Objectives To determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery, and to determine whether the inotropes, adrenaline and dopexamine, used to enhance oxygen delivery influence outcome. Design Randomised controlled trial with double blinding between inotrope groups. Setting York District Hospital, England. Subjects 138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions. Interventions Patients were randomised into three groups. Two groups received invasive haemodynamic monitoring, fluid, and either adrenaline or dopexamine to increase oxygen delivery. Inotropic support was continued during surgery and for at least 12 hours afterwards. The third group (control) received routine perioperative care. Main outcome measures Hospital mortality and morbidity. Results Overall, 3/92 (3%) preoptimised patients died compared with 8/46 controls (17%) (P = 0.007). There were no differences in mortality between the treatment groups, but 14/46 (30%) patients in the dopexamine group developed complications compared with 24/46 (52%) patients in the adrenaline group (difference 22%, 95% confidence interval 2% to 41%) and 28 patients (61%) in the control group (31%, 11% to 50%). The use of dopexamine was associated with a decreased length of stay in hospital. Conclusion Routine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care.

Bone formation or regeneration requires the recruitment, proliferation, and osteogenic differentiation of stem/stromal progenitor cells. A potent stimulus driving this process is mechanical loading. Osteocytes are mechanosensitive cells that play fundamental roles in coordinating loading-induced bone formation via the secretion of paracrine factors. However, the exact mechanisms by which osteocytes relay mechanical signals to these progenitor cells are poorly understood. Therefore, this study aimed to demonstrate the potency of the mechanically stimulated osteocyte secretome in driving human bone marrow stem/stromal cell (hMSC) recruitment and differentiation, and characterize the secretome to identify potential factors regulating stem cell behavior and bone mechanobiology. We demonstrate that osteocytes subjected to fluid shear secrete a distinct collection of factors that significantly enhance hMSC recruitment and osteogenesis and demonstrate the key role of extracellular vesicles (EVs) in driving these effects. This demonstrates the pro-osteogenic potential of osteocyte-derived mechanically activated extracellular vesicles, which have great potential as a cell-free therapy to enhance bone regeneration and repair in diseases such as osteoporosis.

After spinal cord injury (SCI), tissue engineering scaffolds offer a potential bridge for regeneration across the lesion and support repair through proregenerative signaling. Ideal biomaterial scaffolds that mimic the physicochemical properties of native tissue have the potential to provide innate trophic signaling while also minimizing damaging inflammation. To address this challenge, taking cues from the spinal cord's structure, the proregenerative signaling capabilities of native cord components are compared in vitro. A synergistic mix of collagen‐IV and fibronectin (Coll‐IV/Fn) is found to optimally enhance axonal extension from neuronal cell lines (SHSY‐5Y and NSC‐34) and induce morphological features typical of quiescent astrocytes. This optimal composition is incorporated into hyaluronic acid scaffolds with aligned pore architectures but varying stiffnesses (0.8–3 kPa). Scaffolds with biomimetic mechanical properties (<1 kPa), functionalized with Coll‐IV/Fn, not only modulate primary astrocyte behavior but also stimulate the production of anti‐inflammatory cytokine IL‐10 in a stiffness‐dependent manner. Seeded SHSY‐5Y neurons generate distributed neuronal networks, while softer biomimetic scaffolds promote axonal outgrowth in an ex vivo model of axonal regrowth. These results indicate that the interaction of stiffness and biomaterial composition plays an essential role in vitro in generating repair‐critical cellular responses and demonstrates the potential of biomimetic scaffold design.

Background: Patient and Public Involvement (PPI) in research aims to improve the quality, relevance and appropriateness of research. PPI has an established role in clinical research where there is evidence of benefit, and where policymakers and funders place continued emphasis on its inclusion. However, for preclinical research, PPI has not yet achieved the same level of integration. As more researchers, including our team, aim to include PPI in preclinical research, the development of an evidence-based approach is important. Therefore, this scoping review aimed to identify and map studies where PPI has been used in preclinical research and develop principles that can be applied in other projects.Methods: A scoping review was conducted to search the literature in Medline