Who are we…

Researches done: Collaborators:

• 3D bioprinting
• Gene delivery
• Disease Modelling
• Tissue engineering
• Controlled Release
• Bioreactor development
• High-throughput screening
of drugs and materials
• Microparticle-based 3D
culture

Centre for Biomolecular Sciences Divisional Head

Tissue Engineering group Prof. Felicity Rose
Division of Regenerative Medicine and Professor of Biomaterials
Cellular Therapies and Tissue Engineering
Organs transplantation and its current state
 Transplant sum across the globe Year: 2000
(Source: Global Observatory on Donation and Transplantation)
 Transplant sum across the globe Year: 2014
(Source: Global Observatory on Donation and Transplantation)
 Transplant rate across the globe Year: 2000-2014
(Source: Global Observatory on Donation and Transplantation)
 Transplant rate in the Philippines Year: 2000-2014
(Source: Global Observatory on Donation and Transplantation)
 Transplant by Organ Type. Year: 2016
(Source: Organ Procurement and Transplantation Network, OPTN)
 Demand and Supply. Year: 1991-2014
(Source: U.S. Department of Health and Human Services)
Status Quo on Organ Transplantation

• Very High Demand

• Very Low Supply (Donors)
• Moderate to High Mortality Rate
• Very High Cost
Mortality of Transplants from
2012-2016 Based on OPTN
data as of January 31, 2017
Estimated U.S. Average 2011 Billed Charges Per Transplant
(Source: Milliman Inc.)
In 2048…
 Tissue
Engineering
Tissue Engineering

The Central
Dogma of Tissue
Engineering
Source:
http://www.wikilectures.eu/index.p
hp/Tissue_engineering_principle
Methodologies in TERM
TERM via 3D Bioprinting (Murphy & Atala, 2014)
Step 1&2: Imaging
and Design Approach
Step 1: Imaging

• Patient is scanned to obtain 3D

spatiotemporal information
about a specific organ
• Done by using
• Magnetic Resonance Imaging
(MRI)
• Computerized Tomography
(CT) Scan
Step 1&2: Imaging and Design Approach

• 3D image is generated through

a 3D modeling software
(Solidworks, COMSOL etc.)

• Structure refined by
mathematical algorithms for
smoothness, noise reduction,
etc.
Step 1&2: Imaging and Design Approach - @
UoN

Sir Peter Mansfield (Nobel

laureate, discovered MRI)
imaging Centre
Step 3: Material Selection
Methodologies in 3D bioprinting
 Step 3: Materials Selection

• Materials are the “soil” in which

PVA
Synthetic the cells grow to form tissues
PCL
Ca3(PO4)2
• Usually blended to compensate
for lacking characteristics
Cellulose
• Properties required are as follows
Natural Chitosan • Printability
Silk • Biocompatibility Cell
• Degradation kinetics +
Decellular- • Mechanical properties Material
ized Extracellular
Organ/ Matrix
• Material Biomimicry =
Tissue
BIO-INK
 Dolatshahi-Pirouz et al., (2014)
Step 3: Materials Selection - @ UoN RMCT

Vegas et al., (2016)

 Step 3: Materials Selection - @ UoN RMCT

Immobilisation of growth factors in nanofibers Golf-ball microparticles

Wang et al., (2009) Paino et al., (unpublished data)
Step 3: Materials Selection - @ UoN RMCT
Bacteria-instructed synthesis of
polymers for self-selective microbial
binding and labelling
Klaus et al. (2016)
Step 4: Cell Selection
 Step 4: Cell Selection
What are STEM CELLS?
• Stem cells are a class of
undifferentiated cells that are able to
differentiate into specialized cell
types
• To understand better, an
undifferentiated stem cell is
compared to a child that can have
different professions
(totipotent/embryonic/pluripotent
Hierarchy of stem cells stem cell, or ESC/PSC)
(Source:
http://informationonstemcellsweebly.weebly.com/types-of-stem-
 Step 4: Cell Selection
What are STEM CELLS?
• The child (ESC) becomes an adult
multipotent/mesenchymal stem cell
(MSC) when he chooses a major in
Senior High School (STEM, ABS,
GA or HUMMS)
• The adult will become fully
differentiated after choosing a major
in college (Differentiated Cell, DC)
• Fully differentiated cell lines can be
Hierarchy of stem cells reverted back to its embryonic state
(Source:
http://informationonstemcellsweebly.weebly.com/types-of-stem- via induced pluripotency
Step 4: Cell Selection
• Differentiated • Multipotent Stem • Pluripotent Stem
Cells Cells Cells

DCs MSCs PSCs

Different types of cell used in bioprinting. Cells are obtained from fat, bone marrow,
blood, dental pulp, or induced pluripotency.

• Important for correct functioning of the engineered organ

• Cell proliferation must be controlled
• Autologous (self) cells obtained from biopsies
• Cell-Material system should survive bioprinting process and
withstand physiological stresses similar to native organ
Step 5: Bioprinting
Methodologies in 3D bioprinting
Step 5: Bioprinting

Selection of BioPrinters. A) Inkjet-type B) Microextrusion and

C) Laser assisted bioprinter (Source: Vicari, 2014)
 Step 5: Bioprinting

Inkjet BioPrinter
• Also known as drop-on-demand
printers (similar to normal
computer printers, only with z-
axis added)
• Bio-ink in liquid form; deposition
is controlled on defined locations
• Printed liquid undergoes gelation
(via crosslinking), solidifying after Bioprinting via Inkjet deposition
deposition Source: Aspect Biosystems
 Step 5: Bioprinting

Microextrusion BioPrinter
• Yields continuous beads of material
rather than liquid droplets
• Type of material fed to the bioprinter
Bio-ink
are hydrogels and cell spheroids
• Can handle very viscous feed
material; usually uses pseudoplastic The Extrusion Process
(shear thinning) fluids (Source: Paulson Training)
 Step 5: Bioprinting

Laser-Assisted BioPrinter
• Technique borrowed from laser-
induced forward transfer
• Consists of
• pulsed laser beam
• focusing system
• A ribbon: donor slide (usually made
from glass) with laser-energy-
absorbing layer (gold or titanium),
• layer of biological material in liquid Laser Assisted Bioprinter
solution (Source:https://
• Receiving substrate www.youtube.com/watch?
Step 5: Bioprinting –@ UoN RMCT

Prasophthum et
al., 2017
Step 5: Bioprinting –@ UoN RMCT

Centre for Additive

Manufacturing

Saleh et al., 2017

Step 6: Application
Step 6: Bioreactor maturation & implantation

• Bioreactor Maturation
o Required after bioprinting for full development of tissue/organ
o Printed organ is in a controlled biomimicked environment
(temp, pH etc.) with nutrients and oxygen continuously supplied

• Implantation
o Done immediately after harvesting from
bioreactor

• Post-Surgical
Intervention
o Treatments usually include
antibiotics, stents, supplements
etc.
Step 6: Bioreactor maturation & implantation - @
UoN RMCT
Dalby et al.,
2015

Nanokick
Bioreactor
technology
 Step 6: Bioreactor maturation & implantation @
UoN RMCT
Contour velocity field - generation of
Taylor Cells from double chamber
bioreactor

Flow field evolution (t =15s) via solution of

Time-Dependent Navier Stokes Eqn.
System solved via Finite Element Modeling
(Degrees of Freedom: 439,053); Incompressible,
Low Re Navier-Stokes Equation. Core i7
6280HQ, 16 GB DDR4 RAM. Solution time ~ 24h
Step 6: Bioreactor maturation & implantation

Meshing and shear stress plots of the tubular

organ inside the bioreactor.
Where
are
we
NOW?
Well, we’re…..
not quite there yet

Current advancement has:

1. Mini Tissues for drug screening – more advanced drugs!
2. Small patches of skin for tissue regeneration – for burn
victims!
 Too complex… for
/human-body-maps/ images licensed under CC now
• expected to reach
USD 1.82 billion by
2022 (Grand view
research Inc.)
• CAGR of 26.5%
from 2016 to 2021
• Market involves
biomaterials, cells,
bioprinters,
hydrogels

Market Size for Bioprinting

 Bioprinted
The meatball Bioprinted
eyeballs
futur
e:

Bioprinted Bioprinted
leather skin
bag
Thanks for
Listening
Any Questions?