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 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

TreatmentsLiver Transplant

• Pros• Most effective treatment for acute liver failure• High survival rates

• Cons• 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®)• 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 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

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-step-closer-to-artificial-liver-device/

• http://nyp.org/news/hospital/artificial-liver-lives.html• http://artificial-liver.blogspot.com/2009/11/biological-extracorporeal-

liver-assist.html