Transcript TisXell Regeneration System Applications Accelerate Your

TisXell Regeneration System
& Scaffolds
Accelerate Your Cell Proliferation
By
QuinXell Technologies Ltd
•
founded in 2011 as a subsidiarity of Quintech Life Sciences
•
located in Singapore
•
focus on Regenerative Medicine
•
Research on TisXell Regeneration System was initiated as a joint
project between the National University of Singapore (NUS) and
Singapore Polytechnic (SP), with the National University Hospital
(NUH) providing samples for applications
•
Scientific papers supporting the benefits of biaxial bioreactor on
functional tissue growth on 3D scaffolds have been published for more
than 10 years
Application Fields
• Regenerative medicine
• Tissue engineering
• Translational medicine
• Tissue / organ transplant
Cell Types
• Bone Cells
• Stem Cells
• Primary Cells
• Muscle Cells
• Heart cells
• Bioengineered Cells…
The Novel Approach
Type
Advantages
TisXell Regeneration System Integrated perfusion system allows for exchange between
the vessel and reservoir with maximal mass transfer under
low sheer force
Biaxial revolution of the culture vessel led to more
homogenous cellular and ECM deposition – at the surface
and the deeper core of the scaffolds
Cellular scaffolds were secured by stainless steel needles to
avoid scaffold and vessel wall collisions
The Novel Approach
TisXell Regeneration System is unique in its bi-directional revolution.
The biaxial bioreactor rotates simultaneously in two independent axes,
allowing it to spin and tumble simultaneously. If required, the axes can be
controlled to function as a single axis system
The gyroscopic movement leads to an improved flow of fluids within the
bioreactor for accelerated cell proliferation
The TisXell System
TisXell in Motion
TisXell Novel Approach
…(1)
Innovative Design
•
Independently controlled drive axes for biaxial, single axis and swing modes
•
Continuous perfusion with integrated, selectable speed peristaltic pump
•
Oxygenator unit to facilitate gaseous exchange
•
5-port medium reservoir with sensor bank to house optional temperature, pH and
oxygen probes
•
Heat isolated system drivers and controller in separate console
•
System may be placed in a CO2 incubator or used with a process controller
TisXell Novel Approach
…(2)
Advantages in Arm Assembly
– Weight-balanced rotary arm for 500ml or 1000ml spherical
chamber
– For smaller volume requirements, a 50ml “pancake” chamber
with dual-stacker is available
– Built-in sensors to detect arm angle and positions for fully
programmable operations
– Tube holders to secure excess tubing for obstruction free
operation
TisXell Novel Approach
…(3)
Modular Chamber
•
•
•
•
•
•
50, 500 and 1000 mL spherical chamber with detachable base to double up as a
chamber stand
Dual chamber-cap design for easy loading and uploading of tissue scaffolds
without removing tubing
Oxygenator / Gas membrane for gas diffusion
Sterile rotary couplings for controlled continuous perfusion of nutrients through
the culture chamber
Transparent, unobstructed view of tissue constructs during operation
Optional rotary core vessel with increased hydrodynamic shear provides
additional stimulus to enhance cell activity
TisXell Novel Approach
…(4)
Flexible Operation Modes
– Biaxial, uniaxial and swing modes can be independently selected
– Auto, jog and manual functions can be pre-set to various speeds,
directions and arm angles to optimize cell culture conditions
– User-friendly remote touch screen controller for complete
management of system while unit is inside a laminar flow chamber
or a CO2 incubator
50ml Chamber
Small 50ml vessel for
low volume / small
scaffold applications
Designed for dynamic
seeding with “cell
concentrator” that
concentrate cells around
scaffold during seeding
loop operations.
Dual stacker for
simultaneously
operating two
chambers (in
continuous perfusion)
Scaffolds
PCL – the ideal material for applications in the TisXell Regeneration System
•
3D inter-woven polycaprolactone
• Pores are inter-connected and the polymer has been
regarded as cell tissue compatible
• Our scaffolds are biocompatible, showing slow
degradation and assimilation of the polymer over 24
months
• That leads to perfect bone healing, provides adequate
mechanical support and maintains the shape of the
skull without problems
• The scaffolds are durable, load bearing and exhibit
slow degradation - ideal for design that requires
stress transfer to surrounding cells
Different shapes
• available in different sizes and shapes
• Specialized shapes so as:
 mesh
 plug
 strip
• Customized 3D shapes feasible
Approvals
And of course…
…Our scaffolds are FDA Approved for craniofacial applications and
certified by the TÜV Rheinland!
BONE APPLICATIONS
Key Benefits for Bone Applications
• Homogenous cellular distribution
• Rapid stem cell expansion
• Promotes new vascularization
• High viability
• Robust osteogenic differentiation and mineralization
• Increased bone formation after transplantation
Rat Femoral Defect Model
• Created 7 mm defect
• Press-fit 8 mm graft
Healing in TEBG vs. control
CT showing bridging AND mineralization
New blood vessel formation
Mineralization confirmed by histology
S
S
S
S
S
S
Scaling Up
• Minipig model
• Larger volume, anticipate issues of vascularization
• Introduce endothelial progenitor cells (EPC) into cellular mix
Mesenchymal stem cells
(MSC)
Endothelial Progenitor
Cells (EPC)
Cells are viable and randomly distributed
TisXell supports co-culture
of different cell types
Minipig Critical-Size Defect Model
 18 mm segmental defect in tibia
 Monitor over 12 months:
 X-ray, CT, angiography
CT shows bridging at 3 months
fMSC-EPC
MSC
1 mth
3 mth
1 mth
CT-Angiography shows rapid Vascularization
fMSC-EPC
MSC
1 mth
3 mth
1 mth
BONE DIFFERENTIATION STUDIES
…in vitro
Proliferation: Picogreen assay
TisXell: confluent at week 1
Static: far less cells than TisXell group even when they
reached confluence at week 4
Cell distribution, viability & shape
TisXell
High viability throughout 4 wks
Homogenous distribution
Round shape in wk 4
Static:
High viability but necrosis in wk 4
Non-homogenous distribution
Spindle shape in wk 4
Differentiation/Mineralization
ALP activity and von Kossa staining
TisXell group cellular scaffolds have significant higher ALP
activity since day 7 and much positive von Kossa staining
than static group
Differentiation / mineralization:
EM (Week 4)Cellular scaffolds from TisXell are highly mineralized
GENERAL applications
Stem Cell Expansion on Microcarriers
…(1)
•
TisXell has been employed in stem cell research, specifically in cell
suspension expansion on microcarriers
•
Comparison of cell suspension growth in TisXell and spinner flasks are
highlighted in the confocal images
•
Results emphasizes TisXell benefits in accelerating cell growth as reflected
by the higher cell number observed as compared to a spinner flask
Stem Cell Expansion on Microcarriers
…(2)
“A cell seeding
density of 5x104
cell/ml and we
achieved a high cell
density of 8x105
cell/ml at Day 14
(around 16 fold
increase ) by using
the TisXell system “
Green dye indicates viable cells
Heart Patch Research
…(1)
•
Heart failure is a major health problem and the leading cause of morbidity
and mortality of patients in both industrialized nations and developing world
•
The regenerative potential of stem cells sparked interest in stem–cell
therapy for treating and preventing heart failure have transformed
experimental research and led to an explosion in clinical investigation
•
Researchers at the Nanyang Technological Institute (NTU) grows cells on a
customised scaffold to create a "heart patch" for repair of damaged heart
tissue
Heart Patch Research
…(2)
•
The diffusion limitation of oxygen transport in the scaled up tissue is
overcomed by providing interstitial medium flow to an engineered heart
patch using the TisXell system
•
This approached is expected to enhance tissue assembly by way of
improved mass transport.
By combining surface laser patterned
poly(lactide-co-ε-caprolactone) nanofiber scaffold as substrate and
dynamically culturing mesenchymal stem cells in the TisXell system, they
improve the viability and proliferation of cells in the scaffolds and achieve
minimal cell deterioration.
Implant Research
Using Co-Cultures in Animal Studies
Benefits at a glance
...(1)
• Accelerates cell growth, differentiation and cell proliferation, mimicking native
extracellular matrix (ECM), hastening time to result
• Ideal for slow growing cells and of cell co-cultures
• Supports homogenous cell culture at the surface and core of the 3D scaffolds
and microcarriers
• Maintains functionality and viability of co-cultures and tissue constructs
(implants)
Benefits at a glance
...(2)
• Reduces formation of necrotic neo-tissue that interferes with subsequent
implantation process
• For stem cells expansion on microcarriers, a 16-fold cell number increase was
in observed on day 14
• In bone cells, TisXell provided a 25 - 35 % increase in cell proliferation
• On-going research highlights marked proliferation of cell growth in heart patch
research and animal co-culture studies. TisXell undoubtedly, will prove
beneficial to a wide ranging cell-based research
Thank you for attention!
Helpful links:
http://www.quinxell.com
http://www.rowiak.de
Ask for scientific publications!