The treatment of wounds has always been an important topic in medicine. In the ancient times when medical technology was underdeveloped, people even used the flaming method of burning red iron to treat wounds to avoid infection. Today, when medical technology is quite developed, wounds after surgery usually need to be treated by suture or anastomosis so that the wound can heal. Surgery for internal organs of the human body Due to the presence of body fluids, the treatment of wounds becomes more complicated. In addition, whether it is suture or anastomosis, it actually causes secondary damage to the tissue surrounding the wound, which is not conducive to the effective healing of the wound.
A photocurable hydrogel developed by the Northeastern University, Harvard Medical School, MIT, and the University of Sydney, Australia, which can be used to treat wounds in close contact with wounds within 60 seconds. It is closed and does not affect the contraction and relaxation of the organ, but also naturally degrades, and this degradation time can be adjusted according to the type of wound. After degradation, there will be no residue in the body. Let's take a look at a video introducing the new research by Professor Anthony S. Weiss of the University of Sydney.
This new photocurable hydrogel is a Methacrylated Tropoelastin, referred to as MeTro. Compared to existing commercial medical sealants, MeTro has excellent adhesion and mechanical properties, and once it comes into contact with the surface of the tissue, it solidifies into a gel without loss, and then is irradiated by ultraviolet light. Further stabilization. This feature allows the MeTro to be accurately placed in the desired position and tightly coupled to the structure of the tissue surface and locked to each other.
Professor Anthony S. Weiss introduced, “The potential application of this product is very powerful —— including such as car accidents and the treatment of severe internal injuries caused by the theater, as well as improving the effectiveness of hospital surgery. ”“ The next phase of this technology will be a clinical trial. MeTro is effective under a range of different setting conditions and can solve problems that other commercial medical sealants cannot solve. We are now ready to transfer our research to testing on the human body. I hope that MeTro can be quickly used in clinical applications to save more lives. & rdquo; Elastagen is commercializing this technology.
Let's take a look at this magical medical UV gel MeTro from the perspective of a chemist.
The golden rule for elastic tissue engineering materials is that the material must be a mold-forming, highly elastic, biocompatible, human protein-based polymer that can be embedded in a variety of cells and can proliferate on the surface of the material. A wide variety of elastomeric materials are available, such as polysiloxanes, polyurethanes, polyhydroxyalkanoates, polycitrate glycol esters, polyglycerides and hybrid alginates/polyacrylamides. However, most synthetic chemical elastomers have one or the other limitations. For example, high temperature and biotoxic agents may be required during the synthesis process, making them incompatible with possible cell coating. What MeTro uses is a biomimetic approach that uses a new engineering elastic material derived from elastin that is widely found in human elastic tissue. For example, elastin is contained in the blood vessels, skin, heart, bladder, and elastic cartilage of the human body. While tropoelastin is the natural monomer precursor of elastin, the recombinant elastin based on photocrosslinking can form protein tissue within one minute, which will bring about equivalent elastic tissue.
Most of the elastin in the human body is obtained by the specific oxidation of lysine by lysyl oxidase in the uterus to cause slow cross-linking of the tropoelastin. A variety of cross-linking methods are used to produce three-dimensional elastin-based hydrogels from recombinant human elastin, α-elastin and elastin-like polypeptides. These hydrogels generally have good biocompatibility and the ability to support cell growth both in vitro and in vivo. However, low mechanical properties and cell penetration that is not uniform to the three-dimensional structure of these hydrogels is a problem. In addition, some biotoxic conditions such as chemical cross-linking agents, organic solvents, extended UV irradiation and high pressure used in the manufacture of these hydrogels make it impossible for hydrogels to be viable in the formation process. Embedding. The synthetic route used here is a short-time photo-induced cross-linking of methacrylated elastin, resulting in
An elastin-based hydrogel having a highly elastic three-dimensional loadable cell. The tropoelastin used contained 35 lysine residues per molecule. This method can control the physical properties of the resulting elastomeric hydrogel, including pore properties, swelling properties, and mechanical properties, by varying the degree of methacrylate esterification and polymer concentration.
Synthesis of Methacrylated Elastinogen (MeTro)
The elastin was dissolved in PBS (10% w/v), and esterification was carried out by adding methacrylic anhydride (MA) at 4 & deg; C for 12 hours. The solution was then dialyzed against 4°C in distilled water for 48 hours and lyophilized to give methacrylated elastin (MeTro). Different degrees of esterification can be obtained using different concentrations (e.g., 8, 15, 20%) of methacrylic anhydride.
Preparation of hydrogels for performance testing
MeTro macromonomers with different degrees of methacrylate were used to make photocrosslinked MeTro hydrogels. Different concentrations of MeTro in PBS (eg 5, 10, 15% w/v) were added with 0.5% photoinitiator Irgacure 2959 under 4°C (chemical name: 1-[4-(2-hydroxyethoxy) )-Phenyl]-2-hydroxy-2-methylacetone). The solution was placed between two slides separated by a 150 micron septum using a 10 microliter pipette, and then irradiated with 6.9 mW/cm² UV light (wavelength 360 & ndash; 480 nm) for 35 seconds. Photocrosslinked MeTro gel.
The synthesized MeTro hydrogel has controllable physical properties and can be used in a three-dimensional elastic environment in which cells are embedded and a two-dimensional film in which cells adhere and grow. These hydrogels can be made into a variety of shapes and sizes and exhibit the following advantages over other hydrogels and synthetic elastomers derived from tropoelastin:
1. MeTro gel can be rapidly formed in 35 seconds, which is much shorter than the time required for chemically crosslinked elastin-based hydrogels (about 24 hours);
2. Photocrosslinking MeTro gel in aqueous solution can eliminate the use of toxic cross-linking agents and organic solvents in the synthesis of other hydrogels;
3. The potential for rapid cell coating by MeTro allows cells to be significantly dispersed into the matrix, overcoming cell-to-three dimensions due to common problems such as low porosity, poor interstitial connectivity and small pore size. The problem of minimal matrix penetration;
4. Unlike other synthetic elastomers such as polyurethane, the use of this biodegradable MeTro hydrogel does not cause biotoxicity due to degradation in vivo, as this gel is obtained from human proteins. ;
5. Elastin-based materials are more stable than some other biodegradable elastomers such as PGS, which provides mechanical support prior to the formation of new tissue;
6. The full secreted elastin amino acid sequence, including the presence of a cell-interacting C-terminus, provides an endogenous integrin & alpha; Vβ 3 cell binding site for MeTro gel, allowing for cellular interaction.
Some mechanical properties of MeTro hydrogel materials with different degrees of methacrylate esterification The hydrogel MeTro material based on human protein-loaded cells synthesized by this method has excellent performance, including high ductility and stress. And the recoverability after removal, as well as the rapid polymerization ability and the synthesis method are easy, and can be applied to three-dimensional cell embedding and two-dimensional cell planting. These features allow MeTro to build a unique multifunctional tissue engineering material that is required for elasticity while allowing cell embedding and surface growth. It is believed that once this photocured product is commercialized, it will bring a huge revolution to wound repair and clinical surgery.
Reference material https://sydney.edu.au/news-opinion/news/2017/10/05/_squirtable_-elastic-surgical-glue-seals-wounds-in-60-seconds.html
N.Annabi, S. M. Mithieux, P. Zorlutuna, G. Camci-Unal, A. S. Weiss, A.Khademhosseini, Engineered cell-laden human protein-based elastomer.Biomaterials 34, 5496–5505 (2013).
NasimAnnabi, Yi-Nan Zhang, Alexander Assmann, Ehsan Shirzaei Sani, George Cheng,Antonio D. Lassaletta, Andrea Vegh, Bijan Dehghani, Guillermo U. Ruiz-Esparza,Xichi Wang, Sidhu Gangadharan, Anthony S. Weiss, Ali Khademhosseini, Engineeringa highly elastic human protein–based sealant for surgical applications, ScienceTranslational Medicine 9, 7466-7479 (2017)