• Repairing tendons with silk proteins

    From ScienceDaily@1:317/3 to All on Tue May 3 22:30:40 2022
    Repairing tendons with silk proteins

    Date:
    May 3, 2022
    Source:
    Terasaki Institute for Biomedical Innovation
    Summary:
    Researchers have developed a silk composite for significantly
    improved tendon regeneration and repair.



    FULL STORY ==========================================================================
    Just mentioning a ruptured Achilles tendon would make anyone wince. Tendon injuries are well known for their lengthy, difficult and often incomplete healing processes. Sudden or repetitive motion, experienced by athletes
    and factory workers, for example, increases the risk of tears or ruptures
    in the tendons; thirty percent of all people will have a tendon injury,
    with the risk being highest in women. What's more, those who suffer from
    these injuries are more prone to further injuries at the site or never
    recover fully.


    ========================================================================== Tendons are bands of fibrous connective tissue that attach muscles
    to bones.

    They are soft tissues connected to stiff bones; this creates a
    complex interface with a very specific structure. Following injury,
    this structure is disrupted, and the connective tissue changes from a
    linear to a kinked formation. Excess scarring can also occur, changing
    the tendon's mechanical properties and its ability to bear loads.

    During the body's natural healing processes, tendon and other cells
    are recruited to reconstruct the tendon's original matrix of aligned
    connective tissue fibers. But this reconstruction can take weeks to months
    and the resultant tendon is often imperfect. This results in weakness,
    chronic pain and decreased quality of life.

    Possible treatments for tendon injuries include tendon tissue grafts from patients or donors, but these pose risks such as infections, transplant rejection or necrosis. Synthetic transplants have been attempted, but mechanical, biocompatibility and biodegradation issues have hampered
    these efforts.

    Another approach is to use mesenchymal stem cells (MSCs), specialized
    cells that play a pivotal role in tissue regeneration. At the wound site,
    they can differentiate into various cells types and produce signaling
    molecules which regulate immune response, cellular migration, and new
    blood vessel formation; this enables tissue regeneration.

    However, treatment methods using systemic infusion, direct injection or
    genetic modification of MSCs present their own difficulties: infusion
    lacks targeting specificity to the injury site, direct injection requires prohibitively high cell numbers, and genetic modification is inefficient
    and produces cells that are difficult to isolate.



    ==========================================================================
    Yet another approach has been to construct biomaterial frameworks,
    or scaffolds, on which to introduce MSCs and growth factors in order
    to generate new tendon tissue. A collaborative team from the Terasaki
    Institute for Biomedical Innovation (TIBI) has utilized this approach
    to develop a method which has yielded significant improvements in MSC
    tendon regeneration.

    The team first turned to silk fibroin, a silk protein produced by
    the Bombyx mori silkworm. In addition to its use in beautiful silk
    fabrics, silk fibroin is used in optical and electrical devices, and in
    several biomedical applications, from suture materials to bioengineered ligaments, bone and even corneal tissue. Because of its superior strength, durability, biocompatibility and bio-degradative qualities, silk fibroin
    is ideal for use in scaffolds for tendons.

    In order to improve the scaffold's ability for tissue regeneration, the
    team next paired silk fibroin with GelMA, a gelatin-based, water-retaining
    gel, due to GelMA's biocompatibility, controllable degradation, stiffness
    and ability to promote cell attachment and growth.

    "The synergistic effects of GelMA's capacity for supporting regenerative
    tissue formation and the structural advantages of silk fibroin make
    our composite material well suited for tendon repair," said HanJun Kim,
    Ph.D., D.V.M, TIBI's team leader on the project.

    They prepared mixtures with varying ratios of silk fibroin and GelMA
    (SG) and fabricated them into thin nanofiber sheets. They then tested
    the sheets for fiber structure and stretchiness and chose an optimum formulation with the best mechanical properties. They also observed
    that the silk fibroin imparted an increased porosity to the material;
    this enhances tendon repair.



    ==========================================================================
    The optimized SG sheets were seeded with MSCs and subjected to various
    tests to measure MSC compatibility and differentiation, growth factor production, and genetic activity triggering matrix formation.

    The MSCs on the SG sheets showed an increase in cell viability
    and proliferation over those on silk fibroin sheets without GelMA
    (SF). Genetic analysis showed that relevant gene activity in SG MSCs
    was significantly increased, in contrast to those on SF sheets, which
    was decreased.

    Staining tests revealed that the MSCs on the SG sheets showed a more
    than 80% attachment rate and had an elongated shape characteristic of
    cells attached to a surface, as opposed to a 60% attachment rate, with spherically-shaped cells observed on SF and GelMA only surfaces.

    Further tests on a growth factor secreted by MSCs seeded onto nanofiber
    sheets showed that the growth factors produced by the MSCs on the SG
    sheets were best able to repair injured tendon tissue cultivated in a
    culture dish.

    Experiments were also conducted on live rats with injured Achilles
    tendons.

    MSC-seeded nanofiber sheets were implanted onto the injury site and the
    SG sheets promoted the most accelerated healing, with reduced injury
    sites and the formation of well-aligned, densely packed tendon fibers
    and remodeled muscle components.

    "Tissue remodeling for tendon repair is especially difficult to achieve,"
    said Ali Khademhosseini, Ph.D., TIBI's Director and CEO. "The work done
    here significantly advances that achievement." Authors are: Yumeng Xue,
    HanJun Kim, Junmin Lee, Yaowen Liu, Tyler Hoffman, Yi Chen, Xingwu Zhou,
    Wujin Sun, Shiming Zhang, Hyun-Jong Cho, JiYong Lee, WonHyoung Ryu,
    Chang Moon Lee, Samad Ahadian, Mehmet R. Dokmeci, Bo Lei, KangJu Lee,
    and Ali Khademhosseini.

    This work was supported by the National Institutes of Health (EB021857, EB022403 and R01EB021857).


    ========================================================================== Story Source: Materials provided by Terasaki_Institute_for_Biomedical_Innovation. Note: Content may be edited
    for style and length.


    ========================================================================== Journal Reference:
    1. Yumeng Xue, Han‐Jun Kim, Junmin Lee, Yaowen Liu, Tyler
    Hoffman, Yi
    Chen, Xingwu Zhou, Wujin Sun, Shiming Zhang, Hyun‐Jong Cho,
    JiYong Lee, Heemin Kang, WonHyoung Ryu, Chang‐Moon Lee, Samad
    Ahadian, Mehmet R. Dokmeci, Bo Lei, KangJu Lee, Ali Khademhosseini.

    Co‐Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet
    Seeded with Mesenchymal Stem Cells for Tendon Regeneration. Small,
    2022; 2107714 DOI: 10.1002/smll.202107714 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/05/220503091508.htm

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