Bone grafts and biomaterials substitutes for bone defect repair: A review.

It is of great importance to develop multifunctional bioactive scaffolds, which combine angiogenesis capacity, osteostimulation, and antibacterial properties for regenerating lost bone tissues. In order to achieve this aim, we prepared copper (Cu)-containing mesoporous bioactive glass (Cu-MBG) scaffolds with interconnective large pores (several hundred micrometer) and well-ordered mesopore channels (around 5 nm). Both Cu-MBG scaffolds and their ionic extracts could stimulate hypoxia-inducible factor (HIF)-1a and vascular endothelial growth factor(VEGF) expression in human bone marrow stromal cells(hBMSCs). In addition, both Cu-MBG scaffolds and their ionic extracts significantly promoted the osteogenic differentiation of hBMSCs by improving their bone-related gene expression (alkaline phosphatase (ALP), osteopontin(OPN) and osteocalcin (OCN)). Furthermore, Cu-MBG scaffolds could maintain a sustained release of ibuprofen and significantly inhibited the viability of bacteria. This study indicates that the incorporation of Cu2þ ions into MBG scaffolds significantly enhances hypoxia-like tissue reaction leading to the coupling of angiogenesis and osteogenesis. Cu2þ ions play an important role to offer the multifunctional properties of MBG scaffold system. This study has demonstrated that it is possible to develop multifunctional scaffolds by combining enhanced angiogenesis potential, osteostimulation, and antibacterial properties for the treatment of large bone defects.

Copper-containing mesoporous bioactive glass scaffolds with multifunctional properties of angiogenesis capacity, osteostimulation and antibacterial activity

Bioinorganics and biomaterials: bone repair.

It is expected that the projected increased usage of implantable devices in medicine will result in a natural rise in the number of infections related to these cases. Some patients are unable to autonomously prevent formation of biofilm on implant surfaces. Suppression of the local peri-implant immune response is an important contributory factor. Substantial avascular scar tissue encountered during revision joint replacement surgery places these cases at an especially high risk of periprosthetic joint infection. A critical pathogenic event in the process of biofilm formation is bacterial adhesion. Prevention of biomaterial-associated infections should be concurrently focused on at least two targets: inhibition of biofilm formation and minimizing local immune response suppression. Current knowledge of antimicrobial surface treatments suitable for prevention of prosthetic joint infection is reviewed. Several surface treatment modalities have been proposed. Minimizing bacterial adhesion, biofilm formation inhibition, and bactericidal approaches are discussed. The ultimate anti-infective surface should be “smart” and responsive to even the lowest bacterial load. While research in this field is promising, there appears to be a great discrepancy between proposed and clinically implemented strategies, and there is urgent need for translational science focusing on this topic.

https://www.mdpi.com/1422-0067/15/8/13849/pdf

Antibacterial Surface Treatment for Orthopaedic Implants

Antibacterial metals and alloys for potential biomedical implants.

A dual function of copper in designing regenerative implants

Current strategies in implant technology are directed to generate bioactive implants that are capable to activate the regenerative potential of the surrounding tissue. On the other hand, implant-re...

Antimicrobial and bone-forming activity of a copper coated implant in a rabbit model.

Copper (Cu) based coatings can reduce infections for titanium (Ti) implants. However, Cu is also cytotoxic. To examine the balance of antibacterial versus adverse tissue effects, this study aimed at evaluating a Cu coating regarding in vivo Cu release and local inflammatory reactions for 72 h. TiAl6V4 plates received either plasma electrolytic oxidation only (Ti), or an additional galvanic Cu deposition (Ti-Cu). No Staphylococcus aureus were found in vitro on Ti-Cu after 24 h. Following simultaneous intramuscular implantation of two Ti and two Ti-Cu plates into nine rats, serum Cu was elevated until 48 h and residual Cu on explanted samples reduced accordingly after 48 h. Total and tissue macrophages around implants increased until 72 h for both series, and were increased for Ti-Cu. As numbers of total and tissue macrophages were comparable, macrophages were probably tissue-derived. MHC-class-II-positive cells increased for Ti-Cu only. T-lymphocytes had considerably lower numbers than macrophages, did not increase or differ between both series, and thus had minor importance. Tissue reactions increased beyond Cu release, indicating effects of either surface-bound Cu or more likely the implants themselves. Altogether, Ti-Cu samples possessed antibacterial effectiveness in vitro, released measurable Cu amounts in vivo and caused a moderately increased local inflammatory response, demonstrating anti-infective potential of Cu coatings.

https://iopscience.iop.org/article/10.1088/1748-6041/8/3/035009/pdf

In vivo evaluation of copper release and acute local tissue reactions after implantation of copper-coated titanium implants in rats.

To stimulate bone regeneration, the design of bioactive implants is a great challenge in current orthopedic research. We reasoned that implants should be suitable both to stimulate osteogenic differentiation of mesenchymal stem cells and prevent infections at the site of implantation. Therefore, we focus on copper ions, which are known to exert antimicrobial effects. On the other hand, copper is essential for the cell physiology, including the formation of the extracellular matrix. We studied the influence of copper ions on mesenchymal stem cells at various concentrations and identified the limits of copper concentrations for cell survival. Below the critical concentration for cell survival we analysed proliferation and osteogenic differentiation of the cells in the presence of copper ions. We found that copper stimulated the proliferation of the mesemchymal stem cells at 0.1 mM. Osteogenic differentiation decreased after 14 days at a concentration of 0.05 - 0.1 mM copper ions in osteogenic medium measured by the expression of osteogenic proteins, like alkaline phosphatase (ALP), bone sialoprotein (BSP) and collagen I (COL). We argue that at the implant surface a higher concentration of copper could prevent biofilm formation of bacteria and physiological concentrations in the vicinity of the implant would stimulate stem cell expansion. Together, copper is an interesting agent to control both bacteria and stem cells in the field of implant technology.

A Dual Role of Copper on the Surface of Bone Implants

The invention relates to a method for producing an anti-infective coating on implants that contain titanium or are composed of titanium. The aim of the invention is to provide a coating method with which it is possible, for implants made of titanium or that contain titanium, to combine the optimization of the mechanical properties achieved with the anodic oxidation type II with the optimization of the anti-infective properties. According to the invention, the implants are anodically oxidized in an alkaline solution, then metal having anti-infective properties is electrodeposited on said surface, and afterwards the oxide layer containing metal is solidified.

Cornelia Prinz

Papers

A dual function of copper in designing regenerative implants

Antimicrobial and bone-forming activity of a copper coated implant in a rabbit model.

In vivo evaluation of copper release and acute local tissue reactions after implantation of copper-coated titanium implants in rats.

A Dual Role of Copper on the Surface of Bone Implants

Method for producing an anti-infective coating on implants