Assessing the osseointegration potential of a strontium releasing nanostructured titanium oxide surface: A biomechanical study in the rabbit tibia plateau model.

OBJECTIVES To investigate the impact of a Ti-Sr-O technology, applied to either a turned surface or an SLA surface, on the mechanical robustness of osseointegration, benchmarked against the SLActive surface. MATERIAL AND METHODS Ti discs (6.25-mm-diameter and 2-mm-thick) with three different surfaces were inserted on the proximal-anterior part of the tibial plateau of adult Swedish loop rabbits: (I) turned surface modified with Ti-Sr-O (turned + Ti-Sr-O), (II) SLA surface modified with Ti-Sr-O (SLA + Ti-Sr-O), and (III) SLActive surface (SLActive). Following a healing period of 2 weeks and 4 weeks, the pull-out (PO) force needed to detach the discs from the bone was assessed, as a surrogate of osseointegration. RESULTS The SLActive surface exhibited statistically significant higher median PO forces, compared with the SLA + Ti-Sr-O surfaces at both 2- and 4 weeks post-op (p > .05). In this study, no single turned + Ti-Sr-O surface disk was integrated. CONCLUSIONS The tested Ti-Sr-O technology failed to enhance osseointegration; however, this finding may be related to the inappropriateness of the rabbit tibia plateau model for assessing third-generation implant surface technologies, due to the limited diffusion and clearance at the disk-bone interface

Tourniquets do not increase the total blood loss or re-amputation risk in transtibial amputations

AIM: To investigate the total blood loss (TBL) and the safety with respect to the re-amputation rate after transtibial amputation (TTA) conducted with and without a tourniquet. METHODS: The study was a single-centre retrospective cohort study of patients with a primary TTA admitted between January 2013 and April 2015. All patients with a primary TTA were assessed for inclusion if the amputation was performed because of arteriosclerosis or diabetic complications. All patients underwent a standardized TTA procedure that was performed approximately 10 cm below the knee joint and performed with sagittal flaps. The pneumatic tourniquet, when used, was inflated around the femur to a pressure of 100 mmHg above the systolic blood pressure. The number of blood transfusions within the first four postoperative days was recorded. The intraoperative blood loss (OBL), which is defined as the volume of blood lost during surgery, was determined from the suction volume and by the weight difference of the surgical dressings. The trigger for a blood transfusion was set at a decrease in the Hgb level < 9.67 g/dL (6 mmol/L). Transfusions were performed with pooled red blood cells containing 245 mL per portion, which equals 55 g/L of haemoglobin. The TBL during the first four postoperative days was calculated based on the haemoglobin level and the estimated blood volume. The re-amputation rate was evaluated within 30 d. RESULTS: Seventy-four out of 86 consecutive patients who underwent TTA within the two-year study period were included in the analysis. Of these, 38 were operated on using a tourniquet and 36 were operated on without using a tourniquet. There were no significant preoperative differences between the groups. The patients in both groups had a postoperative decrease in their Hgb level compared with preoperative baseline values. The patients operated on using a tourniquet received approximately three millilitres less blood transfusion per kilogram body weight compared with patients operated on without a tourniquet. The duration of surgery was shorter and the OBL was less for the tourniquet group than the non-tourniquet group, whereas no significant difference was observed for the TBL. The TBL median was 859 mL (IQR: 383-1315) in the non-tourniquet group vs 737 mL (IQR: 331-1218) in the tourniquet group (P = 0.754). Within the 30-d follow-up period, 9 patients in the tourniquet group and 11 in the non-tourniquet group underwent a re-amputation at the trans-femoral level. The use of a tourniquet showed no statistically significant association with the 30-d re-amputation at the femur level in the multiple logistic regression model (P = 0.78). The only variable with a significant association with re-amputation was age (OR = 1.07; P = 0.02). CONCLUSION: The results indicate that tourniquets do not cause severe vascular damage with an increased postoperative bleeding or failure rate as the result

A Modular Albumin-Oligonucleotide Biomolecular Assembly for Delivery of Antisense Therapeutics

Antisense nucleic acid drugs are susceptible to nuclease degradation, rapid renal clearance, and short circulatory half-life. In this work, we introduce a modular-based recombinant human albumin-oligonucleotide (rHA-cODN) biomolecular assembly that allows incorporation of a chemically stabilized therapeutic gapmer antisense oligonucleotide (ASO) and FcRn-driven endothelial cellular recycling. A phosphodiester ODN linker (cODN) was conjugated to recombinant human albumin (rHA) using maleimide chemistry, after which a complementary gapmer ASO, targeting ADAMTS5 involved in osteoarthritis pathogenesis, was annealed. The rHA-cODN/ASO biomolecular assembly production, fluorescence labeling, and purity were confirmed using polyacrylamide gel electrophoresis. ASO release was triggered by DNase-mediated degradation of the linker strand, reaching 40% in serum after 72 h, with complete release observed following 30 min of incubation with DNase. Cellular internalization and trafficking of the biomolecular assembly using confocal microscopy in C28/I2 cells showed higher uptake and endosomal localization by increasing incubation time from 4 to 24 h. FcRn-mediated cellular recycling of the assembly was demonstrated in FcRn-expressing human microvascular endothelial cells. ADAMTS5 in vitro silencing efficiency reached 40%, which was comparable to free gapmer after 72 h incubation with human osteoarthritis patients’ chondrocytes. This work introduces a versatile biomolecular modular-based “Plug-and-Play” platform potentially applicable for albumin-mediated half-life extension for a range of different types of ODN therapeutics