Microgels based on Infernan, a glycosaminoglycan-mimetic bacterial exopolysaccharide, as BMP-2 delivery systems

Encapsulated vaterite-calcite CaCO3 particles loaded with Mg2+ and Cu2+ ions with sustained release promoting osteogenesis and angiogenesis

“…Vascular endothelial growth factor (VEGF) is widely used in bone tissue engineering research for the improvement of tissue vascularization, either alone or in combination with BMP-2 ( Liu et al, 2020 ; Fitzpatrick et al, 2021 ). However, significant disadvantages are associated with these protein growth factors-based therapeutics, including the sever complications caused by the supraphysiological dose applied, the instability in the fabrication process, and the high cost ( Ruehle et al, 2019 ; Gelebart et al, 2022 ). Repeated clinical applications of BMP-2 have not been approved as safe and effective by the United States Food and Drug Administration (FDA) ( SSED, 2022 ).…”

Interactions between infernan and calcium: From the molecular level to the mechanical properties of microgels

“…The presence of Ca 2+ stabilizes xanthan in its ordered helical conformation, where the main binding sites are likely constituted between the terminal pyruvate groups of the side chains, while the main chains play a minor role in the cation complexation (Bergmann, Furth, & Mayer, 2008;Lambert, Milas, & Rinaudo, 1985). Recently, we have shown that a bacterial EPS secreted by the deep-sea hydrothermal vent bacterium Alteromonas infernus, called infernan (GY785 EPS), was also able to gel in the presence of Ca 2+ (Zykwinska et al, 2019;Gélébart et al, 2022). Similarly to xanthan, infernan is also a highly branched heteropolysaccharide.…”

“…In contrast to xanthan, native infernan of high molecular weight (HMW), 2,000,000 g/mol, cannot gel. However, a physical Ca 2+ gel was formed by a medium molecular weight (MMW) derivative, EPS DR (240,000 g/mol), obtained by radical depolymerization of the native HMW EPS (Zykwinska et al, 2019;Gélébart et al, 2022). Besides gelling properties with divalent cations, the negatively charged EPS is also able to bind to positively charged proteins, such as basic growth factors, and this property has a huge potential in tissue engineering (Merceron et al, 2012;Rederstorff et al, 2017;Zykwinska et al, 2018;Zykwinska et al, 2019;Gélébart et al, 2022).…”

“…However, a physical Ca 2+ gel was formed by a medium molecular weight (MMW) derivative, EPS DR (240,000 g/mol), obtained by radical depolymerization of the native HMW EPS (Zykwinska et al, 2019;Gélébart et al, 2022). Besides gelling properties with divalent cations, the negatively charged EPS is also able to bind to positively charged proteins, such as basic growth factors, and this property has a huge potential in tissue engineering (Merceron et al, 2012;Rederstorff et al, 2017;Zykwinska et al, 2018;Zykwinska et al, 2019;Gélébart et al, 2022). Indeed, growth factors constitute a key element in tissue engineering strategies since they stimulate essential cellular processes (proliferation, migration, differentiation).…”

“…Growth factor delivery systems, such as microgels, have intensely been explored to enhance growth factor bioactivity and sustain their local release to the surrounding microenvironment (Caballero Aguilar, Silva, & Moulton, 2019;Subbiah & Guldberg, 2019). By associating both physicochemical (gelling) and biological (GAG-mimetic) properties of infernan derivatives, we have recently developed growth factor-loaded microgels for cartilage and bone engineering purposes (Zykwinska et al, 2019;Gélébart et al, 2022).…”