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1. Collagen Fibril Abnormalities in Human and Mice Abdominal Aortic Aneurysm

   Jones, B. ; Tonniges, J. R. ; Debsk, A.i ; Albert, B. ; Yeung, D. A. ; Gadde, N. ; Mahajan, A. ; Sharma, N. ; Calomeni, E. P. ; Go, M. ; et al ( August 2020 , Biomedical Engineering Society 2020 Annual Meeting)

   null (Ed.)

   Introduction: Vascular diseases like abdominal aortic aneurysms (AAA) are characterized by a drastic remodeling of the vessel wall, accompanied with changes in the elastin and collagen content. At the macromolecular level, the elastin fibers in AAA have been reported to undergo significant structural alterations. While the undulations (waviness) of the collagen fibers is also reduced in AAA, very little is understood about changes in the collagen fibril at the sub-fiber level in AAA as well as in other vascular pathologies. Materials and Methods: In this study we investigated structural changes in collagen fibrils in human AAA tissue extracted at the time of vascular surgery and in aorta extracted from angiotensin II (AngII) infused ApoE−/− mouse model of AAA. Collagen fibril structure was examined using transmission electron microscopy and atomic force microscopy. Images were analyzed to ascertain length and depth of D-periodicity, fibril diameter and fibril curvature. Tissues were also stained using collagen hybridizing peptide (CHP) and analyzed using fluorescent microscopy and second harmonic generation (SHG) microscopy to locate regions of healthy and degraded collagen. Results: Abnormal collagen fibrils with compromised D-periodic banding were observed in the excised human tissue and in remodeled regions of AAA in AngII infused mice (Figure 1). These abnormal fibrils were characterized by statistically significant reduction in depths of D-periods and an increased curvature of collagen fibrils. These features were more pronounced in human AAA as compared to murine samples. Additionally, regions of abnormal collagen were located within the remodeled areas of AAA tissue and were distinct from healthy collagen regions as ascertained using CHP staining and SHG (Figure 1). Thoracic aorta from Ang II-infused mice, abdominal aorta from saline-infused mice, and abdominal aorta from non-AAA human controls did not contain abnormal collagen fibrils. Conclusions: The structural alterations in abnormal collagen fibrils appear similar to those reported for collagen fibrils subjected to mechanical overload or chronic inflammation in other tissues. Detection of abnormal collagen could be utilized to better understand the functional properties of the underlying extracellular matrix in vascular as well as other pathologies. 

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2. Second harmonic generation characterization of collagen in whole bone

   https://doi.org/10.1364/BOE.391866  

   Pendleton, Emily G. ; Tehrani, Kayvan F. ; Barrow, Ruth P. ; Mortensen, Luke J. ( July 2020 , Biomedical Optics Express)

   Bone is a unique biological composite material made up of a highly structured collagen mesh matrix and mineral deposits. Although mineral provides stiffness, collagen’s secondary organization provides a critical role in bone elasticity. Here, we performed polarimetric analysis of bone collagen fibers using second harmonic generation (SHG) imaging to evaluate lamella sheets and collagen fiber integrity in intact cranial bone. Our polarimetric data was fitted to a model accounting for diattenuation, polarization cross-talk, and birefringence. We compared our data to the fitted model and found no significant difference between our polarimetric observation and the representation of these scattering properties up to 70µm deep. We also observed a loss of resolution as we imaged up to 70µm deep into bone but a conservation of polarimetric response. Polarimetric SHG allows for the discrimination of collagen lamellar sheet structures in intact bone. Our work could allow for label-free identification of disease states and monitor the efficacy of therapies for bone disorders.

    

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3. Ex-vivo quantification of ovine pia arachnoid complex biomechanical properties under uniaxial tension

   https://doi.org/10.1186/s12987-020-00229-w  

   Conley Natividad, Gabryel ; Theodossiou, Sophia K. ; Schiele, Nathan R. ; Murdoch, Gordon K. ; Tsamis, Alkiviadis ; Tanner, Bertrand ; Potirniche, Gabriel ; Mortazavi, Martin ; Vorp, David A. ; Martin, Bryn A. ( December 2020 , Fluids and Barriers of the CNS)

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   Abstract Background The pia arachnoid complex (PAC) is a cerebrospinal fluid-filled tissue conglomerate that surrounds the brain and spinal cord. Pia mater adheres directly to the surface of the brain while the arachnoid mater adheres to the deep surface of the dura mater. Collagen fibers, known as subarachnoid trabeculae (SAT) fibers, and microvascular structure lie intermediately to the pia and arachnoid meninges. Due to its structural role, alterations to the biomechanical properties of the PAC may change surface stress loading in traumatic brain injury (TBI) caused by sub-concussive hits. The aim of this study was to quantify the mechanical and morphological properties of ovine PAC. Methods Ovine brain samples (n = 10) were removed from the skull and tissue was harvested within 30 min post-mortem. To access the PAC, ovine skulls were split medially from the occipital region down the nasal bone on the superior and inferior aspects of the skull. A template was used to remove arachnoid samples from the left and right sides of the frontal and occipital regions of the brain. 10 ex-vivo samples were tested with uniaxial tension at 2 mm s −1 , average strain rate of 0.59 s −1 , until failure at < 5 h post extraction. The force and displacement data were acquired at 100 Hz. PAC tissue collagen fiber microstructure was characterized using second-harmonic generation (SHG) imaging on a subset of n = 4 stained tissue samples. To differentiate transverse blood vessels from SAT by visualization of cell nuclei and endothelial cells, samples were stained with DAPI and anti-von Willebrand Factor, respectively. The Mooney-Rivlin model for average stress–strain curve fit was used to model PAC material properties. Results The elastic modulus, ultimate stress, and ultimate strain were found to be 7.7 ± 3.0, 2.7 ± 0.76 MPa, and 0.60 ± 0.13, respectively. No statistical significance was found across brain dissection locations in terms of biomechanical properties. SHG images were post-processed to obtain average SAT fiber intersection density, concentration, porosity, tortuosity, segment length, orientation, radial counts, and diameter as 0.23, 26.14, 73.86%, 1.07 ± 0.28, 17.33 ± 15.25 µm, 84.66 ± 49.18°, 8.15%, 3.46 ± 1.62 µm, respectively. Conclusion For the sizes, strain, and strain rates tested, our results suggest that ovine PAC mechanical behavior is isotropic, and that the Mooney-Rivlin model is an appropriate curve-fitting constitutive equation for obtaining material parameters of PAC tissues. 

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4. Composition and structure of porcine digital flexor tendon‐bone insertion tissues

   https://doi.org/10.1002/jbm.a.36162  

   Chandrasekaran, Sandhya ; Pankow, Mark ; Peters, Kara ; Huang, Hsiao‐Ying Shadow ( August 2017 , Journal of Biomedical Materials Research Part A)

   Tendon‐bone insertion is a functionally graded tissue, transitioning from 200 MPa tensile modulus at the tendon end to 20 GPa tensile modulus at the bone, across just a few hundred micrometers. In this study, we examine the porcine digital flexor tendon insertion tissue to provide a quantitative description of its collagen orientation and mineral concentration by using Fast Fourier Transform (FFT) based image analysis and mass spectrometry, respectively. Histological results revealed uniformity in global collagen orientation at all depths, indicative of mechanical anisotropy, although at mid‐depth, the highest fiber density, least amount of dispersion, and least cellular circularity were evident. Collagen orientation distribution obtained through 2D FFT of histological imaging data from fluorescent microscopy agreed with past measurements based on polarized light microscopy. Results revealed global fiber orientation across the tendon‐bone insertion to be preserved along direction of physiologic tension. Gradation in the fiber distribution orientation index across the insertion was reflective of a decrease in anisotropy from the tendon to the bone. We provided elemental maps across the fibrocartilage for its organic and inorganic constituents through time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS). The apatite intensity distribution from the tendon to bone was shown to follow a linear trend, supporting past results based on Raman microprobe analysis. The merit of this study lies in the image‐based simplified approach to fiber distribution quantification and in the high spatial resolution of the compositional analysis. In conjunction with the mechanical properties of the insertion tissue, fiber, and mineral distribution results for the insertion from this may potentially be incorporated into the development of a structural constitutive approach toward computational modeling. Characterizing the properties of the native insertion tissue would provide the microstructural basis for developing biomimetic scaffolds to recreate the graded morphology of a fibrocartilaginous insertion. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3050–3058, 2017.

    

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5. Real time full-color imaging in a Meta-optical fiber endoscope

   https://doi.org/10.1186/s43593-023-00044-4  

   Fröch, Johannes E. ; Huang, Luocheng ; Tanguy, Quentin A. A. ; Colburn, Shane ; Zhan, Alan ; Ravagli, Andrea ; Seibel, Eric J. ; Böhringer, Karl F. ; Majumdar, Arka ( June 2023 , eLight)

   Endoscopes are an important component for the development of minimally invasive surgeries. Their size is one of the most critical aspects, because smaller and less rigid endoscopes enable higher agility, facilitate larger accessibility, and induce less stress on the surrounding tissue. In all existing endoscopes, the size of the optics poses a major limitation in miniaturization of the imaging system. Not only is making small optics difficult, but their performance also degrades with downscaling. Meta-optics have recently emerged as a promising candidate to drastically miniaturize optics while achieving similar functionalities with significantly reduced size. Herein, we report an inverse-designed meta-optic, which combined with a coherent fiber bundle enables a 33% reduction in the rigid tip length over traditional gradient-index (GRIN) lenses. We use the meta-optic fiber endoscope (MOFIE) to demonstrate real-time video capture in full visible color, the spatial resolution of which is primarily limited by the fiber itself. Our work shows the potential of meta-optics for integration and miniaturization of biomedical devices towards minimally invasive surgery.

    

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