unit 1

1. BIOMATERIALS SUBJECT CODE: BM106114BM

2. Biomaterials:- A multidisciplinary department

3. 316L SS Titanium, UHMWPE etc. 316L SS +UHMWPE=Device Shape + Device=Recipient response Vice versa The size, strength, technical performance of a product, process, or material

4. Definitions “A biomaterial is a nonviable material used in a medical device, intended to interact with biological systems”. Williams, 1987 -A biomaterial is any substance that has been engineered to interact with biological systems for a medical purpose - either a therapeutic (treat, augment, repair or replace a tissue function of the body) or a diagnostic one.

5. Definitions “Biomaterial Science is the study (from the physical and/or biological perspective) of materials with specific reference to their interaction within the biological environment”. “Biocompatibility” is the ability of a material to perform with an appropriate host response in a specific application”. Williams, 1987

6. What is host response? Host-response is the reaction of a living system (tissues, blood, biological fluid etc.) to the presence of an external material. Examples of “Appropriate host responses” • Resistance to blood clotting • Resistance to bacterial colonization • Normal uncomplicated healings. Examples of “Specific Applications” • Hemodialysis membrane • Urinary catheter • Hip Joint prosthesis

7. BIOMATERIALS SOCIETIES • American society for artificial internal organs(ASAIO), founded in 1954. • The administrative home of a nascent biomaterials effort, was established at Clemson University, Clemson, South Carolina in 1969. Started annual International Biomaterials Symposia in 1969. The first was “Use of Ceramics in Surgical Implants.” • In 1974–1975, these symposia evolved into the Society for Biomaterials, the world’s first biomaterials society. • The European Society for Biomaterials was founded in 1975. • The Canadian Biomaterials Society was founded in 1973. • The Japanese Society for Biomaterials was formed in 1978. • The Controlled Release Society, focused for drug delivery, was founded in 1978. • The Society for Biomaterials and Artificial Organs – India founded in 1986. • The Tissue Engineering and Regenerative Medicine International Society (TERMIS) formed in 2005.

8. UNIT -1

9. UNIT-2 MATERIALS USED IN MEDICINE: • Fabrics • Biologically Functional Materials • Ceramics • Natural materials • Composites, thin films • Grafts and coatings • Pyrolytic Carbon for long-term medical Implants • Porous materials • Nano biomaterials

10. UNIT-3 HOST REACTIONS TO BIOMATERIALS • Inflammation • Wound healing and the Foreign body response • Systemic toxicity and Hypersensitivity • Blood coagulation and Blood-materials Interactions • Tumorigenesis DEGRADATION OF MATERIALS IN BIOLOGICAL ENVIRONMENT • Degradation of Polymers • Metals and Ceramics.

11. UNIT-4 APPLICATION OF BIOMATERIALS: • Cardiovascular Applications • Dental implants • Adhesives and Sealants • Opthalmologic Applications • Orthopedic Applications • Drug Delivery System • Sutures • Bioelectrodes • Biomedical Sensors and Biosensors.

12. Prerequisites of Biomaterials An (ideal) biomaterial must be: • Inert or specifically interactive • Biocompatible • Mechanically and chemically stable or • Biodegradable • Processable (for manufacturability) • Non-thrombogenic (if blood-contacting) • Sterilizable

13. Mechanical properties of Biological materials and Biomaterials

14. Toxicity and Biocompatibility • A biomaterial should not be toxic • It deals with the substances that migrate out of biomaterials. • There is no general set of criteria, for a material to qualify as being biocompatible. – The time scale over which the host is exposed to the material or device must be considered

15. Tissue Response to Implants

16. Tissue Response to Implants - Contd 1. Minimal Response: Thin layer of fibrous tissue Silicon rubber, PTFE, PMMA, Ceramics, alloys 2. Chemically Induced response: Acute, mild inflammation Absorbable sutures, resins 4. Physically Induced response: Inflammation to particulates PTFE, PMMA, Nylon, Metals 3. Chemical (2) : Chronic and Severe Inflammation Degradable material, Metallic corrosion 5. Physical (2) : Tissue growth into porous material Polymer, ceramic, metal, Composites 6. Necrotic response: Layer of necrotic Debris Bone cement, surgical adhesives

17. Interfacial Response Based on Interfacial response, there are four types of biomaterials: 1. Nearly inert, smooth surface 2. Nearly inert, microporous surface 3. Controlled reactive surface 4. Resorbable

18. Performance of Implants

19. Performance of Implants (contd..) • The performance of an implant after insertion can be considered in terms of reliability. Ex. There are four major factors contributing to the failure of hip joint replacements: fracture, wear, infection, and loosening of implants

20. STANDARDS Different standards: • ISO – International Organization for Standardization • ASTM – American Soceity for Testing Materials • BSI – British Standards Institute • AISI – American Institute of Steel and Iron • BIS – The Bureau of Indian Standards

21. STANDARDSContd..

22. Regulation Contd..

23. Regulation Contd..

24. Regulation Contd..

25. Classification of Biomaterials Inert, Interactive, Living and replacing materials • Inert biomaterials: Implantable materials with little or no counter reaction from the body. • Interactive biomaterials: Implantable materials designed to elicit a specific benign tissue reaction, such as integration, adhesion, etc. • Living biomaterials: Implantable materials that possibly contain living cells at time of implantation, regarded by the host tissue as tolerable tissue, and are actively resorbed and/or remodeled. • Replacement biomaterial: Implantable materials made of living tissue that has been cultivated from the patient own cells outside the body.

26. Classes of Biomaterials

27. Important Definitions • Biological response: Host response towards a material. • Biodegradation: Breakdown of a material in a biological system. • Bioactive material: A biomaterial intended to cause or modulate a biological activity. • Bioactivity: Degree of wanted (positive) reaction from tissues. • Inherent thrombogenicity: Establishment of a thrombus that is controlled by material surface properties (thrombus=blood plug, genicity=“cause”). • Osseointegration: It is a description of the clinical performance of bone that interact with a biomaterial (osseous=bone). • Bone Binding: The establishment of a continuity between implants and living bone through physical/biochemical processes. • Osteoconduction: Ability to support the growth of bone tissue over the surface or down into pores, channels, or pipes of an implant or graft. • Osteogenesis: It is the process of bone formation and development induced by implant material. • Osteoinduction: It is the process in which osteogenesis is encouraged. Osteoinduction is defined as ‘action or process of stimulating osteogenesis’. • Osteolysis:Wearing down of bones

28. Contd.. • Necrosis: The death of body tissue. It occurs when too little blood flows to the tissue. • Thrombus: It is a blood clot that forms in a vessel and remains there. • Thromboemboli: They are blood clots that travel from the site where they formed to another location. • Hemocompatibility: Compatibility of implanted materials with circulating blood. • Thrombogenicity: Thrombogenicity is one aspect of hemocompatibility and is defined as the ability of a device which stimulates and/or promotes the formation of a thrombus • Host response:Response of a living system to the presence of a material. • Foreign body capsule: It is a dense avascular layer of collagen around the implant which acts as both a structural and biological barrier between the tissue and implant • Carcinogenicity: It is the ability of a chemical, material, or agent to either stimulate tumor occurrence inducing cancer or increase its incidence when it is implanted.

29. Contd.. • Mineralization:It is the precipitation of minerals into a structure such as biomaterials or prosthetic devices. • Aseptic loosening: clinically detectable loosening of a joint replacement prosthesis that is NOT caused by infection. Typically found in association with osteolysis due to inflammation caused by wear particles.

30. Contd.. • Apoptosis:programmed cell death, characterized by endonuclease digestion of DNA • Ectopic calcification:Ectopic calcification is a condition in which calcification arises in tissues that are not within the osseous system but in connective or other tissues usually not manifesting osteogenic properties. • Stress shielding:refers to the process that leads to decreases in bone density around orthopedic implants that are caused by the relatively high flexural stiffness of the prosthesis. Reduced bending unloads the outer fibers of femur leading to a state of stress shielding. The change in the load distribution increases stresses in some regions and reduces them in others.

31. PROPERTIES OF MATERIALS UNIT-1

32. Material properties • Mechanical Properties (bulk) • Elasticity, viscoelasticity, brittle fracture, fatigue, ductile • Consideration of Thermal & optical (bulk) properties which are significant in the context of biomaterials • Surface Properties • List of Characterization techniques • The bulk of a biomaterial presents physical and chemical properties of the material that remain during the lifetime of the implant. • The surface properties is mainly defined by chemical, microstructure and it interacts with the host tissue directly.

33. Atoms & Molecules • Energy as a agent is responsible to hold atoms or molecules together • Thus, four attractive forces are present in this universe

34. TYPE OF ELECTROMAGNETIC FORCES THAT HOLDS ATOMS TOGETHER

35. HIERARCHICAL STRUCTURES TENDONS Can break by nanograms of force Alpha chains are constructed of joined amino acid units, and the amino acids are molecules of carbon, oxygen, nitrogen, and hydrogen atoms in defined ratios and orders tendon can support many kg of force

36. BULK PROPERTIES OF MATERIALS • Mechanical Properties (ability to carry loads dependably without undue deflection or premature failure) • Thermal Properties • Optical Properties Hydrocarbon:3 nm, surface energy ~22 ergs/cm2 Polar organic molecules: >1 nm, surface energy ~45 ergs/cm2 Adsorbed water:<1 nm, surface energy ~72 ergs/cm2 Metal oxide: ~ 5 nm, surface energy ~200 ergs/cm2 Bulk: surface energy ~1000 ergs/cm2 Interface between air and material:~22 ergs/cm2

37. Bulk Properties contd.. • Intrinsic properties:-Bulk properties of biomaterial depend upon composition & type of atom or molecules (stiffness of a metal, density and heat capacity). Note:-stiffness of a polymer is not an intrinsic property, because the stiffness measured by attempting to stretch the polymer in a particular direction depends on whether or not the molecules are preferentially aligned in that direction • Extrinsic property:-Bulk properties of biomaterial depend on attributes such as the average grain (crystal) size, number and distribution of defects in the crystal structure (Yield strength, Stiffness of polymer) • Bulk properties of biomaterials also depend on how atoms or molecules are arranged (microstructure). • Ex. Are the molecules locally packed in a regular array? • Do the molecules locally all point in the same direction?

38. Microstructure and Properties -Structures in solids occurs in hierarchy of sizes (Slide No. 35). -Internal or electronic structure of atoms occurs at the scale 0.2 nm(0.0002 µm or 2×e-8 cm) which are responsible for interatomic bonds(this is beyond the resolving power of most powerful direct observational technique). -At the scale greater than 0.2 nm can be detected by various techniques (ex. XRD, STM, field ion microscopy etc.) -At a very large-scale 3D arrangement of atoms in crystals can be observed. -at 1 nm to 105 nm another type of structural organization exist known as microstructure. “Microstructure of a material is a specification of the structural features at length scales that cannot be differentiated with the naked eye”

39. Example of microstructure and grains contd.. • When atoms of molten samples are incorporated into crystals during freezing, many small crystals are formed initially and grow until they impinge on each other, and all the liquid is used up. At this point the sample is completely solid. • Thus, most crystalline solids (metal and ceramics) are composed of many small crystals or crystallites called grainsand are tightly packed and firmly bound together. • This is the microstructure which can be seen my magnification with resolution 1 to 100 µm. • Grain size is one of the most important features that can be evaluated by different techniques. • Fine-grained samples are generally stronger than coarse-grained specimens of a given material. • Another important feature that can be identified is the coexistence of two or more phases in some solid materials. The grains of a given phase will all have the same chemical composition and crystal structure, but the grains of a second phase will be different in both these aspects. Phenomena never occurs in samples of pure elements but does occur in mixtures of different elements or compounds where the atoms or molecules can be dissolved in each other in the solid state just like they are in liquid or in gas state.

40. Mechanical Properties

41. Deformation • When a load (force) is applied to an object, it may translate, rotate, or deform. • To understand mechanical properties of matter here we are only concerned about deformation. • To define deformation, we need dimension of the object. Where: F=Force Applied at top & bottom faces =Cross sectional area to applied force

42. Contd.. Nominal stress == Engineering stress Note:-Ratio is called nominal stress because actual value of the area (cross-section) to which the load is applied will change as the sample deforms in response to the load. Stress may be tensile when sample is pulled and it may be compressive when it is pushed. -SI Unit is

43. Contd… Nominal Strain= Engineering Strain=length change per unit length === • where denotes the extension ratio, i.e., the ratio of final length to initial length. • =Initial length • =Change in length caused by applied stress. Note:- Relation between stress & strain is summarized as stress-strain plot, which is drawn at a constant strain rate

44. True Stress True Stress = -Considering if the applied force is scaled with reference to the actual cross-sectional area of the sample, [A] during stress-strain test. -Remember that measuring the changes of A during stress-strain test is very difficult, so nominal stress is often used instead of true stress.

45. True Strain Consider sample of initial length be stretched to a length , and then to length Calculated separately, the corresponding nominal strains are as follows: and The nominal strain for the deformation directly from length to length would be calculated as: But; ≠ + This is the limitation of nominal strain when we consider collective effect of sequential strains.

46. Contd.. • To overcome this limitation, we have to consider the length change of the sample is measured in very small increments , with each increment being scaled relative to the length of the sample immediately prior to that increment. • Thus, a small increment in true strain is defined as: • The true strain corresponding to deformation from length to can then be found by integrating the above expression between limits and .

47. Contd.. • Similarly, from to length the equation will be • The sum of these true strains is: • True strains behave properly when we try to add them.

48. Interconversion of nominal and true stressesand strains • Assume sample volume does not change during deformation. Means at initial stage when sample length is and CS area is and at final stage when sample length is and CS area is there is no change in volume. • Then • At that stage in the deformation, . the true stress is: • The interconversion between nominal and true strains is :

49. SHEAR STRESS AND SHEAR STRAIN • When force F acts parallel to a pair of opposite faces (top & bottom CS area). Ratio of force and area is called shear stress. • Similarly, as shown in top figure rectangular sample is distorted at an angle of “θ”. This shape change is used to describe shear strain

50. STRESS–STRAIN CURVE Yield Point • Used to define and quantify several mechanical properties of a material.