This document provides a summary of the biocompatibility of polymethylmethacrylate (PMMA) resins. It discusses the various uses of PMMA in dentistry and daily life. It then examines the composition of PMMA resins and how they are classified. The document analyzes the release of substances from PMMA resins like residual monomers, formaldehyde, and other components. It also evaluates the systemic and local toxicity of PMMA as well as its tissue compatibility, microbial effects, implantation studies, reactions in pulp and oral tissues, and potential to cause allergies.

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BIOCOMPATIBILITY OF
POLYMETHYLMETHACRYLATE
RESINS
Presented by:
Dr. Hashmat Gul
Demonstrator,
Dental Materials.
AMC, NUST.
1. INTRODUCTION

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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

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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

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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

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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.

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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.

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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

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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

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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.

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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

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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

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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.

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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

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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

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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

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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

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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.

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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

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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.

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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)

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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

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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