Applications of Metals for Bone Regeneration

Abstract

The regeneration of bone tissue is a main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, while it should be resorbed even in the time frame needed for complete regeneration up to the condition of restitution ad integrum. In this context, the modes of action of CaP-based substitute materials have been frequently investigated and it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also on osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between the formation of new bone tissue and material degradation has not been found until now. The addition of different substances such as collagen or growth factors and also of different cell types have already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are differently used as basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designated for bone regeneration with the aim to give an overview of currently existing knowledge about the effects of metals in the field of bone regeneration.

Molecular mechanisms of osteogenesis and antibacterial activity of Cu-bearing Ti alloy in a bone defect model with infection in vivo

“…Our study revealed that new bone was bound to Ti6Al4V-6.5wt%Cu alloy more tightly than to Ti6Al4V alloy, indicating that Ti6Al4V-6.5wt%Cu alloy has better biocompatibility. Studies have shown that copper ions significantly promote osteogenic differentiation of hBMSCs by improving expression of bone-related genes like alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) [ [26] , [27] , [28] ]. Our immunohistochemical staining showed that the expression of osteogenic proteins in bone tissue around the infected bone defects filled with Ti6Al4V-6.5wt%Cu alloy was significantly higher than that filled with Ti6Al4V alloy.…”

An introduction to bone tissue engineering

“…68 The release of metallic ions could also be beneficial for the regeneration of bone as many metallic ions are important for the proper function of the body. 69…”

Challenges in Bone Tissue Regeneration: Stem Cell Therapy, Biofunctionality and Antimicrobial Properties of Novel Materials and Its Evolution

“…Both options can result in complications such as allergic reactions or secondary fractures [ 67 , 68 ]. Another approach uses the functional role of metal ions in the physiological and cellular environment to induce cell proliferation or osteogenic differentiation [ 54 ]. Based on the suggested approach, D’Mello et al [ 55 ] observed bone healing of calvarial defects in rats using copper-loaded chitosan scaffolds.…”

“…Recent research has focused more on the creation of biodegradable materials such as magnesium alloys, ceramics and polymers. Improvements have been achieved by modifying the materials, for example with nanoparticles to increase antibiotic effects [ 70 , 71 , 72 ] or cell functionality [ 73 , 121 , 194 ], with metal ions to take advantage of their functional role in the physiological and cellular environment [ 54 , 55 , 56 ] or with proteins or RNAs to induce osteosynthesis [ 16 , 17 , 18 , 19 , 20 ]. The use of magnesium alloys shows promising potential as a bone graft substitute [ 65 , 195 ], not only because of its mechanical properties but also because of its physiological ability to induce the migration of osteoblasts to the implantation site as they migrate to environments of high Mg ion concentrations [ 56 ].…”

“…Biodegradable metal scaffolds made from magnesium alloys have shown promising results in bone regeneration and have recently attracted more attention [ 50 , 51 , 52 , 53 ]. Metal ions are used in the modification or supplementation of scaffolds to improve their regenerative or antimicrobial abilities as they have regulatory effects in cells [ 54 , 55 , 56 ]. Ceramics were seen as the most promising candidate because of their chemical similarities to natural bone [ 14 , 57 ].…”