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    Development of Boron-Containing PVA-Based Cryogels with Controllable Boron Releasing Rate and Altered Influence on Osteoblasts
    (Mdpi, 2023) Ceylan, Seda; Dimmock, Ryan; Yang, Ying
    Cryogel formation is an effective approach to produce porous scaffolds for tissue engineering. In this study, cryogelation was performed to produce boron-containing scaffolds for bone tissue engineering. A combination of the synthetic polymer, poly(vinyl alcohol) (PVA), and the natural polymers, chitosan and starch, was used to formulate the cryogels. Boron was used with a dual purpose: as an additive to alter gelation properties, and to exploit its bioactive effect since boron has been found to be involved in several metabolic pathways, including the promotion of bone growth. This project designs a fabrication protocol enabling the competition of both physical and chemical cross-linking reactions in the cryogels using different molecular weight PVA and borax content (boron source). Using a high ratio of high-molecular-weight PVA resulted in the cryogels exhibiting greater mechanical properties, a lower degradation rate (0.6-1.7% vs. 18-20%) and a higher borax content release (4.98 vs. 1.85, 1.08 nanomole) in contrast to their counterparts with low-molecular-weight PVA. The bioactive impacts of the released borax on cellular behaviour were investigated using MG63 cells seeded into the cryogel scaffolds. It was revealed that the borax-containing scaffolds and their extracts induced MG63 cell migration and the formation of nodule-like aggregates, whilst cryogel scaffolds without borax did not. Moreover, the degradation products of the scaffolds were analysed through the quantification of boron release by the curcumin assay. The impact on cellular response in a scratch assay confirmed that borax released by the scaffold into media (similar to 0.4 mg/mL) induced bone cell migration, proliferation and aggregation. This study demonstrated that boron-containing three-dimensional PVA/starch-chitosan scaffolds can potentially be used within bone tissue engineering applications.
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    Molecular Weight-Dependent Boron Release Effect in PVA/Chitosan Cryogels and In Vitro Mineralization Evaluations by Osteoblast Cells
    (Wiley, 2025) Ceylan, Seda; Arici, Sule; Ege, Duygu; Yang, Ying
    Cryogels were fabricated by combining polyvinyl alcohol (PVA) and chitosan of varying molecular weights (Mw). In this study, the effects of chitosan Mw, types of boron-containing molecules on network formation, and boron release rate in resulted cryogels were investigated. The PVA/chitosan blend maintained a constant 4.5% (w/v) polymer content. PVA to chitosan weight ratio of 6:1 was maintained and fixed. Five percent w/w boric acid and borax (sodium tetraborate) crosslinkers were added in PVA and chitosan mixtures to construct cryogels. The freeze-dried specimens underwent crosslinking evaluation, chemical composition analysis by FTIR, and boron release studies by ICP-MS. The pore morphology and the swelling capacity of the cryogel have been assessed by SEM and incubation in water, respectively. Mechanical test was also used to evaluate the effect of borax and Mw of chitosan on cryogels' mechanical properties. It was demonstrated that the types of boron supply had a significant role on the cryogelation capability. For different chitosan Mw, the cryogels made using borax showed stable cryogels. In contrast, even after altering the chitosan Mw, the formula with boric acid was unable to create stable cryogels. In addition, boron release assay showed that the quantity of free boron in the incubation solutions decreased as the Mw of the chitosan component of the cryogel was reduced. Cell culture studies with MC3T3-E1 pre-osteoblast cells in the cryogels indicated that borax-crosslinked samples exhibited sustained cell viability. Alizarin red staining assay was used to study mineralization capacity of boron-containing hydrogels, which confirmed increase of mineralization in low molecular weight chitosan groups.