Neovasculature in 3D-PLGA/nHAp Scaffolds for Murine Critical Sized Bone Defect Regeneration by Photoacoustic Imaging: A Preliminary Study

Abstract: Reconstruction of large bone defects remains a challenge in the orthopaedic clinic. Genetic modification of biomaterial scaffold provides the opportunity to control the cellular microenvironment by inducing expression of tissue inductive factors to promote angiogenesis and osteogenesis. Angiogenesis in tissue-engineering scaffolds is essential for supplying oxygen and nutrients to the cells, removing waste products, and ultimately functionalizing implanted scaffolds. However, it was difficult to visualize and measure angiogenesis in three-dimensional (3D) scaffolds or new bone in bone tissue engineering in vivo and non-invasively. Photoacoustic microscopy (PAM) is a novel imaging modality that can acquire volumetric data in a non-invasive manner. In this study, we fabricated lentivirus-mediated genetic modification of 3D-PLGA/nHAp scaffold (PH), which can deliver recombinant lentivirus carrying cytokine gene-pdgfb (LV-pdgfb). In vitro, the modified scaffolds (PHp) continuously released bioactive LV-pdgfb particles for up to 5 days, and expressed PDGF-BB and significantly promoted migration of bone marrow-derived MSCs (BMSCs). In vivo, we detected that there were significant increasing of expressing of pdgfb and angiogenesis related genes. In this preliminary study, by using acoustic-resolution PAM (AR-PAM) and optical-resolution PAM (OR-PAM), we have investigated the blood vessels pattern in mouse calvaria in vivo. We have confirmed that PAM is a useful tool in evaluating neovasculature in bone tissue. In the future, we will quantify the neovasculature in 3D-scaffold which assisted bone regeneration by PAM scanning, and correlate the neovasculature with new bone regeneration in a murine calvarial critical bone defect model in the future work

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Cartilage tissue engineering for obesity-induced osteoarthritis : Physiology, challenges, and future prospects

Osteoarthritis (OA) is a multifactorial joint disease with pathological changes that affect whole joint tissue. Obesity is acknowledged as the most influential risk factor for both the initiation and progression of OA in weight-bearing and non-weight-bearing joints. Obesity-induced OA is a newly defined phenotypic group in which chronic low-grade inflammation has a central role. Aside from persistent chronic inflammation, abnormal mechanical loading due to increased body weight on weight-bearing joints is accountable for the initiation and progression of obesity-induced OA. The current therapeutic approaches for OA are still evolving. Tissue-engineering-based strategy for cartilage regeneration is one of the most promising treatment breakthroughs in recent years. However, patients with obesity-induced OA are often excluded from cartilage repair attempts due to the abnormal mechanical demands, altered biomechanical and biochemical activities of cells, persistent chronic inflammation, and other obesity-associated factors. With the alarming increase in the number of obese populations globally, the need for an innovative therapeutic approach that could effectively repair and restore the damaged synovial joints is of significant importance for this sub-population of patients. In this review, we discuss the involvement of the systemic and localized inflammatory response in obesity-induced OA and the impact of altered mechanical loading on pathological changes in the synovial joint. Moreover, we examine the current strategies in cartilage tissue engineering and address the critical challenges of cell-based therapies for OA. Besides, we provide examples of innovative ways and potential strategies to overcome the obstacles in the treatment of obesity-induced OA. The translational potential of this article: Altogether, this review delivers insight into obesity-induced OA and offers future research direction on the creation of tissue engineering-based therapies for obesity-induced OA.</p

Investigation of bioeffects of G protein-coupled receptor 1 on bone turnover in male mice

Maintenance of healthy bone quality and quantity requires a well-coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts. Chemerin is a novel adipokine with known functions such as regulating immunity and energy homeostasis through activation of chemokine-like receptor 1 (CMKLR1). G protein-coupled receptor 1 (GPR1) is the second mammalian chemerin receptor with similar binding affinity as CMKLR1. In male GPR1–/– mice, a phenotype with significantly low bone mineral density was observed. We hypothesise that GPR1 might participate the process of bone remodelling. In this study, we investigated the role of GPR1 in regulating bone mass maintenance in male mice, and for the first time, revealed that GPR1–/– male mice manifested seriously trabecular bone loss and lower serum testosterone levels compared to the wild type animals. Accordingly, the mRNA expression of biomarkers related to both osteoblast [collagen type I alpha 2 (Col1A2), osteocalcin (OCN)] and osteoclast [tartrate-resistant acid phosphatase (TRAP), Cathepsin K, NFATc1] were significantly decreased or increased in GPR1–/– mice relative to the wild type, respectively. However, other osteogenic markers, Osterix and ALP levels, were increased. Microcomputed tomography scanning and histological analyses proved that there was a myriad of trabecular bone loss in GPR1–/– mice. In the meantime, GPR1–/– mice presented a significant decrease in serum testosterone level. Taken together, these findings suggested that chemerin–GPR1 signalling might be directly or indirectly communicated with testosterone synthesis on bone turnover regulation. Further detailed studies are required to unveil how chemerin–GPR1 participates in bone metabolism. The translational potential of this article: More studies and knowledge about GPR1 regulating function in bone turnover might supply a novel therapeutic target for osteoporosis in the future