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

BIOMATERIALS (1)

Dr. Judit Pongrácz

Three dimensional tissue cultures and tissue

engineering – Lecture 7

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

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

TÁMOP-4.1.2-08/1/A-2009-0011

Natural biomaterials I

Proteins:

• Collagen

• Fibrin

• Silk

Polysaccharydes:

• Agarose

• Alginate

• Hyaluronic acid

• Chitosan

TÁMOP-4.1.2-08/1/A-2009-0011

Natural biomaterials II

Advantages:

• In vivo source, large quantities available

• Binding sites for cells and adhesion molecules

• Biocompatibility granted

Disadvantages:

• Lot-to-lot variability

• Potential immune reaction because of impurity

• Limited range of mechanical propertes

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

TÁMOP-4.1.2-08/1/A-2009-0011

Collagen II

Collagen molecule

300nm 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

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

Tissue

factor

Common pathway

Cross-linked fibrin clot

Trauma

Va

XIIIa

XII XIIa

XI XIa

IXa IX

Thrombin (IIa) Prothrombin(II)

Fibrinogen (I)

X Xa X

VIIa VII

VIIIa

Fibrin (Ia)

Damaged surface

Trauma

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

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

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

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

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 material

Used for:

– Enzyme immobilization or encapsulation

– Encapsulation of whole cells, isolating them from the

immune system

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

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

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

BIOMATERIALS (2)

Dr. Judit Pongrácz

Three dimensional tissue cultures and tissue

engineering – Lecture 8

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

TÁMOP-4.1.2-08/1/A-2009-0011

Synthetic biomaterials I

Organic polymers:

• PGA, PLA, PLGA

• PEG

• Peptides

Inorganic:

• Ceramic

• Metal

• Hydroxyapathite

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

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

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

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

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

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