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Restoring neural tissue with hydrogels based on modified pectins

VLADIVOSTOK (RU), August 2020 — Scientists have developed implantable hydrogels based on plant polysaccharides (pectins) that can play the role of an artificial extracellular matrix, a special network of molecules that fills the space between body cells. The development can be used as a medium for growing tissues and organs, as well as for drug delivery and brain recovery after removal of malignant tumors glioblastomas.

The hydrogels, developed at the Far Eastern Federal University School of Biomedicine (FEFU SBM), are plant carbohydrate-based materials made of pectins modified by bioengineering methods. They are suitable for neural tissue restoration after brain tumors and other damages caused by trauma or neurodegenerative disease that involve cell death or loss of functional activity of cells and their environment.

"Some variations of our extracellular hydrogel matrices are capable of suppressing the cell proliferation in glioma, a malignant brain tumor. Their chemical modifications can be used to secure the normal neural stem cells potential, preserving them in an undifferentiated state, saving their viability and potential for the future. This is interesting for the development of cellular biotechnologies in regenerative medicine," said Vadim Kumeiko, Ph.D., the head of the research group and FEFU SBM’s deputy director for development. "Certainly, bioengineering solutions associated with the use of extracellular matrices from pectins need to be carefully checked. However, we expect that in the future our hydrogels can be implanted in the brain tumor resection area in order to kill the tumor cells remaining after the operation."

The scientist explained that in the human body, the extracellular space is a complex molecular network, i.e., a matrix, which consists of two main components: protein and carbohydrate. The neural system matrix differs from the matrix of many other tissues because it has more carbohydrate and resembles marmalade or marshmallow in its physicochemical properties. This varies from a more elastic and rigid matrix with a protein component predominance typical for connective tissues. It is almost impossible for cells to move along the carbohydrate matrix.

"This is the way nature intended so that in adult organisms brain cells do not easily migrate to new areas and do not form new electrical connections too quickly. Because if they do, it can lead, for example, to the loss of memory, acquired skills and knowledge. Imagine you know a foreign language in the evening, but during the night cells migrated and you forgot everything," explained Dr. Kumeiko.

The problem is that tumor cells control the rigidness of extracellular space by adding protein components to it. In doing so, they pave a pathway for themselves to run away in order to metastasize and form new tumors in other areas of the body.

"The matrix with a predominance of the carbohydrate component, implanted after the tumor was removed, will not only inhibit the growth and proliferation of cells, but will also be perfect as a delivery vehicle for highly toxic drugs,” Dr. Kumeiko said. “Such drugs will be released from it gradually, causing less harm to the body as a whole and killing the remaining tumor cells. At the next stage, it is possible to stimulate the regeneration and growth of neural cells by implanting injection of a tougher matrix containing a large proportion of proteins into the operated area."

In the future, the scientists plan to investigate the effect of pectin matrix composition on the rate of drug release, and what combination of carbohydrate and protein components will allow restoring neural tissue without scars or excessive density typical for tumor tissue.

 The current study is published in the International Review of Neurobiology.

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DOI: 10.1016/bs.irn.2020.03.025