MSGID: 1:317/3 627201ba   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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   
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   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.   
      
      
      
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   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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