Dr. Alagiriswamy A A , (M.Sc, PhD, PDF) Asst. Professor (Sr. Grade),

1. Dr. Alagiriswamy A A, (M.Sc, PhD, PDF) Asst. Professor (Sr. Grade), Dept. of Physics, SRM-University, Kattankulathur campus, Chennai ABCs of Biomaterials UNIT III Lecture 4

2. CLASSIFICATION OF BIOMATERIALS • Biomaterials can be divided into three major classes of materials: • Metals • Polymers • Ceramics (including carbons, glass ceramics, and glasses).

3. Biological responses ; requirements • Changing the chemistry at the surface • Inducing roughness/porosity at the surface • Incorporate surface reactive materials (bioresorbable; helps in slow replacement by tissue) • Should not secrete oxidizing agents • Reduce corrosion rate of biomaterials

4. METALLIC IMPLANT MATERIALS • Must be corrosion resistant • Good fatigue properties • Other compatible issues • Stainless steel • Cobalt-chromium alloys • Titanium alloys • Metallic implants are used for two primary purposes. • To replace a portion of the body such as joints, long bones and • skull plates. • Fixation devices are used to stabilize broken bones

5. CONSTITUENTS OF STEEL

6. Other features • less chromium content should be utilized (because Cr is a highly reactive metal) • Make use of austenite type steel (less magnetic properties) • Lowered carbon content • Inclusion of molybdenum helps corrosion resistance • Electroplating technique (increases corrosion resistance)

7. APPLICATIONS OF SS STEEL

8. COBALT CHROMIUM ALLOYS • Cobalt based alloys are used in one of three forms • Cast; as prepared • Wrought (fine structure with low carbon contents ; pure forms) • Forged Cobalt based alloys are better than stainless steel devices because of low corrosion resistance

9. More details • Cast alloy: • a wax model of the implant is made and • ceramic shell is built around the wax model • When wax is melted away, the ceramic mold has the shape • of the implant • Molten metal alloy is then poured in to the • shell, cooling, the shell is removed to obtain • metal implant.

10. Wrought alloy: • possess a uniform microstructure with fine grains. • Wrought Co-Cr –Mo alloy can be further strengthened by cold work. • Forged Alloy: • produced from a hot forging process. • Forging of Co-Cr –Mo alloy requires sophisticated press and complicated tooling. • Factors make it more expensive to fabricate a device

11. TITANIUM BASED ALLOYS • The advantage of using titanium based alloys as implant materials are • low density • good mechano-chemical properties • The major disadvantages • relatively high cost • reactivity.

12. More details • a light metal • Titanium exists in two allotropic forms, • The low temperature -form has a close-packed hexagonal crystal structure with a c/a ratio of 1.587 at room temperature • Above 882.50C -titanium having a body centered cubic • structure which is stable • Ti-6 Al-4V alloy is generally used in one of three conditions • wrought, forged or cast

13. THREE CLASSES OF CERAMICS (according to their reactivity) • completely resorbable • More reactive (Calcium phosphate) – over a span of times • Yielding mineralized bone growing from the implant surface • surface reactive • Bioglass ceramics ; Intermediate behavior • Soft tissues/cell membranes • nearly inert • Less reactive (alumina/carbons) even after thousands of hours • how minimal interfacial bonds with living tissues.

14. DIFFERENT VARIETIES OF CARBON (NEARLY INERT CERAMICS) • Pyrolitic carbon; • Pyrolysis of hyrdocarbon gas (methane) ≤ 15000 degrees • Low temperature isotropic (LTI) phase • Good bonding strength to metals (10 Mpa – 35 Mpa) • Inclusion of Si with C, wear resistance increases drastically • Vitreous carbon (glassy carbon); • controlled pyrolysis of a polymer such as phenol formaldehyde • resin, rayon and polyacrylonitrile • Low temperature isotropic phase • Good biocompatibility, but strength and wear resistance are not good as LTI carbons • Turbostratic carbon (Ultra low temperature isotropic carbons (ULTI)) • Carbon atoms are evaporated from heated carbon source and • condensed into a cool substrate of ceramic, metal or polymer. • Good biocompatibility

15. Alumina (Aluminium oxide) • Natural single crystal alumina known as sapphire • High-density alumina ; prepared from purified alumina powder by isostatic pressing and subsequent firing at 1500-17000C. • -alumina has a hcp crystal structure (a=0.4758 nm and c=1.2999nm) • load bearing hip prostheses and dental implants, hip and knee joints, tibial plate, femur shaft, shoulders, vertebra, and ankle joint prostheses Alumina ceramic femoral component Porous network ; SEM images • high corrosion resistance • wear resistance • Surface finishing • small grain size • biomechanically correct design • exact implantation technique

16. Bioglass • Glass Ceramics • To achieve a controlled surface reactivity that will induce a direct chemical bond between the implant and the surrounding tissues. • Also known as 45S5 glass. It is composed of SiO2, Na2O, CaO and P2O5. • 45 wt.% of SiO2 and 5:1 ratio of CaO to P2O5. Lower Ca/P ratios do not bond to bone. • Bioglass and Ceravital; fine-grained structure with excellent mechanical and thermal properties • The composition of Ceravital is similar to bioglass in Sio2 content but differ in CaO,MgO,Na2O. • Bioglass implants have several advantages like • high mechanical properties • surface biocompatible properties. Ceravital

17. Resorbable Ceramics (first resorbable implant material-Plaster of Paris). • Should not have variable resorption rates • Should not have poor mechanical properties. • Two types of orthophosphoric acid salt namely -tricalcium phosphate (TCP) and hydroxyapatite (HAP) (classified on the basis of Ca/P ratio). • The apatite- [Ca10 (PO4)6 (OH)2] crystallizes into the hexagonal rhombic system. The unit cell has dimensions of a = 0.9432 mm and c = 0.6881 nm. • The ideal Ca/P ratio of hydroxyapatite is 10/6 and the calculated density is 3.219 g/ml. • The substitution of OH- with F- gives a greater structural stability due to the fact that F- has a closer coordination than the hydroxyl, to the nearest calcium.

18. POLYMERS • Elastomers; able to withstand large deformations and • return to their original dimensions after releasing the • stretching force. • Plastics; are more rigid • materials • Thermoplastic (can be • reused, melted) • Thermosetting (can’t) • Elastomers include, butyl rubber, chlorosulfonated polyethylene, epichlorohydrin,rubber, polyurethane,natural rubber and silicone rubber. • Polymers toxicity • Residual monomers due to incomplete polymerization/catalyst used for polymerization may cause irritations.

20. Polyethylene structures • The first polyethylene [PE,(-CH2-CH2-)n] was made by reacting • ethylene gas at high pressure in the presence of a peroxide catalyst for starting polymerization; yielding low density polyethylene (LDPE). • By using a Ziegler-Natta catalyst, high-density polyethylene (HDPE) • can be produced at low pressure; (first titanium-based catalysts) • The crystallinity usually is 50-70% for low density PE and 70-80% or high density PE • ultra high molecular weight polyethylene (UHMWPE) …??????

21. ACRYLIC RESINS (organic glass) • The most widely used polyacrylate is poly(methyl • methacrylate, PMMA) ; The features of acrylic polymers ; • high toughness/strength, • good biocompatibility properties • brittle in comparison with other polymers • excellent light transparency • high index of refraction. Causes allergic reactions

22. BONE CEMENT MIXING AND INJECTION • PMMA powder + MMA liquid mixed in a ratio of 2:1 in a dough, to cure • Injected in the femur (thigh bone) • The monomer polymerizes and binds together the preexisting polymer particles.

23. Hydrogels Interaction with H2O, but not soluble PHEMA; absorbs 60 % of Water, machinable when dry

24. Interesting features • The soft, rubbery nature coupled with minimal mechanical/frictional irritation to the surrounding tissues. • (2) Low or zero interfacial tension with surrounding biological fluids and tissues, thereby, minimizing the driving force for protein adsorption and cell adhesion • (3) Hydrogels allow the permeating and diffusion of low • molecular weight metabolities,waste products and salts as do living tissues. HYDROGELS

25. POLYURETHANES • Polyther-urethanes; block copolymers (variable length blocks that aggregate in phase domains) • Good physical and mechanical characteristics • Are hydrophilic in nature • Good biocompatibility (blood compatibility) • Hydrolytic heart assist devices • Non-cytotoxic therapy Consists of hard and soft segments BIOMATERIALS

26. POLYAMIDES (Nylons) • Obtained through condensation of diamine and diacid derivative. • Excellent fiber forming properties due to inter-chain hydrogen bonding and high degree of crystallinity, which increases the strength in the fiber direction. • Hydrogen bonds play a major role • As a catheter • Hypodermic syringes • Diamino hexane + adipic acid October 23, 2014 BIOMATERIALS

27. Biological responses ; requirements • Changing the chemistry at the surface • Inducing roughness/porosity at the surface • Incorporate surface reactive materials (bioresorbable; helps in slow replacement by tissue) • Should not secrete oxidizing agents • Reduce corrosion rate of biomaterials

28. Biosensors (in vitro/in vivo); • analytical devices which convert biological response into a useful electrical signal • to determine the concentration of substances either directly or indirectly • areas of biochemistry, bioreactor science, physical chemistry, electrochemistry, electronics and software engineering, and others http://www.lsbu.ac.uk/biology/enztech/

29. Principle of biosensors (bio-recognition systems)

30. WORKING PRINCIPLE OF BIOSENSOR • biocatalyst (a) converts the substrate to product. • This reaction is determined by the transducer (b) • which converts it to an electrical signal. • The output from the transducer is amplified (c), • processed (d) and displayed (e). output • distribution of charges • light-induced changes • mass difference BIOMATERIALS

31. Three so-called 'generations' of biosensors; • First generation; normal product of the reaction diffuses to • the transducer and causes the electrical response. • Second generation; involve specific 'mediators' between • the reaction and the transducer in order to generate • improved response. • Third generation; reaction itself causes the response and no • product or mediator diffusion is directly involved.

32. Brief applications of biosensor(s) • Clinical diagnosis and biomedicine • Farm, garden and veterinary analysis • Process control: fermentation control and analysis food and drink • production and analysis • Microbiology: bacterial and viral analysis • Pharmaceutical and drug analysis • Industrial effluent control • Pollution control and monitoring/Mining, industrial and toxic gases • Military applications

33. Tissue engineering (also referred to as “regenerative medicine) • By restoring, maintaining, enhancing the tissue, and finally functionalize the organs • Tissue can be grown inside or outside • Finally to exploit the living cells in many ways • To create products that improve tissue function or heal tissue defects. • Replace diseased or damaged tissue • Because…… • Donor tissues and organs are in short supply • We want to minimize immune system response by using our own cells or novel ways to protect transplant

34. Tissue engineering • Regenerate • Identify the cues that allow for regeneration without scarring • Like growing a new limb • Repair • Stimulate the tissue at a cell or molecular level, even at level of DNA, to repair itself. • Replace • A biological substitute is created in the lab that can be implanted to replace the tissue or organ of interest • The cells themselves • Non-soluble factors within the extracellular matrix (ECM) such as laminins,collagens,and other molecules • Soluble factors such as cytokines, hormones, nutrients, vitamins, and minerals

35. Normal strategies • cell isolation • cell culture • scaffold material choice • cell scaffold co-culture studies • implantation in animals • human trials SUCCESSFULLY ENGINEERED TO SOME EXTENT • Skin • Bone • Cartilage • Intestine

36. Questions?