Transcript October 27, 2015 Team 6 (Abhinav Rawat, Sithalechumi Narayanan)

Bioengineering in Healthcare
BINF 704, Fall 2015
Team #6
Abhinav Rawat
Sithalechumi Narayanan
Outline
• Introduction
• Materials and Methods
– Emergence of Biomaterials in Healthcare
– Third Generation Biomaterial and Their Applications in
Healthcare
• Advantages of Bioengineering
• Case Studies
- Myocardial Tissue engineering
- Bioengineered Blood Vessel
•
•
•
•
Disadvantages of Bioengineering
Conclusion
Reference
Questions
Introduction
• Bioengineering encompasses two closely related
areas of interest
– it applies the principles of engineering science to
understand how living organisms function and
– it applies engineering technologies to design and
develop new devices like diagnostic or therapeutic
instruments or formulation of novel biomaterials for
medical applications, design of artificial tissues or
organs and development of new delivery systems.
• Overall bioengineering focuses on the uses of
biomaterials or similar types of materials or
principles to improve the healthcare services
Introduction Cont..
• Biomaterial in medical terminology is “any natural or
synthetic material (which includes polymer or metal)
that is intended for introduction into living tissue
especially as part of a medical device or implant” .
• So in general biomaterials are the devices those are
used to improve the general healthcare of society and
are fabricated by the process that employs or mimics
biological phenomenon.
• They are being used for the healthcare applications
from ancient times. But subsequent evolution has
made them more versatile and has increased their
utility.
Introduction Cont…
Biting ants where used as Surgical sutures in 9500 B.C to hold human tissue
together.
The Mayans in 600 A.D used Blue Narce Shell as a way of fixing a lost or
damaged tooth.
Introduction Cont…..
Emergence of Biomaterials in
Healthcare
• Biomaterials are being used in healthcare area from a long period of time.
However, visible progress was made in the area of biomaterials since
1940s and substantial development has been observed in therapeutic
medical technologies and implant devices over the past 25 years.
• Over the years there is a transition from the use of metals to natural
tissues or their derivatives and mechanical valves are being replaced by
prosthetic valves made from bovine tissue or harvested porcine valves.
Cont…
• Developments with sensor technology and software algorithms have now
enabled the pacemakers (for Arrhythmia, irregular heart beat) to
automatically respond to varied levels of patient’s physical activity so that
they can alter the stimulation rate accordingly.
Cont…
• As the blood brain barrier does not allow
medication to enter the central nervous
system (CNS), fully implanted programmable
pumps are used to deliver precise doses of
drugs like morphine to reduce severe pain.
One of the most remarkable applications of
biomedical engineering in the area of healthcare over
last decade is deep brain stimulation for the treatment
of degenerative diseases like Parkinson. These
implantable pumps are also being used for the
treatment of non-malignant and cancer pain.
Third Generation Biomaterial and
Their Applications in Healthcare
First generation of biomaterials evolved
during 1950s and 1970s for their
application as medical implants. Basic
goal during the fabrication of these
biomaterials was to maintain a balance
between physical and mechanical
properties together with minimal toxicity
to host tissue.
Ideal properties of the first generation
biomaterials sought by surgeons were (1)
appropriate mechanical properties; (2)
resistance to corrosion in aqueous
environment; and (3) should not elicit
toxicity or carcinogenicity in living tissue.
1960 Charnley uses PMMA, ultrahighmolecular-weight polyethyl end, and
stainless steal for total hip replacement.
Second Generation
•
Second generation biomaterials were developed to be
bioactive.
• A substantial progress was observed in the application of
these materials for orthopedic and dental usage.
• Examples include bioactive glasses, ceramics, glass-ceramics
and composites.
Third Generation
• Further developments with the biomaterial technology are now
translating into the expansion of third generation biomaterials those can
stimulate specific cellular response.
• For example, artificial tissues being fabricated by placing cells within
scaffold materials, which help guide cell proliferation and differentiation.
• . Efforts are also being made to develop scaffolding materials those
possess Nano-scale features in order to mimic the native extracellular
matrix of the host.
• Currently major focus of the researchers is the development of artificial
tissues (as biomaterials) those have architectural features same as the
natural counterpart.
• Development and use of biomaterials is expected to augment in coming
years. New prognostic methods are being developed and are becoming
available to assist the progress of innovative approaches for an affordable
healthcare.
Applications of Bioengineering
Application
For
Myocardial Tissue Engineering
Cardiac Repair
Orthopedic and Musculoskeletal
Medicines
Bone Repair, muscles, tendons
Skin Tissue Regeneration
Skin Repair
Disposable Medical Devices
Biodegradable material
Drug eluting Stents
Deliver Drug in a controlled manner
Implantable Biosensors
Detect and monitor Biomarkers
Polymer Therapeutics
Drug delivery systems
Lab on a Chip
Several Lab Functions on a single chip
Gene Therapy
Repair ailing tissue or organ
Advantages of Bioengineering
• Bioengineering is one of the most viable option which has a
potential to improve the existing healthcare scenario.
• It uses biomaterials and tissue engineering concepts for the
repair of damaged tissue.
• Major goal here is to repair or regenerate the tissue or
organ than to remove it.
• Bioengineering has also shown a good progress in
diagnostics and newer methods are being developed which
can make the detection easy and accurate.
• With the current progress in biomaterials we expect a
future healthcare which will be available at an affordable
price and with better services.
Outline
• Introduction
• Materials and Methods
– Emergence of Biomaterials in Healthcare
– Third Generation Biomaterial and Their Applications in Healthcare
• Advantages of Bioengineering
• Case Studies
- Myocardial Tissue engineering
- Bioengineered Blood Vessel
•
•
•
•
Disadvantages of Bioengineering
Conclusion
Reference
Questions
Case study 1 – Myocardial Tissue
Engineering
• Recently tissue engineering is evolving as a potential therapy
for cardiac repair. Research activities have attempted to
regenerate the ailing heart with epicardial implantation of
bioengineered tissue patch pre-seeded with bone marrow
cells or BM-derived mesenchymal stem cells.
• Both natural and synthetic polymers like collagen, fibrin, PGA,
PLGA etc are being used for these applications. Animal
derived tissues like bovine pericardia in combination with
engineered cell sheet to create a sandwich like cardiac patch
is also being used to regenerate ischemic heart in rat model.
Schematic representation of use of cardiac
bandages/patches for treatment of ischemic heart
Whole heart bioengineering?
• Scientists at the MMRL are at the leading edge in the quest to
bioengineer a human heart for transplantation.
• The team has two ultimate goals.
- One, to further advance the methodology and generate acellular heart
scaffolds of human size.
- Two, to repopulate these acellular heart constructs with heart cells
derived from the skin of patients and ultimately generate fully functional
human-size hearts suitable for transplantation.
• The Director of the Stem Cell Center at the MMRL, is working
to reprogram fibroblasts from human skin biopsies so as to
create billions of heart cells and cardiovascular progenitors
derived from induced-pluripotent stem cell (iPS) that will be
used to repopulate the scaffolds in the process of generating
new hearts.
New scaffold technologies
Hydrogels are the broad
class of cross-linked
polymeric networks those
absorb large amount of
water or any other
biological fluid without
showing any alternations in
their 3-D architecture.
Retention of water by
hydrogels makes them
appropriate for various
biomedical applications.
Hydrogels as Promising Scaffolds for Healthcare
Applications
• A study used rats with damaged hearts and attempted to fix
the damage by injecting their cell-laced hydrogel, “remuscularizing” the area and fixing the characteristic damage
of a heart attack.
• When injected into the hearts of rats, the hydrogel saw about
73% of the stem cells survive, compared with just 12%
survival while suspended in a normal injection fluid.
• This hydrogel allows the cells to live and grow, installing
themselves in the body and integrating healthily. Heartdamaged rats injected with hydrogel-loaded stem cells saw a
15% increase in pumping efficiency for the treated ventricle,
compared with just 8% for regularly used stem cell therapies.
Case Study 2 – Bioengineered Blood
Vessel
Bioengineered Blood Vessel
• A team of doctors at Duke University Hospital helped create a
bioengineered blood vessel and implanted it into the arm of a
patient with end-stage kidney disease.
• The new vein is an off-the-shelf, human cell-based product
with no biological properties that would cause organ
rejection.
• The vein is engineered by cultivating donated human cells on
a tubular scaffold to form a vessel. The vessel is then cleansed
of the qualities that might trigger an immune response.
• When implanted in animals, the vein grafts actually adopt the
cellular properties of a blood vessel. They don’t just elude
rejection; they become indistinguishable from living tissue as
cells grow into the implant.
Few other Case studies
• Regenerating a new kidney – there are hundreds of
thousands of patients suffering from kidney disease.
- NIDDK supported researchers to break new grounds on this
front by first stripping cells from a donor organ and using the
remaining collagen scaffold to help guide the growth of new
tissue. To regenerate viable kidney tissue, researchers seeded
the kidney scaffolds with epithelial and endothelial cells.
- The resulting organ tissue was able to clear metabolites,
reabsorb nutrients, and produce urine both in vitro and in
vivo in rats. The creation of transplantable tissue to
permanently replace kidney function is a leap forward in
overcoming the problems of donor organ shortages and the
morbidity associated with immuno-suppression in organ
transplants.
Few other case studies - continued
• Skin tissue regeneration - Adipose derived stem cells (ADSC’s)
is other potential cell source which has shown a capacity to
stimulate both collagen synthesis and migration of dermal
fibroblasts together with improved wrinkling and wound
healing property in vivo.
• Chronic non-healing diabetic foot ulcers – severe
complication – limb loss. Current standard methods of
treatment are aimed at controlling infection. Healing rates are
poor with standard treatment. A new strategy - tissue
engineering - allowing the application of healthy living skin
cells to assist in the healing process. Dermagraft (Smith &
Nephew) is a neonatal-derived bioengineered tissue
comprised of dermal fibroblasts.
Conclusion
• Current healthcare and diagnostics has many constraints like
it is expensive, has limited accuracy or there is no strategy to
treat some of the diseases (e.g., cancer). So there is a great
demand to improve the current healthcare facilities.
• It is one of the most viable option which has a potential to
improve the existing healthcare scenario. It uses biomaterials
and tissue engineering concepts for the repair of damaged
tissue.
• It has also shown a good progress in diagnostics and newer
methods are being developed which can make the detection
easy and accurate. With the current progress in biomaterials
we expect a future healthcare which will be available at an
affordable price and with better services.
Disadvantages of Bioengineering
Disadvantages of Bioengineering
• One of the main arguments against bioengineering is
that humans are not fit to play the role of god.
• Legal, ethical limits to bioengineering is still debated.
• Expensive
• Requires time consuming research
• On one hand, bioengineering raises hopes for
dramatic improvements in various human conditions.
On the other hand it raises fears of a ‘Brave New
World’ in which the human essence is lost.
Bioengineering – unethical?
Regenerative medicine
can be used to
treat/repair but if it was
to be used to enhance
human race, for
example: germ line
gene therapy, then it
becomes unethical.
Future!!!
References
• Bhat S, Kumar A. Biomaterials and bioengineering tomorrow’s healthcare.
Biomatter. 2013;3(3):e24717. doi:10.4161/biom.24717.
• Marston, WA. Dermagraft, a bioengineered human dermal equivalent for
the treatment of chronic nonhealing diabetic foot ulcer. Expert Rev Med
Devices. 2004 Sep;1(1):21-31.
• http://www.nibib.nih.gov/science-education/science-topics/tissueengineering-and-regenerative-medicine
• https://allscienceconsidered.wordpress.com/2009/11/28/bioengineeringthe-key-to-a-better-life-or-frankensteins-monster/
• http://news.harvard.edu/gazette/story/2007/03/legal-ethical-limits-tobioengineering-debated/
• http://www.extremetech.com/extreme/215033-new-hydrogel-can-keepstem-cells-alive-for-heart-repair
• https://www.mmrl.edu/organ-bioengineering/
• http://www.humacyte.com/press/surgeons-at-duke-university-hospitalimplant-bioengineered-vein/
Questions??