BIOCOMPATILITY of DENTAL MATERIALS

Biomaterial may be defined as a non living designed to interact with biological system

Biocompatibility is the ability to elicit an appropri-ate biological response in a given application in the body

Biological response will changes in the host, the application material, material its self

A materials may be said to be biocompatible when it has the quality of being non destructive in the biological environtment

A single material may not be acceptable in all application

Possible interaction between material and environment:

- postoperative sensitivity - toxicity - hypersensitivity/allergic - corrosion In the development of any biomaterial

must be consider: - strength - esthetic - functional &

biocompatibility

Measuring Biocompatibility

Is not simple About the interactions between dental

material oral tissue and technologies for testing improve

Must be extensively screened for biocompatibility before are used in human

- in vitro (primary test, initials test) - animal (in vivo, secondary test)

- usage test

Advantages and Disadvantages

In vitro test Advantages: - quick to perform - lest expensive - can be standardized - large scale screening - good experiment control - good excellence for

mechanism of interaction Disadvantages : relevance to in vivo is questionable

In vivo test : Advantages: - allows complex systemic interaction - response more comprehensive - more relevant Disadvantages: - relevance to use of materials

questionable - time consuming - legal / ethical concerns - difficult to control - difficult to interpret and quantity

Usage test Advantages : - relevance to use of material is

assured Disadvantages: - very expensive - very time consuming - major legal/ethical issue - can be difficult to control - difficult to interpret and quantity

ANSI / ADA Specification 41 3 category of test (1982): - initial test - secondary test - usage test : a. placement of the materials in

intended b. first in larger animal / primates c. Food & drug Administration approval ISO 10993 - ISO 10993 ( 1992) - ISO 7405 (1997) revised

Standard that regulate the measurement of biocompatible

The reason

The vast advance of cellular & molecular biology

The variety of test available for assessing biocom-patibility of material

The lack of standardization of these test

Recommended Levels of Biologic Testing (ANSI /ADA)

Initials Tests - Short term systemic toxicity test: Oral route - Acute systemic toxicity test: Intravenous route - Inhalation toxicity test - Hemolysis test - Ames mutagenicity test - Styles cell transformation test - Dominant lethal test - In vitro cytotoxicity test (Cr release) - Cytotoxicity test (Millipore filter) - Tissue culture agar overlay test

Secondary Tests - Subcutaneous implant test - Bone Implant - Sensitization test - Oral mucous membrane irritation

test

Usage Test - Oral mucous membrane irritation

test - Pulp and dentin test - Pulp capping and pulpotomy test - Endodontic usage test - Bone implant usage test

Short Term Systemic Toxicity Test (Oral route)

Penetapan toksisitas material jangka pendek Hewan coban: 40 tikus, 8 minggu, 130-150 mg

BB Kandang: 33 x 28 x 16 cm, 5 tikus, diet

standart Material dibuat serbuk

larutan/suspensi atau dicampur dlm makanan (dosis 1 g/kg BB)

Cara pemberian materi: dgn alat intragastric needle, atau stomach tube (kontrol dgn aquadest)

Observasi: 7 hari, amati perub. dan timbang BB/hr

Euthanasia dgn eter (inhalasi) kmd necropsy Interprestasi: mati, toksik klinik, BB, jaringan

Acute Systemic Toxicity Test(Intravenous route)

Hewan coba, perkandangan spt STSTT oral Materi: dilarutan dlm 0,9% NaCl, Cara pemberian: suntikan i.v pada vena

cauda dgn dosis 5 ml/100 g BB, bila tak larut extract 4 g dipotong kecil-kecil, masukkan dlm 20 ml saline normal, di autoclve 121o C 1 jam, semua extrac disuntikkan

Pengamatan: observasi selama 7 hari Euthanasia dgn eter dan necropsy Interprestasi: mati, toksik klinik, BB, jaringan

Hemolysis Test

Evaluasi aktivitas hemolitik pada bahan yang kontak lama

Rational: - hemolitik dasar: pelepasan Hb - hemolitik komponen solubel dan permukaan fisik: total hemoltik Material: centrifuge, waterbath, test tube,

spectro-fotometer, tabung pipa darah Prosedur: - Darah kelinci oksalat : 0,2 ml di hemilisis dalam 10 ml akuades (dibaca pada λ : 545 nm : 0,8 ± 0,5 o.d)

- Bahan 5 gr (dipotong 0,5 mm) dlm 10 ml saline normal dlm waterbath 37oC selam 30 menit

- Kontrol + : 0,2 ml lar. darah dlm 10 ml akuades - Kontrol - : 0,2 ml lar. darah dlm 10 ml saline

normal (o.d < 0,3) (o.d sampel – o.d kontrol neg) % hemolisis = ------------------------------------

x100% (o.d kontrol pos - o.d kontrol neg) Uji antar mean statistik Respon hemolisis > respon kultur jaringan

Subcutaneous implant test

Hewan coba: tikus Rational: Prosedur: - implan 3 mm (Ǿ) x 10 mm (p) - insisi 0,5 cm kemudian diseksi tumpul + I

cm - evaluasi pada 48 jam, 2 minggu dan 12

minggu. (inflamasi, nekrosis, pertinent changes) - Kriteria : tidak ada reaksi inflamasi / reaksi ringan, moderat, parah

Ketentuan implan

- Bahan diterima : a. tdk ada/reaksi ringan pd minggu 2 dan

12 b. reaksi moderat pd minggu ke hilang

pada 12 - Bahan ditolak: a. ada reaksi ringan pd minggu ke 2

meningkat ke moderat/ parah pada ke 12 b. Reaksi moderat pada minggu 2 dan 12 c. Reaksi parah pada minggu 2 dan 12

Biocompatibility of Dental Materials (2)

Reaction of pulp

Microleakage: …………………….. (nanoleakage)

- contracting during polymerization - wear - thermal cycling saliva invasion microorganism inflammation/infection

Dental bonding - bonding to dentin has proven more

difficult a. organic and inorganic b. wettability >> EDTA, Na-

hypochloride c. lower mineral content (in dentin) - occurred hybrid layer of resin & collagen - removal of smear layer caused: a. its juxtaposes resin & dentin

without barrier b. make any microleakage more

significant c. acid are potential source irritation

Dentin bonding agent

cytotoxicity: HEMA 100 X less toxic than bis-GMA

- combination HEMA and other resin, act synergis

tically - some resin component enhance the

growth of oral bacteria - the ability of resin based material to

increase plaque formation

Resin base materials release (Resin composite: organic & inorganic

phase) - freshly set chemically & light cured resin

cause moderate cytotoxicity, and reduced 24-72

hours (with dentin barrier) - be mediated by resin component release - light cure < chemically cure (depend on :

efficiency of the light and type of resin) - reaction diminished 5 – 8 weeks and an increase in reparative dentin

CURRENT BIOCOMPATIBILITY ISSUES IN DENTISTRY

Latex

- 6-7% surgical personnel may be allergic to latex

- 42% dental personnel: dermatoses of hands & finger

- hypersensitivity reaction was cause by true

latex, accelerator or antioxidant (in processing) Nickel

- the most allergenic metal (10-20%)

- is a known cross-reactivity between Ni and Pd

patient who are allergic Ni will be allergic to Pd

- Ni sulfide is a respiratory carcinogen

- Ni+ is a mutagenic in human

Beryllium - Beo & Be + is a carcinogenic - acidic environment enhance Be

release from Ni-Cr - Be - containing particle (dust) that

are inhaled cause berylliosis

Mercury - access to the body via the skin or

vapor - toxic effect is 3 µg/kg

Estrogenicity - bisphenol A (BPA & BPAD) is a estrogenic effect - evidence comes from estrogen receptor-

BPA binding Residual Resin - to be allergy because exposure to

unpolymeri- zed materials. - have significant toxic effect (invitro test) - the use of glove is not effective in

preventing to monomer resins - resin component have been to transverse

the dentin

Effect of Metal Ions on Tissues

Cytotoxicity / allergenic / carcinogenic - the rate metal ion release depend on: a. form of metal / alloys b. great of chemical reactivity - mechanical preparation - residual stress - cleaner surface c. composition alloy & specific

environment

Amalgam and casting alloys

Amalgam: - by corrosion product release (γ2) - marginal microleakage - mercury residu

Glass ionomer - freshly prepared is mildly cytotoxixity - fluoride release (cytotoxicity in

vitro) - increased dentin permeability after

etching

Liners, Varnishes & non resin cement Liners (CaOH) : - pH alkaline (12) extreem cytotoxicity - containing resin mild to moderate in

culture varnish containing copal & polystyrene - resin component dissolve - formation pinpoint holes Non resin ZnPO4 : low pH and leaching of Zn Zn OE : suppresses nerve transmission and

anti inflammatory Bleach agent- peroxide can rapidly traverse the dentin- chemically burn the gingiva

Reaction of Oral Soft Tissue to Restorative material

- product of bacterial plaque & accumulate - buffering & protein-bonding to mitigate

cytotoxic - direct contact resin composite with

fibroblast caused leach out un polymerized

component - roughness surface - hypersensitivity of the acrylic & diacrylic monomers

Reaction bone & soft tissue to implant materials

(osseointegration / biointegration)

Van der Waals force Mechanical entrapmentCompressive forceChemically bond

Mechanical entrapmentPhysiologically reaction(Calcification process)

Bioactive - Ceramic

TISSUE BIOGLASS

Cation & silica Dissolution network

Na – O - Si

Si – O – Si

H

OHH – O – Si - Silanol formation

Si – O – Si O Si – O – Si O

Silica gel forms bycondensation of silanols(silane chain)

Ca & PO4Ca & PO4

CO3

OH-

F-

Calcium-phosphate-rich mineral forms

Ca-P mineral crystallizes into a hydroxy, carbonate, Fluorapatite layer

Ca10(PO4)6(OH)F

Attachment between metal and tissue

Diffusion oxygen and metals ion into tissue

Diffusion hydrogen and oxygen into tissue to form hydroxides

Diffusion of mineral or atoms from electrolyte in to the oxides

Dissolution of oxide metal ion (corrosion)

Adsorption at biomolecular Desorption for replacement of

biomolecular Fragmentation of modification of

biomolecular