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    Aligned ‘noodles’ could pave way for lab-grown biological tissue

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    Researchers have achieved a significant milestone in their work to create a biomaterial that can be used to grow biological tissues outside the human body.

    The development of a new fabrication process to create aligned nanofiber hydrogels could offer new possibilities for tissue regeneration after injury and provide a way to test therapeutic drug candidates without the use of animals.

    Jeffrey Hartgerink, professor of chemistry and bioengineering at Rice University and colleagues, developed peptide-based hydrogels that mimic the aligned structure of muscle and nerve tissues. Alignment is critical for the tissues’ functionality, but it is a challenging feature to reproduce in the lab, as it entails lining up individual cells.

    For over 10 years, the team has been designing multidomain peptides (MDPs) that self-assemble into nanofibers. These resemble the fibrous proteins found naturally in the body, much like a spiderweb at nanoscale.

    In their latest study, published in the journal ACS Nano, the researchers discovered a new method to create aligned MDP nanofiber “noodles.” By first dissolving the peptides in water and then extruding them into a salty solution, they were able to create aligned peptide nanofibers—like twisted strands of rope smaller than a cell. By increasing the concentration of ions, or salt, in the solution and repeating the process, they achieved even greater alignment of the nanofibers.

    “Our findings demonstrate that our method can produce aligned peptide nanofibers that effectively guide cell growth in a desired direction,” explains lead author Adam Farsheed, who recently received his PhD in bioengineering from Rice. “This is a crucial step toward creating functional biological tissues for regenerative medicine applications.”

    One of the key findings of the study was an unexpected discovery: When the alignment of the peptide nanofibers was too strong, the cells no longer aligned. Further investigation revealed that the cells needed to be able to “pull” on the peptide nanofibers to recognize the alignment.

    When the nanofibers were too rigid, the cells were unable to exert this force and failed to arrange themselves in the desired configuration.

    “This insight into cell behavior could have broader implications for tissue engineering and biomaterial design,” says Hartgerink. “Understanding how cells interact with these materials at the nanoscale could lead to more effective strategies for building tissues.”

    Additional coauthors are from Rice and the University of Houston.

    The National Institutes of Health, the National Science Foundation, and the Welch Foundation supported the work. The content in this news release is solely the responsibility of the authors and does not necessarily represent the official views of the funding organizations.

    Source: Rice University

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    ‘Origami organs’ could regenerate tissue

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    A new kind of bioactive “tissue paper” is made of materials derived from organs that are thin and flexible enough to fold into an origami bird.

    The technology could potentially be used to support natural hormone production in young cancer patients and aid wound healing.

    “It’s versatile and surgically friendly.”

    The tissue papers are made from structural proteins excreted by cells that give organs their form and structure and are combined with a polymer to make the material pliable.

    For the study, researchers used individual types of tissue papers made from ovarian, uterine, kidney, liver, muscle, or heart proteins obtained by processing pig and cow organs. Each tissue paper had specific cellular properties of the organ from which it was made.

    “This new class of biomaterials has potential for tissue engineering and regenerative medicine as well as drug discovery and therapeutics,” says corresponding author Ramille Shah, assistant professor of surgery and assistant professor of materials science and engineering at Northwestern University. “It’s versatile and surgically friendly.”

    For wound healing, the tissue paper could provide support and the cell signaling needed to help regenerate tissue to prevent scarring and accelerate healing, Shah says.

    The tissue papers are made from natural organs or tissues. The cells are removed, leaving the natural structural proteins—known as the extracellular matrix—that then are dried into a powder and processed into the tissue papers. Each type of paper contains residual biochemicals and protein architecture from its original organ that can stimulate cells to behave in a certain way.

    In the lab of reproductive scientist Teresa Woodruff, the tissue paper made from a bovine ovary was used to grow ovarian follicles when they were cultured in vitro. The follicles (eggs and hormone-producing cells) grown on the tissue paper produced hormones necessary for proper function and maturation.

    “This could provide another option to restore normal hormone function to young cancer patients who often lose their hormone function as a result of chemotherapy and radiation,” says Woodruff, a coauthor of the study that appears in Advanced Functional Materials.

    A strip of the ovarian paper with the follicles could be implanted under the arm to restore hormone production for cancer patients or even women in menopause.

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    Further, the tissue paper made from various organs separately supported the growth of adult human stem cells. Scientists placed human bone marrow stem cells on the tissue paper, and all the stem cells attached and multiplied over four weeks.

    “I knew right then I could make large amounts of bioactive materials from other organs.”

    “That’s a good sign that the paper supports human stem cell growth,” says first author Adam Jakus, who developed the tissue papers. “It’s an indicator that once we start using tissue paper in animal models it will be biocompatible.”

    The tissue papers feel and behave much like standard office paper when they’re dry, Jakus says. He simply stacks them in a refrigerator or a freezer. They can even be folded into an origami bird.
    “Even when wet, the tissue papers maintain their mechanical properties and can be rolled, folded, cut, and sutured to tissue,” he says.

    An accidental spill of 3D printing ink sparked the invention of the tissue paper. Jakus was attempting to make a 3D printable ovary ink similar to the other 3D printable materials he previously developed to repair and regenerate bone, muscle and nerve tissue. When he went to wipe up the spill, the ovary ink had already formed a dry sheet.

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    “When I tried to pick it up, it felt strong,” he says. “I knew right then I could make large amounts of bioactive materials from other organs. The light bulb went on in my head. I could do this with other organs.”

    “It is really amazing that meat and animal by-products like a kidney, liver, heart, and uterus can be transformed into paper-like biomaterials that can potentially regenerate and restore function to tissues and organs. I’ll never look at a steak or pork tenderloin the same way again.”

    Jakus was a Hartwell postdoctoral fellow in Shah’s lab for the study and is now chief technology officer and cofounder of the startup company Dimension Inx, LLC, which Shah also cofounded. The company will develop, produce, and sell 3D-printable materials primarily for medical applications. The Intellectual Property is owned by Northwestern University and will be licensed to Dimension Inx.

    The Center for Reproductive Health After Disease of the National Centers for Translational Research in Reproduction and Infertility, Google, and the Hartwell Foundation supported the work.

    Source: Northwestern University