In Vitro Evaluation of Pore Size Graded Bone Scaffolds with Different Material Composition.

The demand for biomimetic and biocompatible scaffolds in equivalence of structure and material composition for the regeneration of bone tissue is relevantly high. This article is investigating a novel three-dimensional (3D) printed porous structure called bone bricks with a gradient pore size mimicking the structure of the bone tissue. Poly-ɛ-caprolactone (PCL) combined with ceramics such as hydroxyapatite (HA), ß-tricalcium phosphate (TCP), and bioglass 45S5 were successfully mixed using a melt blending method and fabricated with the use of screw-assisted extrusion-based additive manufacturing system. Bone bricks containing the same material concentration (20 wt%) were biologically characterized through proliferation and differentiation tests. Scanning electron microscopy (SEM) was used to investigate the morphology of cells on the surface of bone bricks, whereas energy dispersive X-ray (EDX) spectroscopy was used to investigate the element composition on the surface of the bone bricks. Confocal imaging was used to investigate the number of differentiated cells on the surface of bone bricks. Proliferation results showed that bone bricks containing PCL/HA content are presenting higher proliferation properties, whereas differentiation results showed that bone bricks containing PCL/Bioglass 45S5 are presenting higher differentiation properties. Confocal imaging results showed that bone bricks containing PCL/Bioglass 45S5 are presenting a higher number of differentiated cells on their surface compared with the other material contents.

Biomimetic dual sensing polymer nanocomposite for biomedical applications.

There is a growing need for sensing materials that can provide multiple sensing capabilities for wearable devices, implantable sensors, and diagnostics tools. As complex human physiology requires materials that can simultaneously detect and respond to slow and fast pressure fluctuations. Mimicking the slow adaptive (SA) and fast adaptive (FA) mechanoreceptors in skin can lead to the development of dual sensing electrospun polymer nanocomposites for biomedical applications. These dual sensing nanocomposites can provide simultaneous sensing of both slow and fast pressure fluctuations, making them ideal for applications such as monitoring vital signs, detecting a wider range of movements and pressures. Here we develop a novel dual sensing PVDF-HFP-based nanocomposite that combines the advantages of capacitive and piezoelectric properties through controling electrospinning environment and processing parameters, polymer solution composition, and addition of nucleating agents such as Carbon Black (CB) to enhance the crystalline development of ß-phase, fibre thickness, and morphology. The developed PVDF-HFP/CB nanocomposite presents and response to both slow and fast pressure fluctuations with high capacitance (5.37 nF) and output voltage (1.51 V) allowing for accurate and reliable measurements.

Accelerated Degradation of Poly-ε-caprolactone Composite Scaffolds for Large Bone Defects.

This research investigates the accelerated hydrolytic degradation process of both anatomically designed bone scaffolds with a pore size gradient and a rectangular shape (biomimetically designed scaffolds or bone bricks). The effect of material composition is investigated considering poly-ε-caprolactone (PCL) as the main scaffold material, reinforced with ceramics such as hydroxyapatite (HA), ß-tricalcium phosphate (TCP) and bioglass at a concentration of 20 wt%. In the case of rectangular scaffolds, the effect of pore size (200 µm, 300 µm and 500 µm) is also investigated. The degradation process (accelerated degradation) was investigated during a period of 5 days in a sodium hydroxide (NaOH) medium. Degraded bone bricks and rectangular scaffolds were measured each day to evaluate the weight loss of the samples, which were also morphologically, thermally, chemically and mechanically assessed. The results show that the PCL/bioglass bone brick scaffolds exhibited faster degradation kinetics in comparison with the PCL, PCL/HA and PCL/TCP bone bricks. Furthermore, the degradation kinetics of rectangular scaffolds increased by increasing the pore size from 500 µm to 200 µm. The results also indicate that, for the same material composition, bone bricks degrade slower compared with rectangular scaffolds. The scanning electron microscopy (SEM) images show that the degradation process was faster on the external regions of the bone brick scaffolds (600 µm pore size) compared with the internal regions (200 µm pore size). The thermal gravimetric analysis (TGA) results show that the ceramic concentration remained constant throughout the degradation process, while differential scanning calorimetry (DSC) results show that all scaffolds exhibited a reduction in crystallinity (Xc), enthalpy (Δm) and melting temperature (Tm) throughout the degradation process, while the glass transition temperature (Tg) slightly increased. Finally, the compression results show that the mechanical properties decreased during the degradation process, with PCL/bioglass bone bricks and rectangular scaffolds presenting higher mechanical properties with the same design in comparison with the other materials.

Poly-ε-Caprolactone 3D-Printed Porous Scaffold in a Femoral Condyle Defect Model Induces Early Osteo-Regeneration.

Large bone reconstruction following trauma poses significant challenges for reconstructive surgeons, leading to a healthcare burden for health systems, long-term pain for patients, and complex disorders such as infections that are difficult to resolve. The use of bone substitutes is suboptimal for substantial bone loss, as they induce localized atrophy and are generally weak, and unable to support load. A combination of strong polycaprolactone (PCL)-based scaffolds, with an average channel size of 330 µm, enriched with 20% w/w of hydroxyapatite (HA), ß-tricalcium phosphate (TCP), or Bioglass 45S5 (Bioglass), has been developed and tested for bone regeneration in a critical-size ovine femoral condyle defect model. After 6 weeks, tissue ingrowth was analyzed using X-ray computed tomography (XCT), Backscattered Electron Microscopy (BSE), and histomorphometry. At this point, all materials promoted new bone formation. Histological analysis showed no statistical difference among the different biomaterials (p > 0.05), but PCL-Bioglass scaffolds enhanced bone formation in the center of the scaffold more than the other types of materials. These materials show potential to promote bone regeneration in critical-sized defects on load-bearing sites.

Multi-Layer Biosensor for Pre-Symptomatic Detection of Puccinia strifformis, the Causal Agent of Yellow Rust.

The yellow rust of wheat (caused by Puccinia striiformis f. sp. tritici) is a devastating fungal infection that is responsible for significant wheat yield losses. The main challenge with the detection of this disease is that it can only be visually detected on the leaf surface between 7 and 10 days after infection, and by this point, counter measures such as the use of fungicides are generally less effective. The hypothesis of this study is to develop and use a compact electrochemical-based biosensor for the early detection of P. striiformis, thus enabling fast countermeasures to be taken. The biosensor that was developed consists of three layers. The first layer mimics the wheat leaf surface morphology. The second layer consists of a sucrose/agar mixture that acts as a substrate and contains a wheat-derived terpene volatile organic compound that stimulates the germination and growth of the spores of the yellow rust pathogen P. s. f. sp. tritici. The third layer consists of a nonenzymatic glucose sensor that produces a signal once invertase is produced by P. striiformis, which comes into contact with the second layer, thereby converting sucrose to glucose. The results show the proof that this innovative biosensor can enable the detection of yellow rust spores in 72 h.

Geometry-Based Computational Fluid Dynamic Model for Predicting the Biological Behavior of Bone Tissue Engineering Scaffolds.

The use of biocompatible and biodegradable porous scaffolds produced via additive manufacturing is one of the most common approaches in tissue engineering. The geometric design of tissue engineering scaffolds (e.g., pore size, pore shape, and pore distribution) has a significant impact on their biological behavior. Fluid flow dynamics are important for understanding blood flow through a porous structure, as they determine the transport of nutrients and oxygen to cells and the flushing of toxic waste. The aim of this study is to investigate the impact of the scaffold architecture, pore size and distribution on its biological performance using Computational Fluid Dynamics (CFD). Different blood flow velocities (BFV) induce wall shear stresses (WSS) on cells. WSS values above 30 mPa are detrimental to their growth. In this study, two scaffold designs were considered: rectangular scaffolds with uniform square pores (300, 350, and 450 µm), and anatomically designed circular scaffolds with a bone-like structure and pore size gradient (476-979 µm). The anatomically designed scaffolds provided the best fluid flow conditions, suggesting a 24.21% improvement in the biological performance compared to the rectangular scaffolds. The numerical observations are aligned with those of previously reported biological studies.

Bone Bricks: The Effect of Architecture and Material Composition on the Mechanical and Biological Performance of Bone Scaffolds.

Large bone loss injuries require high-performance scaffolds with an architecture and material composition resembling native bone. However, most bone scaffold studies focus on three-dimensional (3D) structures with simple rectangular or circular geometries and uniform pores, not able to recapitulate the geometric characteristics of the native tissue. This paper addresses this limitation by proposing novel anatomically designed scaffolds (bone bricks) with nonuniform pore dimensions (pore size gradients) designed based on new lay-dawn pattern strategies. The gradient design allows one to tailor the properties of the bricks and together with the incorporation of ceramic materials allows one to obtain structures with high mechanical properties (higher than reported in the literature for the same material composition) and improved biological characteristics.

Novel 3D Bioglass Scaffolds for Bone Tissue Regeneration.

The design of scaffolds with optimal biomechanical properties for load-bearing applications is an important topic of research. Most studies have addressed this problem by focusing on the material composition and not on the coupled effect between the material composition and the scaffold architecture. Polymer-bioglass scaffolds have been investigated due to the excellent bioactivity properties of bioglass, which release ions that activate osteogenesis. However, material preparation methods usually require the use of organic solvents that induce surface modifications on the bioglass particles, compromising the adhesion with the polymeric material thus compromising mechanical properties. In this paper, we used a simple melt blending approach to produce polycaprolactone/bioglass pellets to construct scaffolds with pore size gradient. The results show that the addition of bioglass particles improved the mechanical properties of the scaffolds and, due to the selected architecture, all scaffolds presented mechanical properties in the cortical bone region. Moreover, the addition of bioglass indicated a positive long-term effect on the biological performance of the scaffolds. The pore size gradient also induced a cell spreading gradient.

Investigating the Influence of Architecture and Material Composition of 3D Printed Anatomical Design Scaffolds for Large Bone Defects.

There is a significant unmet clinical need to prevent amputations due to large bone loss injuries. We are addressing this problem by developing a novel, cost-effective osseointegrated prosthetic solution based on the use of modular pieces, bone bricks, made with biocompatible and biodegradable materials that fit together in a Lego-like way to form the prosthesis. This paper investigates the anatomical designed bone bricks with different architectures, pore size gradients, and material compositions. Polymer and polymer-composite 3D printed bone bricks are extensively morphological, mechanical, and biological characterized. Composite bone bricks were produced by mixing polycaprolactone (PCL) with different levels of hydroxyapatite (HA) and ß-tri-calcium phosphate (TCP). Results allowed to establish a correlation between bone bricks architecture and material composition and bone bricks performance. Reinforced bone bricks showed improved mechanical and biological results. Best mechanical properties were obtained with PCL/TCP bone bricks with 38 double zig-zag filaments and 14 spiral-like pattern filaments, while the best biological results were obtained with PCL/HA bone bricks based on 25 double zig-zag filaments and 14 spiral-like pattern filaments.

Duration of anti-treponemal immunoglobulin M seroreversion after successful syphilis treatment in HIV-positive and -negative patients.

Treponemal immunoglobulin M (IgM) antibody detection is currently among serologic tests used for syphilis diagnosis. However, the exact role of these antibodies is unclear. In this retrospective study of 326 (198 HIV positive and 128 negative) patients with early syphilis and positive IgM serology, data were analysed to investigate the time of IgM seroreversion after treatment and correlation with covariate factors. Median time of IgM seroreversion in the study population was 9 months (range 3-84, interquartile range 5-12). No statistically significant difference was observed between HIV-positive and -negative patients. At 12 months, 80.1% of the patients had a negative IgM test. At 6 months, 100% of HIV-positive patients had a fourfold decrease or greater in Venereal Disease Research Laboratory titres, but only 35.4% had a negative treponemal IgM. Secondary and early latent stage patients had a slower seroreversion of IgM (Hazard Ratio (HR) = 0.73, p = 0.064 and HR = 0.60, p = 0.023, respectively) than those with primary syphilis. A very strong association was observed of time to seroreversion of treponemal IgM with baseline VDRL titre (p < 0.001). Treponemal IgM antibody detection often cannot distinguish between active and successfully treated syphilis. Treponemal IgM may only be useful in the cases recommended in the guidelines, and in cases of untreated syphilis, it could support but not confirm the diagnosis.

The Potential of Polyethylene Terephthalate Glycol as Biomaterial for Bone Tissue Engineering.

The search for materials with improved mechanical and biological properties is a major challenge in tissue engineering. This paper investigates, for the first time, the use of Polyethylene Terephthalate Glycol (PETG), a glycol-modified class of Polyethylene Terephthalate (PET), as a potential material for the fabrication of bone scaffolds. PETG scaffolds with a 0/90 lay-dawn pattern and different pore sizes (300, 350 and 450 µm) were produced using a filament-based extrusion additive manufacturing system and mechanically and biologically characterized. The performance of PETG scaffolds with 300 µm of pore size was compared with polycaprolactone (PCL). Results show that PETG scaffolds present significantly higher mechanical properties than PCL scaffolds, providing a biomechanical environment that promotes high cell attachment and proliferation.

Norwegian scabies presenting as erythroderma in HIV: A case report.

Crusted scabies is a rare and extreme manifestation of scabies that is observed mainly among immunosuppressed patients. We describe the case of a 55-year-old patient with a history of HIV infection and injection drug use. The patient was not on any antiretroviral therapy during the previous year, was malnourished and was living in unsanitary conditions. He had extensive, generalized, thick, hyperkeratotic, crusting, papular lesions, which had evolved over the previous month. Hyperkeratotic areas were fissured and linear excoriations were noted diffusely. The rash was distributed on the entire body from the scalp to the toes, with mild itching. Microscopic examination of the scale revealed numerous scabies mites and eggs. The patient was treated with topical scabicidal agents, which resulted in complete resolution. Because of the extremely contagious nature of crusted scabies, as well as its potential for complete cure with an appropriate therapy, there should be a high degree of suspicion for this disease in patients with AIDS, even when the lesions do not have the classical appearance. Nosocomial transmission of scabies from patients with AIDS is a risk, and protective measures, early diagnosis, and therapy are essential.