Biomineral/Agarose Composite Gels Enhance Proliferation of Mesenchymal Stem Cells with Osteogenic Capability

Abstract

Hydroxyapatite (HA) or calcium carbonate (CaCO3) formed on an organic polymer of agarose gel is a biomaterial that can be used for bone tissue regeneration. However, in critical bone defects, the regeneration capability of these materials is limited. Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into bone forming osteoblasts. In this study, we loaded MSCs on HA- or CaCO3-formed agarose gel and cultured them with dexamethasone, which triggers the osteogenic differentiation of MSCs. High alkaline phosphatase activity was detected on both the HA- and CaCO3-formed agarose gels; however, basal activity was only detected on bare agarose gel. Bone-specific osteocalcin content was detected on CaCO3-formed agarose gel on Day 14 of culture, and levels subsequently increased over time. Similar osteocalcin content was detected on HA-formed agarose on Day 21 and levels increased on Day 28. In contrast, only small amounts of osteocalcin were found on bare agarose gel. Consequently, osteogenic capability of MSCs was enhanced on CaCO3-formed agarose at an early stage, and both HA- and CaCO3-formed agarose gels well supported the capability at a later stage. Therefore, MSCs loaded on either HA- or CaCO3-formed agarose could potentially be employed for the repair of critical bone defects.

Influence of photobiomodulation therapy on root development of rat molars with open apex and pulp necrosis

“…Agarose has already been used to regenerate osseous, cartilaginous, and neural tissues. 12,13,14 Furthermore, the final irrigation with 17% EDTA performed herein plays an important role. The EDTA solution induces the dentin to release growth factors that provide cell differentiation and expression of dentin sialoprotein (DSPP).…”

“…10 Nowadays, natural and synthetic scaffolds have been used in tissue engineering. 11,12 Among natural scaffolds, agarose gel presents favorable characteristics for transplantation procedures, for being bioinert and nontoxic, decreasing potential immune rejection in rats. 12,13,14 Photobiomodulation (PBM) therapy is a form of light therapy that utilizes non-ionizing light sources, including lasers, and promotes biostimulatory effects on different cell types, both in vitro and in vivo.…”

“…11,12 Among natural scaffolds, agarose gel presents favorable characteristics for transplantation procedures, for being bioinert and nontoxic, decreasing potential immune rejection in rats. 12,13,14 Photobiomodulation (PBM) therapy is a form of light therapy that utilizes non-ionizing light sources, including lasers, and promotes biostimulatory effects on different cell types, both in vitro and in vivo. 15,16,17,18 Thus, PBM stimulates cell growth, increases cell metabolism, improves cell regeneration, promotes tissue response, and accelerates dentin regeneration after pulp exposure.…”

Photobiomodulation therapy improves multilineage differentiation of dental pulp stem cells in three-dimensional culture model

“…32,36,37 Also, agarose has been considered a bioinert scaffold with nontoxic properties. 20 PBM is an emerging technique in which exposure to low-level laser light (red and near infrared radiation) or LEDs stimulates cellular function by the activation of mitochondrial respiratory chain components, resulting in initiation of a signaling cascade that promotes activation of some signaling circuitries resulting in increased cellular metabolism and proliferation. 21 Considering that PBM could allow a significant increase in viability, proliferation, migration, and differentiation of stem cells, the 3-D culture associated to its use may be a therapeutic opportunity in regenerative dentistry.…”

“…Among various 3-D culture models, the agarose gel (a polysaccharide of D-galactose and 3,6-anhydro-L-galactopyranose derived from the cell walls of red algae) presents favorable characteristics in relation to implantation: it is bioinert, nontoxic, and decreases the potential immune rejection in rats. 20 Another important aspect is the positive influence of cultures under nutritional deficit conditions in the response of hDPSCs to PBM, improving cell growth. 9 This happens because the nutritional deficit condition promotes an alteration of the redox state toward cell oxidation, and the cellular response to PBM is near optimal and stronger when potential redox is shifted.…”