skip to main content


Title: Biodegradable Mg-Sc-Sr Alloy Improves Osteogenesis and Angiogenesis to Accelerate Bone Defect Restoration
Magnesium (Mg) and its alloys are considered to be biodegradable metallic biomaterials for potential orthopedic implants. While the osteogenic properties of Mg alloys have been widely studied, few reports focused on developing a bifunctional Mg implant with osteogenic and angiogenic properties. Herein, a Mg-Sc-Sr alloy was developed, and this alloy’s angiogenesis and osteogenesis effects were evaluated in vitro for the first time. X-ray Fluorescence (XRF), X-ray diffraction (XRD), and metallography images were used to evaluate the microstructure of the developed Mg-Sc-Sr alloy. Human umbilical vein/vascular endothelial cells (HUVECs) were used to evaluate the angiogenic character of the prepared Mg-Sc-Sr alloy. A mix of human bone-marrow-derived mesenchymal stromal cells (hBM-MSCs) and HUVEC cell cultures were used to assess the osteogenesis-stimulating effect of Mg-Sc-Sr alloy through alkaline phosphatase (ALP) and Von Kossa staining. Higher ALP activity and the number of calcified nodules (27% increase) were obtained for the Mg-Sc-Sr-treated groups compared to Mg-treated groups. In addition, higher VEGF expression (45.5% increase), tube length (80.8% increase), and number of meshes (37.9% increase) were observed. The Mg-Sc-Sr alloy showed significantly higher angiogenesis and osteogenic differentiation than pure Mg and the control group, suggesting such a composition as a promising candidate in bone implants.  more » « less
Award ID(s):
2142610
NSF-PAR ID:
10394211
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Journal of Functional Biomaterials
Volume:
13
Issue:
4
ISSN:
2079-4983
Page Range / eLocation ID:
261
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    The aim of this study was to develop a novel biodegradable magnesium (Mg) alloy for bone implant applications. We used scandium (Sc; 2 wt %) and strontium (Sr; 2 wt %) as alloying elements due to their high biocompatibility, antibacterial efficacy, osteogenesis, and protective effects against corrosion. In the present work, we also examined the effect of a heat treatment process on the properties of the Mg‐Sc‐Sr alloy. Alloys were manufactured using a metal casting process followed by heat treatment. The microstructure, corrosion, mechanical properties, antibacterial activity, and osteogenic activity of the alloy were assessed in vitro. The results showed that the incorporation of Sc and Sr elements controlled the corrosion, reduced the hydrogen generation, and enhanced mechanical properties. Furthermore, alloying with Sc and Sr demonstrated a significantly enhanced antibacterial activity and decreased biofilm formation compared to control Mg. Also, culturing Mg‐Sc‐Sr alloy with human bone marrow‐derived mesenchymal stromal cells showed a high degree of biocompatibility (>90% live cells) and a significant increase in osteoblastic differentiation in vitro shown by Alizarin red staining and alkaline phosphatase activity. Based on these results, the Mg‐Sc‐Sr alloy heat‐treated at 400°C displayed optimal mechanical properties, corrosion rate, antibacterial efficacy, and osteoinductivity. These characteristics make the Mg‐Sc‐Sr alloy a promising candidate for biodegradable orthopedic implants in the fixation of bone fractures such as bone plate‐screws or intramedullary nails.

     
    more » « less
  2. Magnesium (Mg) alloys are being investigated as a biodegradable metallic biomaterial because of their mechanical property profile, which is similar to the human bone. However, implants based on Mg alloys are corroded quickly in the body before the bone fracture is fully healed. Therefore, we aimed to reduce the corrosion rate of Mg using a double protective layer. We used a magnesium-aluminum-zinc alloy (AZ91) and treated its surface with micro-arc oxidation (MAO) technique to first form an intermediate layer. Next, a bioceramic nanocomposite composed of diopside, bredigite, and fluoridated hydroxyapatite (FHA) was coated on the surface of MAO treated AZ91 using the electrophoretic deposition (EPD) technique. Our in vivo results showed a significant enhancement in the bioactivity of the nanocomposite coated AZ91 implant compared to the uncoated control implant. Implantation of the uncoated AZ91 caused a significant release of hydrogen bubbles around the implant, which was reduced when the nanocomposite coated implants were used. Using histology, this reduction in the corrosion rate of the coated implants resulted in an improved new bone formation and reduced inflammation in the interface of the implants and the surrounding tissue. Hence, our strategy using a MAO/EPD of a bioceramic nanocomposite coating (i.e., diopside-bredigite-FHA) can significantly reduce the corrosion rate and improve the bioactivity of the biodegradable AZ91 Mg implant. 
    more » « less
  3. The demand for bone substitutes is increasing in Western countries. Bone graft substitutes aim to provide reconstructive surgeons with off-the-shelf alternatives to the natural bone taken from humans or animal species. Under the tissue engineering paradigm, biomaterial scaffolds can be designed by incorporating bone stem cells to decrease the disadvantages of traditional tissue grafts. However, the effective clinical application of tissue-engineered bone is limited by insufficient neovascularization. As bone is a highly vascularized tissue, new strategies to promote both osteogenesis and vasculogenesis within the scaffolds need to be considered for a successful regeneration. It has been demonstrated that bone and blood vases are piezoelectric, namely, electric signals are locally produced upon mechanical stimulation of these tissues. The specific effects of electric charge generation on different cells are not fully understood, but a substantial amount of evidence has suggested their functional and physiological roles. This review summarizes the special contribution of piezoelectricity as a stimulatory signal for bone and vascular tissue regeneration, including osteogenesis, angiogenesis, vascular repair, and tissue engineering, by considering different stem cell sources entailed with osteogenic and angiogenic potential, aimed at collecting the key findings that may enable the development of successful vascularized bone replacements useful in orthopedic and otologic surgery. 
    more » « less
  4. In this study, lithographic ceramic manufacturing was used to create solid chips out of hydroxyapatite, tricalcium phosphate, zirconia, alumina, and SiAlON ceramic. X-ray powder diffraction of each material confirmed that the chips were crystalline, with little amorphous character that could result from remaining polymeric binder, and were composed entirely out of the ceramic feedstock. Surface morphologies and roughnesses were characterized using atomic force microscopy. Human bone marrow stem cells cultured with osteogenic supplements on each material type expressed alkaline phosphatase levels, an early marker of osteogenic differentiation, on par with cells cultured on a glass control. However, cells cultured on the tricalcium phosphate-containing material expressed lower levels of ALP suggesting that osteoinduction was impaired on this material. Further analyses should be conducted with these materials to identify underlying issues of the combination of material and analysis method. 
    more » « less
  5. Engineering bone tissue requires the generation of a highly organized vasculature. Cellular behavior is affected by the respective niche. Directing cellular behavior and differentiation for creating mineralized regions surrounded by vasculature can be achieved by controlling the pattern of osteogenic and angiogenic niches. This manuscript reports on engineering vascularized bone tissues by incorporating osteogenic and angiogenic cell‐laden niches in a photocrosslinkable hydrogel construct. Two‐step photolithography process is used to control the stiffness of the hydrogel and distribution of cells in the patterned hydrogel. In addittion, osteoinductive nanoparticles are utilized to induce osteogenesis. The size of microfabricated constructs has a pronounced effect on cellular organization and function. It is shown that the simultaneous presence of both osteogenic and angiogenic niches in one construct results in formation of mineralized regions surrounded by organized vasculature. In addition, the presence of angiogenic niche improves bone formation. This approach can be used for engineered constructs that can be used for treatment of bone defects.

     
    more » « less