Tissue+Engineering

Tissue engineering utilizes three main materials: the cell, the scaffold and growth factors.
 * The cell supplies the matrix material for conduction of cellular processes. Cells can be classified as autogenic, allogenic or xenogenic. Pertaining to stem cells, they can be classified as embryonic (ES) or adult stem cells. ES cells are arguably have the most controversial ethical concerns.
 * Type of ES cells: fertilized embryonic, somatic nuclear transfer (related to cloning)
 * Adult stem cells: Haemotpoetic (HSC) and mesenchymal (MSC) both found in bone marrow. Bone cells are easier to harvest, although investigations re moving towards cell harvesting from fat tissue.
 * The scaffold typically provided the architectural environment upon with cells are active.
 * Grow factors are used to provoke desire cellular responses and it often a means by engineers to direct cellular processes.

Focus has shifted from tissue engineering to stem cell research, due to the profilerative power of stems cells to become virtually any cell. Recent efforts attempt to combine the design aspects of tissue engineering with the regenerative prospects of stem cell research.There is a modern trend of merging aspects of tissue engineering (TE) and materials science to create bio-hybrids. Bioglass serves as an excellent candidate for bone scaffold. Its only deficiency is low mechanical strength and toughness.

Candidate cells for tissue engineering are:


 * ~ Cell Type ||~ Source ||~ Possible Differentiated Cells ||~ Advantages ||~ Disadvantages ||
 * Primary adult || mature cells extracted from tissue ||  || * autologous cells to avoid immuno-rejection || * low growth potential
 * high senesence ||
 * Foetal cells || extracted from foetal tisse (7-10 wks gestation) ||  || * higher profilerative power that adult cells
 * lower senesence ||  ||
 * Adult Stem cells || from the bone marrow: haematopoietic stem cell (HSC) and mesenchymal stem cells (MSCs) || * HSCs - eosinophils, erythrocytes, megakaryocytes, osteoclasts and B and T cells.

As stem cells differentiate, a hierarchy of differentiability is establish with each succeeding generation:
 * MSCs - several connective tissue cell types,including osteocytes, chondrocytes, adipocytes, tenocytes, myocytes and bone marrow stromal cells ||  || * ethical issues ||
 * Embryonic Stem (ES) cells ||  ||   ||   || * ethical issues ||
 * Pluripotent - primordial germ cell -> embryonic germ (EG), embryonic stem (ES) cells, embryonic carcinoma (EC) cells. Pluripotent cells can differentiate into all cell types derived from the three germ layers, except the embryo.
 * Totipotent - embryo and trophoblast
 * Multipotent - adult cells
 * Unipotent - committed progenitor cells

The first ES cells where carcinoma-derived. Self-renewal is triggered by a series of //transcription factors//, i.e. Nanog, OCT4, Wnt.

As quoted by Dr. Polak, three questions have been targeted in the TE field:

//(a) Can pure populations of cells be derived in sufficient// //numbers for implantation?// //(b) Can the necessary requirements of ‘good medical// //practice’ be achieved (ie xeno-free)?// //(c) How can potential problems of tissue rejection be// //resolved?//

Methods to obviate the immuno-rejection issue include exploiting undifferentiated mesenchymal cells (MSC) which do not express the cell surface markers are appear //immunoprivieledged//. Somatic nuclear transfer is another method used, most commonly in cloning.

Recent research has fueled the theory of cell //plasicity// or //transdifferention// - the ability for cells to switch their fate due to microenvironmental stimuli. Proof of this theory has many therapeutic implications.

Eleven criteria for ideal TE scaffolds as described by Polak: 1. is made from a material that is biocompatible, that is,not cytotoxic; 2. acts as template for tissue growth in three dimensions; for example, collagen is organized parallel to the surface in articular cartilage and perpendicular to the surface in the osteochondral region of an articulating join; 3. has an interconnected macroporous network with pore diameters in excess of 100 mm for cell penetration, tissue ingrowth, vascularization and nutrient delivery throughout the regenerating tissue; 4. bonds to host tissue without formation of intervening scar tissue; 5. exhibits a surface texture and chemistry that promotes cell adhesion, adsorption of biological metabolites, including growth factors; 6. influences the genes in stem cells to enhance differentiation and proliferation of all the phenotypes required for tissue regeneration while not altering clonogenic or proliferative potential of the cells; 7. resorbs at the same rate as the tissue is repaired, with degradation products that are nontoxic and can be easily excreted; 8. can be produced in irregular shapes to match the tissue defect; 9. has mechanical properties sufficient to withstand applied stresses in clinical applications; 10. has the potential to be commercially produced to the required ISO (International Standards Organisation) and FDA (Food and Drug Administration) regulatory standards at a cost suitable for routine clinical use; 11. does not alter clonogenic and proliferative potential of stem cells.

Materials used in Tissue Engineering [\polak]

alcohol), poly(acrylic acid), poly(propylene fumarateco-ethylene glycol) ||
 * ~ Class ||~ Materials ||
 * Biological polymer || collagen, fibrin, agarose, gelatine, alginates, hyluronan, chitosan, collagen/glycosaminoglycan. ||
 * Synthetic polymer || polylactic acid (PLA), polyglycolic acid (PGA) PLA/PGA copolymers, polycaprolactone, poly(ethylene oxide), poly(vinyl
 * Ceramic || hydroxyapatite (HA), carbonate or silicon-substituted HA, tri-calcium phosphates and alumina ||
 * Glasses || SiO2–CaO–Na2O–P2O5 compositions ||
 * Sol-gel derived and foams || SiO2–CaO–P2O5 compositions ||
 * Biocomposites ||  ||