The Korea Research Institute of Standards and Science (KRISS) has discovered a new principle that will promote wound healing and regeneration by controlling the microenvironment of living tissue. It is expected to be an important clue in the development of wound healing medicines and research on fibrotic diseases and cancer.
The KRISS bioimaging team identified the mechanism of fibrosis involved in wound healing and regeneration through research using skin cells. In addition, we presented a method to control fibrosis at a local site by mechanically and precisely controlling the microenvironment of biological tissue surrounding a wound.
Fibrosis is a phenomenon in which biological tissues harden due to the secretion of collagen in the extracellular matrix surrounding cells. A representative example is the scab that forms on a wound. At normal levels, it plays an important role in wound healing and regeneration, but if it is excessive, it can lead to diseases that harden organs such as the liver, lungs, and heart, or autoimmune diseases such as scleroderma.
Since fibrosis occurs when fibroblasts differentiate into myofibroblasts, controlling fibrosis requires understanding the in vivo environmental conditions under which this differentiation occurs.
KRISS researchers observed through an optical microscope that fibroblast differentiation was most active when the amount of elastin in the skin extracellular matrix was 20%. The normal level of elastin is 10%, and as this level increases, the elasticity of biological tissue increases. This achievement proves that changes in the composition of the surrounding microstructure are important in controlling the fibrosis phenomenon.
Analysis results of biological tissue microenvironment where fibrosis occurs. Left: Microstructure of elastin and collagen observed with a scanning electron microscope Middle: 3D distribution of elastin and collagen observed with a non-linear optical microscope Right: Interaction between one cell and extracellular matrix (elastin and collagen) observed with a scanning electron microscope Although this requires several experimental processes over several days, nonlinear optical microscope imaging has the advantage of allowing direct imaging while maintaining the unique characteristics of biomolecules. Source: Korea Research Institute of Standards and Science
In addition, through precise protein analysis, the research team identified proteins involved in regulating the mechanical elasticity of biological tissues and proved through experiments that the differentiation of fibroblasts can be promoted by regulating these proteins.
Existing fibrosis control research adopted a chemical method of adding growth factors such as EGF to cells to promote fibroblast differentiation. It is mainly used in wound patches, regenerative creams, etc. On the other hand, this achievement is a method of controlling the differentiation of fibroblasts by mechanically changing the elasticity of biological tissue in a local area. It is safer than existing methods because it can prevent unexpected chain reactions that growth factors can cause within cells.
This achievement was created through the combination of KRISS’s nonlinear optical imaging technology and protein precise analysis technology. Nonlinear optical imaging technology allows collagen in the sample to be observed label-free and without staining, preventing extremely small amounts of the sample from being damaged during the staining process. Precise protein analysis technology is a technology that can accurately quantitatively analyze proteins present in biological samples, providing information on intracellular proteins according to the elastin content in the sample.
This achievement can be applied to the development of complementary medicines for wound healing through control of the biological tissue microenvironment and to research on treatments for related diseases such as liver fibrosis, pulmonary fibrosis, and cardiac fibrosis. Additionally, the amount of elastin is known to affect cancer cell proliferation, so it is expected to contribute to research on cancer growth control.
Kim Se-hwa, head of the KRISS bioimaging team, explains biological tissues observed with a nonlinear optical microscope. Source: Korea Research Institute of Standards and Science
Kim Se-hwa, head of the KRISS bio-imaging team, said, “This achievement is the fruit of the fusion of KRISS’s unrivaled cutting-edge bio-measurement technology,” and added, “We will continue to expand our research into various fibrosis mechanisms by using organ cells, not skin cells, in the future.”
The research results were published online in October in the international academic journal ‘Biomaterials Research’.
#Terminology explanation
[1] Fibrosis: A phenomenon in which extracellular matrix, such as collagen, is secreted by activated fibroblasts. It can be seen as the end result of persistent infections, autoimmune reactions, allergic reactions, exposure to chemicals and radiation, and reactions to physical wounds, and the phenomenon or stimulation essential for recovery from such stimulation may occur repeatedly or severely, or the fibrosis process may become uncontrolled. In some cases, it leads to pathological phenomenon.
[2] Cellular microenvironment: The chemical or mechanical microenvironment, including cell populations and the extracellular matrix surrounding the cell populations.
[3] Fibroblast: A cell that synthesizes tissue components such as collagen to create a skeleton that supports cells. In healthy tissues, fibroblasts maintain tissue structure and are involved in wound healing.
[4] myofibroblast: A cell with a phenotype intermediate between a fibroblast and a smooth muscle cell. It has been reported that differentiation is possible through various stimuli. Plays a major role in fibrosis in organs such as liver, lungs, etc. It plays a role in regenerating damaged tissue by producing extracellular matrix during the healing process of wound tissue.
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2023-12-31 09:10:00
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