EFFECTS OF IONIC DISSOLUTION PRODUCTS FROM BIOACTIVE GLASS-CERAMIC SCAFFOLDS ON THE CELLULAR AND MOLECULAR RESPONSE OF ENDOTHELIAL CELLS AND FIBROBLASTS UNDER HYPERGLYCEMIA

HARO DURAND L; BALDI ALBERTO; BOCCACCINI A; GORUSTOVICH A; FANOVICH MARÍA A

Mar del Plata

Jornada; Reunion Anual de Sociedades de Biociencia; 2019

SAIC-SAFE-SAB-SAP

Several aspects of tissue repair are altered in diabetes mellitus (DM) i.e., endothelial cells and fibroblasts are affected by cellular dysfunction in a hyperglycemic (HG) environment. Thus, it is of biomedical interest to study different therapeutic strategies to optimize the repair and/or regeneration of tissues under HG conditions. The aim of this work was to study the cellular and molecular response of ionic dissolution products (IDPs) released from 3D porous bioactive glass-ceramic scaffolds manufactured from a 45S5 glass (% w/w composition: 45% SiO2, 24.5% Na2O, 24.5% CaO, and 6% P2O5) added with 2% of B2O3 (45S5.2B) in primary cultures of dermal fibroblasts (DFs) and endothelial cells (ECs) grown in HG (30 mM D-glucose). The results showed that IDPs from the 45S5.2B scaffolds positively modulate the in vitro proliferative and migratory response in both ECs and DFs grown under HG in comparison with controls. Further, IDPs improve the ability of ECs to form tubules in vitro. The supernatant from DFs grown in HG during 7 d and post-stimulated with IDPs for 2 d, showed significantly higher levels of secretory VEGF and it was able to increase the proliferative response of ECs. On the other hand, the IDPs from 45S5.2B were able to modulate key cellular signaling pathways altered in HG conditions. This was corroborated by changes in the phosphorylation status of MEK/ERK1/2, JNK/p38, PI3K/AKT, and a significant increase of relative levels of SIRT-1 and Nrf-2. Additionally, IDPs modulated the expression levels of procaspase 3/caspase 3, Bax and Bcl-2. These findings may be relevant in regenerative medicine since 45S5.2B scaffolds could act as inorganic agents that positively modulate the cellular and molecular response thus promoting processes of tissue repair and/or regeneration in patients with DM.