Development of hydrogel scaffold containing the flavonoid naringenin to modulate peri-implant tissue repair: an in vitro study

Abstract

The success of osseointegrated dental implants installation depends on an effective anchorage of these components to the maxillary bone tissue and on the deposition and mineralization of the extracellular matrix (ECM) around them. These events are related to bone tissue cells metabolism to the implant surface, as well as the responsiveness of these cells to an inflammatory stimulus. The incidence of failures in the installation of osseointegrated implants in the oral cavity may be related to the increased expression of matrix metalloproteinases (MMPs) enzymes, which remodel the peri-implant tissue; however, their overexpression could enhance ECM degradation, delaying or hampering the repair process. MMPs are endogenously controlled by tissue inhibitors of metalloproteinases (TIMPs) proteins. The balance between the synthesis of MMPs and TIMPs ensures tissue homeostasis and the process of tissue repair and remodeling. Therefore, it is necessary the development of adjuvant therapies that can favor the peri-implant tissue repair. Among different strategies for this purpose, the use of flavonoids has shown anti-inflammatory, antioxidant, and MMPs inhibition potential, positively modulating different functions of several types of cells. Naringenin (NA) citrus flavonoid has been investigated regarding its therapeutic effects on bone, such as bone defects repair; thus, this study aimed to develop a gelatin methacryloyl (GelMA) hydrogel scaffold containing NA to improve osteoblast (Ob) metabolism and MMPs/TIMPs regulation, using in vitro model. GelMA hydrogel scaffold will be fabricated and characterized by its morphology, adsorption, and NA release. NA cytocompatible concentration will be defined by the evaluation of cell viability rate and for this purpose, Ob will be seeded on GelMA hydrogel containing two different concentrations of NA. Then, GelMA hydrogel containing or not NA (in a concentration previously defined) will be individually placed in cell culture plates and Ob will be cultured on them. Next, cells will be stimulated or not with tumor necrosis factor alpha (TNF-±). The effects of the hydrogel on Ob proliferation, spreading, alkaline phosphatase (ALP) activity, mineralized matrix deposition, and MMPs and TIMPs synthesis will be assessed. The data obtained will be statistically analyzed considering their distribution and homoscedasticity characteristics. (AU)