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Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

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Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s P rogrammes at the University of Pécs and at the University of Debrecen Identification number : TÁMOP-4.1.2-08/1/A-2009-0011. - PowerPoint PPT Presentation

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Page 1: Biomaterials (1)

Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011

Page 2: Biomaterials (1)

BIOMATERIALS (1)

Dr. Judit PongráczThree dimensional tissue cultures and tissue engineering – Lecture 7

Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011

Page 3: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Biomaterials used in tissue engineering• Biocompatibility• Tissue friendly• Surface chemistry• Porosity• Controlled biodegradation• Mechanical properties• Drug/bioactive compound inclusion and

controlled release • Support of ECM formation

Page 4: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Natural biomaterials IProteins:• Collagen• Fibrin• Silk

Polysaccharydes:• Agarose• Alginate• Hyaluronic acid• Chitosan

Page 5: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Natural biomaterials IIAdvantages:• In vivo source, large quantities available• Binding sites for cells and adhesion

molecules• Biocompatibility grantedDisadvantages:• Lot-to-lot variability• Potential immune reaction because of

impurity• Limited range of mechanical propertes

Page 6: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Collagen I• Rich in vivo sources• Most studied biomaterial• Fibrous structure, unique amino acid

composition• Binding sites for integrins• RGD sites for integrin binding• Superior biocompatibility• Supports large spectra of cell differentiation

as a scaffold

Page 7: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Collagen II

Collagen molecule300nm long and 1.5nm diameter thick

Collagen alpha chain

Assembly into microfibril

Assembly into mature collagen fibril

Aggregation of collagen fibrils to form a collagen fibre

Page 8: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Fibrin• Fibrinogen is easily obtained

from (human) plasma• Application as a hydrogel:

addition of thrombin• Suitable for supporting ES

cell differentiation• Differentiated cells can be

also cultured in fibrin scaffold

• Widely used also in combination with other scaffolds

• Recent applications: cardiovascular, cartilage, bone, neuronal tissue engineering

Tissue factor (extrinsic) pathway

Contact activation (intrinsic) pathway

Tissuefactor

Common pathway

Cross-linked fibrin clot

Trauma

Va

XIIIa

XII XIIa

XI XIa

IXaIX

Thrombin (IIa)Prothrombin(II)

Fibrinogen (I)

X Xa X

VIIa VIIVIIIa

Fibrin (Ia)

Damaged surface

Trauma

Page 9: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Silk I• Produced within specialized glands of some

arthropods• Overlapping beta-sheet structure, repeating

aa motifs• Availability of recombinant analogs are

increasing• Bombix mori silk consists of Fibroin and

Sericin • Excellent mechanical properties, fibroin is

biocompatible• Bone, cartilage and ligament engineering

Page 10: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Silk II• Chemical modification, like RGD groups

enhances Ca2+ deposition and bone cell differentiation

• Silk promoted more intensive chondrogenesis than collagen used as a scaffold material for cartilage engineering

• Very slow degradation, bone tissue replaces the silk scaffold

Page 11: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Polysaccharide-based biomaterials• Polymers consisting of sugar monomers• Plant (seaweed) or animal origin• Careful choice needed because of potential

immune reactions• Most frequently used as hydrogels• Can be injected directly at the site of injury• Supports cell growth and differentiation

Page 12: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Agarose• Main source: Red algae and seaweed• Polysaccharide, Galactose-based backbone• Biologically inert, no immune response• Stiffness and mechanical parameters can be

easily manipulated• Used for scaffolding cartilage, heart, nerve

tissues• Supports SC differentiation • Versatile application possibilities

Page 13: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Alginate• Polysaccharide from the cell walls of brown algae,

acidic compound, cationic salts are used• Sodium-alginate: E-401, food additive, gastronomic

use, heavy metal binding, fat binding• Potassium-alginate: Emulsifier, stabilizer in food

industry

• Calcium-alginate: Water-insoluble gel-like materialUsed for: – Enzyme immobilization or encapsulation– Encapsulation of whole cells, isolating them from

the immune system

Page 14: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Hyaluronan (Hyaluronic acid)• Non-sulfated GAG molecule• Hyaluronic acid is a major component of the ECM

(hyalinic cartilage, skin)• Multiple cell surface receptor binding and cell

adhesion sites available • Role in wound healing, tissue repair• ES cell compatibility: supports ES cell

differentiation, survival and proliferation• Many tissues contain hyaluronic acid• Hyaluronan gels used in nerve, cartilage, skin,

adipose TE

Page 15: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Chitosan• Derived from the deacetylation of chitin;

strongly cationic • Commercially derived from crustacean

exoskeleton• Bondages, wound dressing, enhanced blood

clotting

Page 16: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Chitosan in bone TE• Chitosan facilitates the differentiation of

osteocytes• At slightly acidic pH chitosan-Ca-phosphate

composite is an injectable gel. At physiological pH it gels anchoring osteocytes

• Native or collagen-linked chitosan enhances monocytes to differentiate into osteoclasts

Page 17: Biomaterials (1)

BIOMATERIALS (2)

Dr. Judit PongráczThree dimensional tissue cultures and tissue engineering – Lecture 8

Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011

Page 18: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Synthetic biomaterials IOrganic polymers: • PGA, PLA, PLGA• PEG• Peptides

Inorganic:• Ceramic• Metal• Hydroxyapathite

Page 19: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Synthetic biomaterials II• High reproducibility• Industrial-scale production• Easy control of mechanical properties• Easy control of degradation rate• Shaping is easy• Often lack sites for cell adhesion• Biocompatibility is often questionable• SC compatibility and differentiation

supporting is not obvious• Immune reactions are possible

Page 20: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Poly-(lactic-co-glycolic acid)PLGA• FDA approved scaffold material• Degradation rate modulation is available• Frequently used in adipose, neural, bone,

cartilage TE• Supports ES cell differentiation, proliferation,

survival• Biocompatible• No immune reaction• Mixed polymer, various ratios are available• Degradation products are acidic, therefore

may alter cell metabolism

Page 21: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Poly-(ethylene glycol), PEG• Commonly used biocompatible polymer • PEGylation of proteins: modulation of

degradation/absorbtion• PEG chemical modification available (e.g.

heparin, peptides, RGD motifs• Frequently used as a scaffold material in SC,

bone, cartilage, nerve, liver, vascular TE• RGD peptides, BMP, TGF-b release regulation

Page 22: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Peptide-based biomaterials• Short amino acid sequences • Self-assembly: ampholitic nature• Combining the advantages of synthetic

materials and natural scaffolds: – Self assembling structure– Binding sites– Purity and consistent quality

• IKVAV: neurite outgrowth, sequence from laminin

• RGD: cellular adherence promotion

Page 23: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Ceramic-based biomaterials• Inorganic, formed with heat, porous, brittle• Bioactive glass is used as a material for

implants• Hydroxyapatite (in bone it’s natural)• Used in bone tissue engineering only• Combination with biopolimers, drug delivery

enhanced

Page 24: Biomaterials (1)

TÁMOP-4.1.2-08/1/A-2009-0011

Metals• Alumina• Titanium alloys• Bio-inert materials• Withstands to continuous mechanical load,

e.g. heart valves, joint replacements, dental implants

• Used in orthopaedic surgery • May cause immunological reactions – metal

allergy