Abstract

Titanium (Ti)-based alloys are widely used in tissue regeneration with advantages of improved biocompatibility, high mechanical strength, corrosion resistance, and cell attachment. To obtain bioactive bone–implant interfaces with enhanced osteogenic capacity, various methods have been developed to modify the surface physicochemical properties of bio-inert Ti and Ti alloys. Nano-structured hydroxyapatite (HA) formed by micro-arc oxidation (MAO) is a synthetic material, which could facilitate osteoconductivity, osteoinductivity, and angiogenesis on the Ti surface. In this paper, we applied MAO and steam–hydrothermal treatment (SHT) to produce HA-coated Ti, hereafter called Ti–M–H. The surface morphology of Ti–M–H1 was observed by scanning electron microscopy (SEM), and the element composition and the roughness of Ti–M–H1 were analyzed by energy-dispersive X-ray analysis, an X-ray diffractometer (XRD), and Bruker stylus profiler, demonstrating the deposition of nano-HA particles on Ti surfaces that were composed of Ca, P, Ti, and O. Then, the role of Ti–M–H in osteogenesis and angiogenesis in vitro was evaluated. The data illustrated that Ti–M–H1 showed a good compatibility with osteoblasts (OBs), which promoted adhesion, spreading, and proliferation. Additionally, the secretion of ALP, Col-1, and extracellular matrix mineralization was increased by OBs treated with Ti–M–H1. Ti–M–H1 could stimulate endothelial cells to secrete vascular endothelial growth factor and promote the formation of capillary-like networks. Next, it was revealed that Ti–M–H1 also suppressed inflammation by activating macrophages, while releasing multiple active factors to mediate osteogenesis and angiogenesis. Finally, in vivo results uncovered that Ti–M–H1 facilitated a higher bone-to-implant interface and was more attractive for the dendrites, which promoted osseointegration. In summary, MAO and SHT-treated Ti–M–H1 not only promotes in vitro osteogenesis and angiogenesis but also induces M2 macrophages to regulate the immune environment, which enhances the crosstalk between osteogenesis and angiogenesis and ultimately accelerates the process of osseointegration in vivo.

Highlights

  • Regeneration-related tissue engineering has been implicated in many aspects of tissue transplantation to regain the biological function of a tissue or entire organ (Wobma and VunjakNovakovic, 2016)

  • As the steam–hydrothermal treatment (SHT) time increased, the nano-particle size and roughness became larger with time extension; among them, the roughness of Ti–M–H8 was 2,050 nm, which was notably higher than that in other groups (Figure 1B)

  • The release of Ca ions on the surface of all samples was decreased with no significant difference in a time-dependent manner (Figure 1D)

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Summary

Introduction

Regeneration-related tissue engineering has been implicated in many aspects of tissue transplantation to regain the biological function of a tissue or entire organ (Wobma and VunjakNovakovic, 2016). Autografts are considered as the “gold standard” of bone transplantation, they do have some disadvantages, including potential donor site morbidity and vessel injuries, which constrain their application in clinics (Gulick and Yoder, 2002; Lavender et al, 2020). In recent decades, researchers have introduced biological or synthetic tissue engineering including, but not limited to, the use of bioactive scaffolds, growth factors, stem cells, and three-dimensional (3D) bioprinting to replace the three grafts mentioned above, which are applied to repair and regenerate bone tissues (Khademhosseini and Langer, 2016)

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