**1. Introduction**

158 Biomaterials – Physics and Chemistry

Xia, H.; Rayson, G.D., (2002) 113Cd NMR Spectrometry Of Cd Binding Sites On Algae And

2001) pp. 157-167 ISSN: 1093-0191..

Higher Plant Tissues, *Advances in Environmental Research*, vol. 7, no. 1 (November

Cardiovascular diseases are a worldwide problem being a significant cause of morbity and mortality every year. Patients requiring heart valve replacements include those exhibiting degenerative valvular diseases and rheumatic fever. The pathological processes include stenosis, fibrosis, myxoid change and calcification. The fibrosis causes a reaction to normal haemodynamic while the myxoid change reduces tensile strength of the valve due to replacement of dense collagenous tissue by loose tissue rich in glycosaminoglycans. Moreover, these pathologies can be observed in normal valves or fibrotic valves (Lindop, 2007).

Fortunately, the development of cardiovascular prostheses, either synthetic or biological, has allowed to increase life expectancy and has improved the quality of life of patient requiring either heart valves (Flanagan & Pandit, 2003; Schoen & Levi, 1999; Vesely, 2005) or vascular grafts (Matsagas et al., 2006; Monn & West, 2008; Schmidt & Baier, 2000). The implant technology for cardiovascular systems made use of raw materials of different origins. For example, metallic materials and synthetic polymers have been widely used in mechanical valves for the replacement of diseased heart valves. However, some complications such as alterations in the hemodynamical function and thrombus formation have been found (Zilla et al., 2008).

Biological prostheses provide some answers to these complications, although the bioprostheses do not fulfil their objectives satisfactorily, since they display others complications once implanted. The complications of tissue valves include calcification, remnant tissue immunogenicity, inflammatory degradation, mechanical damage and lack of repair (Zilla et al., 2008). Therefore, the need for safe, economic, physiologically acceptable and viable biomaterial has motivated the modification of collagen-rich tissues.

Collagenous tissues are alternative raw materials for the manufacture of medical devices due to their physical and biomechanical properties. These tissues promote cell interactions, exhibit good ion and macromolecular binding capacity in addition to their electrostatic, hemostatical and immunological properties (Li, 2007). Since 1960s, perichardial tissues and the porcine heart valves are two of the most widely used biological tissues in the construction of cardiovascular devices. The introduction of these biological biomaterials was

Decellularization, Stabilization and Functionalization of

tissue

perichardium

Collagenous Tissues Used as Cardiovascular Biomaterials 161

The crystal lattice of collagen fibers are embedded in an amorphous matrix. The amorphous matrix is composed mainly by glycosaminoglycans as proteoglycans (sulphated glycosaminoglycans bound to proteins). In this matrix, in addition to the fibers, tissue cells and interstitial fluid (water or electrolytes) are embedded. The glycosaminoglycans are negatively charged polysaccharides of varying degrees of complexity. The glycosaminoglycan polymers consist of repeating disaccharide units, usually consisting of a hexosamine and an uronic acid (Yeung et al., 2001). The charged negatively units contribute to the elasticity and hydration of the tissues (Mavrilas et al., 2005), but may attract counter-ions, which could intervene in the processes of calcification of bioprostheses. The repetitive disaccharide unit of glycosaminoglycans mainly presents in native bovine perichardium is shown in figure 2.

Fig. 2. Repetitive disaccharide units of common glycosaminoglycans in bovine perichardial

The different soft tissues including cartilage, tendons, ligaments, skin and perichardium have the capacity of support mechanical load of variable magnitude. Therefore, the properties of the tissue depend on the number and the arrangement of collagen fibers, which can be parallel or perpendicular to the surface or randomly distributed in the matrix. The hierarchical nature of collagen confers to the tissue its structural complexity. The fibrous nature of bovine perichardial tissue is revealed in figure 3. In perichardial tissue, a multi-laminate structure is

observed with difference in both serosa (Fig. 3b) and rugosa surface (Fig. 3a).

Fig. 3. SEM micrographs for the fibrosa (a) and the serosa surface (b) of native bovine

linked to the tissue crosslinking to increase durability. However, due to some complications in the stabilized tissue, several post-crosslinking protocols have been proposed to address these complications. More recently, biological scaffolds derived from acellular tissue has been used in tissue engineering and regenerative medicine.

Therefore, this chapter deals with the processing of collagenous tissue for the preparation of cardiovascular biomaterials. The processing techniques include the extraction of cellular and nuclear material by various decellularization methods, the preservation of tissue through of crosslinking reactions, hydrogen-bond interactions or interstitial space filling, and the functionalization or the blocking of free groups with various low molecular and macromolecular substances.
