Osteogenic and Immunomodulatory Effects of Novel Bone Adhesives for Use in Sternal Fixation

Median sternotomy is a procedure that involves cutting open the sternum longitudinally and is the most common method to access to the heart and surrounding valves for cardiothoracic surgery. Following the procedure, closure of the sternum with stainless steel wires remains the current standard of care. Despite the widespread use of this closure technique, post-operative complications pose life-threatening consequences. Sternal separation occurs in up to 8% of cases and results in a 40% mortality rate. Glass polyalkenoate cements (GPCs) are adhesives that have the potential to augment the mechanical union of the two sternal halves by wire cerclage. This dissertation relates to the biocompatibility testing of proprietary GPCs for use in sternal fixation and repair. The GPCs investigated are based on the same novel strontium and zinc containing bioactive glass (mole fraction: SiO2:0.48, ZnO:0.36, CaO:0.12, SrO:0.04). Two GPCs were formulated (GPCA and GPCB) and their effect on osteogenic differentiation and immunomodulation was assessed in vitro. Bone mineralization, collagen formation and alkaline phosphatase activity were found to be significantly elevated in response to GPCA’s dissolution products. However, all three osteogenic markers were inhibited when cultured with GPCA in direct and indirect culture set-ups. GPCB also reduced these markers in comparison to control cultures, but performed significantly better than GPCA. For immune studies, GPC dissolution products and GPC particles were tested for their ability to affect the secretion of cytokines peripheral blood mononuclear cells (PBMCs). Additionally, the size, shape and concentration of fragmented GPC particles were characterized. The results showed that GPCA ionic products had an anti-inflammatory effect, where they significantly reduced the secretion of TNF-α secreted from PBMCs stimulated with LPS. Conversely, the particles released from GPCA significantly stimulated the secretion TNF-α and IL-6 compared to control cultures. Overall, GPC B significantly outperformed GPC A and was selected for animal testing, where it was implanted subcutaneously in rats for 6 and 12 weeks. Polymethyl-methacrylate (PMMA) bone cement was used as a baseline control, and histological assessment revealed no adverse tissue reaction in response to GPCB. Additionally, relative expression of pro-inflammatory and osteogenic genes was assessed in the tissue surrounding implants and revealed no significant differences in expression between the GPC and control. It is concluded that GPCs based on the novel Sr/Zn glass system have varied biocompatibility which depends on the cement composition. Based on the obtained results, the formulated adhesive may offer optimal fixation for patients undergoing cardiac surgery and reduce post-operative complications.