Two Stage Repair of Composite Craniofacial Defects with Antibiotic Releasing Porous Poly(methyl methacrylate) Space Maintainers and Bone Regeneration

Craniofacial defects resulting from trauma and resection present many challenges to reconstruction due to the complex structure, combinations of tissues, and environment, with exposure to the oral, skin and nasal mucosal pathogens. Tissue engineering seeks to regenerate the tissues lost in these defects; however, the composite nature and proximity to colonizing bacteria remain difficult to overcome. Additionally, many tissue engineering approaches have further hurdles to overcome in the regulatory process to clinical translation. As such these studies investigated a two stage strategy employing an antibiotic-releasing porous polymethylmethacrylate space maintainer fabricated with materials currently part of products approved or cleared by the United States Food and Drug Administration, expediting the translation to the clinic. This porous space maintainer holds the bone defect open allowing soft tissue to heal around the defect. The space maintainer can then be removed and one regenerated in the defect. These studies investigated the individual components of this strategy. The porous space maintainer showed similar soft tissue healing and response to non-porous space maintainers in a rabbit composite tissue defect. In humans, the porous space maintainers were well tolerated and maintained a soft tissue envelope for closure after implantation of a bone regeneration technology. The antibiotic-releasing space maintainers showed release of antibiotics from 1-5 weeks, which could be controlled by loading and fabrication parameters. In vivo, space maintainers releasing a high dose of antibiotics for an extended period of time increased soft tissue healing over burst release space maintainers in an infected composite tissue defect model in a rabbit mandible. Finally, stabilization of bone defects and regeneration could be improved through scaffold structures and delivery of a bone forming growth factor. These studies illustrate the possibility of the two stage strategy for repair of composite tissue defects of the craniofacial complex

Controllable Internal Mixing in Coalescing Droplets Induced by The Solutal Marangoni Convection of Surfactants with Distinct Headgroup Architectures

Through several complementary experiments, an investigation of the bulk and interfacial flows that emerged during the coalescence of two water-in-oil droplets with asymmetric compositional properties was performed. By adding surfactant to one of the coalescing droplets and leaving the other surfactant-free, a strong interfacial tension gradient (i.e., solutal Marangoni) driving energy between the merging droplets generated pronounced internal mixing. The contributions of two distinct types of surfactant, anionic ammonium lauryl sulfate (ALS) and cationic cetyltrimethylammonium bromide (CTAB) on the rate of coalescence bridge expansion and on the generation of opposing flows during coalescence were investigated. All coalescence experiments supported the power law relation between the radius of the expanding connective liquid bridge and time, rb ∝ t1/2. However, the presence of surfactant decreased the magnitude of the prefactor in this relationship due to induced interfacial solutal Marangoni convection. Experiments showed that packing efficiency, diffusivity, and bulk concentration of the selected surfactant are vital in solutal Marangoni convection and thus the degree and timescale of internal mixing between merging droplets, which has yet to be adequately discussed within the literature. Denser interfacial packing efficiency and lower diffusivity of CTAB produced stronger opposing bulk and interfacial flow as well as greater bulk mixing. A discussion of how optimized surfactant selection and solutal Marangoni convection can be used for passively inducing convective mixing between coalescing drops in microfluidic channels when viscosity modulation is not feasible is provided

Probing yield stress fluids with a vibrational rheometer

Low volume fraction colloidal gels can possess small yield stresses that are able to trap particles or bubbles within the matrix indefinitely. At rest, the stress applied to the network by a probe particle is limited by the density difference between the probe and continuous phase materials. However, vibration of the sample is an acceleration that causes the inertial particles to impart a stress on the fluid; the stress that results from a vibration is also a function of the frequency and amplitude of the vibration. The microscale fluid properties around the probe particles can be elucidated by studying the effects of vibration on the sample. While applying a vertical mechanical vibration to the sample (1 to 5 mm amplitude, 10 to 100 Hz), we make use of high speed particle tracking to record particle trajectories and measure strain, yielding, flow, and recovery of various complex fluid networks. The measurements enable comparison of the suspension and yielding behaviour of complex fluids with similar rheology but greatly varying microstructures, allowing determination of the optimal approaches to stabilisation of various formulations. Dispersions of colloidal microgels, nanofibres, and wormlike micelles are used in different combinations to explore the robustness of disparate structures to repeated perturbations. Measurements are made of local strain, elasticity, yield stress, and sedimentation rate and compared to continuum predictions for yield stress fluids with more homogeneous microstructures. Please click Additional Files below to see the full abstract

Microstructure and yielding of microfiber gels

Large aspect ratio cellulose nanofibers are able to a form poroelastic network at low volume fractions via aggregation and entanglement, forming a gel without significantly modifying viscosity[1]. The gels have a small but useful yield stress and a better ability to suspend particles than non-interacting higher volume fraction glasses[2] because the sparse fiber networks can significantly restructure at small strains. Yielding behavior can thus strongly depend on the fluid microstructure[3]. We study here deformation and yielding of aqueous cellulose fiber gels. Confocal imaging shows how gel yield stress relates to structural deformation rate because of localized network restructuring. Such response is advantageous to applications like surface coatings, nasal sprays, cosmetics, and foods. Understanding the mechanism of rate- and length-scale dependent yielding, and relating microstructure changes to bulk rheology[4], will enhance our ability to formulate, model, and design complex fluids with novel performance. References [1] - Solomon MJ, Spicer PT. Microstructural regimes of colloidal rod suspensions, gels, and glasses. Soft Matter, 6, 1391 (2010). [2] - Emady H, Caggioni M, Spicer P. Colloidal microstructure effects on particle sedimentation in yield stress fluids. J Rheol. 57, 1761 (2013). [3] - Joshi YM. Dynamics of colloidal glasses and gels. Annu Rev Chem Biomol Eng. 5, 181, (2014). [4] - Hsiao L, Newman RS, Glotzer SC, Solomon MJ. Role of isostaticity and load-bearing microstructure in the elasticity of yielded colloidal gels. Proc Natl Acad Sci, 109, 16029, (2012

Plain language summary of the CheckMate 816 study results: nivolumab plus chemotherapy given before surgery for non–small-cell lung cancer

Immunotherapy; Neoadjuvant treatment; Presurgery treatmentImmunoteràpia; Tractament neoadjuvant; Tractament preoperatoriInmunoterapia; Tratamiento neoadyuvante; Tratamiento preoperatorioWhat is this summary about?: In this article, we summarize results from the ongoing phase 3 CheckMate 816 clinical study that were published in The New England Journal of Medicine in 2022. The goal of CheckMate 816 was to find out if nivolumab, an immunotherapy that activates a person's immune system (the body's natural defense system) to fight cancer, plus chemotherapy works better than chemotherapy alone when given before surgery in people with non-small-cell lung cancer (NSCLC) that can be removed surgically (resectable NSCLC). What happened in the study?: Adults who had not previously taken medications to treat NSCLC and whose cancer could be removed with surgery were included in CheckMate 816. During this study, a computer randomly assigned the treatment each person would receive before surgery for NSCLC. In total, 179 people were randomly assigned to receive nivolumab plus chemotherapy, and 179 people were randomly assigned to receive chemotherapy alone. The researchers assessed whether people who received nivolumab plus chemotherapy lived longer without the cancer geting worse or coming back and whether there were any cancer cells left in the tumor and lymph nodes removed by surgery. The researchers also assessed how adding nivolumab to chemotherapy affected the timing and outcomes of surgery and whether the combination of these drugs was safe. What were the results?: Researchers found that people who took nivolumab plus chemotherapy lived longer without the cancer getting worse or coming back compared with those who took chemotherapy alone. More people in the nivolumab plus chemotherapy group had no cancer cells left in the tumor and lymph nodes removed by surgery. Most people went on to have surgery in both treatment groups; the people who took nivolumab plus chemotherapy instead of chemotherapy alone had less extensive surgeries and were more likely to have good outcomes after less extensive surgeries. Adding nivolumab to chemotherapy did not lead to an increase in the rate of side effects compared with chemotherapy alone, and side effects were generally mild and manageable. What do the results of the study mean?: Results from CheckMate 816 support the benefit of using nivolumab plus chemotherapy before surgery for people with resectable NSCLC.The CheckMate 816 study was sponsored by Bristol Myers Squibb