected, revealing a concentration of 89 μM (25 μg/mL). The total phenolic concentration of the extract was 1.07 mM +/− 0.11. The in vitro cytotoxicity assays revealed the biocompatible profile of the Artemisia extract in hPDLSCs without exhibiting any osteogenic potential. After 24 h of incubation with HSC-3, Artemisia extract (10 µM) decreased cancer cell viability by 99% and artemisinin by 64%, and increased the expression of Caspase 3 and 9 almost six and two times, respectively. Conclusions: In summary, our preliminary findings suggest that A. absinthium extract exhibits a toxic effect against carcinoma cell lines without affecting healthy human periodontal ligament stem cells.

Background: A promising strategy to enhance bone regeneration is the use of bioactive materials doped with metallic ions with therapeutic effects and their combination with active substances and/or drugs. The aim of the present study was to investigate the osteogenic capacity of human periodontal ligament cells (hPDLCs) in culture with artemisinin (ART)-loaded Ce-doped calcium silicate nanopowders (NPs); Methods: Mesoporous silica, calcium-doped and calcium/cerium-doped silicate NPs were synthesized via a surfactant-assisted cooperative self-assembly process. Human periodontal ligament cells (hPDLCs) were isolated and tested for their osteogenic differentiation in the presence of ART-loaded and unloaded NPs through alkaline phosphatase (ALP) activity and Alizarine red S staining, while their antioxidant capacity was also evaluated; Results: ART promoted further the osteogenic differentiation of hPDLCs in the presence of Ce-doped NPs. Higher amounts of Ce in the ART-loaded NPs inversely affected the mineral deposition process by the hPDLCs. ART and Ce in the NPs have a synergistic role controlling the redox status and reducing ROS production from the hPDLCs; Conclusions: By monitoring the Ce amount and ART concentration, mesoporous NPs with optimum properties can be developed towards bone tissue regeneration demonstrating also potential application in periodontal tissue regeneration strategies.

Background: Artemisia absinthium (A. absinthium) is a perennial plant valued for its antibacterial, antioxidant, and anti-inflammatory properties, exhibiting broader therapeutic potential. Given the need to deliver low doses of A. absinthium extract, mesoporous silica nanoparticles have attracted considerable attention as promising nanocarriers due to their distinctive physical and chemical properties. Methods: Physicochemical characterization of the materials was performed and biological assays were conducted to investigate the ROS, antibacterial and antioxidant activity of A. absinthium extract encapsulated within cerium- and calcium-doped mesoporous silica nanoparticles (MNSiCaCe) against both aerobic and anaerobic bacteria. Results: FTIR, SEM, and BET analysis confirmed successful synthesis of the MNSiCaCe. Phytochemical profiling of Artemisia absinthium extract using HPLC revealed the presence of artemisinin and a rich composition of phenolic and flavonoid constituents, with a total phenolic content of 182 ± 3.6 mg GAE/100 g dry plant material and a total flavonoid content of 42.5 ± 0.6 mg QE/100 g. Quantitative drug loading profiling demonstrated that while plain MNSi nanocarriers achieved a loading capacity of 16.96%, the MNSiCaCe enhanced this threshold to 43.11%. The in vitro controlled-release kinetics exhibited a highly prolonged and slow-release profile of the MNSiCaCe. The materials demonstrated excellent hemocompatibility and high mitochondrial activity with human periodontal ligament cells (hPDLCs). Elevated ROS generation was observed under conditions where antibacterial activity was most pronounced. While the artemisinin-doped nanoparticles showed notable antibacterial effects, the complete Artemisia absinthium-loaded nanoparticles achieved a significantly greater reduction in bacterial viability probably due to the synergistic interaction between artemisinin and the extract’s rich polyphenol profile. Conclusions: These findings highlight MNSiCaCe as a promising and safe nanocarrier system for drug delivery, with strong antibacterial potential, offering valuable applications in antibacterial therapies.