Biomaterials (1)

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

2. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat theUniversity of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011 Dr. Judit Pongrácz Threedimensionaltissuecultures and tissueengineering – Lecture 7 Biomaterials(1)

3. Biomaterialsusedintissueengineering • Biocompatibility • Tissue friendly • Surface chemistry • Porosity • Controlled biodegradation • Mechanical properties • Drug/bioactive compound inclusion and controlled release • Support of ECM formation

4. NaturalbiomaterialsI • Proteins: • Collagen • Fibrin • Silk • Polysaccharydes: • Agarose • Alginate • Hyaluronicacid • Chitosan

5. Naturalbiomaterials II • Advantages: • In vivo source, largequantitiesavailable • Bindingsitesforcells and adhesionmolecules • Biocompatibilitygranted • Disadvantages: • Lot-to-lotvariability • Potentialimmunereactionbecause of impurity • Limited range of mechanicalpropertes

6. CollagenI • Rich in vivo sources • Most studied biomaterial • Fibrous structure, unique aminoacidcomposition • Binding sites for integrins • RGD sites for integrin binding • Superior biocompatibility • Supports large spectra of cell differentiation as a scaffold

7. CollagenII Collagenalphachain Collagenmolecule 300nm long and 1.5nm diameterthick Assembly intomicrofibril Assembly intomaturecollagenfibril Aggregation of collagenfibrilstoform a collagenfibre

8. Fibrin Contactactivation (intrinsic) pathway • 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 Damagedsurface Tissuefactor (extrinsic) pathway XII XIIa Trauma XI XIa IX IXa VIIa VII Tissue factor VIIIa Trauma X Xa X Commonpathway Va Prothrombin(II) Thrombin (IIa) Fibrinogen (I) Fibrin (Ia) XIIIa Cross-linked fibrin clot

9. SilkI • Produced within specialized glands of some arthropods • Overlapping beta-sheet structure, repeating aa motifs • Availability of recombinant analogs are increasing • Bombixmori silk consists of Fibroinand Sericin • Excellent mechanical properties, fibroin is biocompatible • Bone, cartilage and ligament engineering

10. SilkII • 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

11. Polysaccharide-basedbiomaterials • 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

12. 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

13. Alginate • Polysaccharidefromthecellwalls of brownalgae, acidiccompound, cationicsaltsareused • Sodium-alginate: E-401, foodadditive, gastronomicuse, heavy metal binding, fatbinding • Potassium-alginate: Emulsifier, stabilizerinfoodindustry • Calcium-alginate: Water-insolublegel-likematerial • Usedfor: • Enzymeimmobilizationorencapsulation • Encapsulation of wholecells, isolatingthemfromtheimmunesystem

14. 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

15. Chitosan • Derived from the deacetylationof chitin; strongly cationic • Commercially derived from crustacean exoskeleton • Bondages, wound dressing, enhanced blood clotting

16. Chitosan in bone TE • Chitosanfacilitatesthedifferentiation of osteocytes • Atslightlyacidic pH chitosan-Ca-phosphatecomposite is an injectablegel. Atphysiological pH itgelsanchoringosteocytes • Nativeorcollagen-linkedchitosanenhancesmonocytestodifferentiateintoosteoclasts

17. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat theUniversity of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011 Dr. Judit Pongrácz Threedimensionaltissuecultures and tissueengineering – Lecture 8 Biomaterials(2)

18. SyntheticbiomaterialsI • Organicpolymers: • PGA, PLA, PLGA • PEG • Peptides • Inorganic: • Ceramic • Metal • Hydroxyapathite

19. SyntheticbiomaterialsII • 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

20. 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

21. 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-brelease regulation

22. Peptide-basedbiomaterials • Shortaminoacidsequences • Self-assembly: ampholiticnature • Combiningtheadvantages of syntheticmaterials and naturalscaffolds: • Selfassemblingstructure • Bindingsites • Purity and consistentquality • IKVAV: neuriteoutgrowth, sequencefromlaminin • RGD: cellularadherencepromotion

23. Ceramic-basedbiomaterials • 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

24. 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