biomaterials (1)
DESCRIPTION
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 PresentationTRANSCRIPT
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
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
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 IProteins:• Collagen• Fibrin• Silk
Polysaccharydes:• Agarose• Alginate• Hyaluronic acid• Chitosan
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
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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 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
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
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
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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
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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
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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
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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
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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
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Chitosan• Derived from the deacetylation of chitin;
strongly cationic • Commercially derived from crustacean
exoskeleton• Bondages, wound dressing, enhanced blood
clotting
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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 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
TÁMOP-4.1.2-08/1/A-2009-0011
Synthetic biomaterials IOrganic polymers: • PGA, PLA, PLGA• PEG• Peptides
Inorganic:• Ceramic• Metal• Hydroxyapathite
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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
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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
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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
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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
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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
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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