5-- Dental Composite Material- Biocompatibility: Vidal

Biocompatibility: Craig's textbook

Ability of a material to elicit an appropriate biological response in a given application in the body

Biocompatibility: Schmalz and Arenholt-bindslev

Ability of a material to perform with an appropriate host response when applied as intended

A single material may not be

biologically acceptable in all applications

Measuring Biocompatibility

In Vitro tests

Animal Tests

Usage tests or clinical trials

this type of test requires the placement of a material in contact with a cell, enzyme, or some other isolated biological system

In vitro

what kind of cells are used in in vitro testing

primary cells (better) and cell lines

Primary cells are taken directly from an ____/____ and clutured and grow for a ____ time

animal/tissue

limited time

do primary cells retain the characteristics of cells in vivo

yes retain many

in vivo tests are more relevant to measuring ______ of material

cytotoxicity

cell lines Have been transformed to allow them to grow _____ in culture

indefinitely

do cell lines retain in vivo characteristics

do not retain all but exhibit retained features

Examples of in vitro tests

Cell cytoxicity tests, membrane permeability tests, cell immune function test, changes in cell cycle or activation of complement systems

Mutagenesis tests: assess the effect of a biomaterial on a cell's genetic material

what is the significance of in vitro testing

to reduce the number or required animal tests

Animal tests involve

mammals (mice, rats, hamsters, guinea pigs, etc) - same complexity as humans

Material is NOT placed in the animal with regard to its final use

WHY?

Allow for the complex interactions between a material and functioning, complete biological system to occur

More comprehensive and relevant than in vitro tests

Disadvantages in animal tests

More expensive, time consuming, often involve significant ethical concerns and oversight, difficult to interpret and quantify

Example of animal tests:

Mucous membrane irritation test

Determine whether a material causes inflammation to mucous membrane or skine

Example of animal tests:

Skin sensitization

Materials are injected intradermally, followed by secondary treatment with adhesive patches containing the test substance

Example of animal tests:

Implantation test

Evaluate materials that will contact the subcutaneous tissue or bone (common for periodontal and endodontic treatment materials)

usage tests involve ____ or _____

animals (large) or humans

in usage tests, material is placed _____ to its intended clinical use

IDENTICAL

Ability to mimic the clinical use of the material in every regard, including time, location, environment, and placement techniques

when a human is used in a usage test it is called a

RCT

what is the gold standard test

usage tests

Disadvantages to usage tests

VERY expensive, time consuming, ethical/legal concerns, difficult to interpret and quantify results

Usage tests:

Dental pulp irritation tests

Materials are placed in Class V cavity preparation in intact non-carious teeth

Teeth are extracted and sectioned for microscopic examination

Necrosis and inflammation are classified according to their intensity

Usage tests:

Intraosseous implant test

Materials are inserted into the jaw of test animals

Primates, dogs, miniature pigs, guinea pigs, and rats

Tissue reaction is assessed histologically as well as the tissue in contact with the implant

Usage test:

Mucosa and gingival usage tests

Material is placed in cavity preparation with subgingival extensions

Responses are characterized according to the number of mononuclear inflammatory cells in the epithelium and adjacent connective tissues

- Difficulties: Presence of existing inflammation, rough margins of restorative materials, over- or under- contour of the restoration

Correlation among tests is ____ ____ _____

- Not always possible

what is the most cost effective and accurate types of studies

in vitro + animal + usage

can a single test determine biocompability?

no

Biocompatibility is assessed by various _____ according to specific _____ in which a comparison with products already on the market plays an important role

experts, guidelines

there are lots of different ways to assess biocompatibility, thus evaluations may not generate ____ _____

identical results

- it is the dentists obligation to not rely on these assessments blindly but rather to question them critically

Regulatory agencies require ______ testing and provide guidance on how the tests should be performed

biocompatability

what are the 3 regulatory agencies

International organization for standardization (ISO)

the US Food and drug administration (FDA)

and the conformité Européenne (CE)

The FDA recognized human health substances as what

only two categories

- drugs or devices

Dental restorative materials are classified as

devices

Preclinical evaluation of biocompatibility of medical devices used in dentistry - Test methods for dental materials

Initial tests:

- Assess biological reaction to materials (cytotoxicity, sensation, and systemic toxicity). Some done in vitro, other in animals

Supplementary tests:

- Assess chronic toxicity, carcinogenicity, biodegradation (many in animals)

Manufatueres evaluate the device to

determine if it could cause an adverse biological response

Manufactures perform _______ ______

biocompatibility testing

The FDA reviews the testing results before authorizing the device for ______ _____

market sale

Biocompatibility of dental materials

Reactions of pulp

Reactions of other soft tissues to restorative materials

Reactions of bone and soft tissues to implant materials

Reactions of pulp

Dentin bonding/bonding agents

Resin-based materials

Amalgam and casting alloys

Glass ionomers

Liners, varnishes, and non-resin cements

Bleaching agents

Reactions of the pulp - dentin bonding agents

Smear layer is removed in etch and rinse protocol which increases dentin ______ --> acids used for etching can be _____ (etch and rinse vs self etch)

permeability

irritating to the pulp

HEMA and Bis-GMA (monomers) have cytotoxicity when applied in contact with ____, but have lees cytotxicity when a ______ barrier is present (at least 0.5 mm)

cells

dentin

HEMA can ____ through dentin via dentinal tubules and cause ____ ____

diffuse

pulpal irritation

There is a low pulpal inflammatory response when RBC is placed in cavities with at least _____ mm of remaining dentin. Reactions are diminished within weeks

0.5

when there is incomplete polymerizatinon of adhesives, resin based restorative materials release unbound _____ _____ immediately after setting and later which is _____ to the pulp and gingival cells

free monomers

cytotoxic

Reactions of pulp: Resin-based materials

Microleakage and nanoleakage at adhesive interfaces do present permeability and/or gaps leading to _____ ____ --> pulp _____

bacterial infiltration

inflammation

Good _____ _____ is key to avoid pulpal irritation, but material selection is also important

marginal sealing

restorative materials can alter ____ ____ and dentin ____

pulpal responses, repair

what is the main concern of biocompatability with resin-based materials

estrogenicity of biphenol A (BPA)

BPA can be a _______ product of some methacrylate used in resin composite and sealants, but levels of BPA release are extremely ___ (diet is the main source of BPA exposure in most countries)

degredation

low

BPA release can be minimized by proper ____ _____ the material, using rubber dam isolation, remove

light curing

which dental sealant does not contain BPA

3M Clinpro

high copper amalgam is ____, low copper amalgam that has set for 24 hours does not inhibit ____ ___

toxic

cell growth

low-copper amalgam are ____ ____, high-copper amalgam causes ___ reactions in implantation tests

well tolerated

severe

Amalgam and Casting alloys: Usage tests

______ pulpal irritation when placed in shallow cavities or in deep cavities using a line

minimal

Amalgam and Casting alloys: when used in deep cavities with no liner =

pain (thermal and electric conductivity)

Amalgam and Casting alloys: Alloys used for restorations crown and dentures may have _____ ____ on cells if released

adverse effects

Metal ions released from alloys are likely to contact the ____ and _____ tissues than the pulp (more likely to affect by the cement retaining the restoration)

gingival and mucosal

Pulp biocompatibility to Glass ionomers is attributed to the ____ nature of and ___ molecular weight of the polyacrylic acid - unable to ___ through detnin

weak, high, diffuse

Pulp biocompatibility is pretty good

Glass ionomers: usage tests

mild pulp reactions, absent after 1 month

Glass ionomers: sensitivity to pain is increased after placing GI in cervical cavities possibly related to increased _____ after conditioning the dentin

permeability

Alkaline liners are used in exposed pulps but caused _____, coagulation of hemorrhagic exudate of the superficial pulp

necrosis

not used anymore

Calcium hydroxide-based materials containing resin is ____ irritating and able to stimulate ____ ____ formation quicker than calcium hydroxide

less, dentin bridge

Common brands:

- TheraCal LC = resin-modified calcium silicate cement

- Biodentine= tricalcium silicate-based material

MTA is a ____ _____-based cement

Calcium silicate

____ ____ is the main soluble component in MTA

calcium hydroxide

MTA stimulates formation of a thick ____ _____ with no inflammatory response

dentin bridge

MTA stimulates dentin _______ through solubilization of non-collagenous proteins from the dentin

remineralization

Induces cell proliferation, migration, and differentiation to odontoblast-like cells

SUMMARY: Biocompatibility depends on the

material composition, location, and interactions with the oral cavity

SUMMARY: Diverse reactions can occur if

Material release their components and whether those components are toxic, immunogenic, or mutagenic