Osteogenic and Immunomodulatory Effects of Novel Bone Adhesives for Use in Sternal Fixation
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".