Dr. Alagiriswamy A A, (M.Sc, PhD, PDF) Asst. Professor (Sr. Grade), Dept. of Physics, SRM-University, Kattankulathur campus, Chennai

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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 March 24,

2 Orthopedic screws/fixation Drug Delivery Devices Polymers Skin/cartilage Ocular implants Bone replacements Metals Synthetic BIOMATERIALS Ceramics Heart valves Dental Implants Implantable Microelectrode s Semiconductor Materials Biosensors Dental Implants

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 March 24,

4 CLASSIFICATION OF BIOMATERIALS Biomaterials can be divided into three major classes of materials: Metals Polymers Ceramics (including carbons, glass ceramics, and glasses). March 24,

5 First Generation Implants ad hoc implants specified by physicians using common and borrowed materials most successes were accidental rather than by design Examples First Generation Implants gold fillings, wooden teeth, PMMA dental prosthesis steel, gold, ivory, etc., bone plates glass eyes and other body parts dacron and parachute cloth vascular implants

6 METALLIC IMPLANT MATERIALS Stainless steel Cobalt-chromium alloys Titanium alloys Must be corrosion resistant Good fatigue properties 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 followed by the healing process Either first generation or second ones March 24,

7 CONSTITUENTS OF STEEL Type % C %Cr % Ni %Mn % other elements Si Si 316, 18-8sMo Mo, 1.0 Si 316L Mo, 0.75Si 430F Si, 0-6 Mo LECTURE 3 7

8 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) March 24,

9 Devices Alloy Type Jewitt hip nails and plates 316 L Intramedullary pins 316 L Mandibular staple bone plates 316L Heart valves 316 Stapedial Prosthesis 316 Mayfield clips (neurosurgery) 316 Schwartz clips (neurosurgery) 420 Cardiac pacemaker electrodes 304 March 24,

10 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 March 24,

11 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. March 24,

12 Wrought alloy: Forged Alloy: possess a uniform microstructure with fine grains. produced from a hot forging process. Wrought Co-Cr Mo alloy can be further strengthened by cold work. Forging of Co-Cr Mo alloy requires sophisticated press and complicated tooling. Factors make it more expensive to fabricate a device March 24,

13 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 oreactivity. March 24,

14 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 at room temperature Above 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 March 24,

15 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. March 24,

16 Polymer Specific Properties Biomedical uses Polyethylene Polypropylene Tetrafluoroethylene Low cost, easy Possibility excellent electrical insulation properties, excellent chemical resistance, toughness and flexibility even at low temperatures Excellent chemical resistance, weak permeability to water vapors good transparency and surface reflection. Chemical inertness, exceptional weathering and heat resistance, nonadhesive, very low coefficient of friction Tubes for various catheters, hip joint, knee joint prostheses Yarn for surgery, sutures Vascular and auditory prostheses, catheters tubes March 24,

17 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% for high density PE ultra high molecular weight polyethylene (UHMWPE)?????? March 24,

18 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 March 24,

19 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. March 24,

20 Hydrogels Interaction with H2O, but not soluble PHEMA; absorbs 60 % of Water, machinable when dry March 24,

21 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. March 24,

22 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 LECTURE 5 BIOMATERIALS 22

23 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 + adipic acid March 24, 2014 BIOMATERIALS 23

24 Next-Generation biomaterials for Tissue implantation Skin implantation March 24,

25 Primary exposed underlying Promote controlled THERAPY GOALS Preserve viability of structures Prevent infection Long term reconstruction Durable skin cover optimize later healing Permit mobility of Sensation to key areas March 24,

26 Spine, Cranial maxillofacial Dental Vascular Bone Cartilage March 24,

27 Types of Implants Implants may be Cemented Porous coated Mesh of holes on implant surface Secured as bone in grows

28 Types of coated implants

29 Requirements Non-toxic, noncarcinogenic, nonallergic, Biocompatible Excellent physical properties, corrosion resistant, fatigue strength Sterilizable, Choice of design Low cost, ofcourse Rate, modes of degradation should follow the intended ways March 24,

30 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. March 24,

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 31

32 Tissue engineering (also referred to as regenerative medicine) By restoring, maintaining, enhancing the tissue, and finally functionalize the organs Tissue can be outside grown inside or 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 March 24,

33 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 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 March 24,

34 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 Normal strategies

35 Advances in Biomaterials Technology Cell matrices for 3-D growth and tissue reconstruction Biosensors, Biomimetic, and smart devices Controlled Drug Delivery/ Targeted delivery Biohybrid organs and Cell immunoisolation New biomaterials - bioactive, biodegradable, inorganic New processing techniques

36 Test Conditions: Value Location ph 6.8 Intracellular 7.0 Interstitial Blood po Interstitial (mm Hg) 40 Venous 100 Arterial Temperature Normal Core Normal Skin Mechanical Stress 4x10 7 N m -2 Muscle (peak stress) 4x10 8 N m -2 Tendon (peak stress) Stress Cycles (per year) 3x10 5 Peristalsis 5x10 6-4x10 7 Heart muscle contraction Length of implant: Day: Month: Longer: where used: skin/blood/brain/mucosal/etc.

37 Challenges To more closely replicate complex tissue architecture and arrangement in vitro To better understand extracellular and intracellular modulators of cell function To develop novel materials and processing techniques that are compatible with biological interfaces To find better strategies for immune acceptance

38 Skin Implantation March 24,

39 Biosensors (in vitro/invivo); analytical devices which convert biological response into a useful electrical signal to determine the concentration substances either directly or indirectly areas of biochemistry, bioreactor science, physical chemistry, electrochemistry, electronics and software engineering, and others of March 24,

40 Principle of biosensors (bio-recognition systems) March 24,

41 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 LECTURE 6 BIOMATERIALS 41

42 Special materials March 24,

43 Autograft A graft, or portion of living tissue, taken from one part of the body and placed in another site on the same individual. Allograft Grafts between two or more individuals allogenic (genetically different although belonging to or obtained from the same species) at one or more loci. Xenograft Grafts from one species of tissues to other species; Bone marrow engineering March 24,

44 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. March 24,

45 DIFFERENT VARIETIES OF CARBON (NEARLY INERT CERAMICS) Pyrolitic carbon; Pyrolysis of hyrdocarbon gas (methane) 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 March 24,

46 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 C. -alumina has a hcp crystal structure (a= 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 high corrosion resistance wear resistance Surface finishing small grain size biomechanically correct design exact implantation technique Alumina ceramic femoral component Porous network ; SEM images March 24,

47 Glass Ceramics Bioglass To achieve a controlled surface reactivity that will induce a direct chemical bond between the implant and the surrounding tissues. 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. Ceravital Bioglass implants have several advantages like high mechanical properties surface biocompatible properties. March 24,

48 GLASS CERAMICS Bioglass and Ceravital are two glass ceramics, fine-grained structure with excellent mechanical/thermal properties, which are used in implants. Bioglass (composed of SiO2, Na2O, CaO and P2O5) Ceravital s composition is similar to bioglass in Sio2 content but differ in CaO,MgO,Na2O. highly reactive to aqueous medium and bioactive Drawbacks: - brittleness, low fracture-resistance due to mechanical weakness March 24,

49 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 = mm and c = nm. The ideal Ca/P ratio of hydroxyapatite is 10/6 and the calculated density is 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. March 24,

50 Questions? March 24, 2014