Osseointegration of Antimicrobial Acrylic Bone Cements Modified with Graphene Oxide and Chitosan

Abstract

Acrylic bone cement (ABC) is one of the most used materials in orthopedic surgery, mainly for the fixation of orthopedic implants to the bone. However, ABCs usually present lack of biological activity and osseointegration capacity that leads to loosening of the prosthesis. This work reports the effect of introducing graphene oxide (GO) and chitosan (CS), separately or together, in the ABC formulation on setting performance, mechanical behavior, and biological properties. Introduction of both CS and GO to the ABC decreased the maximum temperature by 21% and increased the antibacterial activity against Escherichia coli by 87%, while introduction of only CS decreased bending strength by 32%. The results of cell viability and cell adhesion tests showed in vitro biocompatibility. The in vivo response was investigated using both subdermal and bone parietal implantations in Wistar rats. Modified ABCs showed absence of immune response, as confirmed by a normal inflammatory response in Wistar rat subdermal implantation. The results of the parietal bone implantation showed that the addition of CS and GO together allowed a near total healing bone–cement interface, as observed in the micrographic analysis. The overall results support the great potential of the modified ABCs for application in orthopedic surgery mainly in those cases where osseointegration is required.

The Role of Chitosan and Graphene Oxide in Bioactive and Antibacterial Properties of Acrylic Bone Cements

“…Additionally, the implantation in Wistar rats' parietal bone showed an increase in the cement's osseointegration with CS. This osseointegration was higher when the formulation presented CS + GO, with which a near-total healing bone-cement interface was reached in the bone defect [101]. However, it was evidenced by the reduction in the mechanical properties and the increase in the residual monomer content.…”

“…Tunney et al [96] and Dunne et al [97] added between 1 and 5 wt.% of chitosan in the solid phase of the cement and found no antibacterial activity against S. epidermidis, S. aureus, and S. capitis. However, Valencia et al [101,109] and Shi et al [120] report antibacterial activity against S. aureus, S. Epidermidis, and E. coli of cements added with 15% d of CS.…”

“…Valencia et al [109] reported that GO's presence did not generate any cytotoxic effect in ABCs. The same group [101] implanted GO-loaded cement in the parietal bone of Wistar rats. They reported that GO improved the osseointegration of the cement since it accelerated the sealing process.…”

“…On the other hand, the GO provides mechanical reinforcement and does not present cytotoxicity in most reported investigations. The combination of both components, individually [101,109] or like a nanocomposite [102], has shown synergy in the biological and mechanical properties since there were increases in mechanical properties, up to 69%, and in viability, proliferation, and cellular adhesion of human osteoblasts and MG-63 cell culture in contact with these cements. Additionally, Wistar rats parietal bone implants for 3 months showed more excellent osseointegration in the cements that contained both loads.…”

Antibacterial Bio-Based Polymers for Cranio-Maxillofacial Regeneration Applications

“…Other authors have also used chitosan to induce porosity and roughness to the cement while incorporating additional elements to achieve the desired antibacterial properties. In this sense, Valencia Zapata et al combined both chitosan and graphene oxide nanoparticles into an acrylic bone cement, which supported good cell viability of human osteoblasts while having both antibacterial and osteogenic properties [97,98]. Similarly, De Mori et al, designed a complex PMMA-based cement which was loaded with silver nanowires to achieve antibacterial properties; chitosan to achieve porosity, reduce the maximum setting temperature, and maintain appropriate mechanical properties; and methacryloyl chitosan to promote cross-linking with MMA, reducing the quantity of the monomer to use [99].…”