Near-infrared analysis of nanofibrillated cellulose aerogel manufacturing

Biomaterial aerogel fabrication by freeze-drying must be further improved to reduce the costs of lengthy freeze-drying cycles and to avoid the formation of spongy cryogels and collapse of the aerogel structures. Residual water content is a critical quality attribute of the freeze-dried product, which can be monitored in-line with near-infrared (NIR) spectroscopy. Predictive models of NIR have not been previously applied for biomaterials and the models were mostly focused on the prediction of only one formulation at a time. We recorded NIR spectra of different nanofibrillated cellulose (NFC) hydrogel formulations during the secondary drying and set up a partial least square regression model to predict their residual water contents. The model can be generalized to measure residual water of formulations with different NFC concentrations and the excipients, and the NFC fiber concentrations and excipients can be separated with the principal component analysis. Our results provide valuable information about the freeze-drying of biomaterials and aerogel fabrication, and how NIR spectroscopy can be utilized in the optimization of residual water content.Peer reviewe

Critical-sized cartilage defects in the equine carpus

Aim: The horse joint, due to its similarity with the human joint, is the ultimate model for translational articular cartilage repair studies. This study was designed to determine the critical size of cartilage defects in the equine carpus and serve as a benchmark for the evaluation of new cartilage treatment options. Material and Methods: Circular full-thickness cartilage defects with a diameter of 2, 4, and 8 mm were created in the left middle carpal joint and similar osteochondral (3.5 mm in depth) defects in the right middle carpal joint of 5 horses. Spontaneously formed repair tissue was examined macroscopically, with MR and mu CT imaging, polarized light microscopy, standard histology, and immunohistochemistry at 12 months. Results: Filling of 2 mm chondral defects was good (77.8 +/- 8.5%), but proteoglycan depletion was evident in Safranin-O staining and gadolinium-enhanced MRI (T-1Gd). Larger chondral defects showed poor filling (50.6 +/- 2.7% in 4 mm and 31.9 +/- 7.3% in 8 mm defects). Lesion filling in 2, 4, and 8 mm osteochondral defects was 82.3 +/- 3.0%, 68.0 +/- 4.6% and 70.8 +/- 15.4%, respectively. Type II collagen staining was seen in 9/15 osteochondral defects but only in 1/15 chondral defects. Subchondral bone pathologies were evident in 14/15 osteochondral samples but only in 5/15 chondral samples. Although osteochondral lesions showed better neotissue quality than chondral lesions, the overall repair was deemed unsatisfactory because of the subchondral bone pathologies. Conclusion: We recommend classifying 4 mm as critical osteochondral lesion size and 2 mm as critical chondral lesion size for cartilage repair research in the equine carpal joint model.Peer reviewe

Bath concentration of anionic contrast agents does not affect their diffusion and distribution in articular cartilage in vitro

Objective: Differences in contrast agent diffusion reflect changes in composition and structure of articular cartilage. However, in clinical application the contrast agent concentration in the joint capsule varies, which may affect the reliability of contrast enhanced cartilage tomography (CECT). In the present study, effects of concentration of x-ray contrast agents on their diffusion and equilibrium distribution in cartilage were investigated. Design: Full-thickness cartilage discs (d = 4.0 mm, n = 120) were detached from bovine patellae (n = 24). The diffusion of various concentrations of ioxaglate (5, 10, 21, 50 mM) and iodide (30, 60, 126, 300 mM) was allowed only through the articular surface. Samples were imaged with a clinical peripheral quantitative computed tomography scanner before immersion in contrast agent, and after 1, 5, 9, 16, 25, and 29 hours in the bath. Results: Diffusion and partition coefficients were similar between different contrast agent concentrations. The diffusion coefficient of iodide (473 ± 133 μm2/s) was greater (P ≤ 0.001) than that of ioxaglate (92 ± 46 μm2/s). In full-thickness cartilage, the partition coefficient (at 29 h) of iodide (71 ± 5%) was greater (P ≤ 0.02 with most concentrations) than that of ioxaglate (62 ± 6%). Conclusions: Significant differences in partition and diffusion coefficient of two similarly charged (-1) contrast agents were detected, which shows the effect of steric interactions. However, the increase in solute concentration did not increase its partition coefficient. In clinical application, it is important that contrast agent concentration does not affect the interpretation of CECT imaging

Diffusion and near-equilibrium distribution of MRI and CT contrast agents in articular cartilage

Charged contrast agents have been used both in vitro and in vivo for estimation of the fixed charge density (FCD) in articular cartilage. In the present study, the effects of molecular size and charge on the diffusion and equilibrium distribution of several magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were investigated. Full thickness cartilage disks ( = 4.0 mm, n = 64) were prepared from fresh bovine patellae. Contrast agent (gadopentetate: Magnevist, gadodiamide: Omniscan™, ioxaglate: Hexabrix™ or sodium iodide: NaI) diffusion was allowed either through the articular surface or through the deep cartilage. CT imaging of the samples was conducted before contrast agent administration and after 1, 5, 9, 16, 25 and 29 h (and with three samples after 2, 3, 4 and 5 days) diffusion using a clinical peripheral quantitative computed tomography (pQCT) instrument. With all contrast agents, the diffusion through the deep cartilage was slower when compared to the diffusion through the articular surface. With ioxaglate, gadopentetate and gadodiamide it took over 29 h for diffusion to reach the near-equilibrium state. The slow diffusion of the contrast agents raise concerns regarding the validity of techniques for FCD estimation, as these contrast agents may not reach the equilibrium state that is assumed. However, since cartilage composition, i.e. deep versus superficial, had a significant effect on diffusion, imaging of the nonequilibrium diffusion process might enable more accurate assessment of cartilage integrity

Effects of irradiation in the mandibular bone loaded with dental implants. An experimental study with a canine model

Radiation therapy may compromise the quality of bone around dental implants, and its ability to regenerate, remodel, and revascularize. This study aimed to describe the irradiation effect on the bone microstructure of the mandible using dental implants in a canine model. Five beagle dogs were exposed to 40 Gy fractionated radiation. In total, 20 dental implants were inserted, two in the irradiated and two in the non-irradiated side. The mandible bone blocks were subjected to 3D micro-computed tomography (µCT) imaging, later evaluated histomorphometrically by light microscopy and scanning electron microscopy. Alterations in irradiated bone were observed under µCT imaging showing an increased anisotropy, porosity, and pore volume. Bone surface-to-bone volume decreased. The bone to implant contact index was significantly reduced in the irradiated bone (75.6% ± 5.8%) as compared to the non-irradiated bone (85.1% ± 6.8%). In the irradiated mandible, osteocytes with their filopodial processes, the bone beneath the periosteum, and subperiosteal veins showed structural differences but were not significant, whereas the diameter of Haversian canals were smaller statistical significant as compared to the control side. The study highlights that radiation dosage of fractioned 40 Gy causes alterations in the alveolar bone microstructure with compatible osseointegration and clinically stable dental implants

Critical-sized cartilage defects in the equine carpus

Abstract Aim: The horse joint, due to its similarity with the human joint, is the ultimate model for translational articular cartilage repair studies. This study was designed to determine the critical size of cartilage defects in the equine carpus and serve as a benchmark for the evaluation of new cartilage treatment options. Material and methods: Circular full-thickness cartilage defects with a diameter of 2, 4, and 8 mm were created in the left middle carpal joint and similar osteochondral (3.5 mm in depth) defects in the right middle carpal joint of 5 horses. Spontaneously formed repair tissue was examined macroscopically, with MR and µCT imaging, polarized light microscopy, standard histology, and immunohistochemistry at 12 months. Results: Filling of 2 mm chondral defects was good (77.8 ± 8.5%), but proteoglycan depletion was evident in Safranin-O staining and gadolinium-enhanced MRI (T1Gd). Larger chondral defects showed poor filling (50.6 ± 2.7% in 4 mm and 31.9 ± 7.3% in 8 mm defects). Lesion filling in 2, 4, and 8 mm osteochondral defects was 82.3 ± 3.0%, 68.0 ± 4.6% and 70.8 ± 15.4%, respectively. Type II collagen staining was seen in 9/15 osteochondral defects but only in 1/15 chondral defects. Subchondral bone pathologies were evident in 14/15 osteochondral samples but only in 5/15 chondral samples. Although osteochondral lesions showed better neotissue quality than chondral lesions, the overall repair was deemed unsatisfactory because of the subchondral bone pathologies. Conclusion: We recommend classifying 4 mm as critical osteochondral lesion size and 2 mm as critical chondral lesion size for cartilage repair research in the equine carpal joint model