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Integrating carrier drug therapy with recent advances in liver tissue regeneration, this paper proposes a novel nanomedicine-based approach to drug delivery, with the aim of enhancing the regenerative capacity of hepatocytes and improving liver function after partial hepatectomy. The proposed decellularized liver matrix provides excellent biocompatibility and similarity to natural liver components, while the molecules encapsulated in the carrier (tannic acid) promote liver regeneration. In in vitro cultures, the 0.001 mg/mL TA-mPEG-DLM group consistently outperformed the blank group in terms of albumin synthesis: Day 1 (11.1 ± 2.4 vs. 8.2 ± 0.7), Day 3 (5.8 ± 1.3 vs. 4.2 ± 0.4), and Day 5 (1.6 ± 0.3 vs. 1.2 ± 0.2) (μg/100% proliferation rate/well/day). In a liver-injured in vivo model, the 0.5 mg/mL TA-mPEG-DLM group outperformed the blank group in terms of relative liver weight: Day 3 (3.50 ± 0.09% vs. 3.22 ± 0.03%) and Day 7 (4.13 ± 0.21% vs. 3.72 ± 0.06%). Furthermore, the TA-mPEG-DLM group outperformed the blank group in terms of Ki-67 expression in hepatocytes on Day 7 (192.7 ± 34.1% vs. 150.4 ± 11.6%). Taken together, these findings indicate that the proposed drug delivery strategy is a promising approach to liver regeneration following partial hepatectomy with potential for clinical translation. [ABSTRACT FROM AUTHOR]

Although liver cirrhosis is a common condition and cause of death, treatment methods remain limited; for example, instead of facilitating hepatocyte regeneration, they may only alleviate or resolve symptoms. Notably, studies have indicated that liver fibrosis is reversible; moreover, prompt and appropriate treatment can prevent liver fibrosis from developing into liver cirrhosis. In this study, a hepatocyte growth factor (HGF)/heparin-immobilized decellularized liver matrix (HGF/heparin-DLM) was fabricated for hepatocyte regeneration in a model of acute d -galactosamine–induced liver injury. Various initial concentrations (0.2, 0.4, 0.6, 0.8, 1 mg/mL) were used for the immobilization of heparin on DLM films. The amounts of immobilized heparin on the DLM films at these concentrations were 4.7 ± 1.1, 12.2 ± 2.7, 18.2 ± 5.1, 21.9 ± 3.8, and 29.1 ± 1.1 μg/cm2, respectively. The relative viability and albumin synthesis of the hepatocytes on the HGF/heparin-DLM films were 19% and 26% greater than those of the hepatocytes cultured in regular petri dishes on day 3, respectively. The LDH and albumin of the injured hepatocytes on the HGF/heparin-DLM films were 95% lower and almost 2.7 times higher than those cultured in regular petri dishes on day 5, respectively. In sum, the HGF/heparin-DLM films were effective in hepatocyte culturing and repairing d -galactosamine–induced hepatocyte damage. Thus, they have potential for future clinical applications. ● HGF/heparin-DLM films (with hepatocytes) can mimic the microenvironment of the native liver. ● HGF/heparin-DLM films (without hepatocytes) can mitigate d -galactosamine–induced injury. ● The placement of the HGF/heparin-DLM films on the fibrotic liver surface may be a potential therapeutic approach. [ABSTRACT FROM AUTHOR]