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
