Biocompatibility of dental materials- kelly

Biocompatibility of dental materials

1. BIOCOMPATIBILITY OF DENTAL MATERIALS 1 DR.KELLY NORTON POST GRADUATE STUDENT DEPT. OF PROSTHODONTICS V.S. DENTAL COLLEGE

2. Introduction Biocompatibility refers to the study of interaction of various materials with human tissues. Materials used in dentistry come into direct contact with the hard tissues of teeth, the oral mucosa, the pulp & the periapical tissues . Due to this intimate, long term contact, the materials should exhibit a high degree of biocompatibility. For the biocompatibility of a biomaterial , it is not only important that minimal diffusible substances are released when it is in body contact, but the material must also solve the purpose for which it has been designed . 2

3. Biocompatibility is formally defined as the ability of a material to elicit an appropriate biological response in a given application in the body. ( Craig) 3

4. 4 They should not sensitize and produce allergic reactions. They should not undergo biodegradations. They should not be carcinogenic. They should not contain any toxic diffusible substances which get released and enter into the circulatory system . They should not be harmful to soft & hard tissues of the oral cavity in particular and the whole body in general . BIOCOMPATIBILITY REQUIREMENTS

5. Why is BIOCOMPATIBILITY RELEVANT TO the DENTIST ? 5

6. BIOLOGICAL INTERFACE Placement of a material in the body creates an interface that is normally not present. This interface is not static, rather it is the site of many dynamic interactions between the material & the body through which the body may alter the material or the material may alter the body . 6 The activity of this interface depends on: The location of material . Its duration in the body. The properties of the material . Health of the host . 4 types of interaction can take place : 1 . Between the material and oral cavity. 2 . Between the material and the pulp (Via the dentinal tubules). 3 . Between the material and periodontium. 4 . Between the material and the periapical bone.

7. ADVERSE FFECTS OF DENTAL MATERIALS 7

8. TOXICITY Toxicity of a material describes the ability to damage a biological system by chemical means. Placement of a foreign material in the body carries the possibility of toxicity Dental materials may release certain substances which can cause toxicity. 8

9. IMMUNOTOXICITY substances leached from materials can alter immune system cells , resulting in enormous biological consequences because of the amplifying nature of immune cells . This may lead to : 1 . Impaired host defence . 2 . Tissue damage. glutathione content of human monocytes which helps in maintaining oxidative stress in cells: mercury ions are known to increase whereas palladium ions decrease the cells’ glutathione content. 9

10. SYSTEMIC TOXICITY 10 SYSTEMIC TOXICITY Here site of application & site of adverse reactions are different. Almost all dental materials release substances into the oral cavity, from where they may enter the systemic circulation via different routes. According to the time frame: 1. Acute (up to an exposure period of 24 h) 2 . Subacute (up to 3 months) 3 . Chronic toxicity are differentiated

11. LOCAL TOXICITY 11 Inflammation of the gingiva in contact with a porcelain- fused-to-metal crown Pulp necrosis after application of resin fillings • Substances released from dental materials may generate a reaction (e.g., inflammation or necrosis) in adjacent tissues such as oral mucosa/ gingiva, pulp or alveolar bone. There may be other factors like : Bacterial accumulation on the surface, at the margin, or under a material . Mechanical/physical irritation , such as pressure caused by dentures.

12. INFLAMMATION Histologically , the inflammatory response is characterized by 1. Edema of the tissue. 2 . Inflammatory cells infiltration such as neutrophils (in the short term) or monocytes and other lymphocytic cells(in the long term). 12 INFLAMMATORY RESPONSE IS COMPLEX BUT INVOLVES THE ACTIVATION OF HOST’S IMMUNE SYSTEM TO WARD OFF SOME THREAT

13. Allergy An allergic reaction to a substance can be triggered if the organism was previously sensitized to this compound . Dental materials may cause allergies of type I (immediate reaction) and type IV (delayed reaction). 13 IgE , IgG -Monocytes & T cells

14. 14 Examples 1. Contact urticaria : A local immediate erythemal or pruritic reaction at the site of epidermal or mucosal contact following occupational exposure to latex proteins in disposable gloves. 2 . Delayed reaction : Specific sensitized T lymphocytes, which react with the allergen and release lymphokines , eliciting an inflammatory reaction. e.g. Pronounced gingivitis of an orthodontic patient (nickel-containing device) who revealed a positive reaction in a patch test. .

15. OTHER REACTIONS 15 Genotoxicity Refers to the ability of substance released from materials to cause alterations of the genome DNA. Mutagenicity It is the ability of a substance to pass genetic damage on the next generation. e.g. – Ni, Cu and Be are known mutagens. Carcinogenicity: It is the ability of a material or substance released from it to induce malignant tumors . Teratogenicity : It is the ability of certain substance to cause malformation during embryonic development .

16. KEY PRINCIPLES THAT DETERMINE ADVERSE EFFECTS FROM MATERIALS 16 METAL CORROSION OR MATERIAL DEGRADATION SURFACE CHARACTERISTICS AND ROUGHNESS Biological response of corrosion products depends on: Amount Composition Form Location in tissues Biological environment in contact also determines the corrosion property for eg : salivary esterases accelerate breakdown of dental resins Ingestion of acidic substances may alter corrosion of alloys or ceramics Cast metals solidify first at the investment mold surface, and subsequently, the hottest area solidifies last . This transitional cooling process creates a composition gradient, which may lead to dissolution or corrosion behavior that is quite unpredictable. For metals, a rough surface promotes corrosion and plaque accumulation , which increases the release of ions that may lead to adverse effects ..

17. Measuring the biocompatibility: The initial tests (Phases I and II) are of a short duration, simple and cost effective. Only after completing initial test, the material progresses from simpler in vitro tests to the more complicated in vivo tests. Usage test can be performed in animals or humans (clinical trial). These usage tests are gold standard , in that they give the ultimate answer that whether a material is biocompatible or not. Biocompatibility of a material cannot be evaluated by using a single test rather than a group of various techniques. 17

18. IN VITRO TEST 18 Done outside a living organism Placement of a material or its component in contact with a cell system, enzyme or other biological system Test tube, cell culture dish, flask , or other container CLASSIFICATION OF IN VITRO TESTS DIRECT TEST INDIRECT TEST MATERIAL CONTACT EXTRACT CONTACT

19. 1. TESTS FOR CYTOTOXICITY CELL DEATH – measure CELL NUMBER OR GROWTH before and after exposure to that material. DIRECT CONTACT TEST cells are placed in a well of a cell-culture dish, where they attach. The material is then placed in the test system. If the material is not cytotoxic, cells will remain attached to the well and will proliferate over time. If the material is cytotoxic, cells may stop growing or exhibit cytopathic changes or detach from the well The morphology of the fibroblasts indicates that they are alive and are not suffering from a toxic response The fibroblasts are rounded and detached indicating that they are either dead or dying. 19

20. Membrane permeability 20 Measures cytotoxicity by the ease with which a dye can pass through a cell membrane , because membrane permeability is equivalent to or very nearly equivalent to cell death 1. Vital dyes: they are actively transported into viable cells, where they are retained unless cytotoxic effects increase the permeability of the membrane. Eg . Neutral red 2. Non vital dyes: these are not actively transported and are taken up if membrane permeability has been compromised by cytotoxicity . Eg . Trypan blue

21. 21 2.TESTS FOR CELL METABOLISM OR CELL FUNCTION: Use biosynthetic or enzymatic activity of cells to assess cytotoxic response Usually assess DNA synthesis or Protein synthesis Types: MTT (dimethyl- thiazole -diphenyl - tetrazolium bromide) XTT ( methoxy -nitro – sulphophenyl - tetrazolium carboxanilide ) NBT (nitro blue tetrazolium ) WST (water soluble tetrazolium ) ALAMAR BLUE TEST – quantitatively measure cell proliferation using a fluorescent indicator that allows continuous monitoring of cells over time. COLORIMETIC ASSAYS

22. 22

23. 23 TESTS THAT USE BARRIERS(INDIRECT TESTS) Agar overlay method , A monolayer cell culture is used. The cell stained with neutral red vital stain dye. Then agar layer is placed over the cells on which the test material is incubated for 24 hrs. Agar forms a barrier between the cells and the material. If the test material is cytotoxic, it will lead to loss of dye within cells as lysis occurs.

24. 24 Millipore filter assay , A cellulose acetate filter having 0.45µm filter is used Cells are grown on one side of the filter and the test material placed on the opposite side of filter. Any leachable substance from the test material must diffuse through the pores to exert a cytotoxic effect on the cells.

25. DENTIN DISC BARRIER TEST A dentin disk forms a barrier between the test material and the target cells 25 The material is placed on one side (A) of the dentin disk (B) in the device used to hold the dentin disk. Collection fluid ( cell culture medium or saline) is on the other side of the disk (C). Components of the material may diffuse through the dentin and the effect of the medium on cell metabolism can then be measured .

26. 3.MUTAGENESIS ASSAYS 1. Ames test: It uses mutant stocks of salmonella typhimurium that require exogenous histidine. Native stocks of bacteria do not require exogenous histidine. If the mutant stocks bacteria are treated with a mutagen there will be a mutation back to the normal state and growth in histidine free medium will occur. 26 Assess the effect of a biomaterial on a cell’s genetic material 2. STYLES CELL TRANSFORMATION TEST : done in mammalian cell. 

27. IN VITRO TEST 27 ADVANTAGES Quick to perform Least expensive Can be standardized Large scale screening Good experimental control DISADVANTAGES Questionable relevance to the final in vivo use of the material Lack of inflammatory or other tissue protective mechanisms in the in vitro environment

28. ANIMAL TEST usually involving mammals such as mice, rats, hamsters, or guinea pigs , and are distinct from usage tests in that the material is not placed in the animal with regard to its final use 28

29. 1.MUCOUS MEMBRANE IRRITATION TEST Determines whether the material causes inflammation to mucous membrane or abraded skin Placing the test materials and positive and negative controls into contact with rabbit oral tissue. The animals are then sacrificed and biopsy specimens are prepared for histological evaluation of inflammatory changes. 29

30. 2.SKIN- SENSITIZATION TEST The materials are injected INTRADERMALLY to test for development of skin hypersensitivity reactions. The injection is followed by adhesive patches containing the test substance. If hypersensitivity developed from initial injection, the patch will elicit an inflammatory response. 30

31. 3. IMPLANTATION TESTS For implantation tests, materials are implanted subcutaneously, intramuscularly, or in the bone of an experimental animal . After different periods of implantation of the material in the tissues (between 1 week and several months), the adjacent tissue is investigated macroscopically and microscopically. After a short implantation time (1–2 weeks), degrees of inflammation surrounding the implant will primarily be assessed. 31 Formation of an abscess at the interface between material and connective tissue

32. ANIMAL TEST 32 ADVANTAGES Allows complex systemic interactions Response more comprehensive than in vitro test More relevant than in vitro test DISADVANTAGES Questionable relevance to the final in vivo use of the material Expensive Time consuming Legal/ethical concerns Difficult to control Difficult to interpret and quantify

33. IN USAGE TEST 33 LARGER ANIMALS or IN HUMAN VOLUNTEERS Requires that material be placed in a situation identical to its intended clinical use GOLD STANDARD DENTAL PULP IRRITATION TEST MUCOSA AND GINGIVAL USAGE TEST INTRAOSSEOUS IMPLANT TEST

34. 1. DENTAL PULP IRRITATION TEST 34 TEST MATERIAL PLACED IN CLASS V CAVITY PREPARED IN INTACT, NON CARIOUS TEETH TEETH REMOVED, SECTIONED FOR MICROSCOPIC EXAMINATION TISSUE NECROSIS AND INFLAMMATION GRADED ACCORDING TO INTENSITY RECENT APPROACH IS TO USE TEETH WITH INDUCED PULPITIS WHICH ALLOW EVALUATION OF THE TYPE AND AMOUNT OF REPARATIVE DENTIN FORMED AS AN INFLAMMED PULP REACTS DIFFERENTLY TO RESTORATIVE MATERIALS

35. 2. Intraosseous Implant Test Materials used for dental implants are inserted into the jaw . Criteria for implant success Early implant success 1-3 years Intermediate implant success 3-7 years Long term implant success >7 years Tests used Passage of periodontal probe along side of the implant Mobility of the implant Radiographic evidence 35 Available data from these studies show that implants based on titanium or ceramics, are generally well tolerated by the surrounding tissue .

36. 3 .MUCOSA AND GINGIVAL USAGE TESTS Materials are placed in cavity preparations with sub gingival extensions. Slight, moderate or severe based on amount of inflammatory cells depending on the number of mononuclear inflammatory cells (mainly lymphocytes and neutrophils) in the epithelium and adjacent connective tissues Disadvantages: Presence of plaque Preexisting inflammation in the gingival tissue Surface roughness of the restorative material Over contouring and under contouring of the restoration. 36

37. IN USAGE TEST 37 ADVANTAGES Relevance to the use of material is assured DISADVANTAGES Very Expensive Time consuming Major Legal/ethical concerns Can be Difficult to control Difficult to interpret and quantify

38. DIAGNOSTIC TESTS ON PATIENT 38 ALLERGY TESTS: P atch test: - ( Type IV) adhesive tapes containing the potential allergens are adhered to the clinically sound skin of the patient’s back. During the following days, after the tape has been removed, the skin is evaluated for test reactions after 2 and 3 days, but later checks (after 5 and 7 days) are also necessary to detect late reactions P rick test:- (Type I) the allergen is applied as a drop to the skin and then the skin is pricked through the drop. After 5-30 minutes, the skin reaction is assessed .

39. ANALYSIS OF INTRAORAL ALLOYS CHIP TEST To know the composition of alloy A small amount of alloy particles (chips) is produced intraorally using a silicon carbide stone or a tungsten carbide bur. The alloy particles are collected on a small, circular, self-adhesive graphite plate which conducts electricity and further subjected to Energy Dispersive X-ray Analysis The chip test is not able to examine a correct processing of the alloys, which must be considered a disadvantage of this test because a correct processing is of decisive influence on corrosion and, thus, also on tissue compatibility 39

40. Selection of the test methods to assess compatibility 40

41. STRATEGIES FOR EVALUATING BIOCOMPATIBILITY 41 A, the earliest strategy, in which the testing strategy is focused on toxicity only. Unspecific toxicity refers to tests not necessarily related to the use of the material, whereas tests under specific toxicity are more relevant. Clinical trials are equivalent to usage tests in this scheme. B, the contemporary strategy used in most standards documents

42. Disadvantages 1. It is seen that the materials that cleared the first two tests were not entirely harmless at the clinical usage level. E.G. ZOE when tested in vitro completely kills every cell in the culture, but in clinical practice, the same cement has been successfully used for many years with no evidence of pulp damage. 2. It is time consuming since it is performed in a sequential manner. 42

43. Newer schemes for the progression A, the pyramid scheme of is retained, but it is acknowledged that primary and secondary tests will play a continuing (but decreased) role as the progress of the testing continues. B, the usage test has the most stature and the most common progression of tests is from primary to secondary to usage, but the need to go through several iterations between testing types is acknowledged. 43

44. ANSI/ADA Specification 41 This was approved by the council on scientific affairs in 1972 and was updated in 1982 to include tests for mutagenicity. This specification uses the linear paradigm for materials screening and divides testing into initial, secondary, and usage tests. ISO 10993- It is the international standards for testing the biocompatibility of dental materials. Unlike ANSI/ADA document no. 41, the IS0 10993 standard is not restricted to dental materials. The standard divides tests into initial and supplementary tests to assess the biological reaction to materials. 44 STANDARDS THAT REGULATE THE MEASUREMENT OF BIOCOMPATIBILITY

45. Biocompatibility Of Various Dental Materials 45

46. BONDING AGENTS 46 May penetrate upto 0.5 mm in dentin and cause supression of cellular metabolism for upto 4 weeks HEMA 100 times less cytotoxic than Bis -GMA Release of MMPs from dentin by virtue of interaction with acid components of dentin adhesives causes degradation of adhesive bond by enzymatic action on exposed collagen within the hybrid layer. The application of an MMP inhibitor, such as chlorhexidine, has been shown to minimize this effect .

47. RESIN BASED COMPOSITES 47 Moderate cytotoxic reactions in cultured cells over 24 to 72 hours of exposure Light-cured resins are less cytotoxic than chemically cured systems highly dependent on the curing efficiency of the light and the type of resin system. The pulpal inflammatory response was low to moderate after 3 days when they were placed in cavities with 0.5 mm of remaining dentine followed by an increase in reparative dentin . With a protective liner or a bonding agent , the reaction of the pulp to resin composite materials is minimal. The dental personnel commonly complain of contact dermatitis and asthma caused by methacrylates

48. Extraoral allergic reactions (type I) after application of a pit and fissure sealant Allergic contact dermatitis of a dentist after contact with resin-based composites 48

49. Chemical burn after inadvertent contact of phosphoric acid with gingiva Gingivitis adjacent to a cervical composite resin filling 49

50. PRECAUTIONS Beneath a composite resin restoration, a suitable base should be placed to protect the pulp from material components and bacterial toxins Inhalation of composite resin particles during grinding and shaping of a newly placed restoration should be prevented by suitable measures such as a rubber dam or the use of suction/water coolant. Protective shields should be attached to the end of the light guide of polymerization lamps to protect the eyes of dental personnel Dental personnel should always avoid any contact of skin or even gloves with resin-based composites or dentin adhesives, including during instrument cleaning and waste disposal 50

51. DENTAL CASTING ALLOYS 51 The biological response to an alloy depends on the biological effects of released elements, the quantities released , the duration of tissue exposure to these elements, and other factors A number of factors influence the corrosion of dental alloys : Composition of the alloy (particularly at the surface) Surface structure (roughness, presence of oxides) Crevices , pits Thermal treatment/history Combinations of alloys (gold coating, soldering )

52. 52 SYSTEMIC TOXICITY The number of elements released from the dental alloys is far below the dietary intake; for e.g. the amount of zinc released (< 0.1µg /day ) is far below the daily dietary intake (14,250µg /day). No studies have demonstrated systemic toxicity due to cast alloys LOCAL TOXICITY When there is a release of elements from the alloys, and if it is present in more conc. in the sulcus than in saliva, then epithelial cells of the sulcus will be more prone to cytotoxicity. Ni, Cr, Co - Cytotoxic.

53. 53 Allergic Reactions The incidence of nickel allergy is 15% and that of Co and Cr is 8%. Cross –reactive allergy can occur for Pd and Ni. Lichenoid reactions have also been reported in the oral mucosa adjacent to casting alloys. OTHER REACTIONS Vapor form of elements such as beryllium is a common mutagenic threat. Beryllium is also a documented carcinogen in either the metallic or ionic state. Beryllium-containing particles that are inhaled and reach the alveoli of the lungs may cause a chronic inflammatory condition called BERYLLIOSIS

54. gingivitis due to the PFM crowns; after removal of the crowns and seating of temporary resin crowns 54

55. Gold coating of nickel-based and cobalt-based alloys. Pronounced redness of the palate beneath the denture base. 55

56. Perioral allergic reaction after insertion of nickel-containing orthodontic wires ( CuNiTi ) Lichenoid reaction of the mucosa contacting an alloy 56

57. Pronounced gingivitis after seating of ceramic crowns, despite good oral hygiene Dental lab –Inhaled beryllium – berylliosis . 57

58. GLASS IONOMER CEMENTS Freshly prepared ionomer is mildly cytotoxic Resin modified GIC is more cytotoxic Large size of molecules of Polyacrylic Acid unable to diffuse through dentinal tubules Histological studies in usage test shows that any inflammatory infiltrate to GIC is minimal or absent after 1 month . 58

59. Liners, Varnishes, and Nonresin Cements Calcium hydroxide Zinc phosphate Zinc polycarboxylate cement ZOE cement 59

60. CALCIUM HYDROXIDE CEMENT . 85 .  85 60 Systemic toxicity No reported systemic reaction Local toxicity Indirect pulp capping material: Exerts antibacterial effect. Tertiary dentin formation. 3. Decreases the permeability of dentin. NOTE: Tertiary dentin will be triggered only if the remaining dentin thickness(RDT) is 5 to 10 µm. Direct pulp capping material: When in direct contact with the pulp, produces superficial coagulation necrosis. This acts like a stimulus for the differentiation of secondary odontoblasts that lay down tertiary dentin. Allergic Reaction No reported allergic reaction Other reaction No evidence of mutagenic or carcinogenic reaction

61. ZINC PHOSPHATE CEMENT 61 Systemic toxicity No reported systemic reaction Local Toxicity The acidity of the cement initially after mixing is very high due to presence of phosphoric acid (pH is around 3.5 during application). Subsequently, it increases towards neutrality within 24-48 hours. Precautions to be taken are as follows: The powder/liquid ratio should never be reduced to increase the working time, as this increases the acid content. The placement of a protective layer of a dentin bonding agent, ZOE, varnish, or calcium hydroxide is needed . Allergic Reaction No reported allergic reaction Other reaction No evidence of mutagenic or carcinogenic reaction

62. Zinc phosphate cement that was left in the sulcus after cementation results in periodontal destruction and bone loss 62

63. Zinc polycarboxylate cement Polyacrylate cements evoke a pulpal response similar to that caused by ZOE, with a slight-to-moderate response after 3 days and only mild, chronic inflammation after 5 weeks. Reparative dentin formation is minimal with these cements, and thus they are recommended only in cavities with intact dentin in the floors of the cavity preparations. 63

64. ZINC OXIDE EUGENOL CEMENT 64 Reaction of the gingiva after temporary cementation of a crown with a zinc oxide and eugenol cement. Systemic toxicity No reported systemic reaction Local Toxicity Pulp reaction The cement can produce a cytotoxic reaction when directly applied to the pulp. If there is a complete dentin layer between the pulp and the cement, no inflammatory reaction will occur. [LEAST IRRITATING OF ALL THE CEMENTS : pH 6.6 -8 i.e. Mild pulpal response] Eugenol has the capability to block transmission of action potentials of the nerves, hence, this cement has an obtundant (soothing) effect when used in deep cavities.

65. 65 Allergic Reaction Eugenol can induce an allergic response in some individuals. Allergic contact dermatitis has also been reported in dental personnel handling the cement. Other reaction Eugenol was mutagenic in the mouse micronucleus test .This effect could not be reproduced in transgenic Mice. Based on these findings, the use of ZOE materials is not contraindicated

66. PRECAUTIONS DURING CEMENTATION Apply petroleum jelly to the surrounding soft tissues Clean the excess cement after luting the prosthesis Any residues of cement left in the gingival sulcus will lead to inflammation 66

67. DENTAL CERAMICS 67 SYSTEMIC TOXICITY Risk of silicosis among dental technicians due to inhalation of ceramic dust. Silicosis is a lung diseases characterized by shortness of breath, cough, fever, and cyanosis. Dust removal measures should be followed in the laboratory.  LOCAL TOXICITY Most ceramics are biocompatible . ALLERGIC REACTION No reported allergic reaction. OTHER REACTIONS Zirconium oxide ceramics show some amount of radioactivity due to contaminants such as thorium and uranium. However, the radioactivity level is not very significant.

68. IMPRESSION MATERIALS 68 Addition Silicone Hydrocolloids Polysulphides - contain lead peroxide, among others, which can cause acute and severe systemic toxic effects when swallowed or inhaled Polyether ZnoE least biocompatibility applies to condensation silicones NONTOXIC ALLERGIC REACTIONS

69. Direct and repeated skin contact by dental personnel, however, should be avoided. Contact with the eyes, which may happen when mixing a liquid catalyst into a putty impression material by hand, should also be avoided, such as by wearing protective glasses or by using a paste catalyst. It is important for the subgingival area of the sulcus to be carefully controlled for remnants of impression material, particularly in patients with deep periodontal pockets. 69

70. POLY-METHYLMETHACRYLATE RESINS Denture base materials: MMA Monomer is the main cause for hyper sensitization Hypersensitivity has been documented to the acrylic and diacrylic monomers, certain curing agents, antioxidants, amines, and formaldehyde For the patients most of these materials have been reacted in polymerization and thus are less prone Two aspects are of particular importance: monomer– polymer conversion and residual monomer content. 70

71. True allergy of oral mucosa to denture base material is very rare Residual monomer (methyl methacrylate) is believed to be responsible for allergic reactions in susceptible patients Allergic acrylic stomatitis – diffuse erythema, edema & occasionally small vesicles and erosions Heat polymerized is better than Autopolymerized resin 71

72. Dentist suffering from an allergy to methyl methacrylate contact dermatitis Pronounced inflammation of the palatal mucosa beneath a polymethyl methacrylate denture with papillary hyperplasia 72

73. SOFT DENTURE LINERS & ADHESIVES Release of plasticizers Extremely cytotoxic Denture adhesives show severe cytotoxic reactions in-vitro Large amount of formaldehyde Allowed significant microbial growth 73

74. Reaction of bone & soft tissues to implant material a ) Reaction to ceramic implant material Very low toxic effects. Oxidized state corrosion resistant B) Reactions to Resorbable Materials Well-tolerated by tissues in vivo Resorbability of these materials depends on the volume of material implanted and because these materials degrade into acidic byproducts which may invoke an inflammatory response. E.G. Co-polymer of polylactic acid (PLA) and polyglycolic acid (PGA), natural polymers such as cross-linked collagen, starch, and cellulose. Used for Resorbable Sutures, fracture fixation plates and screws, guided tissue membranes, and controlled drug-release systems. 74

75. C ) REACTION TO PURE METALS & ALLOYS ‘ Metal’ oldest type of oral implant material Initially selected on the basis of the ‘ease of fabrication’ Stainless steel, chromium-cobalt-molybdenum, titanium and its alloys Most commonly used is titanium(Ti-6Al-4V) Titanium’s biocompatibility is associated with its fast oxidizing capacity. Corrosion resistant & allows osseointegration 75

76. Soft tissue : Epithelium forms a bond with implant similar to that of tooth Connective tissue apparently does not bond to the titanium, but forms a tight seal that seems to limits ingress of bacteria & its products 76 In recent years, Titanium allergy has been noted at a low prevalence rate of 0.6% and presents with urticaria , eczema, redness of the mucosa.

77. BARRIER MATERIALS Latex : The incidence of latex allergy is about 9.7% and 6% among patients and dental staff, respectively. Latex products can produce either: 1. Type 1 immediate atopic/anaphylactic reaction - due to proteins present in natural latex 2. Type 1V delayed hypersensitivity reaction (allergic contact dermatitis): due to accelerators and antioxidants used in latex manufacturing. 77

78. Precaution to be taken are as follows: Non latex synthetic materials such as nitrile and styrene ethylene butadiene styrene should be used. Polyethylene or polyvinyl chloride rubber dams can be used instead of latex 78 Contact urticaria following occupational exposure to latex proteins in disposable gloves severe irritative hand dermatitis (non allergic) caused by frequent hand washing and wearing of disposable gloves

79. REVIEW OF LITERATURE 79

80. Surface biocompatibility of differently textured titanium implants with mesenchymal stem cells Dental Materials. 2015;31(3):235-243 Objective: To assess the interaction between implants and dental pulp stem cells (DPSCS) in vitro by means of 3D cell culture in order to better simulate physiological conditions. Methods. Sorted CD34+ DPSCS were seeded onto dental implants having either a rough surface (TRIVENT) or one coated with a ceramic layer mimicking native bone (TIUNITE). The preservation of DPSC viability during osteogenic differentiation by an MTT assay was evaluated and compared Results: Both surfaces are equally biocompatible, however, the study suggests that TRIVENT, with its roughness, is capable of promoting cell differentiation a bit earlier than the TIUNITE surface, although the latter promotes greater cell proliferation. 80

81. N-ACETYL CYSTEINE ALLEVIATES INFLAMMATORY REACTION OF ORAL EPITHELIAL CELLS TO POLY (METHYL METHACRYLATE) EXTRACT Acta Odontologica Scandinavica . 2015;73(8):616-625. Objectives. The purpose of this in vitro study was to determine whether the cytotoxicity of self-curing polymethyl methacrylate (PMMA) dental resin to oral epithelial cells was eliminated by mixing the antioxidant amino acid derivative, n-acetyl cysteine (NAC) with the material. Materials and methods. Rat and human oral epithelial cells cultured on polystyrene were incubated in culture medium with or without extract from self-curing PMMA dental resin, with or without pre-mixing with NAC. Formaldehyde content and the amount of released NAC in the extract were evaluated. Conclusion. The cytotoxicity of self-curing PMMA dental resin to oral epithelial cells was eliminated by mixing the resin with NAC . 81

82. Evaluation of effect of galvanic corrosion between nickel-chromium metal and titanium on ion release and cell toxicity. The Journal of Advanced Prosthodontics. 2015;7(2):172. . The purpose of this study was to evaluate the metal ion release caused by electrochemical corrosion due to contact between metals and to assess the cell toxicity effect. A prosthesis was made of a base metal on the titanium abutment using three types of Ni-Cr alloys with different components and compositions. The amount of metal ions released was increased by galvanic corrosion in all of the groups in which Ni-Cr alloys were in contact with titanium. Cytotoxicity was significantly increased in all of the groups in which Ni-Cr alloys containing Beryllium were in contact with titanium. Conclusion: The release of metal ions was increased by galvanic corrosion due to contact between base metal and titanium, and it can cause adverse effects on the tissue around the implant by inducing cytotoxicity. 82

83. 23 83 Recent reports have questioned whether metal sensitivity may occur after exposure to titanium. This clinical report demonstrates the emergence of facial eczema in association with a titanium dental implant placed for a mandibular overdenture supported by 2 implants. Complete remission was achieved by the removal of the titanium material. This clinical report raises the possibility that in rare circumstances , for some patients, the use of titanium dental implants may induce an allergic reaction . Suspected association of an allergic reaction with titanium dental implants: A clinical report - Hiroshi Egusa (J Prosthet Dent 2008;100:344-347)

84. 23 84 Facial eczema Ten months after removal of dental implants

85. 23 85 Oral photographs of patient before and 10 months after removal of dental implants. A, Edentulous maxillary arch. B, Edentulous mandibular arch

86. CONCLUSION due to rise in number of patients with allergies from different materials, the practicing dentists should be aware about the allergies documented to known materials For establishing diagnosis, it is essential to obtain proper history related to allergy, clinical examination and confirmatory tests. It is mandatory for the clinician to know and understand the biocompatibility of the dental materials, so as to provide maximum advantage & minimum risk to the patient. 86

87. REFERENCES 87 Restorative dental materials (13th edition) – G. Craig & John H. Powers Biocompatibility of dental materials –Gottfried Schmalz & Dorthe Arenholt – Bindslev PHILLIPs’ Science of dental material (12th edition) Naddeo P, Laino L, La Noce M, Piattelli A, De Rosa A, Iezzi G et al. Surface biocompatibility of differently textured titanium implants with mesenchymal stem cells. Dental Materials. 2015;31(3):235-243. Nishimiya H, Yamada M, Ueda T, Sakurai K. N-acetyl cysteine alleviates inflammatory reaction of oral epithelial cells to poly (methyl methacrylate) extract. Acta Odontologica Scandinavica . 2015;73(8):616-625 .

88. Syed M. Allergic reactions to dental materials- A systematic review. Jcdr . 2015 Egusa H, ko N, shimazu T, yatani H. Suspected association of an allergic reaction with titanium dental implants: A clinical report. The journal of prosthetic dentistry. 2008;100(5):344-347. Lee J, song K, ahn S, choi J, seo J, park J. Evaluation of effect of galvanic corrosion between nickel-chromium metal and titanium on ion release and cell toxicity. The journal of advanced prosthodontics. 2015;7(2):172. 88

89. 89