Biophysical Stimuli as the Fourth Pillar of Bone Tissue Engineering.

The repair of critical bone defects remains challenging worldwide. Three canonical pillars (biomaterial scaffolds, bioactive molecules, and stem cells) of bone tissue engineering have been widely used for bone regeneration in separate or combined strategies, but the delivery of bioactive molecules has several obvious drawbacks. Biophysical stimuli have great potential to become the fourth pillar of bone tissue engineering, which can be categorized into three groups depending on their physical properties: internal structural stimuli, external mechanical stimuli, and electromagnetic stimuli. In this review, distinctive biophysical stimuli coupled with their osteoinductive windows or parameters are initially presented to induce the osteogenesis of mesenchymal stem cells (MSCs). Then, osteoinductive mechanisms of biophysical transduction (a combination of mechanotransduction and electrocoupling) are reviewed to direct the osteogenic differentiation of MSCs. These mechanisms include biophysical sensing, transmission, and regulation. Furthermore, distinctive application strategies of biophysical stimuli are presented for bone tissue engineering, including predesigned biomaterials, tissue-engineered bone grafts, and postoperative biophysical stimuli loading strategies. Finally, ongoing challenges and future perspectives are discussed.

Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: A meta-analysis.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been used to predict the prognosis of patients with sepsis with inconsistent results. This meta-analysis aimed to clarify the prognostic value of NLR in patients with sepsis. METHODS: A comprehensive literature search for relevant studies, published prior to March 2019, was conducted using PubMed, Web of Science, and the China National Knowledge. Infrastructure database. Standard mean differences (SMDs) with 95% confidence intervals (CI) were used to evaluate the NLR of patients with sepsis retrospectively. Hazard ratios (HRs) with 95% CIs were used to evaluate the prognostic value of NLR in patients with sepsis. RESULTS: Patients from 14 studies (n = 11,564) were selected for evaluation. Nine studies (1371 patients) analyzed the NLR in these patients. The pooled results showed significantly higher NLR in non-survivors than in survivors (random-effects model: SMD = 1.18, 95% CI; 0.42-1.94). Nine studies (10,685 patients) evaluated the prognostic value of NLR for sepsis; the pooled results showed that higher NLR was associated with poor prognosis in patients with sepsis (fixed-effects model: HR = 1.75, 95% CI; 1.56-1.97). Subgroup analysis revealed that study design, cut-off NLR, or primary outcome did not affect the prognostic value of NLR in patients with sepsis. CONCLUSION: This meta-analysis indicates that NLR may be a helpful prognostic biomarker of patients with sepsis and that higher NLR values may indicate unfavorable prognoses in these patients.