Bio-compatibility testing and the evidence base for perimucosal implants

Question 1

Classification of biomaterials (4)

Answer 1

By material
By application
By tissue interaction
By risk

Question 2

Classification by materials (5)

Answer 2

Metals (e.g. permucosal implants, dental amalgam, gold crowns)
Polymers (e.g. denture base, impression materials)
Ceramics and glasses (e.g. ceramic crowns, bone graft substitutes)
Composites (e.g. resin composites, glass-ionomer cements, hybrids)
“Natural” or biological materials (e.g. cat gut sutures)

Question 3

Classification by application (4)

Answer 3

Cardiovascular system (e.g. replacement heart valves)
Nervous system (e.g. Cochlear implants)
Skin & integument (e.g. sutures)
Skeletal system
-bone (e.g. joint replacement)
-tooth (e.g. Dental materials)
Perio., Endo., Restorative, Orthodontic, etc.etc.

Question 4

Classification by tissue reaction (3)

Answer 4

“Bioinert” (e.g. PTFE GoreTex® membrane for guided tissue regeneration)
“Bioactive” (e.g. 45S5 Bioglass or Perioglass® bone substitute)
Bioresorbable (e.g. PLLA/PGA resorbable sutures)

Question 5

Classification by risk (3)

Answer 5

Important in the context of medical devices regulations and safety testing, classified as Class I (low), II (intermediate) and III (high) risk on basis of:
Type of exposure
-surface/skin contact
-indwelling
-blood contacting
Length of exposure
-<24 hours (temporary)
-days
-permanent

Question 6

What is biocompatibility (4)

Answer 6

“The ability of a material to perform in a specific application with an appropriate host response.” D. F. Williams (Liverpool).
The term is more complex than simply a description of “non-toxicity”
Non-toxicity is only part of biocompatibility (and even then a complex part)
Biocompatibility is a site- and application-specific term

Question 7

Pre-market testing (5)

Answer 7

Required by law for new biomaterials
Tests based on ISO 10993 guidelines
Part 1 provides guidelines on test selection, determined by evaluation of material risks and clinical application.
Tests include cytotoxicity, haemolysis, irritation, systemic toxicity, & genotoxicity.
Additional studies not legally required, but data (e.g. publications) may be submitted towards CE marking or FDA approval.

Question 8

Testing biocompatibility (5)

Answer 8

In vitro evaluation
-cell-free models (e.g. simulated body fluid)
-cell culture
In vivo evaluation (testing in animals)
Clinical testing and trial (pre-market)
Post-market surveillance (e.g. Adverse Reaction Reporting Project)
Biocompatibility tests are used as part of the process leading to award of a “CE mark”.

Question 9

In vitro determination of biocompatibility: advantages and disadvantages (5)

Answer 9

Advantages
-rapid
-cost-effective
-reproducible
-ethically straightforward/ non-controversial
Disadvantages
-poor model of complex situation

Question 10

In vivo determination of biocompatibility: advantages and disadvantages (5)

Answer 10

Advantages
-whole complex animal model
Disadvantages
-expensive
-intermediate reproducibility 
-ethical debate/ controversy
-not always a reliable model of human body, tissue or disease

Question 11

Clinical trial to determine biocompatibility: advantages and disadvantages (4)

Answer 11

Advantage
-real human use/ clinical mode
Disadvantages
-expensive
-some ethical issues
-not always good representation of real clinical practice (e.g. often performed by skilled/ specialised clinicians, pts selected, etc)

Question 12

Post-market surveillance (5)

Answer 12

May provide early warning of hazard or side-effect of treatment
Some adverse reactions are extremely rare and may only be detected by PMS
Strengthens the evidence-base for the use of a biomaterial or device as part of a treatment
While no real disadvantages, implementation may be expensive
PMS is required by law

Question 13

Pre-market testing (5)

Answer 13

Required by law for new biomaterials
Tests based on ISO 10993 guidelines
Part 1: guidelines on test selection, determined by ***

Question 14

“Branemark” osseointegrating implant (5)

Answer 14

Orthopaedic surgeon
1950s research in bone metabolism
Used viewing chamber made from titanium
Placed 1st set of titanium 2-stage dental implants in patient in 1965
Survival data shown in Toronto in 1982. Commercial system launched in 1985.
While titanium highlighted, Branemark also pioneered careful surgery and patient selection

Question 15

In vitro biocompatibility of titanium (TiO2) conclusions (3)

Answer 15

TiO2 surface biocompatible.
Readily colonised by
cultured osteoblasts.
Rough modified surfaces were superior in terms of cell response (e.g. collagen type I production).
BUT sceptical whether this is useful for clinical use

Question 16

in vivo biocompatibility of titanium (TiO2) (2)

Answer 16

Concluded that HaP was superior to a titanium alloy in terms of osseointegration
BUT (a) Titanium alloys not used in dental implantology and (b) HaP cylinders were used, not coated metallic implants
BUT how many of these papers are valuable