Tag: biomaterials

Biomaterials for Improving Ovarian Tissue Transplantation

Biomaterials for Improving Ovarian Tissue Transplantation

Cryopreservation of ovarian tissue and its subsequent transplantation represent a big hope to preserve fertility in young women who have defeated cancer. Ovary revascularization is a crucial factor impacting the outcome of the engraftment. Limited oxygenation may have severe consequences on the ovarian reserve, with a significant loss of follicles. New frontiers in reproductive technology aim to reduce the ischemic/hypoxic window following auto-transplantation procedures. Biomaterials supplemented with ovarian-derived endothelial cells could be the solution to enhance vascular regeneration in the transplanted tissue.

In this study, we propose a combined Advanced Therapeutic Medicinal Product (ATMP) obtained from the association of cryopreserved ovarian tissue with a 3D dermal substitute — a biocompatible and bioactive scaffold employed in regenerative medicine — pre-seeded with vascular system cells previously isolated from the same ovarian tissue. This pre-seeding, known as inosculation, is a bioengineering approach aimed at enhancing revascularization by promoting the formation of novel vascular networks within the scaffold prior to implantation. The goal of the research is to demonstrate that a such graft can boost the growth of new vessels (Fig. 1), potentially improving the ovary survival and functionality.

To evaluate the effectiveness of this approach, several techniques were employed including synchrotron radiation-based X-ray phase-contrast microtomography (SR PC-microCT). As a volumetric imaging technique, SR PC-microCT enables three-dimensional visualization of the inner anatomical structures of the proposed ATMP at high spatial and contrast resolution, with the additional advantage of being non-destructive. Scans were carried out at the SYRMEP Imaging beamline of Elettra. The findings obtained by the X-ray images were complemented by histology and immunohistochemical analyses, adhesion and proliferation assays, gene expression and immunofluorescence. 

A bovine collagen-based scaffold, Integra®, was selected among various dermal substitute materials tested and was used as a support for ovarian transplantation in subsequent in vivo experiments on mouse models. Histology clearly demonstrates the presence of endothelial cells within the Integra® matrix, exhibiting a tendency to form vascular structures. Red-blood cells can be also observed inside the developing vessels (Fig. 2a). Similarly, Fig. 2b shows a virtual slice obtained by X-ray PC microCT of a sample region at the interface between the ovarian tissue and the Integra® support. In agreement with the histological data, the X-ray image shows a massive accumulation of dense structures within the scaffold, which may be attributed to a high concentration of endothelial cells. Notably, SR PC microCT enables the cells distribution within the scanned blocks to be tracked, revealing a migration of the endothelial cells from the matrix into the tissue with a preferential side of accumulation. Supplementary videos are available on the full paper website (please follow the link at bottom of this page).

Read more on Elettra website

 

Seeing more deeply into nanomaterials

Seeing more deeply into nanomaterials

New 3D imaging tool reveals engineered and self-assembled nanoparticle lattices with highest resolution yet—7nm—about 1/100,000 of the width of a human hair

From designing new biomaterials to novel photonic devices, new materials built through a process called bottom-up nanofabrication, or self-assembly, are opening up pathways to new technologies with properties tuned at the nanoscale. However, to fully unlock the potential of these new materials, researchers need to “see” into their tiny creations so that they can control the design and fabrication in order to enable the material’s desired properties.

This has been a complex challenge that researchers from the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory and Columbia University have overcome for the first time, imaging the inside of a novel material self-assembled from nanoparticles with seven nanometer resolution, about 1/100,000 of the width of a human hair. In a new paper published on April 7, 2022 in Science, the researchers showcase the power of their new high-resolution x-ray imaging technique to reveal the inner structure of the nanomaterial. 

The team designed the new nanomaterial using DNA as a programmable construction material, which enables them to create novel engineered materials for catalysis, optics, and extreme environments. During the creation process of these materials, the different building blocks made of DNA and nanoparticles shift into place on their own based on a defined “blueprint”—called a template—designed by the researchers. However, to image and exploit these tiny structures with x-rays, they needed to convert them into inorganic materials that could withstand x-rays while providing useful functionality. For the first time, the researchers could see the details, including the imperfections within their newly arranged nanomaterials.

Read more on the BNL website

Image: An artist’s impression of how the researchers used x-ray tomography as a magnifying lens to see into the inner structure of nanomaterials

We all love science!

We all love science!

#LightSourceSelfie from users of the Australian Light Source

Marta Krasowska (Associate Professor), Sarah Otto (PhD Student) and Stephanie MacWilliams (Early Career Researcher) are scientists based at the University of South Australia. They share a passion for soft matter research and conduct experiments at ANSTO’s Australian Synchrotron. Their research questions relate to structural ordering in soft matter and its relevance in applications such as food, personal care products, biomaterials and pharmaceuticals.

In their #LightSourceSelfie, Marta, Sarah and Stephanie discuss what attracted them to this area of research, how they felt the first time they conducted experiments at the Australian Synchrotron, the support they receive from the team based at the facility, their top tips for surviving night shifts and how their research will benefit from the new BioSAX beamline, which is part of the synchrotron’s major upgrade. When it came to single words to describe their research, they agreed on “Challenging, unpredictable and super rewarding!”

Unravelling the molecular structure, self-assembly, and properties of a cephalopod protein variant

Unravelling the molecular structure, self-assembly, and properties of a cephalopod protein variant

Cephalopods, such as the loliginid in Figure 1A, are known for their remarkable ability to rapidly change the color and appearance of their skin. These capabilities are enabled in part by unique structural proteins called reflectins, which play essential roles in optical behavior of cephalopod skin cells. Moreover, reflectins have demonstrated exciting potential as functional materials within the context of biophotonic and bioelectronic systems. Given reflectins’ demonstrated significance from both fundamental biology and applications perspectives, some research effort has been devoted to resolving their three-dimensional (3D) structures. However, the peculiar sequence composition of reflectins has made them extremely sensitive to subtle changes in environmental conditions and prone to aggregation, thus significantly complicating the study of their structure-function relationships and precluding their definitive molecular-level structural characterization. In this work, we have elucidated the structure of a reflectin variant at the molecular level, demonstrated a robust methodology for controlling its assembly and optical properties.


We began our studies by rationally selecting a prototypical reflectin variant (RfA1TV) by using a bioinformatics-guided approach (Figure 1B). Next, we not only produced the variant in high yield and purity but also optimized conditions for maintaining this protein in a monomeric state (Figure 1C). We then probed the protein with small angle X-ray scattering (SAXS) using the Austrian SAXS beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. For this purpose, a well-dispersed solution of RfA1TV was prepared in a low-pH buffer and transferred into a glass capillary, which was positioned in the path of an incident X-ray beam. The X-rays scattered by the solution-borne RfA1TV molecules formed a 2-D pattern on a Pilatus3 1M detector (Figure 1D). Subsequently, radial averaging and image calibration of the two-dimensional data furnished corresponding one-dimensional curves, which were further processed, analyzed, and correlated with other experiments to obtain insight into the protein’s geometry (Figure 1E).

Read more on the Elettra website

Image: (A) A camera image of a Doryteuthis pealeii squid. (B) An illustration of the selection of the prototypical truncated reflectin variant (RfA1TV) from full-length Doryteuthis pealeii reflectin A1. (C) A digital camera image of a solution of primarily monomeric RfA1TV (Upper) and a corresponding cartoon of RfA1TV monomers (Lower Inset). (D) An illustration of the SAXS analysis of the reflectin variant, wherein incident X-rays are scattered by the solution-borne proteins to furnish a corresponding scattering pattern. (E)The 3D structure of RfA1TV (random coils – gray, helices – orange, β-strands – purple). 

Credit: This figure has been adapted from M. J. Umerani*, P. Pratakshya* et al.Proc. Natl. Acad. Sci. U.S.A 117, 32891-32901 (2020).