Tissue engineering

“Imagine a world where transplant patients
do not wait for a donor or a world where burn
victims leave the hospital without disfiguring
scars. Imagine implant materials that can
"grow", reshape themselves, or change their
function as the body requires”
-Professor M.V. Sefton

Dr. Nabarun Biswas
Indoor Medical Officer
SU-2, MMCH

 Year: 2090 AD
 Patient’s age: 85 years
 Problem: liver failure, renal failure with valvular
heart disease
 He was sent to central tissue bank, where his
tissue samples were preserved.
 There his liver, kidney and heart valve was
engineered and replaced
 He was cured and got back to normal life

What is Tissue engineering?
It is the application of engineering and life
science towards the development of
biologic substitute to restore, maintain or
improve functions.

History of TE
 1987: Definition
 1997: Dolly (Somatic cell nuclear transfer)
 1998: Geron corp. figures out how to extend telomeres
 2006: invention of iPSC

Basic science behind T.E.
Cell biology & biochemistry
Stem cell
biology
Cell
signaling
biology
Scaffold
design
Bioreactor
design
Engineered tissue
Material science and engineering

Where this concept came from
 Tissues have ability to repair
themselves
 Some tissues have
extraordinary power to
regenerate & replace old/
diseased tissue
– Bone,
– Skin
– Gut mucosa
– Blood cell
– Endothelium

Opportunities
Tissue engineering provide treatment for a wide range of
diseases:
 Skin  burn , skin defects
 Cardiac muscle  heart failure
 Heart valves  valvular defects
 Cartilage  degenerative & traumatic disease
 Trachea & bronchus  congenital / malignancy
 Bladder  malformation , cystectomy
 Sphincter  incontinence
 Pancreas  DM type-1
 Blood vessel  atheroma, trauma
 Esophagus Stenosis, malignancy
 Small intestine  failure, crohn’s, cancer

Goal of tissue engineering
 Replacement or repair of diseased
or traumatized tissue or whole organ
 Models to test therapeutic efficacy
& toxicity

Sources of cells for Tissue
engineering
1. Somatic cell
2. Stem cell

Somatic cell
 Fully differentiated
 Obtained from normal
tissue
 Cells may be autologous or
allogeneic
 Examples:
– Epidermal cells
– Chondrocyte
– Bladder wall

Stem cells
 Stem cells are
undifferentiated or non
specialized cells that are
able to renew themselves
indefinitely , through cell
division
 Also able to differentiate
into one or more types of
specialized cells in tissue
after appropriate stimuli.

Stem cell related terms
 Totipotent
 Pluripotent
 Multipotent
 Unipotent
 Reprogramming
– Nuclear transfer
– Gen manipulation
– Viral transduction

Classification of Stem cell
 Embryonic stem cell
 Fetal stem cell
 Adult /somatic stem cell
 Induced pluripotent stem cell

Embryonic stem cell
 J. Thompson, 1998
 Source: IVF
 Totipotent & pluripotent
 Availability
 Expansion in vitro
 Risk of malignancy
 Autologous : NO
 Ethical concern: Yes

Fetal stem cell
 Aborted fetus
 Source: BM, blood
 Pluripotent
 Availability
 Expansion in vitro
 Autologous: No
 Ethical concern: Yes

Somatic stem cells (SSCs)
 SSCs
resident in
different tissue
& organs
 Responsible
for replacing
old/ diseased
cells

Mesenchymal stem cell
 Multipotent
 Differentiate into
mesodermal tissue
 Collected from ileac
crest aspiration,
liposuction & cord blood
 Availability
 Expansion
 Autologous
 Ethical concern

Induced pluripotent stem cell
 Discovered in 2006 by Yamanka
 Somatic cell reprogrammed to stem cell by genetic
manipulation
 Embryonic stem cell like
 Using retroviral / lenti viral transfection
 Cells taken from skin biopsy or blood sample
 Autologous
 Pluripotent
 May lead to activation of oncogenic genes to
prevent Adeno / Sandi virus vector used

Material science and engineering
Where these tissues are
cultured?
– In vivo
– In vitro
Cells
Signal
molecules
Scaffold
Tissue
Engineering
Tissue
Regeneration
In vivo
In vitro

Component of Material science
Material science involves 2 components
1. Scaffold :where cells are seeded
2. Bioreactors : which provide appropriate
physical environment

Scaffold
 Scaffold , that gives physical support and shape
to the engineered tissue, mimicking extra
cellular matrix.
 Allows cells to attach, delivers cell signals
necessary to guide cell growth, migration &
differentiation to form a functional tissue
 Rigid/ semi rigid, 3 Dimensional & porous.

Scaffold
 This animation of a
rotating Carbon
nanotube shows its 3D
structure.
 They are biocompatible,
biodegradable and
bioreabsorbable

Types of scaffold (Artificial)

Approach to cell seeding into
scaffold
 Static cell seeding
 Dynamic cell seeding
 Magnetic cell seeding
 Pressure & vacuum seeding
 Photopolymerised hydrogels
 Bioreactor perfusion system
Aim: rapid seeding, high
efficiency, effective penetration

Bioreactors
a) Spinner Flask:
b) Rotating Wall
c) Hollow Fiber
d) Perfusion
e) Controlled Mechanics

Risk of cell based therapy
 Tumour formation
 Genetic abnormalities
 Transmission of infection
 Poor viability & loss of function
 Differentiation into undesired cell type
 Rejection
 Side effect of immunosuppression

Future directions
 Tissue engineering and regenerative strategies
hold our great hope for effectively repairing or
replacing tissue in a wide number of human
diseases.
 Those patients who suffer from some form of
presently incurable disease, injury or birth
defect can get benefit from tissue engineering

Future directions………….cont.
Some of those may be…….
 One million children with juvenile diabetes
 8.2 million people with cancer
 58 million with heart disease
 Four million suffering from Alzheimer's disease
 10 million with osteoporosis
 43 million arthritis sufferers
 250,000 people paralyzed by spinal cord injuries
 500,000 with Parkinson's disease
www.stemcellresearchfoundation.org/WhatsNew/Benefit.htm

Tissue engineering

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