Biocompatibility Evaluation and Pre-

clinical Testing of medical devices

A.Sabareeswaran,MVSc(Path), PhD
Histopathology laboratory,
Bio Medical Technology Wing,
Sree Chitra Tirunal Institute for Medical
Sciences and Technology.
 Design- medical
Materials
device
Metal,
Engineering,
polymer,ceramic
Technology

MEDICAL
DEVICE
Evaluation
Physicochemical Clinical use

Biological- Specialities – cardio,

biocompatibility neuro, ortho, etc.,
evaluation
STANDARDS: MEDICAL DEVICES
 International Organization for Standardization: ISO

 The United States Pharmacopoeia, The National Formulary: USP

 American Standard for Testing Material: ASTM

 Food and Drug Administration : FDA

 Center for Devices and Radiological Health : CDRH

 European Union Directives : EU

 Association for the Advancement of Medical Instrumentation : AAMI

 Organization for Economic Co-Operation and Development : OECD

Central Drug Standards Control Organization (CDSCO)

India's main regulatory body for pharmaceuticals and medical
devices
INTERNATIONAL ORGANIZATION FOR
STANDARDIZATION (ISO)

Risk based
classification
Class I, IIa,b, III

 CDSCO
classification
 Class A,B,C,D
Role of Pathology in medical device
evaluation
Application Physico-
(material Chemical
identification) Characterisation

Biocompatibility
Device Evaluation Evaluation
(Animal Trials- (cytotoxicity,
Preclinical) haemocompatibility,
toxicology)

Clinical trials Clinical Use

BIOCOMPATIBILITY is the ability
of a material to perform with an
appropriate host response in a
specific application.
By Prof. David Williams
 Biomaterials in living tissue can

Change over a period of time

surface chemistry, physical character

Cause biological reactions

Initiate different tissue responses in relation
to material, host
 Application
 Cardio Vascular  Etc.,
 Orthopedic
 Muscular
 Neural
 Dental
 Eye
 Ear
Stents, vascular grafts
Artificial Heart valves
fabric sewing ring

Chitra-TTK

Highly polished, metal cage

Highly polished polymer disc

Orthopedic application

What is the best combination?

Dental application
 Biocompatibility evaluation– Biomaterials
 Metals,
 Polymers and
 Ceramics

 Pre clinical evaluation – Medical devices

 Single or Combination of biomaterials
 Design
 BIOLOGICAL RESPONSE
• Injury
• Protein adsorption
Early
phase • Provisional matrix

• Acute inflammation
Inflamma • Chronic inflammation
tory • Foreign body tissue reaction
phase

• Fibrosis/fibrous tissue(soft) new bone

Healing • Scar tissue
phase
 Biological safety

 History and evolution

of the tissue response

 Final
integration/resorption
/degradation
 Local effects after implantation
ISO10993-6
 Intramuscular implantation
 Subcutaneous implantation
 Bone implantation
 Neural implantation

(Rat, Guinea pig, Rabbit, Dog, sheep, goat,

Pig)
Intramuscular implant

Paravertebral
muscle

1 week, 4 weeks, 12
weeks

> 12 weeks- long

term

Color Atlas of Tissue Response to Biomaterials

by Mira Mohanty, A Sabareeswaran, Sulekha Baby, Joseph Sebastian, Caroline S Diana
 Implant site
muscle

Color Atlas of Tissue Response to Biomaterials

by Mira Mohanty, A Sabareeswaran, Sulekha Baby, Joseph Sebastian, Caroline S Diana
Biocompatible-Nonbiocompatible

ONE WEEK

TWELVE WEEKS TWELVE WEEKS

 Bone implantation

Rabbit – femur bone (cortical bone)

1 week, 4 weeks, 12 weeks

> 12 weeks- long term

Color Atlas of Tissue Response to Biomaterials

by Mira Mohanty, A Sabareeswaran, Sulekha Baby, Joseph Sebastian, Caroline S Diana
Histology – bone- implant interface- osseointegration
Coronary stent
evaluation
 ISO25539-
2:2012(en)Cardio
vascular
implants —
Endovascular
devices — Part 2:
Vascular stents
 CORONARY STENTS
7 days- sub acute thrombosis (SAT)

4 weeks- Neointimal hyperplasia(NIT)

 26 weeks- long term effect, remodelling

 Histology - Coronary
blood vessel with stent
struts

Color Atlas of Tissue Response to Biomaterials

by Mira Mohanty, A Sabareeswaran, Sulekha Baby, Joseph Sebastian, Caroline S Diana
Chitra –TTK
mechanical
heart valve
ISO 5840-1:2015
Vascular graft
ISO 7198:2016
 Vascular graft- anastomoses, mid region

Color Atlas of Tissue Response to Biomaterials

by Mira Mohanty, A Sabareeswaran, Sulekha Baby, Joseph Sebastian, Caroline S Diana
 Steps in soft tissue processing- Paraffin
embedding
Grossing Tissue processing Embedding-paraffin

Sectioning –rotary Staining

microtome 29
 Steps in hard tissue processing- Resin
embedding

Bone Embedding Cutting- linear precision saw

processing

Staining
Microscopy Grinding &
Polishing
SCTIMST

Thank you