22/03/2014
1
BIOCOMPATIBILITY OF
POLYMETHYLMETHACRYLATE
RESINS
Presented by:
Dr. Hashmat Gul
Demonstrator,
Dental Material...
22/03/2014
2
USES
IN DENTISTRY DAILY LIFE
Construction of
Dentures
Orthodontic Devices.
Individual Impression Trays
Tempor...
22/03/2014
3
COMPOSITION OF PMMA RESINS
POWDER LIQUID
Polymer
Polymethylmethacrylate beads
Initiator
A peroxide such as be...
22/03/2014
4
HEAT CURE LIGHT CURE
Composition: Generally based on PMMA.
Setting: Initiated by heat decomposition
of the in...
22/03/2014
5
RELEASE OF SUBSTANCES & DEGRADATION
Residual Monomer
The unreacted monomer that is not firmly incorporated in...
22/03/2014
6
RELEASE OF SUBSTANCES & DEGRADATION
Clinical Correlation Between Residual Monomer
Concentration & Irritation ...
22/03/2014
7
RELEASE OF SUBSTANCES & DEGRADATION
MONOMERS INITIATORS STABALIZERS ACCELERATOR
IN LC-BDP
REACTION
PRODUCT OF...
22/03/2014
8
SYSTEMIC TOXICITY
In-vivo study in Irritants Released Oral LD50 Acute Systemic Toxicity
Rats, Oral administra...
22/03/2014
9
SYSTEMIC TOXICITY
Effects of MMA
Cardiovascular effects e.g. a relaxing effect, on the non-striated muscles o...
22/03/2014
10
SYSTEMIC TOXICITY
Route Of Administration of MMA, Humans
Patients leaching substances from PMMA resins throu...
22/03/2014
11
CYTOTOXICITY & TISSUE COMPATABILIY
The cellular compatibility of solid specimens, aqueous resin extracts, fo...
22/03/2014
12
CYTOTOXICITY & TISSUE COMPATABILIY
KB cells: human oral keratinocytes ,
BF cells: human mucosal fibroblasts....
22/03/2014
13
CYTOTOXICITY & TISSUE COMPATABILIY
Clinical Practice Advice
To lower Cytotoxicity , it is recommended to sto...
22/03/2014
14
MICROBIAL EFFECTS
PMMA acrylics and permanent soft relining
materials may promote the growth of
Fungi such a...
22/03/2014
15
MICROBIAL AFFECTS
Candida albicans & “denture stomatitis”
The pellicle of dentures of stomatitis patients co...
22/03/2014
16
IMPLANTATION STUDIES
Local reactions are primarily dependent on the amount of substances leached and their
t...
22/03/2014
17
PULP REACTIONS
Auto-polymerizing PMMA resins caused pulp irritations when used for temporary
restorations.
C...
22/03/2014
18
REACTIONS OF THE GINGIVA & ORAL MUCOSA
Factors Contributing To The Development And Severity Of Denture Stoma...
22/03/2014
19
BURNING MOUTH SYNDROME
Clinical study of 22 patients
with BMS
5 cases: allergy to MMA +
high residual monome...
22/03/2014
20
5. ALLERGIES
ALLERGIES
MMA
a. CONTACT DERMATITIS MMA classified as an important contact allergen
b. An Exten...
22/03/2014
21
ALLERGIES
Almost all other components of PMMA acrylates can cause an allergy
The initiator , dibenzoyl perox...
22/03/2014
22
MUTAGENICITY AND CARCINOGENICITY
Older studies reported generation of fibrous sarcomas and carcinomas after
...
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Biocompatibility of Polymethylmethacrylate resins

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PDF, Polymethylmethacrylate Uses, Classification, Composition, Basic Material properties, Release of substances & degradation, Toxicity , Tissue Compatability, Allergies, Mutagenecity & Carcinogenicity.

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Biocompatibility of Polymethylmethacrylate resins

  1. 1. 22/03/2014 1 BIOCOMPATIBILITY OF POLYMETHYLMETHACRYLATE RESINS Presented by: Dr. Hashmat Gul Demonstrator, Dental Materials. AMC, NUST. 1. INTRODUCTION
  2. 2. 22/03/2014 2 USES IN DENTISTRY DAILY LIFE Construction of Dentures Orthodontic Devices. Individual Impression Trays Temporary crowns. Veneering As Bone Cements Acrylic Glass A Base For Various Stains for Artificial Fingernails, Nail Varnish etc Classification Of Denture Base Polymers Type Class Description 1 1 2 2 3 4 5 1 2 1 1 - - - Heat-processing polymers, P/L Heat-processed (plastic cake) Autopolymerised polymers, P/L Autopolymerised polymers (P/L pour type resins) Thermoplastic blank or powder Light-activated materials Microwave-cured material According To The Setting Reaction Heat Polymerizing Light Curing Chemically (Auto)curing. According To ISO 1567
  3. 3. 22/03/2014 3 COMPOSITION OF PMMA RESINS POWDER LIQUID Polymer Polymethylmethacrylate beads Initiator A peroxide such as benzoyl peroxide (0.5%) Pigments Salts of cadmium or iron or organic dyes Monomer Methyl methacrylate Cross-linking agent Ethylene-glycol-dimethacrylate (10%) Inhibitor Hydroquinone (trace) Activator* N N′-dimethyl-p-toluidine (1%) * Only in Self Curing Material 2. BASIC MATERIAL PROPERTIES
  4. 4. 22/03/2014 4 HEAT CURE LIGHT CURE Composition: Generally based on PMMA. Setting: Initiated by heat decomposition of the initiator (mainly dibenzoyl peroxide) into radicals. Composition: Derived partly from PMMA and also from urethane-dimethacrylates. Setting: Initiated by light exposure, at room or oral temperature. Triggered by a redox system. e.g. amine–peroxide redox system. Accelerator, such as a tertiary amine, sulfinic acid, or substituted barbituric acid. SETTING Of PMMA RESINS RELEASE OF SUBSTANCES & DEGRADATION Methods Used To Identify Substances Released From MMA High-performance Liquid Chromatography, Gas Chromatography, Gas Chromatography/Mass Spectroscopy, Infrared Spectroscopy. Factors Effecting The Concentration Of Residual Monomers & Elutable Additives: Polymerization type Polymerization time Polymerization temperature Surface finish and structure
  5. 5. 22/03/2014 5 RELEASE OF SUBSTANCES & DEGRADATION Residual Monomer The unreacted monomer that is not firmly incorporated in the polymer network and may therefore leach. Concentration Of Residual Monomers In Denture Base Polymer Resins HEAT CURE LIGHT CURE AFTER CURING little i.e. 0.1–1.5 wt.% Thickness: Thicker regions < Thin layers. Curing Time: When the Curing Time was extended from 15 min to 12 h at a temperature of 100°C, RM conc. dropped from 1 wt% to less than 0.1 wt% AFTER CURING more i.e. 3–5 wt.% Curing Temp.: An increase in temperature during curing, from 30°C to 60°C, causes a significant decrease in the amount of residual monomers. RELEASE OF SUBSTANCES & DEGRADATION Residual Monomers/Additives Were Extracted By Means Of Aqueous media including distilled water, natural or artificial saliva, Ringer’s solution. Organic diluents (methanol, ethanol, tetrahydrofurane, acetone) HEAT CURE LIGHT CURE In-vivo study: After insertion did not leach MMA. In-vitro studies: Revealed that heat-polymerized acrylic also releases MMA over several days but in significantly smaller quantities than autopolymerized products. In-vivo study: Releases MMA over a period of 1 week after insertion (up to 45 μg/ml saliva). MMA was not found in the urine or blood of the participants. The intra-orally released MMA concentrations were far below the threshold doses.
  6. 6. 22/03/2014 6 RELEASE OF SUBSTANCES & DEGRADATION Clinical Correlation Between Residual Monomer Concentration & Irritation Of The Oral Mucosa. The eluable share of residual monomers & additives should be as low as possible. To minimize the concentration of residual monomers , it is recommended that dentures and orthodontic devices be stored for up to 24 h in warm water (37–50°C) before insertion. RELEASE OF SUBSTANCES & DEGRADATION FORMALDEHYDE HEAT CURE LIGHT CURE Released in much smaller quantities Released in high amounts (40–50 nmol/ml on the1st day) in vitro and in vivo (saliva). Mechanisms of formaldehyde formation First, a primary oxidation of unsaturated methacrylate groups is possible. Secondly, oxygen can copolymerize with methacrylate groups during the initial phase of the polymerization. Decomposition of this copolymer will then result in the formation of formaldehyde.
  7. 7. 22/03/2014 7 RELEASE OF SUBSTANCES & DEGRADATION MONOMERS INITIATORS STABALIZERS ACCELERATOR IN LC-BDP REACTION PRODUCT OF DBP Methyl- methacrylate (MMA) Meth-acrylic acid Ethylene-glycol di- methacrylate Di-benzoyl peroxide (DBP) Hydroquinone Resorcinol Pyro-gallol N,N-dimethyl-p- toluidine (tertiary amine) Phenyl benzoate Benzoic acid Biphenyl 3. SYSTEMIC TOXICITY
  8. 8. 22/03/2014 8 SYSTEMIC TOXICITY In-vivo study in Irritants Released Oral LD50 Acute Systemic Toxicity Rats, Oral administration to calculate LD50 value dibenzoyl peroxide MMA 950 mg/kg body weight 8.4-9 g/kg body weight Very low Very low Rats receiving MMA “orally” through a stomach tube Degradation of MMA by a nonspecific carboxyl esterase Methacrylic acid, identified in blood after 5min. peak after 10–15 min with no Organ damage subsequently metabolized to pyruvate, via the citric acid cycle SYSTEMIC TOXICITY The half-life of MMA In human blood varies between 20 min and 40 min. Studies on dogs MMA released from the bone cement of hip implants also excreted via the lungs
  9. 9. 22/03/2014 9 SYSTEMIC TOXICITY Effects of MMA Cardiovascular effects e.g. a relaxing effect, on the non-striated muscles of blood vessels. GIT : Inhibited peristalsis of the ileum due to inhaled MMA vapor in rat experiments. MMA vapor in dental practices caused vertigo. No serious problems may be caused by inhaling PMMA ingredients. PMMA May irritate the eyes, skin, and respiratory system. SYSTEMIC TOXICITY In-Vivo study, Rats The embryo-fetal toxicity of MMA MMA, when injected intra-peritoneally at LD50 conc. malformations and other injury to embryos or fetuses.
  10. 10. 22/03/2014 10 SYSTEMIC TOXICITY Route Of Administration of MMA, Humans Patients leaching substances from PMMA resins through the oral cavity, Dental personnel and lab technicians MMA-vapor. The Maximum Allowable Concentration Values For MMA In Germany, 50 ppm or 210 mg/m3 compartment air. Legal regulations for dental laboratories are based on A DIRECTIVE regarding hazardous substances and the technical rules for hazardous materials e.g. TRGS 900. 4. LOCAL TOXICITY & TISSUE COMPATIBILITY
  11. 11. 22/03/2014 11 CYTOTOXICITY & TISSUE COMPATABILIY The cellular compatibility of solid specimens, aqueous resin extracts, formaldehyde, and MMA was investigated in permanent cells and primary cultures as well. STUDY 1: By Nakamura & Kawahara 2-week-old aqueous extracts of 2 Heat-cure acrylics and 3 Auto-cure acrylics. Conclusion: MMA and formaldehyde, are volatile. The test solutions did not contain the original conc. of these 2 substances due to the extended extraction time CYTOTOXICITY & TISSUE COMPATABILIY STUDY 2: Toxic reactions caused by solid specimen of two orthodontic acrylic resins in permanent cultures of fibroblasts & keratinocytes. Both products were no longer toxic 30 days after setting 1 light-cure Cytotoxic if the oxygen-inhibited surface layer was not removed 1 Self-cure
  12. 12. 22/03/2014 12 CYTOTOXICITY & TISSUE COMPATABILIY KB cells: human oral keratinocytes , BF cells: human mucosal fibroblasts. STUDY 3: The auto-cure product showed the highest cytotoxicity. The light-cure material was the least cytotoxic. Cytotoxicity of all products decreased after several extractions using aqueous cell culture medium. CYTOTOXICITY & TISSUE COMPATABILIY CONCLUSION: The initial high toxicity immediately after polymerization was due to various released radicals. Compatibility, depends on The general composition (e.g., type of base resin) Material aspects or the formulation of the individual product. No toxic effects in primary human gingival fibroblast cultures and osteoblast-like cells were caused by aqueous 24-h and 7-day extracts of another PMMA-type bone cement. In solid specimens: Only a slight or moderate cytotoxicity exhibited. Auto-polymerizing acrylics are significantly more toxic than heat-polymerizing products.
  13. 13. 22/03/2014 13 CYTOTOXICITY & TISSUE COMPATABILIY Clinical Practice Advice To lower Cytotoxicity , it is recommended to store dentures for 1 day in water to significantly reduce the amount of residual monomers. Heat-polymerizing products should be preferred over auto-polymerizing materials if possible. Patients should be advised not to wear dentures at night at first because this might contribute to irritation of the mucosa due to an accumulation of residual monomers in the tissue. TC50 (median toxic concentration) values of several resin compounds
  14. 14. 22/03/2014 14 MICROBIAL EFFECTS PMMA acrylics and permanent soft relining materials may promote the growth of Fungi such as Candida Bacteria like Escherichia coli, and Pseudomonas aeruginosa. Substances promoting Microbial proliferation MMA Phthalate The cross-linking substance. “microclefts” between permanent soft relining materials and the “hard” denture base + Poor Oral Hygiene stimulate microbial growth An inflamed mucosa (Candidiasis) MICROBIAL EFFECTS SUBSTANCE CONCENTERATION EFFECTS MMA Plasticizers benzyl benzoate benzyl salicylate N,N-dimethyl-p-toluidine The cross-linking agent EGDMA High Conc. (>0.5%) Low Conc. High Conc. High Conc. Low Conc. Bactericidal Promote Bacterial growth Fungicidal Inhibit Bacterial growth Promote Bacterial growth increase the proliferation of Streptococcus sobrinus and Lactobacillus acidophilus
  15. 15. 22/03/2014 15 MICROBIAL AFFECTS Candida albicans & “denture stomatitis” The pellicle of dentures of stomatitis patients contained an increased conc. of cell particles derived from Candida albicans. Salivary compounds that promoted adhesion of Candida Adherence Of Candida promoted by A rough surface structure of PMMA-based dentures. Permanent soft, porous relining materials promoted adhesion in some cases. MICROBIAL AFFECTS Dentures may transfer certain pathogenic & highly virulent microbes from the oral cavity to The Distal Gastrointestinal Tract Respiratory system. Matsuura et al. reported that Staphylococcus aureus colonized dentures and tongues of “resected” patients with extended oral tissue defects at much higher concentration than in edentulous “nonresected” patients
  16. 16. 22/03/2014 16 IMPLANTATION STUDIES Local reactions are primarily dependent on the amount of substances leached and their toxicity. Thus, heat-polymerized products should cause fewer effects than auto- polymerizing materials. In vivo implantation study on rats and rabbits Specimens of various acrylic resin were implanted 1st Day: a mild to severe tissue irritation depending on the product 16th Day:Tissue irritation decreased a reduced release of residual monomers over time. IMPLANTATION STUDIES PMMA implants were also very well tolerated after insertion into the alveolar bone of dogs or the limb bones of baboons. No signs of inflammatory reactions in adjacent tissues were found Residual Monomer Release In vivo study Two PMMA bone cements on rabbits implanted into the femoral bone marrow a reduced release of residual monomers over time. In vitro studies immersion of the mixed specimens into an aqueous environment 50% of the unbound MMA was released within 15 min
  17. 17. 22/03/2014 17 PULP REACTIONS Auto-polymerizing PMMA resins caused pulp irritations when used for temporary restorations. CAUSES Release of residual monomers, particularly during the first days after polymerization. High temperatures during setting (80–120°C) Temperatures higher than 42°C is considered The Critical Temperature regarding irreversible pulpitis. Polymerization of PMMA temporaries should be completed outside the oral cavity. REACTIONS OF THE GINGIVA & ORAL MUCOSA Irritation of the oral mucosa beneath or adjacent to resin restorations is the most severe local clinical adverse effect. Denture stomatitis is characterized by three degrees of severity: PUNCTUAL ERYTHEMA SHEET-LIKE ERYTHEMAS PAPILLARY HYPERPLASIA Small reddish areas that are not elevated above the level of the mucosa; These areas are covered by the denture. Associated with partial or complete dentures. Extensive erythemas that are also located beneath dentures and have a high tendency to bleed. Nodule-like hyperplasia with a diameter of 2–3 mm and a size of 3–4 mm that develop particularly on the palate.
  18. 18. 22/03/2014 18 REACTIONS OF THE GINGIVA & ORAL MUCOSA Factors Contributing To The Development And Severity Of Denture Stomatitis Released substances, mainly MMA and formaldehyde. Microorganisms (e.g., Candida albicans). Dentures with a permanent soft relinings. Experimental clinical study by Austin and Basker Three cases of denture stomatitis were examined The residual monomer conc. exceeded the normal levels by 6–11-fold. It was reported in 1962 that dentures with a residual monomer concentration of 0.6–3% a year after insertion did not cause mucosal irritations. BURNING MOUTH SYNDROME Possible Causes Of Burning Mouth Syndrome
  19. 19. 22/03/2014 19 BURNING MOUTH SYNDROME Clinical study of 22 patients with BMS 5 cases: allergy to MMA + high residual monomer conc. in their dentures Symptoms relieved in 3 pts. On receiving new dentures with a low residual monomer content 11 patients: Causes of BMS a poor dental prosthesis, diseases such as iron deficiency anemia, Addison’s anemia, idiopathic burning mouth. BURNING MOUTH SYNDROME Correlation between BMS & colonization of the oral cavity with H-pylori was investigated. 16% subjects with BMS revealed H-pylori in the tongue mucosa. CONCLUSION Gastritis + BMS Colonization of Tongue with H-Pylori. The oral cavity and oral diseases are important factors for the health/disease of the entire GIT.
  20. 20. 22/03/2014 20 5. ALLERGIES ALLERGIES MMA a. CONTACT DERMATITIS MMA classified as an important contact allergen b. An Extensive URTICARIA without intraoral symptoms was also observed. c. CROSS-ALLERGY: After sensitization with MMA, cross-allergies to other acrylates may develop . The in vitro leukocyte migration inhibition assay revealed that MMA, a specific antigen, causes cellular immunity. Nail varnish or acrylic substances used for artificial fingernails caused allergic reactions (type IV)
  21. 21. 22/03/2014 21 ALLERGIES Almost all other components of PMMA acrylates can cause an allergy The initiator , dibenzoyl peroxide ethylene glycol dimethacrylates Hydroquinone Allergic Contact Reaction in a 58-year-old woman with tingling sensations at the palate & at the tongue; patch test was positive for hydroquinone and the base resin. 6. MUTAGENICITY & CARCINOGENICITY
  22. 22. 22/03/2014 22 MUTAGENICITY AND CARCINOGENICITY Older studies reported generation of fibrous sarcomas and carcinomas after subcutaneous implantation of PMMA. These data were not confirmed by subsequent publications. Long-term studies on industrial workers, exposed to MMA for a long period of time indicated no carcinogenic effect. In General, it may be concluded that the rapid degradation and excretion of MMA should prevent an accumulative toxic effect or severe systemic adverse reactions

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