The ability of the body to constantly maintain metabolism homeostasis while fulling the heightened energy and macromolecule demand is crucial to ensure successful tissue healing outcomes. Studies investigating the local metabolic environment during healing are scarce to date. Here, using Type 2 Diabetes (T2D) as a study model, we investigate the impact of metabolism dysregulation on scaffold-guided large-volume bone regeneration. Our study treated wild-type or T2D rats with 5 mm critical-sized femoral defects with 3D-printed polycaprolactone (PCL) scaffolds with 70% porosity. Metabolomics was leveraged for a holistic view of metabolism alteration as healing progress and correlated to regenerated bone tissue volume and quality assessed using micro-computed tomography (µ-CT), histology, and immunohistology. Semi-targeted metabolomics analysis indicated dysregulation in the glycolysis and TCA cycle – the main energy production pathways, in T2D compared to healthy animals. The abundance of metabolites substrates, i.e., amino acids – for protein/ extracellular matrix synthesis was also affected in T2D. Tissue-level metabolites observations aligned with morphological observation with less newly formed bone observed in T2D than wild-type rats. This study enlightens the metabolism landscape during scaffold-guided large-volume bone regeneration in wild-type vs. T2D to further guide the personalization of the scaffold to drive successful regeneration.

We report a retrospective study of the major complications following one-stage and two-stage bilateral unicompartmental knee replacements (UKR). Between 1999 and 2008, 911 patients underwent 1150 UKRs through a minimally- invasive approach in our unit. Of these, 159 patients (318 UKRs) had one-stage bilateral UKR and 80 patients (160 UKRs) had two-stage bilateral UKRs. The remainder were unilateral UKRs.

The bilateral UKR groups were comparable in age and ASA grade, but more females were in the two-staged group (p=0.019). Mechanical thromboprophylaxis was used in all cases. Major complications were recorded as death, pulmonary embolus, proximal deep vein thrombosis (DVT) and adverse cardiac events within 30 days of surgery.

No statistical differences between the groups were found regarding operating surgeon, tourniquet time or minor complications (excepting distal DVT). Anaesthetic times were greater for the two-stage group (p= 0.0001). Major complications were significantly more common with one-stage bilateral UKR (13 patients, 8.2%) compared to two-stage bilateral UKR (no patients) (p=0.005). Distal DVT was more frequent in the two-stage group (p=0.036).

This series reports significantly higher risks of major complications are associated with one-stage bilateral UKR when compared to two-stage bilateral UKR. There is no evidence that the addition of chemical thrombo-prophylaxis would change this risk. We advocate caution before undertaking a one-stage bilateral UKR.