CHAPTER 17

1. CHAPTER 17 Biological Materials and Biomaterials

2. Biomaterials and Biological Materials • Biomaterial: a systematically and pharmacologically inert substance designed for implantation within or incorporation with living systems. • Examples: Orthopaedic implants, dental implants, artificial heart valves, and joint replacements • Biological materials: materials produced by biological systems. • Examples: bone, ligament, and cartilage tissues

3. Biological Material: Bone • Composition: Mixture of organic and inorganic materials. • Calcium and phosphate ions, similar to Hydroxyapatite (Ca10(PO4)6(OH)2) – 60-70% of dry weight. • Hydroxyapatite (HA): pallet like, 20 to 80 nm long, and 2 to 5 nm thick, HCP. • Collagen: fibrous, tough, flexible, and highly inelastic; provides bone with flexibility- 30% of dry weight. Inorganic portion From Basic Biomechanics, Susan J Hall, McGraw-Hill polymer

4. Bone • Macrostructure: • Cortical (outer shell, compact • Trabecular (inner bone, cancellous) • Trabecular bone filled with bone marrow. • Have different properties. A longitudal section through an adult femur Trabecular bone Cortical bone

5. Mechanical Properties Strain-stress curves of cortical and trabecular bones. Cortical bone is stronger and stiffer than trabecular bone. Bone density plays a critical role in mechanical properties. Trabecular bone has lower strength and high ductility. 5

6. Mechanical Properties • Bone is anisotropic. • It is generally stronger in the direction it is loaded. • Bone is weakest in the transverse direction. • Transversely isotropic or orthotropic models are used to study the behaviour of bone. • Bones are stronger in compression than tension. Anisotrpic: exhibiting properties with different values when measured in different directions. Tension: the force acting on the object is always outward from the object. Compression: the force acting on the object is inward to the object.

7. Bone fracture • Bone supports various modes of loading such as tensile, compressive, bending, torsional, shear, and combined. Bending Shear fractures Tensile fractures

8. Viscoelasticity of Bone • Strain rate during walking is 0.001/s, during running it is 0.03/s, during impact trauma it is 1/s. • As strain rate increases, bone becomes stiffer and stronger and more brittle. • Under high-energy fracture, the excess available energy causes significant damage to the surrounding tissue. • Repeated loading can cause muscles to get tired. • Bone then carries a lot of load. • Microcracks propagate if enough time is not given for healing. • This causes fatigue failure.

9. Bone Remodelling • Wolff’s law: Bone responds to applied stress by remodelling. • Bone senses environmental stimuli and responds accordingly. • It can change its alter its size, shape, and structure. • Principle: Optimize the content of the bone inside the body: keep wherever it is needed, remove from the place it is not needed. • Astronauts suffer bon loss due to weightlessness. • Moderate exercise with low weights reduces the bone loss phenomenon in the aging population.

10. Tendons and Ligaments

11. Tendons and Ligaments • Tendons connect muscles to bone: transfer forces generated by muscle contractions to the bone. • Ligaments connect bone to bone: stabilizes the joint. • The functional loads for tendons are generally higher than those for ligaments. • About 60% of the total weight is water. • About 80% of the dry weight is made up of Type-I collagen.

12. Microstructure • Collagen molecules are secreted by fibroblasts. • These molecules form microfibrils, fibrils (20-150 nanometers) and bundles. • Fibril is the primary load carrying member. • Fibrils are crimped when unloaded. TEM image of fibrils. (ligament sliced by microtome and dehydrated before imagery.) SEM image of fibrils

13. Mechanical Properties • Primarily loaded in tension. • Stress strain curve is non-linear: Has a toe region, linear region and a non-linear region. • Fibrils are sequentially loaded until all the fibrils are loaded, and then sequentially fail. • ‘E’ is measured in “Region 2” (linear region). Tensile Test on Ligament

14. Structure Function Relationship • Wide variability, depending on the tissue. • The amount of collagen in the tissue, collagen fibril density, and the extent of collagen cross-linking directly influence the mechanical properties. • Age, sex, activity level, all influence the collagen content. • Collagen fibril area fraction affects the ultimate stress. • Higher collagen fibril density (fibrils/area) increases E.

15. Constitutive Modelling E=207 MPa Simple Hooke’s law is not useful due to nonlinearity. Complex stress-strain relationships: C, a, and b are parameters to be found empirically. 15

16. Ligament and Tendon Injuries • Muscles are primary stabilizers of joint. • If muscles fail to contract at the right time, ligaments take the load and sometimes fail. • Tendon injuries take place due to aggressive contraction of muscles. • Microscopic tears happen during everyday activities, but they heal over time. • Ligament injuries do not heal easily if synovial fluid is present. • Torn ligaments are often reconstructed with graft tissues.

17. Articular Cartilage

18. Articular Cartilage • Joints of human body experience huge load. • Bone at the joints are covered with articular cartilage. • The articular cartilage reduces wear and friction at the joint and distributes the load over a wide area. • 1-6 mm thick, avascular, no nerve supply. • Made up of porous matrix, water and ions. • 70-90% of the wet weight is water. • 10-20% type II collagen, 4-6% proteoglycans.

19. Microstructure • Four zones of collagen fibril arrangement. • Collagen content is highest in the tangential region while the proteoglycans content is lowest. • In the deep region, the proteoglycans content is highest while the water content is lowest. • Deep zone anchors the cartilage into the subchondral bone.

20. Mechanical Properties • Highly viscoelastic, anisotropic and heterogeneous. • The mechanical behavior of the articular cartilage is due to i) intrinsic property of the matrix ii) flow of the water within the matrix iii) the effects of the presence of ions in the matrix. • Modulus of elasticity varies from 4-400 Mpa. • Usually loaded in compression and shear. • Equilibrium Aggregate modulus (static modulus of the matrix) is measured by confined compression test. • Proteoglycan absorb water, develop strong repulsive forces inside the matrix and thus resist compression (like a inflated tire).

21. Cartilage Degeneration • Cartilage has limited capability to repair itself. • Repeated high stress loading and biochemical changes lead to cartilage degeneration. • Prolonged abnormal joint stress distribution (due to ligament injury) and single traumatic load can also cause cartilage degeneration • If cartilage degenerates, bone-to-bone contact takes place at the joints, resulting in pain. • This is called osteoarthritis. • These joints will have to undergo total reconstruction using metal implants.

22. Biomaterials

23. Biomaterials: Biometals • Biometals come in direct contact with human body fluids. • Used to replace tissue • Support damaged tissue while heeling • Filler material • Biocompatibility : Internal environment of human body is highly corrosive • Metals degrade and release harmful ions • Chemical stability, corrosion resistance, non-carcinogenity and non-toxicity is called biocompatibility. • High fatigue strength (50-100 million cycles) is desired. • Pt, Ti, Zr have good biocompatibility. • Co, Cu, Ni are toxic

24. Stainless Steels as Biometals • 316 L stainless steel (cold worked, grain size of minimum 5) is used most often • 18Cr-14Ni-2.5Mo---F138 • Inexpensive, easily shaped • limited corrosion resistance inside the body • removed after healing • Used as bone screws Fibula Bone plate Spine plate Intramedullary nail

25. Stainless Steel • First used in 1926 • Low carbon content (316L: 18 Cr, 14 Ni, 2.5 Mo) – High carbon content causes corrosion of iron - Cheap, easily formable - grain size of 5 or finer - 30% cold-worked state • Chromium oxidizes to limit corrosion (limited resistance) • Suitable for short term use: bone plates and fixation. • Nickel released due to corrosion can be toxic. • Recently, nickel-free austenitic steel has been developed.

26. Cobalt Based Alloys Cr promotes long term Corrosion resistance by forming passive layer. Ni and W improve Machinability and fabrication • Co-28Cr-6Mo Co-20Cr-15W-10Ni Co-28Cr-6Mo-heat treated Co-35Ni-20Cr-10Mo • Initially hot worked and then cold finished • Used in permanent fixation devices Total knee replacement prosthesis

27. Cobalt Based Alloys • Wide range, easily formable. • Ideal for joint replacement and fracture fixation. • High corrosion resistance (Chromium), fatigue resistance and ductile. • Difficult to form/machine, usually cast (lost wax technique). • Large grain size-less fatigue life. • Wear causes metallic toxicity • Co-Cr alloys have good wear resistance

28. Titanium Alloys • Easily formed, outstanding corrosion resistance • Forms TiO2 layer, very robust. • Low elastic modulus, highly biocompatible • Pure Ti is used in low strength applications • Alpha-beta alloys of Ti like Ti-6Al-4V (F1472) are strengthened by solution heat treatment. • Poor wear resistance and notch sensitivity but Ion implantation improves wear resistance

29. Issues in Orthopaedic Applications • High yield strength, fatigue strength and hardness of implants is desired. • Implant should support healing bone • Low elastic modulus is desired • Implant and bone should carry proportionate amount of load • Implant should not shield the bone from load • Stress shielding stops remodeling of bone and weakens it. • Elastic modulus of bone is only 17 GPa while most alloys have elastic modulus greater than 100 GPa.

30. Biopolymers • Polymers are used in biomedical applications • Cardiovascular, Ophthalmic and Orthopaedic implants • Dental implants, dental cements and denture bases • Low density, easily formed and can be made biocompatible. • Recent development – biodegradable polymers. • Examples: Polyethylene (PET) polyurethane, polycarbonate polyetheretherketone (PEEK) polybutylene terephthalate (PBT) polymethyl methacrylate (PMMA)

31. Cardiovascular Applications • Heart valves can be stenotic or incompetent • Polymers are used to make artificial heart valves • Leaflets are made from biometals • Sewing ring made from PTFE or PET • Connected to heart tissue • Blood clogging is side effect • PTFE is used as vascular graft to bypass clogged arteries. • Blood oxygenators : Hydrophobic polymer membranes used to oxygenate blood during bypass surgery • Air flows on one side and blood on the other side and oxygen diffuses into blood.

32. Opthalmic Applications • Eye glasses, contact lenses and Intraocular implants are made of polymers. • Hydrogel is used to make soft contact lenses • Absorbs water and allows snug fit • Oxygen permeable • Made of poly-HEMA • Hard lenses made from PMMA • Not oxygen permeable • Mixed with Siloxanylalkyl Metacrylate and metacrylic acid to make permeable and hydrophilic. • Intraocular implants are made of PMMA

33. Intraocular Lenses Before and after cataract surgery

34. Orthopaedic Applications • Bone cement: Fills space between implant and bone – PMMA • Centrifuging and vacuum techniques minimize porosity • Used in joint prosthesis (Knee and Hip replacements). • centrifuging and vacuuming techniques used to reduce microporosity. • UHMWPE (Ultra high molecular weight polyethylene is used in bearing surface of implants. • Reduces friction and wear.

35. Other Applications • Drug delivery systems: polylactic acid (PLA) and polyglycolic acid (PGA). • Polymer matrix with drug is implanted inside the body. • Drug is released as the polymer degrades. • Suture materials: high tensile strength and knot pull strength. • Nonabsorbable sutures are generally made of polypropylene, nylon, polyethylene tetraphthalate, or polyethylene. • Absorbable sutures are made of PGA.

36. Ceramics in Biomedical Applications • First used in 1963, generating lot of interest • Biocompatible: very inert, less toxic degeneration products. • Wear resistant, low friction but brittle. • Some lose strength in contact with blood and water. • Good bond with bone. • very stiff, can cause some stress shielding. • Orthopaedic implants and dental.

37. Ceramic implants • High purity alumina: excellent corrosion and wear resistance, biocompatible. • Purity must be 99.8% and grain size of 3 – 6 microns. • Less friction, comparable to healthy hip (10 times less wear debris). • Can cause stress shielding.

38. Ceramic Implants • Dental implants: both for crown and root. • Crown is made up of porcelain, which is also a ceramic. • 4 types of response to biomaterial: toxic (tissue dies), inactive (fibrous tissue around implant), bioactive (bond), resorption (implant dissolves). • Alumina is inert, forms fibrous tissue, OK in dental implants.

39. Tissue connectivity • Porous alumina is used to serve as scaffold. • The bone material grows into the pores available in the ceramic, Osteoconductivity. • Porosity reduces strength: minimal load bearing applications only, provides moderate load-bearing support. • Bioactive ceramics develop adherent interface (glasses with SiO2, Na2O, CaO, P2O5 show bioactivity. • Resorbable ceramics degrade over a period of time and replaced by bone. • Ca3 (PO4)2 matches resorption rate with repair rate.

40. Nanocrystalline Ceramics • Brittleness of ceramics is not desired. • Nanocrystalline ceramics may improve on this inherent weakness of these materials. • Examples: Calcium phosphate hydroxyapatite (HA), calcium carbonate, and bioactive glasses. • Produced using standard powder metallurgy techniques. • Pressure assisted sintering is also used. • Nanocrystalline ceramics with exceptional levels of strength, ductility, and therefore improved toughness. • Still in research stage.

41. Composites in Biomedical Applications • Composite materials offer combination of properties. • New materials to replace natural bone by combining high-density PE (HDPE) with HA are found. • HA (20 to 40% vol) gives the material bioactivity while the polymer gives it the fracture toughness. • Carbon fiber-reinforced thermoplastic composites can be used to produce fracture-fixation devices flexible and strong bone plates to avoid stress shielding. • Bone plates made up of poly-L-lactide (PLLA) reinforced with raw u-HA particles have optimal degradation rate. • Dental implants using composites of SiC and carbon fiber–reinforced carbon are currently researched.

42. Composites in Biomedical Applications • Composites are widely used in joint prosthesis. • Efforts are underway to substitute UHMWPE with PEEK reinforced with carbon fibers to improve its wear resistance. • This composite can also be used to produce a femoral stem for hip implants. • Bioactive composite coatings have been produced by combining bioglass with Ti–6 Al–4 V. • Bone cements are often reinforced with particulate HA to improve bone attachment. • Glass fibers–reinforced PMMA and PC are used for fixed dental bridges and removable dental prosthesis.

43. Corrosion in Implants • Highly corrosive environment, long time (life long). • Pitting corrosion and crevice corrosion are the most common types of corrosion in biometals. • Pitting corrosion usually occurs on the underside of the screw heads that secure the implant. • Crevice corrosion occurs when the metal surface is partially shielded from the surrounding environment. • Crevice corrosion in the countersunk portion of the bone plate is very common in stainless steel implants. • Galvanic corrosion occurs when two metals are in contact. • Fretting corrosion is also common due to repetitive loading (in joint prosthesis).

44. Corrosion in implants • Titanium has superior corrosion resistance. (form a robust passive layer on the outside ) • Cobalt-chromium alloys also behave in the similar manner, however, it is moderately susceptible to crevice corrosion. • The passive layer formed by stainless steel is not very robust. Crevice corrosion in hip implant.

45. Effects of Corrosion • Mechanical integrity of the implants might be compromised. • Corrosion products can result in adverse tissue reaction. • Sometimes, swelling and pain in the tissue surrounding the implant. • The corrosion debris can migrate resulting in periprosthetic bone loss. • This results in loosening of the implant. • This condition is known as osteolysis.

46. Preventing Corrosion in Implants. • Alloying, surface treatment and proper implant design can minimize the corrosion in orthopaedic implants. • Nitridingthe surface of Ti6Al4V implants reduces the chances of fretting corrosion. • Resistance to pitting corrosion can be increased by the addition of 2.5-3.5% molybdenum to the implant material. • Proper implant design to minimize the crevices can eliminate crevice corrosion. • The surface of the implants can also be made passive prior to the implantation through various chemical treatments. • Using the matched parts of the modular implant from the same batch of the same variant of a given alloy reduces the chances of galvanic corrosion.

47. Wear in Biomedical Implants • Joint prosthesis has parts that move. • The consequence of having moving parts is friction and wear. • Inflammatory response and also causes osteolysis. • The shape changes due to wear affecting its normal function. • Biotribology deals with the study of friction and wear in biomedical implants. • Friction and wear are the result of microsurface roughness of the surfaces moving relative to each other. • Irregularities on a ceramic artificial joint surface is 0.005 microns while that on metal surface is 0.01 microns. • The area of contact when these surfaces mate is relatively small (1% of the total area). • Adhesive Wear: Local contact stresses can exceed the yield strength resulting in the bonding and debonding resulting in frictional resistance and wear also causing wear debris.

48. Wear in Implants • Abrasive wear: When a harder surface rubs against a softer surface, wear of the softer surface is produced by a ploughing of the surface by the asperities in the harder surface. • 3 body wear: polyethylene cup with metal head and debris. • Sometimes transfer-film is formed which decreases wear rate by increasing the contact area.

49. Reducing wear • Lubrication is necessary (synovial fluid). • Boundary lubrication: a lubricant film adheres to the bearing surfaces reducing the friction (significant asperity contact). • Fluid film lubrication: fluid film forms between the bearing surfaces completely separating them (no asperity contact). • Mixed lubrication mechanism has the characteristics of both fluid film and thick film lubrications. • Both fluid film and boundary lubrication occurs in the joints at different instances. • Joint coefficient of friction is 0.001. • Changes is biochemistry of synovial fluid can result in wear.

50. Implant wear prevention • Clearance between the mating surfaces are optimized to promote fluid film lubrication. • The surface of the implants is treated to make them harder. - titanium implants are heated to about 11000F in the presence of molecular nitrogen gas. - This will result in solid solution of nitrogen in titanium on the implant surface increasing the surface hardness. • Coating the implant surfaces with very hard material. • Coating the surfaces with amorphous carbon which has very high hardness and low friction. - Plasma assisted CVD is used.