1. September 2, 2015 1 Dr. Alagiriswamy A A, (M.Sc, PhD, PDF) Asst. Professor (Sr. Grade), Dept. of Physics, SRM-University, Kattankulathur campus, Chennai UNIT III Lecture 4 ABCs of Biomaterials

2. 2 CLASSIFICATION OF BIOMATERIALS Biomaterials can be divided into three major classes of materials: Metals Polymers Ceramics (including carbons, glass ceramics, and glasses). September 2, 2015

3. 3 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 Biological responses ; requirements

4. September 2, 2015 4 METALLIC IMPLANT MATERIALS 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  Must be corrosion resistant  Good fatigue properties  Other compatible issues

5. LECTURE 3 5 Type% C%Cr% Ni%Mn% other elements 3010.1516-186-82.01.0Si 3040.0717-198-112.01-Si 316, 18-8sMo0.0716-1810-142.02-3 Mo, 1.0 Si 316L0.0316-1810-142.02.3 Mo, 0.75Si 430F0.0816-181.0-1.51.51.0 Si, 0-6 Mo CONSTITUENTS OF STEEL

6. 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) September 2, 2015 6 Other features

7. September 2, 2015 7 DevicesAlloy Type Jewitt hip nails and plates316 L Intramedullary pins316 L Mandibular staple bone plates316L Heart valves316 Stapedial Prosthesis316 Mayfield clips (neurosurgery)316 Schwartz clips (neurosurgery)420 Cardiac pacemaker electrodes304 APPLICATIONS OF SS STEEL

8. 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 September 2, 2015

9. 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. September 2, 2015 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. 11 TITANIUM BASED ALLOYS The advantage of using titanium based alloys as implant materials are  low density  good mechano-chemical properties The major disadvantages o relatively high cost o reactivity. September 2, 2015

12. 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 882.5 0 C  -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. September 2, 2015 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. September 2, 2015 14  Pyrolitic carbon; Pyrolysis of hyrdocarbon gas (methane) ≤ 1500 0 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 DIFFERENT VARIETIES OF CARBON (NEARLY INERT CERAMICS)

15. September 2, 2015 15 Alumina (Aluminium oxide) high corrosion resistance wear resistance Surface finishing small grain size biomechanically correct design exact implantation technique Alumina ceramic femoral component  Natural single crystal alumina known as sapphire  High-density alumina ; prepared from purified alumina powder by isostatic pressing and subsequent firing at 1500- 1700 0 C.   -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 Porous network ; SEM images

16. September 2, 2015 16 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 SiO 2, Na 2 O, CaO and P 2 O 5. 45 wt.% of SiO 2 and 5:1 ratio of CaO to P 2 O 5. 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 Sio 2 content but differ in CaO,MgO,Na 2 O. Bioglass implants have several advantages like high mechanical properties surface biocompatible properties. Bioglass Ceravital

17. September 2, 2015 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- [Ca 10 (PO 4 ) 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. 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. September 2, 2015

19. 19 Polymer Specific PropertiesBiomedical uses PolyethyleneLow cost, easy Possibility excellent electrical insulation properties, excellent chemical resistance, toughness and flexibility even at low temperatures Tubes for various catheters, hip joint, knee joint prostheses PolypropyleneExcellent chemical resistance, weak permeability to water vapors good transparency and surface reflection. Yarn for surgery, sutures TetrafluoroethyleneChemical inertness, exceptional weathering and heat resistance, nonadhesive, very low coefficient of friction Vascular and auditory prostheses, catheters tubes

20. 20 Polyethylene structures The first polyethylene [PE,(-CH 2 -CH 2 -)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) …?????? September 2, 2015

21. 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 September 2, 2015

22. 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. September 2, 2015

23. 23 September 2, 2015 Hydrogels Interaction with H2O, but not soluble PHEMA; absorbs 60 % of Water, machinable when dry

24. 24 HYDROGELS Interesting features (1) 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. September 2, 2015

25. LECTURE 5 BIOMATERIALS25 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

26. BIOMATERIALS26 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 September 2, 2015

27. 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 September 2, 2015 27 Biological responses ; requirements

28. September 2, 2015 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. September 2, 2015 29 Principle of biosensors ( bio-recognition systems)

30. LECTURE 6 BIOMATERIALS30  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). WORKING PRINCIPLE OF BIOSENSOR  distribution of charges  light-induced changes  mass difference output

31. September 2, 2015 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. 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 LECTURE 3 32 Brief applications of biosensor(s)

33.  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 September 2, 2015 33 Tissue engineering (also referred to as “regenerative medicine)  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. 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 September 2, 2015 34 Tissue engineering  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. cell isolation cell culture scaffold material choice cell scaffold co-culture studies implantation in animals human trials Normal strategies Skin Bone Cartilage Intestine SUCCESSFULLY ENGINEERED TO SOME EXTENT

36. September 2, 2015 Questions?