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Biophysics

Database
Physical mechanisms of the cell development using modelling

G. Forgacs is one of the leading scientists in the Organ Printing Project. Considerable part of his papers is devoted to study of physical mechanisms which underlie biological self-organization, particularly — self-assembly of cell structures. Concept of tissue fluidity firstly proposed in the Malcolm Steinberg’s differential adhesion hypothesis was experimentally validated in G. Forgacs’s studies and became the molecular base for the bioprinting technology. 3d printing of living tissues became possible due to existence of tissue surface tension and the ability of the same cells to stick together into spherical structures, The special «ink» is used in 3d bioprinting — it contains microspheres with 10 — 40 thousands of cells. It is established that, when such 3d bioprinting is used, each type cells migrate at the appropriate place and build up tissues and organs, which forms are defined by the arrangement of matrix particles («biopaper»). Biocompatible matrices, which are used in bioengineering, generally show positive results. However, they can cause a set of undesirable problems, too. For example, matrix immunogenicity, degradation velocity and toxicity of the products, formation of the fibrous tissue during degradation, interaction with adjacent tissues etc. can influence the late fate of transplantation and directly affect biological functions of the bioengineered tissue. Properties of extracellular matrix are extremely critical in the modelling of vascular tissues. Creation of artificial blood vessels with small diameter, which have mechanical strength comparable to those of the native vessels, is still one of the most difficult problems of tissue engineering. To solve that problem, a new approach, where agarous bars were used as building blocks for the form filled with tissue spheroids or cylinders, was developed. Layer-by-layer arrangement of agarous bars and standard multicellular structures (spheroids and cylinders) enable precise regulation of the internal diameter, the wall thickness and the pattern of vessel branching. All the process, which includes removing of the agarous bars, is automated and enables to obtain one-layered, as well as two-layered blood vessels. Such approach has many advantages, and it makes it possible to prevent a lot of problems linked to the presence of exogenous materials. Since constructions obtained are made of cells only, high cell density can be achieved. So the properties of such bioengineered vessels came close to the properties of the naive ones. Moreover, when multicellular cylinders are used as a «bioink», the maturing time decrease and forms of the final structures become more accurate. The important achievement of G. Forgacs and colleagues is the use of bioprinting for reconstruction of frameless blood vessels that enables to obtain vessels of various diameter and shape necessary for transplantation. The next stage of bioprinting must be creation of complicated branched macro- and microvascular systems with the internal diameter from 300 mkm and the wall thickness from 100 mkm, which will be available for clinical implantation.