Artificial Organs and Bioartificial Liver Devices

Abstract

Acute liver failure (ALF) carries mortality rates of 40-80% without transplantation, yet only 10-15% of listed patients receive donor organs due to critical shortages, creating an urgent need for extracorporeal liver support devices that can bridge patients to transplantation or native liver recovery. Bioartificial liver (BAL) devices combine artificial detoxification (albumin dialysis, plasma exchange) with living hepatocyte bioreactors that provide the synthetic and metabolic functions-- urea synthesis, cytochrome P450 drug metabolism, clotting factor production -- that purely mechanical devices cannot replicate. This study developed and evaluated five liver support configurations -- molecular adsorbent recirculating system (MARS), single-pass albumin dialysis (SPAD), fractionated plasma separation and adsorption (Prometheus), a hollow-fibre hepatocyte bioreactor (HF-BAL), and a proposed hybrid platform combining MARS albumin dialysis with a 3D-bioprinted hepatocyte-laden hydrogel bioreactor (Hybrid-BAL) -- using a validated porcine ALF model (n = 36 Landrace pigs, galactosamine-induced hepatotoxicity). Hybrid-BAL achieved the highest 72-hour survival (83.3%, 5/6 animals) compared to MARS (50.0%, 3/6), Prometheus (33.3%, 2/6), HF-BAL (66.7%, 4/6), and untreated controls (16.7%, 1/6; p = 0.008 vs Hybrid-BAL). Ammonia clearance was 68.4 +- 8.2% for Hybrid-BAL versus 42.6 +- 12.4% for MARS (p = 0.002), while urea synthesis -- absent in purely artificial devices -- reached 4.8 +- 0.6 mg/dL/h in Hybrid-BAL, confirming functional hepatocyte metabolic activity. These results establish the hybrid artificial-bioartificial approach as the most effective extracorporeal liver support strategy and provide a systematic framework for evaluating liver assist devices.