Infliximab-based self-healing hydrogel composite scaffold enhances stem cell survival, engraftment, and function in rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is a severe inflammatory autoimmune disease, but its treatment has been very difficult. Recently, stem cell-based therapies have opened up possibilities for the treatment of RA. However, the hostile RA pathological conditions impede the survival and differentiation of transplanted cells, and it remains challenging to fabricate a suitable biomaterial for the improvement of stem cells survival, engraftment, and function. Here we construct an optimal scaffold for RA management through the integration of 3D printed porous metal scaffolds (3DPMS) and infliximab-based hydrogels. The presence of rigid 3DPMS is appropriate for repairing large-scale bone defects caused by RA, while the designed infliximab-based hydrogels are introduced because of their self-healable, anti-inflammatory, biocompatible, and biodegradable properties. We demonstrate that the bioengineered composite scaffolds support adipose-derived mesenchymal stem cells (ADSCs) proliferation, differentiation, and extracellular matrix production in vitro. The composite scaffolds, along with ADSCs, are then implanted into the critical-sized bone defect in the RA rabbit model. In vivo results prove that the bioengineered composite scaffolds are able to down-regulate inflammatory cytokines, rebuild damaged cartilage, as well as improve subchondral bone repair. To the best of the authors' knowledge, this is the first time that using the antirheumatic drug to construct hydrogels for stem cell-based therapies, and this inorganic-organic hybrid system has the potential to alter the landscape of RA study.

Prompt admission to intensive care is associated with improved survival in patients with severe sepsis and/or septic shock.

Objective To investigate the association between time from hospital admission to intensive care unit (ICU) admission (door to ICU time) and hospital mortality in patients with sepsis. Methods This retrospective observational study included routinely collected healthcare data from patients with sepsis. The primary endpoint was hospital mortality, defined as the survival status at hospital discharge. Door to ICU time was calculated and included in a multivariable model to investigate its association with mortality. Results Data from 13 115 patients were included for analyses, comprising 10 309 survivors and 2 806 non-survivors. Door to ICU time was significantly longer for non-survivors than survivors (median, 43.0 h [interquartile range, 12.4, 91.3] versus 26.7 h [7.0, 74.2]). In the multivariable regression model, door to ICU time remained significantly associated with mortality (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.006, 1.017) and there was a significant interaction between age and door to ICU time (OR 0.99, 95% CI 0.99, 1.00). Conclusion A shorter time from hospital door to ICU admission was shown to be independently associated with reduced hospital mortality in patients with severe sepsis and/or septic shock.

Heat treatment effect on the mechanical properties, roughness and bone ingrowth capacity of 3D printing porous titanium alloy.

The weak mechanical strength and biological inertia of Ti-6Al-4V porous titanium alloy limit its clinical application in the field of orthopedics. The present study investigated the influence of different solution temperatures (e.g. 800 °C, 950 °C and 1000 °C) on the mechanical properties, roughness and bone ingrowth capacity of Ti-6Al-4V porous titanium alloy prepared by Electron Beam Melting. It was found that the compressive and shear strength were promoted with the increase of solution temperature because of the transformed crystallinity of Ti-6Al-4V titanium alloy and phase changes from TiAl to TiAl + TiV. In addition, the topological morphology, surface roughness and wettability of the porous titanium alloy scaffolds were improved after heat treatment, and in turn, the adhesion rate and cell proliferation of bone marrow mesenchymal stem cells were enhanced. Compared with the scaffolds before and after heat treatment at 800 °C, the scaffolds heat-treated at 950 °C and 1000 °C achieved better bone ingrowth, extracellular matrix deposition and osseointegration. These findings indicate the great potential of heat treatment in possessing Ti-6Al-4V porous titanium alloy for orthopedic implant.

Additive manufacturing technique-designed metallic porous implants for clinical application in orthopedics.

Traditional metallic scaffold prostheses, as vastly applied implants in clinical orthopedic operations, have achieved great success in rebuilding limb function. However, mismatch of bone defects and additional coating requirements limit the long-term survival of traditional prostheses. Recently, additive manufacturing (AM) has opened up unprecedented possibilities for producing complicated structures in prosthesis shapes and microporous surface designs of customized prostheses, which can solve the drawback of traditional prostheses mentioned above. This review presents the most commonly used metallic additive manufacturing techniques, the microporous structure design of metallic scaffolds, and novel applications of customized prostheses in the orthopedic field. Challenges and future perspectives on AM fabricated scaffolds are also summarized.