Evaluation of MC3T3 Cells Proliferation and Drug Release Study from Sodium Hyaluronate-1,4-butanediol Diglycidyl Ether Patterned Gel

透明质酸钠-1,4-丁二醇二缩水甘油醚图案化凝胶对MC3T3细胞增殖及药物释放研究的评价

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作者:Sumi Bang, Dipankar Das, Jiyun Yu, Insup Noh

Abstract

A pattern gel has been fabricated using sodium hyaluronate (HA) and 1,4-butanediol diglycidyl ether (BDDGE) through the micro-molding technique. The cellular behavior of osteoblast cells (MC3T3) in the presence and absence of dimethyloxalylglycine (DMOG) and sodium borate (NaB) in the pattern gel (HA-BDDGE) has been evaluated for its potential application in bone regeneration. The Fourier transform infrared spectroscopy (FTIR), 13C-nuclear magnetic resonance spectroscopy (13C NMR), and thermogravimetric analysis (TGA) results implied the crosslinking reaction between HA and BDDGE. The scanning electron microscopy (SEM) analysis confirmed the formation of pattern on the surface of HA-BDDGE. The gel property of the crosslinked HA-BDDGE has been investigated by swelling study in distilled water at 37 °C. The HA-BDDGE gel releases DMOG in a controlled way for up to seven days in water at 37 °C. The synthesized gel is biocompatible and the bolus drug delivery results indicated that the DMOG containing patterned gel demonstrates a better cell migration ability on the surface than NaB. For local delivery, the pattern gel with 300 µM NaB or 300 µM DMOG induced cell clusters formation, and the gel with 150 µM NaB/DMOG showed high cell proliferation capability only. The vital role of NaB for bone regeneration has been endorsed from the formation of cell clusters in presence of NaB in the media. The in vitro results indicated that the pattern gel showed angiogenic and osteogenic responses with good ALP activity and enhanced HIF-1α, and Runx2 levels in the presence of DMOG and NaB in MC3T3 cells. Hence, the HA-BDDGE gel could be used in bone regeneration application.

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