Wound disinfection healing
Wound management has always been an important topic in medicine.In ancient times, when medical technology was underdeveloped, people even used horrible methods such as red-hot soldering irons to treat wounds to avoid infection.Nowadays, with the development of medical technology, wounds after surgery usually need to be treated by suture or anastomosis, so that the wound can be healed.For the operation of internal organs of the human body, the treatment of wounds will become more complicated due to the presence of body fluids and so on.In addition, no matter the method of suture or anastomosis, it actually causes secondary damage to the tissue around the wound, which is not conducive to the effective healing of the wound.
By Northeastern University, Harvard medical school, Massachusetts institute of technology and the university of Sydney in Australia, and other institutions to research and development of a light curing water gel, can be in 60 seconds through close contact with the wound to close the wound, and will not affect the organs of the contraction and relaxation, and also can be natural degradation, and the degradation time can be adjusted according to the type of wound.After degradation, there will be no residual in the body.Let's start with professor Anthony s. Weiss of the university of Sydney.
The new photocurable hydrogel is a Methacrylated Tropoelastin, or MeTro.Compared with existing commercial medical sealants, MeTro has excellent adhesion and mechanical properties, and once it comes into contact with the tissue surface, it will solidify into a gel without loss, and then further stabilize by ultraviolet radiation.This feature enables MeTro to be placed precisely where it is needed and to be tightly connected and locked into the structure of the organizational surface.
Professor Anthony s. Weiss said, "the potential applications of this product are very powerful -- including the management of serious internal injuries such as car crashes and war zones, as well as improving the effectiveness of hospital surgery.""The next phase of this technology will be clinical trials. MeTro works under a range of different Settings and can solve problems that other commercial medical sealants cannot.We are now ready to move our research to human testing.I hope MeTro will soon be used in clinical applications to save more lives. Elastagen is commercializing this technology.
Let's take a look at this amazing medical UV adhesive MeTro from the perspective of a chemical man.
The golden rule of elastic tissue engineering materials is that they must be moldable, highly elastic, and biocompatible protein-based polymers that can be embedded in a variety of cells and proliferate on the surface of the material.There are many types of elastomeric materials available, such as polysiloxane, polyurethane, polyhydroxy alkylate, polycitrate glycol ester, polysebacate and heterozygated alginate/polyacrylamide.But most synthetic chemical elastomers have limitations of one kind or another.For example, high temperatures and biotoxic reagents may be required during synthesis, making them incompatible with possible cell coating.MeTro USES a bionic approach, using new engineered elastomeric materials derived from elastin, a protein widely found in human elastic tissue.For example, elastin is found in blood vessels, skin, heart, bladder and elastic cartilage.However, elastin is the natural monomer precursor of elastin, so if the recombinant elastin can form protein tissue through optical cross-linking within one minute, it will bring about equivalent elastic tissue.
Most of the elastin in the human body is obtained by slowly cross-linking the elastin progenitors in utero through the specific oxidation of lysine by lysyl oxidase.Various cross-linking methods are used to produce three-dimensional elastin-based hydrogels from recombinant human elastinogen alpha elastin and elastin-like peptides.These hydrogels are generally biocompatible and capable of supporting cell growth in vitro and in vivo.However, low mechanical properties and cell penetration into these hydrogels with heterogeneous three-dimensional structures are problematic.In addition, some biotoxic conditions such as chemical crosslinkers, organic solvents, prolonged ultraviolet irradiation and high pressure used in the process of manufacturing these hydrogels make it impossible to carry out feasible cell implantation during the formation process of hydrogels.
The synthetic pathway used here is to cross-link the esterified elastinogen with light for a short period of time, thus producing a highly elastic three-dimensional loaded cell elastinogen based hydrogel.The elastinogen used contains 35 lysine residues per molecule.This method can change the degree of esterification of methacrylate and polymer concentration to control the physical properties of the obtained elastic hydrogels, including pore properties, swelling properties and mechanical properties.
Synthesis of methacrylate esterified elastin (MeTro)
Elastin was dissolved in PBS (10% w/v), join methylacrylic acid anhydride (MA) at 4 ° C reaction under 12 hours for the esterification.At 4 ° C with distilled water and then the solution dialysis, 48 hours after lyophilization for methyl acrylic acid esterification of elastin original (MeTro).Products of different esterification degrees can be obtained by using methacrylate anhydride of different concentrations (e.g., 8, 15, 20%).
Preparation of hydrogels for performance testing
MeTro macromolecular monomers with different degrees of methylacrylate esterification were used to make MeTro hydrogels with photocrosslinking.PBS solution of different concentrations of MeTro (such as 5,10,15 % w/v) at 4 ° C under the condition of adding 0.5% of the light initiator Irgacure 2959 (chemical name: 1 - [4 - (2 - hydroxyl ethoxy) - phenyl] 2 methyl - 2 - hydroxy - acetone).10 microliter pipette was used to place the solution between two glass slides separated by 150 micron spacers, and 6.9mW/cm squared UV light (wavelength 360 -- 480 nm) was irradiated for 35 seconds to obtain MeTro gel with optical cross-linking.
The synthesized MeTro hydrogel has controllable physical properties and can be used for the three-dimensional elastic environment of cell embedding and two-dimensional film of cell adhesion and growth.These hydrogels can be made into various shapes and sizes and exhibit the following major advantages over other hydrogels and synthetic elastomers obtained from elastin:
1,MeTro gel can be rapidly formed in 35 seconds, which is much shorter than the time (about 24 hours) normally required for chemically crosslinked elastin based hydrogels.
2,Photocrosslinking MeTro gel in aqueous solution can eliminate the use of toxic crosslinking agents and organic solvents in the synthesis of other hydrogels.
3,The potential of rapid cell coating through MeTro enables cells to be significantly dispersed into the matrix, thus overcoming the problem of minimal cell penetration into the three-dimensional matrix caused by common problems such as low porosity, poor pore connectivity and small pore size.
4,Unlike other synthetic elastomers such as polyurethane, the use of biodegradable MeTro hydrogels does not result in biotoxicity due to degradation in vivo, as the gels are derived from human proteins.
5,Elastinogen-based materials are more stable than some other biodegradable elastomers such as PGS, which provide mechanical support before new tissue forms.
6,Fully secreted elastin amino acid sequences, including the presence of cell-interacting c-terminals, provide MeTro gel with endogenous binding sites of integrin alpha V beta 3 cells for cellular interaction.
Some mechanical properties of MeTro hydrogel materials with different degree of methylacrylate esterification
The hydrogel MeTro material synthesized by this method, which is based on human proteins that can load cells, has extremely excellent properties, including high ductility, stress and recovery after removal, rapid polymerization ability, easy synthesis method, and is suitable for 3d cell embedding and 2d cell implantation.These characteristics make MeTro build a unique multi-functional tissue engineering material that requires elasticity while allowing cell embedding and surface growth.It is believed that this photocuring product, once commercialized, will bring about a huge revolution in wound repair and clinical surgery.
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)