Probing Depth-Dependent Transition-Metal Redox of Lithium Nickel, Manganese, and Cobalt Oxides in Li-Ion Batteries.

Layered lithium nickel, manganese, and cobalt oxides (NMC) are among the most promising commercial positive electrodes in the past decades. Understanding the detailed surface and bulk redox processes of Ni-rich NMC can provide useful insights into material design options to boost reversible capacity and cycle life. Both hard X-ray absorption (XAS) of metal K-edges and soft XAS of metal L-edges collected from charged LiNi0.6Mn0.2Co0.2O2 (NMC622) and LiNi0.8Mn0.1Co0.1O2 (NMC811) showed that the charge capacity up to removing ∼0.7 Li/f.u. was accompanied with Ni oxidation in bulk and near the surface (up to 100 nm). Of significance to note is that nickel oxidation is primarily responsible for the charge capacity of NMC622 and 811 up to similar lithium removal (∼0.7 Li/f.u.) albeit charged to different potentials, beyond which was followed by Ni reduction near the surface (up to 100 nm) due to oxygen release and electrolyte parasitic reactions. This observation points toward several new strategies to enhance reversible redox capacities of Ni-rich and/or Co-free electrodes for high-energy Li-ion batteries.

Impact of long-term exposure to the tyrosine kinase inhibitor imatinib on the skeleton of growing rats.

The tyrosine kinase (TK) inhibitor imatinib provides a highly effective therapy for chronic myeloid leukemia (CML) via inhibition of the oncogenic TK BCR-ABL1. However, off-target TKs like platelet-derived growth factor receptors (PDGF-R) and colony-stimulating factor-1 receptor (c-fms), involved in bone remodeling, are also inhibited. Thus, pediatric patients with CML on imatinib exhibit altered bone metabolism, leading to linear growth failure. As TKI treatment might be necessary for a lifetime, long-term effects exerted on bone in children are of major concern. Therefore, we studied the skeletal long-term effects of continuous and intermittent imatinib exposure in a juvenile rat model. Four-weeks-old male Wistar rats were chronically exposed to imatinib via drinking water over a period of 10 weeks. Animals were exposed to a standard and high imatinib dosage continuously and to the high imatinib dose intermittently. Bone mass and strength were assessed using pQCT, micro-computed tomography (µCT), and biomechanical testing at the prepubertal, pubertal, and postpubertal age. Bone length and vertebral height as well as biochemical markers of bone turnover were analyzed. Femoral and tibial bone length were dose-dependently reduced by up to 24% (p<0.0001), femoral and tibial trabecular bone mass density (BMD) were reduced by up to 25% (p<0.01), and femoral breaking strength was lowered by up to 20% (p<0.05). Intermittent exposure mitigated these skeletal effects. Long-term exposure resulted in reduced vertebral height by 15% and lower trabecular BMD by 5%. Skeletal changes were associated with suppressed serum osteocalcin (p<0.01) and non-significantly elevated serum CTX-I and PINP levels. In conclusion, imatinib mainly impaired longitudinal growth of long bones rather than the vertebrae of growing rats. Interestingly, intermittent imatinib exposure has less skeletal side effects, which may be beneficial in pediatric patients taking imatinib.

Dose-dependent histological alterations in the rat lung following intravenous application of Re-188-labeled microspheres.

PURPOSE: The objective of this study was to determine the dose-effect correlation of pneumopathy after application of Rhenium-188 microspheres (Re-188 MS) in an animal model using histological changes as an end-point. METHODS AND MATERIALS: Wistar rats received an intravenous injection of Re-188 MS yielding doses that ranged from ˜ 2 to ˜ 55 Gy. Lungs were removed after ˜ 25 weeks and prepared for histology. Sections were evaluated using a semi-quantitative 5-tiered score. Dose groups of 10 Gy intervals were statistically analyzed using the Chi-square test with respect to grade and extent of connective tissue accumulation, thickness of vessel walls and accumulation of alveolar macrophages (AM). RESULTS: There was a statistically significant increase in connective tissue content and extent in all dose groups compared to control lungs and at least between each other dose group. The steepest increase in connective tissue was at doses higher than 40 Gy. Starting from that dose, a statistically significant increase of AM accumulation and vessel wall thickness occurred. CONCLUSIONS: There was a clear dose-effect correlation between radiation dose and histological changes. These findings allow an estimation of potential normal tissue damage especially during tumor treatments of liver lesions with radioactive particles in patients with significant liver-to-lung shunts.

Treatment of fractures of the condylar head with resorbable pins or titanium screws: an experimental study.

We aimed to compare in vivo the stability of fixation of condylar fractures in sheep using sonic bone welding and standard titanium screws. We assessed stability of the osteosynthesis and maintenance of the height of the mandibular ramus. Height decreased slightly in both groups compared with the opposite side. The volume of the condyle increased considerably in both groups mainly because callus had formed. The results showed no significant disadvantages for pin fixation compared with osteosynthesis using titanium screws.

Radiation pneumopathy in the rat after intravenous application of (188)Re-labeled microspheres.

PURPOSE: To determine the dose dependence and kinetics of pneumopathy after systemic administration of rhenium-188 ((188)Re)-labeled microspheres in a rat model. METHODS AND MATERIALS: (188)Re-microspheres were injected intravenously into adult Wistar rats (n = 54, age, 8 ± 2 months). The rats were divided into 6 groups according to the intended absorbed dose in the lung (maximum 60 Gy). Gamma camera scans were used to estimate the individual whole lung doses. One control group (n = 5) received nonlabeled microspheres. The breathing rate was measured before and weekly after the treatment using whole body plethysmography until 24 weeks. An increase in the breathing rate by 20% compared with the individual pretreatment control value was defined as the quantal endpoint for dose-effect analyses. RESULTS: A biphasic increase in the breathing rate was observed. The first impairment of lung function occurred in Weeks 3-6. For late changes, the interval to onset was clearly dose dependent and was 17 weeks (10-30 Gy) and 10 weeks (50-60 Gy), respectively. The incidence of the response was highly dependent on the estimated lung dose. The median effective dose for an early and late response was virtually identical (19.9 ± 0.6 Gy and 20.4 ± 3.1 Gy, respectively). A significant correlation was found between the occurrence of an early and a late effect in the same rat, suggesting a strong consequential component. CONCLUSIONS: The effects of radiolabeled microspheres can be studied longitudinally in a rat model, using changes in the breathing rate as the functional, clinically relevant response. The isoeffective doses from the present study using radionuclide administration and those from published investigations of homogeneous external beam radiotherapy are almost similar.

Long-bone critical-size defects treated with tissue-engineered polycaprolactone-co-lactide scaffolds: a pilot study on rats.

The aim of this study was to evaluate the osteogenic potential of embroidered, tissue-engineered polycaprolactone-co-lactide (trade name: PCL) scaffolds for the reconstruction of large bone defects. Ten piled-up PCL scaffolds were implanted in femura with a critical size defect of immunodeficient nude rats for 12 weeks [n = 4, group 1: noncoated, group 2: collagen I (coll I), group 3: collagen I/chondroitin sulfate (coll I/CS), and group 4: collagen I/chondroitin sulfate/human mesenchymal stem cells (coll I/CS/hMSC)]. X-ray examination, computer tomography, and histological analyses of the explanted scaffold pads were performed. The quantification of the bone volume ratio showed a significantly higher rate of new bone formation at coll I/CS-coated scaffolds compared with the other groups. Histological investigations revealed that the defect reconstruction started from the peripheral bone ends and incorporated into the scaffold material. Additionally seeded hMSC on coll I/CS-coated scaffolds showed a higher matrix deposition inside the implant but no higher bone formation was observed. These data imply that the coll I/CS-coated PCL scaffolds have the highest potential for treating critical size defects. The scaffolds, being variable in size and structure, can be adapted to any bone defect.

Pharmacological modification of the epithelial permeability by benzalkonium chloride in UVA/Riboflavin corneal collagen cross-linking.

PURPOSE: To examine the biomechanical effect and the UVA-absorption of a riboflavin/UVA cross-linking method, which suggests leaving the epithelium intact and applying benzalkonium chloride (BAC) on rabbits' corneas. METHODS: In total, 32 eyes from 16 rabbits were divided into 4 groups. Group 1 was treated with intact epithelium and without BAC. In groups 2 and 3, the epithelium was left intact and a hypoosmolar solution of riboflavin that contained BAC 0.02% or 0.04% was used. Group 4 was treated according to the standard protocol with mechanical debridement of the epithelium. After the treatment of both eyes, the rabbits were euthanized to prepare the corneas in order for the determination of the riboflavin absorption coefficient and biomechanical properties. RESULTS: The absorption coefficients of groups 2, 3, and 4 were significantly increased compared to group 1. There were no significant differences between groups 2, 3, and 4. Stress-strain values and Young's modulus for groups 2, 3, and 4 were significantly increased compared to group 1. The stiffening effects did not differ within groups 2, 3, and 4. The resistance to enzymatic digestion was significantly increased in groups 2, 3, and 4 as compared to group 1. CONCLUSIONS: Treatment with BAC 0.02% induces sufficient epithelial permeability for the passage of riboflavin, which enables its stromal diffusion and results in increased corneal stiffening after cross-linking as compared to the standard protocol. Further safety studies will be required before clinical use.

Histologic study of incorporation and resorption of a bone cement-collagen composite: an in vivo study in the minipig.

OBJECTIVE: Calcium phosphates are clinically established as bone defect fillers. They have the capability of osseoconduction and are characterized by a slow resorption process. The present study evaluated the suitability of a newly developed calcium phosphate cement modified with collagen type I. STUDY DESIGN: The modified cement paste was inserted in differently designed defects of 10 minipigs. Further, an alveolar ridge augmentation was performed, applying the cement paste. The cement hardened in situ during the operation, forming a hydroxyapatite collagen composite. Animals were sacrificed after 1, 3, 6, 12, and 18 months. The tissue integration and resorption process was then evaluated using nondecalcified microsections. All animals were evaluated for histology. RESULTS: The implanted material showed osseoconductive characteristics. Resorption started from the edge of the defect zone, and bone substitution followed rapidly. Twelve months after placement of the cement, complete remodeling was observed. CONCLUSION: It can be concluded that the applied hydroxyapatite-collagen cement composite shows good resorption and bone integration.