Additive Manufacturing of Caffeic Acid-Inspired Mineral Trioxide Aggregate/Poly-ε-Caprolactone Scaffold for Regulating Vascular Induction and Osteogenic Regeneration of Dental Pulp Stem Cells.

Ni Tien,Jian-Xun Chen,Ting-You Kuo,Yen-Hong Lin,Alvin Kai-Xing Lee,Ming-You Shie,Jian-Jr Lee

doi:10.3390/cells10112911

Ni Tien, Jian-Xun Chen + Show 5 more

Open Access

https://doi.org/10.3390/cells10112911

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Abstract

Mineral trioxide aggregate (MTA) is a common biomaterial used in endodontics regeneration due to its antibacterial properties, good biocompatibility and high bioactivity. Surface modification technology allows us to endow biomaterials with the necessary biological targets for activation of specific downstream functions such as promoting angiogenesis and osteogenesis. In this study, we used caffeic acid (CA)-coated MTA/polycaprolactone (PCL) composites and fabricated 3D scaffolds to evaluate the influence on the physicochemical and biological aspects of CA-coated MTA scaffolds. As seen from the results, modification of CA does not change the original structural characteristics of MTA, thus allowing us to retain the properties of MTA. CA-coated MTA scaffolds were shown to have 25% to 55% higher results than bare scaffold. In addition, CA-coated MTA scaffolds were able to significantly adsorb more vascular endothelial growth factors (p < 0.05) secreted from human dental pulp stem cells (hDPSCs). More importantly, CA-coated MTA scaffolds not only promoted the adhesion and proliferation behaviors of hDPSCs, but also enhanced angiogenesis and osteogenesis. Finally, CA-coated MTA scaffolds led to enhanced subsequent in vivo bone regeneration of the femur of rabbits, which was confirmed using micro-computed tomography and histological staining. Taken together, CA can be used as a potently functional bioactive coating for various scaffolds in bone tissue engineering and other biomedical applications in the future.

Highlights

Mineral trioxide aggregate (MTA) was first introduced in the 1990s as ProRoot MTA and soon became a revolutionary material in endodontics [1]
Our results demonstrated that the caffeic acid (CA) modifications were able to enhance expressions of vascular endothelial growth factors (VEGF) and Ang-1 and allowed for increased adhesions of VEGF and Ang-1 onto surfaces of the scaffolds, having the potential to lead to enhanced odontogenesis
The CA20 scaffold showed good results in mechanical strength and found apatite precipitate immersed in simulated body fluid (SBF), which indicated the preferred physical and chemical microenvironment for human dental pulp stem cells (hDPSCs) behaviors

Summary

Introduction

Mineral trioxide aggregate (MTA) was first introduced in the 1990s as ProRoot MTA and soon became a revolutionary material in endodontics [1]. The composition of MTA is a calcium silicate-based bioactive ceramics, mainly composed of dicalcium silicate, tricalcium silicate, bismuth oxide, and silicon dioxide [2]. ProRoot MTA was a mixture of bismuth oxide and cement, where the cement has an important role to play in ensuring success of the MTA. MTA was reported to have antimicrobial characteristics, and high biocompatibility and bioactivity due to its capability to deposit hydroxyapatite layers on its surface [1]. The hydroxyapatite layer is an important interface between the MTA and the tooth which enhances biomineralization and tissue regeneration. MTA contains calcium oxide which converts to calcium hydroxide when in contact with humidity, creating a strong alkaline microbacterial environment ideal for tissue regeneration [8]

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