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    Diatom silica frustules-doped fibers for controlled release of melatonin for bone regeneration
    (Pergamon-Elsevier Science Ltd, 2023) Dalgic, Ali Deniz; Atila, Deniz; Tezcaner, Aysen; Gurses, Senih; Keskin, Dilek
    Sustained release of a bioactive agent from a tissue engineering scaffold is one of the most common strategies to improve regenerative potential of the construct. However, depending on the chemistry of the agent, achieving high enough loading and controlled release can be challenging depending on the scaffold materials. These shortcomings can be solved by novel scaffold design fabricated by appropriate techniques and materials for the target tissue. In this study, an electrospun scaffold was designed to improve osteogenic activity of cells and diatom silica frustules were used to sustain loading and controlled release of a hydrophilic molecule, melatonin. Fibrous scaffolds were produced via wet electrospinning of the polymer blend solution poly(hydroxybutyrate-co- hydroxyvalerate (PHBV)/poly(epsilon-caprolactone) (PCL) which contains melatonin loaded diatom frustules. In the 3D fiber matrix diatom frustules were covered with a polymer coat which successfully lowered melatonin release more than half through 7 days achieving a controlled release. Melatonin had a concentration dependent effect on ALP activity of cells, while scaffolds bearing melatonin loaded frustules have significantly improved ALP activity of Saos-2 cells. Developed scaffold system has successfully induced osteogenic activity by controlled melatonin delivery and silica nature of diatom frustules which hold potential use for bone tissue engineering.
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    Injectable Liposome-Loaded Hydrogel Formulations with Controlled Release of Curcumin and ?-Tocopherol for Dental Tissue Engineering
    (Wiley, 2024) Atila, Deniz; Dalgic, Ali Deniz; Krzeminska, Agnieszka; Pietrasik, Joanna; Gendaszewska-Darmach, Edyta; Bociaga, Dorota; Kumaravel, Vignesh
    An injectable hydrogel formulation is developed utilizing low- and high-molecular-weight chitosan (LCH and HCH) incorporated with curcumin and alpha-tocopherol-loaded liposomes (Lip/Cur+Toc). Cur and Toc releases are delayed within the hydrogels. The injectability of hydrogels is proved via rheological analyses. In vitro studies are conducted using human dental pulp stem cells (hDPSCs) and human gingival fibroblasts (hGFs) to examine the biological performance of the hydrogels toward endodontics and periodontics, respectively. The viability of hDPSCs treated with the hydrogels with Lip/Cur+Toc is the highest till day 14, compared to the neat hydrogels. During odontogenic differentiation tests, alkaline phosphatase (ALP) enzyme activity of hDPSCs is induced in the Cur-containing groups. Biomineralization is enhanced mostly with Lip/Cur+Toc incorporation. The viability of hGFs is the highest in HCH combined with Lip/Cur+Toc while wound healing occurs almost 100% in both (Lip/Cur+Toc@LCH and Lip/Cur+Toc@HCH) after 2 days. Antioxidant activity of Lip/Cur+Toc@LCH on hGFs is significantly the highest among the groups. Antimicrobial tests demonstrate that Lip/Cur+Toc@LCH is more effective against Escherichia coli whereas so is Lip/Cur+Toc@HCH against Staphylococcus aureus. The antimicrobial mechanism of the hydrogels is investigated for the first time through various computational models. LCH and HCH loaded with Lip/Cur+Toc are promising candidates with multi-functional features for endodontics and periodontics.