Tissue Engineering

1. Tissue Engineering Wnek G.E., Bowlin G.L. (2004), Marcel Dekker, Inc., New York, Basel pp. 1477-1483

4. Introduction Tissue engineering is a revolutionary addition to to the therapeutic armamentariumum of medicine The intrinsic problem of transplantation is the chronic shortage of tissue organs. Tissue engineering allows the hope of of a regular creation of spare parts of the human body. Tissue engineering is a most significant approach to reconstruct, replace, or repair organs in a way that could not be foreseen 25 years ago.

5. Saints Cosmas and Damian performing a miraculous transplantation Oil painting on panel 168 x 133 cm., attributed to the Master of Los Balbases, Burgos, Spain, c. 1495

6. Reconstructive surgery: In 1970s the development of microsurgery allowed distant tissue transfer and reimplantation (vascular grafts and prosthetic articulation). Tissue engineering is remarkably multidisciplinary, bringing together cell and molecular biologists, biochemists , engineers, pharmacologists, physicians, ..etc. Tissue engineering does open radically new chapter in reconstructive medicine, for it is now deemed possible to reconstruct in the laboratory human living tissues and organs for in vivo, ex vivo, and even in vitro applications.

7. The aim of Tissue engineering is to obtain grafts for in vivo applications. The biological and mechanical functions are of utmost importance. Biological functions: cell therapy Mechanical functions: tissue templates.

8. Tissue-engineered substitutes are three-dimensional reconstructions that can be implanted into the human body, leading to rapid host implantation and acceptance. The substitutes must have at least minimal biological and mechanical functions for such reparative role.

9. Historical perspective Tissue engineering has been considered one of the most influential new technologies for the future biomedicine. • The development of tissue engineering can be seen as heaving two phases: • The phase of exponential development and potential application. Is still continuing to evolve. • The phase brought about a flury of discoveries about stem cells. Stem cells: S.c. had been known for many years. Embrionic S.c. Adult S.c. were found to be much more ubiquitous and to have more lineage plasticity than previously thought. (since 1998)

11. Approaches to tissue-engineering substitutes Three different approaches to tissue-engineered substitutes: Fig.2: p.1478 (www.dekker.com) 1. Seeding of cells into various gels (collagen gels, fibrin and other component) Eugene Bell. It was shown that the incorporation within the depth of these matrices with various types of cells was possible. The true integration of cells into gels allowed them to reorganize the surrounding matrix. Drawback: Week mechanical resistance of the obtained substitutes. The structural integrity may be sufficient for skin, but not so for substitutes in vascular or orthopaedic systems. This problem has been addressed with glycation and magnetic alligement of the collagen fibers.

12. 2. The seeding of cells into scaffolds: Natural Synthetic The cell thrive in the porous material and secrete various amount of extracellular matrix depending on their nature. (developed by Robert Langer’s group MIT). Sponge-like structures from mainly collagenous materials (E. Košťáková, L.Očeretna, the group from TUL). Synthetic scaffolds PGA (Poly(glycolic acid)). There have been countless modifications and additions to the different types of synthetic materials used over the last decade in this approach.

14. The obvious advantage of the scaffold approach is the immediate creation of a three-dimensional structure that already has significant structural properties. Drawback: The intrinsic nature of most of these polymers, which are suture materials, entails slow degradation with an ensuing lowering of pH of surrounding tissues. This leads to a slow but rather protracted low-level inflammatory process. Many groups are therefore attempting to alter the chemical nature of these biomaterials to inhibit this inflammatory process.

15. 3. LEOX group (Quebec, Canada): In this approach various types of cells, mostly of mesencymal origin, are grown in such afashion within a culture flask that they literally embedded themselves in their very oven extracellular matrix. Among many factors, the addition of sodium ascorbate allows the significant appearance of the various components of the extracellular matrix. These sheets are than either stacked or rolled to obtain various tissue substitutes. The re-creation of a totally biological vascular substitute.

16. The main advantage: The absence of extraneous collagens and any synthetic material. Drawback: This approach is time consuming.

17. Critical integrative aspects of tissue engineering Two of these critical aspects, namely Vasularization and inervation, have not received all the attention they deserve. Less important for grafts with nearly exclusively mechanical function such as an aortic synthetic graft or hip prosthesis. • Vascularization: The approach of stimulating the ingrowths of blood vessels into solid organs has not been successful. Such organs rapidly, within hours or even minutes, demanded blood irrigation for survival and proper function.

18. In the Tumour Microcirculation Group, we are studying the blood vessels that supply tumours with oxygen and nutrients and their role in cancer therapy.

19. Skin schaffolds (LOEX group) composed of combination of dermal layer fibroblasts and endothelial cells in such a fashion that a capillary-like systém was reconstructed.