TISSUE ENGINEERING FOR TISSUE AND ORGAN REGENERATION

43.4 TISSUE ENGINEERING FOR TISSUE AND ORGAN REGENERATION

Biomedical applications of collagen have entered a new era in the past decade. The potential use of collagen materials in medicine has increasingly been appreciated as the science and technology advances. One major emerging field of biomedical research which has received rigorous attention in recent years is tissue engineering. Tissue engineering is an interdisciplinary science of biochemistry, cell and molecular biology, genetics, materials science, biomedical engineering, and medicine to produce innovative three-dimensional composites having structure/function properties that can be used either to replace or correct poorly functioning components in humans and animals or to introduce better functional components into these living systems. Thus, the field of tissue engineering requires a close collaboration among various disciplines for success.

Tissue engineering consists primarily of three components: (1) extracellular matrix. (2) cells, and (3) regulatory signals (e.g.. tissue specific growth factors). One of the key elements in tissue engineering is the extracellular matrix which either provides a scaffolding for cells or acts as a delivery vehicle for regulatory signals such as growth factors.

Type I collagen is the major component of the extracellular matrix and is intimately associated with development, wound healing, and regeneration. The development of the type I collagen based matrices described in this review article will greatly facilitate the future development of tissue engineering products for tissue and organ repair and regeneration applications.

To date, collagen-based implants have been attempted for many tissue and organ repair and regeneration applications. A complete historical survey of all potential medical applications of collagen is a formidable task but a selected survey of collagen-based medical products and the research and development activities are summarized in Table 43.6 as a reference.

TABLE 43.6 Survey of Collagen.Based Medical Products, and Research

and Development Activities

DEFINING TERMS

Alanine (Ala): One of the amino acids in collagen molecules. Allysine: The ε -amino group of lysine has been enzymatically modified to an aldehyde group. Apparent density: Calculated as the weight of the dry collagen matrix per unit volume of matrix. Arginine (Arg): One of the amino acids in collagen molecules. Aspartic acid (Asp): One of the amino acids in collagen molecules.

Atelocollagen:

A collagen molecule without the telopeptides.

Chondroitin sulfate: Sulfated polysaccharide commonly found in cartilages,bone, corea, tendon, and skin.

A family fibrous insoluble proteins having a triple helical conformation extending over a major part of the molecule. Glycine is present at every third amino acid in the triple helix and proline and hydroxyproline are required in the triple helix.

Collagen:

Collagenase:

A proteolytic enzyme that specifically catalyzes the degradation of collagen molecules.

Dehydrohydroxylysinonorleucine (deH-HLNL):

A covalently crosslinked product between an allysine and a hydroxylysine residues in collagen fibrils.

D spacing: The repeat distance observed in collagen fibrils by electron microscopic and x-ray diffraction methods.

Elastin: One of the proteins in connective tissue. It is highly stable at high temperatures and in chemicals. It also has rubberlike properties.

Fiber:

A bundled group of collagen fibrils.

Fibril:

A self-assembled group of collagen molecules. Fibroblast: Any cell from which connective tissue is developed. Fibrochondrocyte: Type of cells that are associated with special types of cartilage tissues such

as men iscus of the knee and intervertebral disc of the spine. Fibrous long spacing (FLS): One of the polymorphic forms of collagen where the collagen

molecules are randomly aligned in either head-to-tail, tail-to-tail, or head-to-head orientation.

Gelatin:

A random coiled form (denatured form) of collagen molecules. Glu tamic acid (Glu): One of the amino acids in collagen molecules. Glycine (Gly): One of the amino acids in collagen molecules having the simplest structure.

Glycoprotein:

A compound consisting of a carbohydrate protein. The carbohydrate is generally hexosamine, an amino sugar.

Glycosaminoglycan (GAG):

A polymerized sugar (see polysaccharide) commonly found in various connective tissues.

Helical pitch: Repeating distance within a single polypeptide chain ¡ri a collagen molecule. Hemostat: Device or medicine which arrests the flow of blood. Hydrophilicity : The tendency to attract and hold water. Hydrophobicity: The tendency to repel or avoid contact with water. Substances generally are

nonpolar in character, such as lipids and nonpolar amino acids. Hydroxylysine (Hyl): One of the amino acids in collagen molecules. Hydroxyproline (Hyp): One of the amino acids uniquely present in collagen molecules. Inflammatory cell: Cells associated with the succession of changes which occur in living tissue

when it is injured. These include macrophages, polymorphonuclear leukocytes, and lymphocytes. Intermolecular crosslink: Covalent bonds formed in vivo between a side group of one molecule

and a side group of another molecules, covalent bonds formed between a side group of one molecule and one end of a bifunctional agent and between a side group of a second molecule and the other end of a bifunctional agent.

lntraflbrillar volume: The volume of a flbril excluding the volume occupied by the collagen molecule.

In vitro: In glass, as in a test tube. An in vitro test is one done in the laboratory, usually involving isolated tissues, organs, or cells.

In vivo: In the living body or organism. A test performed in a living organism. Isoelectric point: Generally used to refer to a particular pH of a protein solution. At this pH,

there is no net electric charge on the molecule. Isoleucine (Ile): One of the amino acids in collagen molecules. Leucine (Leu): One of the amino acids in collagen molecules. Lipidi: Any one of a group of fats or fat-like substances, characterized by their insolubility in

water and solubility in fat solvents such as alcohol, ether, and chloroform. Lysine (Lys): One of the amino acids in collagen molecules.

Meniscus:

A C-shaped fibrocartilage anatomically located between the femoral condyles and tibial plateau providing stability and shock absorption and assisting in lubrication of the knee joint.

Macrophage: Cells of the reticuloendothelial system having the ability to phagocytose particulate substances and to store vital dyes and other colloidal substances. They are found in loose connective tissues and various organs of the body.

Mycobacterium:

A genus of acid-fast organisms belonging to the Mycobacteriaceae which includes the causative organisms of tuberculosis and leprosy. They are slender, nonmotile, gram- positive rods and do not produce spores or capsules.

Osteoarthritis:

A chronic disease involving the joint, especially those bearing the weight,

characterized by destruction of articular cartilage, overgrown of bone with impaired function. Permeability: The space within a collagen matrix, excluding the space occupied by collagen

molecules, which is accessible to a given size of molecule.

Pepsin:

A proteolytic enzyme commonly found in the gastric juice. It is formed by the chief cells of gastric glands and produces maximum activity at a pH of 1.5 to 2.0.

Phenolalanine (Phe): One of the amino acids in collagen molecules.

Platelet:

A round or oval disk, 2 to 4 ¡m in diameter, found in the blood of vertebrates. Platelets contain no hemoglobin.

Polydioxanone:

A synthetic polymer formed from dioxanone monomers which degrades by hydrolysis.

A synthetic polymer formed from glycolic acid monomers which degrades by hydrolysis.

Polyglycolic acid (PGA):

Polylactic acid (PL4):

A synthetic polymer formed from lactic acid monomers which degrades by hydrolysis.

Polymorphism: Different types of aggregated states of the collagen molecules.

Polymorphonudear leukocyte:

A white blood cell which possesses a nucleus composed of two or more lobes or parts; a granulocyte (neutrophil, eosinophil, basophil).

Polypeptide: Polymerized amino acid molecules formed by enzymatically regulated stepwise polymer ization in vivo between the carboxyl group of one amino acid and the amino group of a second amino acid.

Polysaccharide: Polymerized sugar molecules found in tissues as lubricant (synovial fluid) or cement (between osteons, tooth root attachment) or complexed with proteins such as glycoproteins or proteoglycans.

Proline (Pro): One of the amino acids commonly occurring in collagen molecules. Proteolytic enzyme: Enzymes which catalyze the breakdown of native proteins. Resorbable collagen: Collagen which can be biodegraded in vivo. Saltlinkage: An electrostatic bond formed between a negative charge group and a positive

charge group in collagen molecules and fibrils. Segment-long-spacing (SLS): One of the polymorphic forms of collagen where all heads of

collagen molecules are aligned in parallel. Soluble collagen: Collagen molecules that can be extracted with salts and dilute acids. Soluble

collagen molecules contain the telopeptides. Telopeptide: The two short nontriple helical peptide segments located at the ends of collagen

molecules. Valine (Val): One of the amino acids in collagen molecules.