Microfiber-Reinforced Composite Hydrogels Loaded with Rat Adipose-Derived Stem Cells and BMP-2 for the Treatment of Medication-Related Osteonecrosis of the Jaw in a Rat Model.

Severe adverse reactions of bisphosphonates and anti-resorptive or anti-angiogenic medications, termed medication-related osteonecrosis of the jaw (MRONJ), have been reported. MRONJ are difficult to completely cure and could cause great pain to patients. Recent studies have shown that mesenchymal stem cell (MSC) therapies are effective for treating MRONJ, but the method of intravenous injection is unstable and increases the risk of producing tumors. In the present study, low-acyl gellan gum (LAGG) hydrogels were modified with hemicellulose polysaccharide microfibers (PMs) to improve the performance of supporting three-dimensional (3D) cell growth. LAGG-PM composite hydrogels were found to be nontoxic to rat adipose-derived stem cells (rADSCs) in vitro. The hydrogels also promoted the secretion of angiogenic factors, induced osteoclastogenesis by conditioned medium, and supported osteogenic marker expression after the addition of human bone morphogenetic protein-2 (BMP-2). Due to its injectability, the LAGG-PM composite hydrogel incorporated with rADSCs and BMP-2 could be applied into the MRONJ lesion site, which promoted mucosal recovery, bone tissue reconstruction, and osteoclastogenesis. This study confirms the potential applications of LAGG-PM composite hydrogels as 3D cell culture platforms and delivery vehicles for the treatment of MRONJ in a rat model.