TY - JOUR
T1 - A bioartificial liver support system integrated with a DLM/GelMA-based bioengineered whole liver for prevention of hepatic encephalopathy
T2 - Via enhanced ammonia reduction
AU - Wu, Guohua
AU - Wu, Di
AU - Lo, James
AU - Wang, Yimin
AU - Wu, Jianguo
AU - Lu, Siming
AU - Xu, Han
AU - Zhao, Xin
AU - He, Yong
AU - Li, Jun
AU - Demirci, Utkan
AU - Wang, Shuqi
PY - 2020/5/21
Y1 - 2020/5/21
N2 - Although bioartificial liver support systems (BLSSs) play an essential role in maintaining partial liver functions and detoxification for liver failure patients, hepatocytes are unanimously seeded in biomaterials, which lack the hierarchal structures and mechanical cues of native liver tissues. To address this challenge, we developed a new BLSS by combining a decellularized liver matrix (DLM)/GelMA-based bioengineered whole liver and a perfusion-based, oxygenated bioreactor. The novel bioengineered whole liver was fabricated by integrating photocrosslinkable gelatin (GelMA) and hepatocytes into a DLM. The combination of GelMA and the DLM not only provided a biomimetic extracellular microenvironment (ECM) for enhanced cell immobilization and growth with elevated hepatic functions (e.g., albumin secretion and CYP activities), but also provided biomechanical support to maintain the native structure of the liver. In addition, the perfusion-based, oxygenated bioreactor helped deliver oxygen to the interior tissues of the bioengineered liver, which was of importance for long-term culture. Most importantly, this new bioengineered whole liver decreased ammonia concentration by 45%, whereas direct seeding of hepatocytes in a naked DLM showed no significant reduction. Thus, the developed BLSS integrated with the DLM/GelMA-based bioengineered whole liver can potentially help elevate liver functions and prevent HE in liver failure patients while waiting for liver transplantation.
AB - Although bioartificial liver support systems (BLSSs) play an essential role in maintaining partial liver functions and detoxification for liver failure patients, hepatocytes are unanimously seeded in biomaterials, which lack the hierarchal structures and mechanical cues of native liver tissues. To address this challenge, we developed a new BLSS by combining a decellularized liver matrix (DLM)/GelMA-based bioengineered whole liver and a perfusion-based, oxygenated bioreactor. The novel bioengineered whole liver was fabricated by integrating photocrosslinkable gelatin (GelMA) and hepatocytes into a DLM. The combination of GelMA and the DLM not only provided a biomimetic extracellular microenvironment (ECM) for enhanced cell immobilization and growth with elevated hepatic functions (e.g., albumin secretion and CYP activities), but also provided biomechanical support to maintain the native structure of the liver. In addition, the perfusion-based, oxygenated bioreactor helped deliver oxygen to the interior tissues of the bioengineered liver, which was of importance for long-term culture. Most importantly, this new bioengineered whole liver decreased ammonia concentration by 45%, whereas direct seeding of hepatocytes in a naked DLM showed no significant reduction. Thus, the developed BLSS integrated with the DLM/GelMA-based bioengineered whole liver can potentially help elevate liver functions and prevent HE in liver failure patients while waiting for liver transplantation.
UR - http://www.scopus.com/inward/record.url?scp=85085264974&partnerID=8YFLogxK
U2 - 10.1039/c9bm01879d
DO - 10.1039/c9bm01879d
M3 - Journal article
C2 - 32307491
AN - SCOPUS:85085264974
VL - 8
SP - 2814
EP - 2824
JO - Biomaterials Science
JF - Biomaterials Science
SN - 2047-4830
IS - 10
ER -