Dr Alagiriswamy A A M Sc Ph D

Dr. Alagiriswamy A A, (M. Sc, Ph. D, PDF) Asst. Professor (Sr. Grade), Dept. of Physics, SRM-University, Kattankulathur campus, Chennai ABCs of Biomaterials UNIT III Lecture 4 19 March 2018 1

CLASSIFICATION OF BIOMATERIALS Biomaterials can be divided into three major classes of materials: Metals Polymers Ceramics (including carbons, glass ceramics, and glasses). 19 March 2018 2

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 19 March 2018 3

METALLIC IMPLANT MATERIALS Stainless steel q Must be corrosion resistant Cobalt-chromium alloys q Good fatigue properties Titanium alloys q Other compatible issues 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 19 March 2018 4

CONSTITUENTS OF STEEL Type %C %Cr % Ni %Mn % other elements 301 0. 15 16 -18 6 -8 2. 0 1. 0 Si 304 0. 07 17 -19 8 -11 2. 0 1 -Si 316, 18 -8 s. Mo 0. 07 16 -18 10 -14 2. 0 2 -3 Mo, 1. 0 Si 316 L 0. 03 16 -18 10 -14 2. 0 2. 3 Mo, 0. 75 Si 430 F 0. 08 16 -18 1. 0 -1. 5 1. 0 Si, 0 -6 Mo LECTURE 3 5

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) 19 March 2018 6

CA SS TION STE S EL OF Devices Alloy Type Jewitt hip nails and plates 316 L Intramedullary pins 316 L Mandibular staple bone plates 316 L PLI Stapedial Prosthesis 316 Mayfield clips (neurosurgery) 316 420 Cardiac pacemaker electrodes AP 316 Schwartz clips (neurosurgery) 19 March 2018 Heart valves 304 7

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 19 March 2018 8

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. 19 March 2018 9

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 19 March 2018 10

TITANIUM BASED ALLOYS The advantage of using titanium based alloys as implant materials are q low density q good mechano-chemical properties The major disadvantages o relatively high cost oreactivity. 19 March 2018 11

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. 50 C -titanium having a body centered cubic structure which is stable • Ti-6 Al-4 V alloy is generally used in one of three conditions wrought, forged or cast 19 March 2018 12

THREE CLASSES OF CERAMICS (according to their reactivity) q completely resorbable • More reactive (Calcium phosphate) – over a span of times • Yielding mineralized bone growing from the implant surface q surface reactive • Bioglass ceramics ; Intermediate behavior • Soft tissues/cell membranes q nearly inert • Less reactive (alumina/carbons) even after thousands of hours • how minimal interfacial bonds with living tissues. 19 March 2018 13

DIFFERENT VARIETIES OF CARBON (NEARLY INERT CERAMICS) q 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 q 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 q 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 19 March 2018 14

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 150017000 C. § -alumina has a hcp crystal structure (a=0. 4758 nm and c=1. 2999 nm) § 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 19 March 2018 15

Glass Ceramics To achieve a controlled surface reactivity that will induce a direct chemical bond between the implant and the surrounding tissues. Bioglass Also known as 45 S 5 glass. It is composed of Si. O 2, Na 2 O, Ca. O and P 2 O 5. 45 wt. % of Si. O 2 and 5: 1 ratio of Ca. O 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 Ca. O, Mg. O, Na 2 O. Ceravital Bioglass implants have several advantages like • • high mechanical properties surface biocompatible properties. 19 March 2018 16

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. 19 March 2018 17

POLYMERS Elastomers; able to withstand large deformations and return to their original dimensions after releasing the stretching force. Plastics; are more rigid materials q Thermoplastic (can be reused, melted) q Thermosetting (can’t) 19 March 2018 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. 18

Polymer Specific Properties Biomedical uses Polyethylene Low 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 Polypropylene Excellent chemical resistance, weak permeability to water vapors good transparency and surface reflection. Yarn for surgery, sutures Tetrafluoroethylene Chemical inertness, exceptional weathering and heat resistance, nonadhesive, very low coefficient of friction Vascular and auditory prostheses, catheters tubes 19 March 2018 19

Polyethylene structures The first polyethylene [PE, (-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) üThe crystallinity usually is 50 -70% for low density PE and 70 -80% or high density PE qultra high molecular weight polyethylene (UHMWPE) …? ? ? 19 March 2018 20

ACRYLIC RESINS (organic glass) The most widely used polyacrylate is poly(methyl methacrylate, PMMA) ; The features of acrylic polymers ; q high toughness/strength, q good biocompatibility properties q brittle in comparison with other polymers q excellent light transparency q high index of refraction. Causes allergic reactions 19 March 2018 21

BONE CEMENT MIXING AND INJECTION q 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. 19 March 2018 22

Hydrogels Interaction with H 2 O, but not soluble PHEMA; absorbs 60 % of Water, machinable when dry 19 March 2018 23

Interesting features HYDROGELS (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. 19 March 2018 24

POLYURETHANES q Polyther-urethanes; block copolymers (variable length blocks that aggregate in phase domains) q Good physical and mechanical characteristics q Are hydrophilic in nature q Good biocompatibility (blood compatibility) q Hydrolytic heart assist devices q Non-cytotoxic therapy Consists of hard and soft segments LECTURE 5 BIOMATERIALS 25

POLYAMIDES (Nylons) Obtained through condensation of diamine and diacid derivative. Excellent fiber forming properties due to interchain 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 19 March 2018 BIOMATERIALS + adipic acid 26

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 19 March 2018 27

Biosensors (in vitro/in vivo); q analytical devices which convert biological response into a useful electrical signal q to determine the concentration of substances either directly or indirectly q areas of biochemistry, bioreactor science, physical chemistry, electronics and software engineering, and others http: //www. lsbu. ac. uk/biology/enztech/ 19 March 2018 28

Principle of biosensors (bio-recognition systems) 19 March 2018 29

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), output § distribution of charges § light-induced changes § mass difference § processed (d) and displayed (e). LECTURE 6 BIOMATERIALS 30

Three so-called 'generations' of biosensors; q First generation; normal product of the reaction diffuses to the transducer and causes the electrical response. q Second generation; involve specific 'mediators' between the reaction and the transducer in order to generate improved response. q Third generation; reaction itself causes the response and no product or mediator diffusion is directly involved. 19 March 2018 31

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 LECTURE 3 32

Tissue engineering (also referred to as “regenerative medicine) q By restoring, maintaining, enhancing the tissue, and finally functionalize the organs q Tissue can be grown inside or outside §To create products that improve tissue function or heal tissue defects. q Finally to exploit the living cells in many ways §Because…… § Replace diseased or damaged tissue §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 19 March 2018 33

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 The cells themselves in the lab that can be implanted Non-soluble factors within the extracellular to replace the tissue or organ of matrix (ECM) such as laminins, collagens, and interest other molecules Soluble factors such as cytokines, hormones, nutrients, vitamins, and minerals 19 March 2018 34

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

Questions? 19 March 2018