Toward a molecular understanding of the conductivity of lithium-ion conducting polyanion polymer electrolytes by molecular dynamics simulation.

With the improved lithium-ion transference number near unity, the low conductivity of single lithium-ion conducting solid polymer electrolytes (SLIC-SPEs) still hinders their application in high-rate batteries. Though some empirical conclusions on the conducting mechanism of SLIC-SPEs have been obtained, a more comprehensive study on the quantitative relationship between the molecular structure factors and ionic conduction performance is expected. In this study, a model structure that contains adjustable main chain and anion groups in the polyethylene oxide (PEO) matrix was used to clarify the influence of molecular structural factors on ionic conductivity and electrochemical stability of SLIC-SPEs. The anionic group was further disassembled into the intermediate group and end group while the main chain structure was distinguished into different degrees of polymerization and various lengths of the spacers between anions. Therefore, a well-defined molecular structure was employed to describe its relationship with ionic conductivity. In addition, the dissociation degree of salts and mobility of ions changing with the molecular structure were also discussed to explore the fundamental causes of conductivity. It can be concluded that the anion group affects the conductivity mainly via the dissociation degree, while the main chain structure impacts the conductivity by both dissociation degree and mobility.

Joint Toxicity of Two Phthalates with Waterborne Copper to Daphnia magna and Photobacterium phosphoreum.

Di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) are two widely used phthalates, while Cu(II) is a common valence state of copper. They have been ubiquitously detected in the aquatic environment, but information on their joint toxicity to aquatic organisms is scarce. In this study, we evaluated the combined effects of copper and these two phthalates to Daphnia magna and Photobacterium phosphoreum by quantifying the acute toxicity expressed by the EC50 (the concentration causing 50 % of maximal effect) value. The toxicity order was DEHP + Cu(II) > DBP + Cu(II) > Cu(II) > DEHP > DBP for both test species. Antagonism effects were found in the joint toxicity of Cu(II) combined with DBP or DEHP using the toxic unit method. These findings have important implications in environmental risk assessment for phthalates in the aquatic environment in the presence of heavy metals.

Antagonistic joint toxicity assessment of two current-use phthalates with waterborne copper in liver of Carassius auratus using biochemical biomarkers.

Di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) are two kinds of widely-used phthalates, whereas Cu (II) is a common valence state of copper. They have been ubiquitously detected in the aquatic environment, but information on their joint toxicity on aquatic organisms is scarce. In this study, we evaluated the combined effects of copper and these two phthalates to the goldfish (Carassius auratus) by detecting the antioxidant responses in liver after exposure for 7 and 21 days. The exposure concentrations were in a range relevant to their levels in the natural aquatic environment. The results indicated that DBP, DEHP and Cu (II) can affect the antioxidant status in fish liver, evidenced by the significant alterations of antioxidant defenses (superoxide dismutase, catalase, glutathione) and malondialdehyde. Antagonistic effects were found in the joint toxicity of Cu (II) and DBP or DEHP using the integrated biomarker response (IBR) index. These findings have important implications in the risk assessments of phthalates mixed with some heavy metals in the aquatic environment.

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.

Characteristics and Sintering Mechanisms of Iron Ores with a High Proportion of High-Al2O3 Limonite.

In this study, a sintering test of high-alumina limonite from Indonesia, matched with an appropriate magnetite concentration, is performed. The sintering yield and quality index are effectively improved by optimizing the ore matching and regulating the basicity. For the optimal coke dosage of 5.8% and basicity of 1.8, the tumbling index of the ore blend is found to be 61.5% and the productivity is 1.2 t/(h·m2). The main liquid phase in the sinter is the silico-ferrite of calcium and aluminum (SFCA), followed by a mutual solution, both of which maintain the sintering strength. However, when the basicity is increased from 1.8 to 2.0, the production of SFCA is found to increase gradually, whereas the mutual solution content decreases dramatically. A metallurgical performance test of the optimal sinter sample demonstrates that the sinter can meet the requirements of small- and medium-sized blast furnace smelting, even for high-alumina limonite ratios of 60.0-65.0%, thereby greatly reducing the sintering production costs. The results of this study are expected to provide theoretical guidance for the practical high-proportion sintering of high-alumina limonite.

Bifunctional Localized High-Concentration Electrolyte for the Fast Kinetics of Lithium Batteries at Low Temperatures.

Traditional lithium batteries cannot work well at low temperatures due to the sluggish desolvation process, which limits their applications in low-temperature fields. Among various previously reported approaches, solvation regulation of electrolytes is of great importance to overcome this obstacle. In this work, a tetrahydrofuran (THF)-based localized high-concentration electrolyte is reported, which possesses the advantages of a unique solvation structure and improved mobility, enabling a Li/lithium manganate (LMO) battery to cycle stably at room temperature (retains 85.9% after 300 cycles) and to work at a high rate (retains 69.0% at a 10C rate). Apart from that, this electrolyte demonstrates superior low-temperature performance, delivering over 70% capacity at -70 °C and maintaining 72.5 mAh g-1 (≈77.1%) capacity for 200 cycles at a 1C rate at -40 °C. Also, even when the rate increases to 5C, the battery could still operate well at -40 °C. This work demonstrates that solvation regulation has a significant impact on the kinetics of cells at low temperatures and provides a design method for future electrolyte design.

Early In Vivo Osteogenic and Inflammatory Response of 3D Printed Polycaprolactone/Carbon Nanotube/Hydroxyapatite/Tricalcium Phosphate Composite Scaffolds.

The development of advanced biomaterials and manufacturing processes to fabricate biologically and mechanically appropriate scaffolds for bone tissue is a significant challenge. Polycaprolactone (PCL) is a biocompatible and degradable polymer used in bone tissue engineering, but it lacks biofunctionalization. Bioceramics, such as hydroxyapatite (HA) and ß tricalcium phosphate (ß-TCP), which are similar chemically to native bone, can facilitate both osteointegration and osteoinduction whilst improving the biomechanics of a scaffold. Carbon nanotubes (CNTs) display exceptional electrical conductivity and mechanical properties. A major limitation is the understanding of how PCL-based scaffolds containing HA, TCP, and CNTs behave in vivo in a bone regeneration model. The objective of this study was to evaluate the use of three-dimensional (3D) printed PCL-based composite scaffolds containing CNTs, HA, and ß-TCP during the initial osteogenic and inflammatory response phase in a critical bone defect rat model. Gene expression related to early osteogenesis, the inflammatory phase, and tissue formation was evaluated using quantitative real-time PCR (RT-qPCR). Tissue formation and mineralization were assessed by histomorphometry. The CNT+HA/TCP group presented higher expression of osteogenic genes after seven days. The CNT+HA and CNT+TCP groups stimulated higher gene expression for tissue formation and mineralization, and pro- and anti-inflammatory genes after 14 and 30 days. Moreover, the CNT+TCP and CNT+HA/TCP groups showed higher gene expressions related to M1 macrophages. The association of CNTs with ceramics at 10wt% (CNT+HA/TCP) showed lower expressions of inflammatory genes and higher osteogenic, presenting a positive impact and balanced cell signaling for early bone formation. The association of CNTs with both ceramics promoted a minor inflammatory response and faster bone tissue formation.

Polyhydroxyalkanoate production from animal by-products: Development of a pneumatic feeding system for solid fat/protein-emulsions.

Fat-containing animal by-product streams are locally available in large quantities. Depending on their quality, they can be inexpensive substrates for biotechnological processes. To accelerate industrial polyhydroxyalkanoate (PHA) bioplastic production, the development of efficient bioprocesses that are based on animal by-product streams is a promising approach to reduce overall production costs. However, the solid nature of animal by-product streams requires a tailor-made process development. In this study, a fat/protein-emulsion (FPE), which is a by-product stream from industrial-scale pharmaceutical heparin production and of which several hundred tons are available annually, was evaluated for PHA production with Ralstonia eutropha. The FPE was used as the sole source of carbon and nitrogen in shake flask and bioreactor cultivations. A tailored pneumatic feeding system was built for laboratory bioreactors to facilitate fed-batch cultivations with the solid FPE. The process yielded up to 51 g L-1 cell dry weight containing 71 wt% PHA with a space-time yield of 0.6 gPHA L-1  h-1 without using any carbon or nitrogen sources other than FPE. The presented approach highlights the potential of animal by-product stream valorization into PHA and contributes to a transition towards a circular bioeconomy.

Electrical Stimulation Therapy and HA/TCP Composite Scaffolds Modulate the Wnt Pathways in Bone Regeneration of Critical-Sized Defects.

Critical bone defects are the most difficult challenges in the area of tissue repair. Polycaprolactone (PCL) scaffolds, associated with hydroxyapatite (HA) and tricalcium phosphate (TCP), are reported to have an enhanced bioactivity. Moreover, the use of electrical stimulation (ES) has overcome the lack of bioelectricity at the bone defect site and compensated the endogenous electrical signals. Such treatments could modulate cells and tissue signaling pathways. However, there is no study investigating the effects of ES and bioceramic composite scaffolds on bone tissue formation, particularly in the view of cell signaling pathway. This study aims to investigate the application of HA/TCP composite scaffolds and ES and their effects on the Wingless-related integration site (Wnt) pathway in critical bone repair. Critical bone defects (25 mm2) were performed in rats, which were divided into four groups: PCL, PCL + ES, HA/TCP and HA/TCP + ES. The scaffolds were grafted at the defect site and applied with the ES application twice a week using 10 µA of current for 5 min. Bone samples were collected for histomorphometry, immunohistochemistry and molecular analysis. At the Wnt canonical pathway, HA/TCP and HA/TCP + ES groups showed higher Wnt1 and ß-catenin gene expression levels, especially HA/TCP. Moreover, HA/TCP + ES presented higher Runx2, Osterix and Bmp-2 levels. At the Wnt non-canonical pathway, HA/TCP group showed higher voltage-gated calcium channel (Vgcc), calmodulin-dependent protein kinase II, and Wnt5a genes expression, while HA/TCP + ES presented higher protein expression of VGCC and calmodulin (CaM) at the same period. The decrease in sclerostin and osteopontin genes expressions and the lower bone sialoprotein II in the HA/TCP + ES group may be related to the early bone remodeling. This study shows that the use of ES modulated the Wnt pathways and accelerated the osteogenesis with improved tissue maturation.

The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases.

Cerebral ischemia, a leading cause of disability and mortality worldwide, triggers a cascade of molecular and cellular pathologies linked to several central nervous system (CNS) disorders. These disorders primarily encompass ischemic stroke, Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, and other CNS conditions. Despite substantial progress in understanding and treating the underlying pathological processes in various neurological diseases, there is still a notable absence of effective therapeutic approaches aimed specifically at mitigating the damage caused by these illnesses. Remarkably, ischemia causes severe damage to cells in ischemia-associated CNS diseases. Cerebral ischemia initiates oxygen and glucose deprivation, which subsequently promotes mitochondrial dysfunction, including mitochondrial permeability transition pore (MPTP) opening, mitophagy dysfunction, and excessive mitochondrial fission, triggering various forms of cell death such as autophagy, apoptosis, as well as ferroptosis. Ferroptosis, a novel type of regulated cell death (RCD), is characterized by iron-dependent accumulation of lethal reactive oxygen species (ROS) and lipid peroxidation. Mitochondrial dysfunction and ferroptosis both play critical roles in the pathogenic progression of ischemia-associated CNS diseases. In recent years, growing evidence has indicated that mitochondrial dysfunction interplays with ferroptosis to aggravate cerebral ischemia injury. However, the potential connections between mitochondrial dysfunction and ferroptosis in cerebral ischemia have not yet been clarified. Thus, we analyzed the underlying mechanism between mitochondrial dysfunction and ferroptosis in ischemia-associated CNS diseases. We also discovered that GSH depletion and GPX4 inactivation cause lipoxygenase activation and calcium influx following cerebral ischemia injury, resulting in MPTP opening and mitochondrial dysfunction. Additionally, dysfunction in mitochondrial electron transport and an imbalanced fusion-to-fission ratio can lead to the accumulation of ROS and iron overload, which further contribute to the occurrence of ferroptosis. This creates a vicious cycle that continuously worsens cerebral ischemia injury. In this study, our focus is on exploring the interplay between mitochondrial dysfunction and ferroptosis, which may offer new insights into potential therapeutic approaches for the treatment of ischemia-associated CNS diseases.

Development and validation of an online calculator to predict the pathological nature of colorectal tumors.

BACKGROUND: No single endoscopic feature can reliably predict the pathological nature of colorectal tumors (CRTs). AIM: To establish and validate a simple online calculator to predict the pathological nature of CRTs based on white-light endoscopy. METHODS: This was a single-center study. During the identification stage, 530 consecutive patients with CRTs were enrolled from January 2015 to December 2021 as the derivation group. Logistic regression analysis was performed. A novel online calculator to predict the pathological nature of CRTs based on white-light images was established and verified internally. During the validation stage, two series of 110 images obtained using white-light endoscopy were distributed to 10 endoscopists [five highly experienced endoscopists and five less experienced endoscopists (LEEs)] for external validation before and after systematic training. RESULTS: A total of 750 patients were included, with an average age of 63.6 ± 10.4 years. Early colorectal cancer (ECRC) was detected in 351 (46.8%) patients. Tumor size, left semicolon site, rectal site, acanthosis, depression and an uneven surface were independent risk factors for ECRC. The C-index of the ECRC calculator prediction model was 0.906 (P = 0.225, Hosmer-Lemeshow test). For the LEEs, significant improvement was made in the sensitivity, specificity and accuracy (57.6% vs 75.5%; 72.3% vs 82.4%; 64.2% vs 80.2%; P < 0.05), respectively, after training with the ECRC online calculator prediction model. CONCLUSION: A novel online calculator including tumor size, location, acanthosis, depression, and uneven surface can accurately predict the pathological nature of ECRC.

Crystal Growth of 3D Poly(ε-caprolactone) Based Bone Scaffolds and Its Effects on the Physical Properties and Cellular Interactions.

Extrusion additive manufacturing is widely used to fabricate polymer-based 3D bone scaffolds. However, the insight views of crystal growths, scaffold features and eventually cell-scaffold interactions are still unknown. In this work, melt and solvent extrusion additive manufacturing techniques are used to produce scaffolds considering highly analogous printing conditions. Results show that the scaffolds produced by these two techniques present distinct physiochemical properties, with melt-printed scaffolds showing stronger mechanical properties and solvent-printed scaffolds showing rougher surface, higher degradation rate, and faster stress relaxation. These differences are attributed to the two different crystal growth kinetics, temperature-induced crystallization (TIC) and strain-induced crystallization (SIC), forming large/integrated spherulite-like and a small/fragmented lamella-like crystal regions respectively. The stiffer substrate of melt-printed scaffolds contributes to higher ratio of nuclear Yes-associated protein (YAP) allocation, favoring cell proliferation and differentiation. Faster relaxation and degradation of solvent-printed scaffolds result in dynamic surface, contributing to an early-stage faster osteogenesis differentiation.

The relative contributions of root uptake and remobilization to the loading of Cd and As into rice grains: Implications in simultaneously controlling grain Cd and As accumulation using a segmented water management strategy.

Cadmium (Cd) and arsenic (As) are loaded into rice grain via two pathways: i) root uptake from the soil and then translocation to the grain, and ii) remobilization of Cd and As previously accumulated within the vegetative tissues to the grain. However, the relative contributions of the two pathways are not well understood in soil-grown rice plants. In this study, we used eight different water management regimes applied at different growth periods to manipulate the concentrations of Cd and As in porewater and then established a mathematical model to estimate the relative importance of the two pathways. Different water management regimes had dramatic and opposite effects on the solubility of Cd and As in soil, and their subsequent accumulation in both straw and grain. Water management applied at different growth periods had markedly different impacts on grain Cd and As concentrations. Water management during grain filling had a much greater impact on grain Cd than on grain As concentrations, whereas water treatment during the vegetative growth stage had a larger effect on grain As concentrations. Under the typical water management practice (i.e. flooding through the vegetative stage followed by drainage during grain filling), grain filling is the key period for the accumulation of Cd in the grain, with 98% of the grain Cd from root uptake during this period and the contribution of remobilization being very limited. In contrast, 95% of the grain As was remobilized from that accumulated within the plant prior to the grain filling, with the tillering, jointing, and heading period each contributing 20-40% of the grain As, whereas root uptake during grain filling contributed minor. These differences can be harnessed to design a segmented water management strategy to control grain Cd and As accumulation simultaneously.

Native feedstock options for the polyhydroxyalkanoate industry in Europe: A review.

The United Nations defined 17 Sustainable Development Goals (SDGs) in 2016 and agreed on fighting to confront the climate change and protecting the oceans and forests. Subsequently, the sustainable production of bioplastics is gradually gaining reputation and significance. With the usage of bioplastics such as biodegradable polyhydroxyalkanoates (PHAs) various SDGs would be tackled, but costs remain a crucial factor for competing against fossil-based plastics. Appropriate local feedstock selection can help to reduce the production costs and minimize transportation routes. In this work, four feedstock generations are introduced and respective conversion strategies to PHA are presented. Whilst the focus is on mapping the abundances of feedstocks and potential PHA production capacities in Europe, utilization of animal by-product streams is also highlighted as a rather unconventional but highly abundant feedstock for PHA production.

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.

Protection of bone marrow-derived CD45+/CD34-/lin- stromal cells with immunosuppressant activity against ischemia/reperfusion injury in rats.

Non-hematopoietic CD45+ precursor cells are not known to differentiate into cardiomyocytes. We found that CD45+/CD34-/lin- stromal cells isolated from mouse bone marrow (BMSCs) potentially differentiated into cardiomyocyte-like cells in vitro. Therefore, we hypothesized that the CD45+/CD34-/ lin- BMSCs might protect rat hearts against ischemia/reperfusion (IR) injury following xeno-transplantation. In the present study, BMSCs were isolated by immunoselection and their cellular phenotype and biochemical properties were characterized. The immunological inertness of BMSCs was examined by the allogeneic and xenogeneic mixed lymphocyte reaction (MLR). The potential role of BMSCs for cardioprotection was evaluated by intravenous introduction of 1 x 10(6) cells into rat IR hearts, induced by left coronary ligation for 45 min and released for 72 h. Changes in cardiac contractility and the degree of myocardial injury were assessed. Our findings indicated that BMSCs expressed the muscle-cell marker alpha-actinin after 5-azacytidine treatment. CD45+/CD34-/lin- stromal cells were characterized as mesenchymal progenitor cells based on the expression of Sca-1 and Rex-1. The MLR assay revealed an immunosuppression of BMSCs on mouse and rat lymphocytes. After xeno-transplantation, the BMSCs engrafted into the infarct area and attenuated IR injury. However, increases in intracardial TGF-beta and IFN-gamma contents of IR hearts were not affected by BMSC treatment. Interestingly, ex vivo evidence indicated that CXCR4, SDF-1 and TGFbeta-1 receptors were up-regulated after the cells were exposed to tissue extracts prepared from rat post-IR hearts. In addition, IFN-gamma treatment also markedly increased Sca-1 expression in BMSCs. Mechanistically, these results indicated that CXCR4/SDF-1 and TGF-beta signals potentially enhanced the interaction of BMSCs with the damaged myocardium, and increased IFN-gamma in post-ischemic hearts might cause BMSC to behave more like stem cells in cardioprotection. These data show that CD45+/CD34-/lin- BMSCs possess cardioprotective capacity. Evidently, the accurate production of soluble factors TGF-beta and IFN-gamma in parallel with increased expression of both TGF-beta and Sca-1 receptors may favor BMSCs to achieve a more efficient protective capacity.

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.

3D printing of silk microparticle reinforced polycaprolactone scaffolds for tissue engineering applications.

Polycaprolactone (PCL) scaffolds have been widely investigated for tissue engineering applications, however, they exhibit poor cell adhesion and mechanical properties. Subsequently, PCL composites have been produced to improve the material properties. This study utilises a natural material, Bombyx mori silk microparticles (SMP) prepared by milling silk fibre, to produce a composite to enhance the scaffolds properties. Silk is biocompatible and biodegradable with excellent mechanical properties. However, there are no studies using SMPs as a reinforcing agent in a 3D printed thermoplastic polymer scaffold. PCL/SMP (10, 20, 30 wt%) composites were prepared by melt blending. Rheological analysis showed that SMP loading increased the shear thinning and storage modulus of the material. Scaffolds were fabricated using a screw-assisted extrusion-based additive manufacturing system. Scanning electron microscopy and X-ray microtomography was used to determine scaffold morphology. The scaffolds had high interconnectivity with regular printed fibres and pore morphologies within the designed parameters. Compressive mechanical testing showed that the addition of SMP significantly improved the compressive Young's modulus of the scaffolds. The scaffolds were more hydrophobic with the inclusion of SMP which was linked to a decrease in total protein adsorption. Cell behaviour was assessed using human adipose derived mesenchymal stem cells. A cytotoxic effect was observed at higher particle loading (30 wt%) after 7 days of culture. By day 21, 10 wt% loading showed significantly higher cell metabolic activity and proliferation, high cell viability, and cell migration throughout the scaffold. Calcium mineral deposition was observed on the scaffolds during cell culture. Large calcium mineral deposits were observed at 30 wt% and smaller calcium deposits were observed at 10 wt%. This study demonstrates that SMPs incorporated into a PCL scaffold provided effective mechanical reinforcement, improved the rate of degradation, and increased cell proliferation, demonstrating potential suitability for bone tissue engineering applications.

In Vivo Investigation of Polymer-Ceramic PCL/HA and PCL/ß-TCP 3D Composite Scaffolds and Electrical Stimulation for Bone Regeneration.

Critical bone defects are a major clinical challenge in reconstructive bone surgery. Polycaprolactone (PCL) mixed with bioceramics, such as hydroxyapatite (HA) and tricalcium phosphate (TCP), create composite scaffolds with improved biological recognition and bioactivity. Electrical stimulation (ES) aims to compensate the compromised endogenous electrical signals and to stimulate cell proliferation and differentiation. We investigated the effects of composite scaffolds (PCL with HA; and PCL with ß-TCP) and the use of ES on critical bone defects in Wistar rats using eight experimental groups: untreated, ES, PCL, PCL/ES, HA, HA/ES, TCP, and TCP/ES. The investigation was based on histomorphometry, immunohistochemistry, and gene expression analysis. The vascular area was greater in the HA/ES group on days 30 and 60. Tissue mineralization was greater in the HA, HA/ES, and TCP groups at day 30, and TCP/ES at day 60. Bmp-2 gene expression was higher in the HA, TCP, and TCP/ES groups at day 30, and in the TCP/ES and PCL/ES groups at day 60. Runx-2, Osterix, and Osteopontin gene expression were also higher in the TCP/ES group at day 60. These results suggest that scaffolds printed with PCL and TCP, when paired with electrical therapy application, improve bone regeneration.