Osteogenic enhancement of modular ceramic nanocomposites impregnated with human dental pulp stem cells: an approach for bone repair and regenerative medicine

Abstract

Abstract Background/aim Human dental pulp-derived mesenchymal stem cells (hDP-MSCs) are a promising source of progenitor cells for bone tissue engineering. Nanocomposites made of calcium phosphate especially hydroxyapatite (HA) offer an impressive solution for orthopedic and dental implants. The combination of hDP-MSCs and ceramic nanocomposites has a promising therapeutic potential in regenerative medicine. Despite the calcium phosphate hydroxyapatite (HA)-based nanocomposites offer a good solution for orthopedic and dental implants, the heavy load-bearing clinical applications require higher mechanical strength, which is not of the HA’ properties that have low mechanical strength. Herein, the outcomes of using fabricated ceramic nanocomposites of hydroxyapatite/titania/calcium silicate mixed at different ratios (C1, C2, and C3) and impregnated with hDP-MSCs both in in vitro cultures and rabbit model of induced tibial bone defect were investigated. Our aim is to find out a new approach that would largely enhance the osteogenic differentiation of hDP-MSCs and has a therapeutic potential in bone regeneration. Subjects and methods Human DP-MSCs were isolated from the dental pulp of the third molar and cultured in vitro. Alizarin Red staining was performed at different time points to assess the osteogenic differentiation. Flow cytometer was used to quantify the expression of hDP-MSCs unique surface markers. Rabbits were used as animal models to evaluate the therapeutic potential of osteogenically differentiated hDP-MSCs impregnated with ceramic nanocomposites of hydroxyapatite/tatiana/calcium silicate (C1, C2, and C3). Histopathological examination and scanning electron microscopy (SEM) were performed to evaluate bone healing potential in the rabbit induced tibial defects three weeks post-transplantation. Results The hDP-MSCs showed high proliferative and osteogenic potential in vitro culture. Their osteogenic differentiation was accelerated by the ceramic nanocomposites’ scaffold and revealed bone defect’s healing in transplanted rabbit groups compared to control groups. Histopathological and SEM analysis of the transplanted hDP-MSCs/ceramic nanocomposites showed the formation of new bone filling in the defect area 3 weeks post-implantation. Accelerate osseointegration and enhancement of the bone-bonding ability of the prepared nanocomposites were also confirmed by SEM. Conclusions The results strongly suggested that ceramic nanocomposites of hydroxyapatite/ titania /calcium silicate (C1, C2, and C3) associated with hDP-MSCs have a therapeutic potential in bone healing in a rabbit model. Hence, the combined osteogenic system presented here is recommended for application in bone tissue engineering and regenerative medicine.

Keywords

• Human dental pulp stem cells
• hDP-MSCs
• Osteogenic differentiation
• Ceramic nanocomposites
• Bioactivity
• Biocompatibility