BIO-ARTIFICIAL LIVER Alan Golde Jr. BME181 March 18

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Transcript BIO-ARTIFICIAL LIVER Alan Golde Jr. BME181 March 18

BIO-ARTIFICIAL LIVER
(EXTRACORPOREAL TEMPORARY LIVER SUPPORT DEVICES)
Alan Golde Jr.
BME181
March 18th 2013
The Liver
• Largest internal organ
• From 1.2-1.6kg (3.2-3.7lb)
• Hepatic cells (hepatocytes) responsible for
liver functions
• Make up 80% of the liver
• Liver is responsible for up to 500 separate
functions
• Removing/excreting body wastes and hormones as well
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as drugs and other foreign substances
Synthesizing plasma proteins, including those
necessary for blood clotting
Helping the body fight infection
Producing bile to aid in digestion
Storing certain vitamins, minerals, and sugars
• Regenerative
• Restoration of function not original form
Complications
• Most common causes of liver failure
• hepatitis A,B,C,D,E
• Alcohol damage
• Fatty liver
• Cirrhosis
• Cancer and drug damage
Treatments
Liver Transplant
• Pros
• Most effective treatment for acute liver failure
• High survival rates
• Cons
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Scarcity of donors
Reduced clotting factors
Immunosuppressant's increase risk for infection
Rejection
Bio-artificial Liver
• Pros
• Keep the patient alive until transplant is available
• Aid in the livers regeneration
• Cons
• Are only a temporary fix
Current Work in BAL’s
• Molecular Absorbent Recycling System (MARS®)
• Teraklin, uses human albumin
• Extracorporeal Liver Assist Device (ELAD®)
• Vitagen, uses immortalized human hepatocytes
• HepatAssist 2000 system
• Circe Biomedical, uses porcine hepatocytes
• Bioartificial Liver Support System (BLSS®)
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Excorp Medical, Inc., uses primary porcine hepatocytes
• LIVERX2000 system
• Algenix, Inc., uses porcine hepatocytes
• Modular Extracorporeal Liver System (MELS®)
• Charite Virchow Clinic-Berlin, uses human hepatocytes
Bio Engines Implantable Device
• Designed to take place of a liver or a
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portion of the liver
Polymer grid-like mesh used as artificial
vasculature resembling that of an actual
liver
Patterned silicon wafers serve as molds
for polymer sheets
Currently being tested on pigs
Clotting issues
Challenges
• Bio-artificial livers should be able to provide at least 10% of liver functioning
• This requires approximately 1010 hepatocytes
• Very difficult acquiring this many hepatocyte cells
• Controversy over the use of porcine cells due to possible transmission of
infections
• Hepatocytes and plasma have very different physio-chemical properties
• Hepatocytes do not perform well when in contact with plasma
• Have a very high oxygen uptake rate
• Hepatocyte cells undergo a lot of stress inside of bio-artificial liver
• Any stress above 5 dyn/cm2 renders cells useless
• Limited volume of the bioreactor
• maximum blood/plasma that can be safely drawn out of liver failure patient is one liter
• Difficult to achieve 10% of liver functioning within 1 liter
• Makes Bio-artificial liver designing very difficult
Future
• Research in:
• Cell sources
• Bioreactor design
• Filtering techniques
• Packaging for implantable devices
Sources
• http://biomed.brown.edu/Courses/BI108/BI108_2002_Groups/liver/we
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bpage/intro.html
Palakkan, A. A., Hay, D. C., PR, A. K., TV, K. and Ross, J. A. (2013),
Liver tissue engineering and cell sources: issues and challenges.
Liver International. doi: 10.1111/liv.12134
http://www.xconomy.com/boston/2007/09/20/bioengine-one-stepcloser-to-artificial-liver-device/
http://nyp.org/news/hospital/artificial-liver-lives.html
http://artificial-liver.blogspot.com/2009/11/biological-extracorporealliver-assist.html