Biomaterial-based cell delivery strategies to promote liver regeneration

Abstract

Chronic liver disease and cirrhosis is a widespread and untreatable condition that leads to lifelong impairment and eventual death. The scarcity of liver transplantation options requires the development of new strategies to attenuate disease progression and reestablish liver function by promoting regeneration. Biomaterials are becoming an increasingly promising option to both culture and deliver cells to support in vivo viability and long-term function. There is a wide variety of both natural and synthetic biomaterials that are becoming established as delivery vehicles with their own unique advantages and disadvantages for liver regeneration. We review the latest developments in cell transplantation strategies to promote liver regeneration, with a focus on the use of both natural and synthetic biomaterials for cell culture and delivery. We conclude that future work will need to refine the use of these biomaterials and combine them with novel strategies that recapitulate liver organization and function in order to translate this strategy to clinical use.

Liver Regeneration and Cell Transplantation for End-Stage Liver Disease

“…Hepatocytes constitute 70% of total liver cells. As the major cell type in the liver, hepatocytes play a vital role in detoxification, metabolism, and coagulation [ 4 ]. KCs are the resident macrophages of the liver, representing about 20% of the nonparenchymal cells.…”

“…Aside from KCs, the liver is also enriched in numerous innate and adaptive immune cells, including natural killer cells (NK cells), natural killer T (NKT cells), neutrophils, γδT cells, dendritic cells (DCs), innate lymphoid cells (ILC), conventional αβT cells and B cells, which help to maintain the homeostasis of immune defense [ 5 ]. HSCs play a role in storing vitamin A and lipids; once injury occurs, HSCs might differentiate into myofibroblasts [ 4 ]. LSECs represent approximately 15 to 20% of the liver cells.…”

“…Cell transplantation is one of the most promising regenerative medicine strategies for treatment of ESLD. A wide variety of cell types can be transplanted to achieve liver regeneration enhancement [ 4 ].…”

“…However, human ESCs are not yet readily used in clinics due to ethical concerns. iPSCs are generally derived from the reprogramming of mature somatic cells, which exhibit ESC features and advantages over ESCs for in vitro hepatocyte differentiation and maturation [ 4 ]. The breakthrough in generating iPSCs has not only overcomes the ethical issues and histological incompatibility associated with ESCs, but also enables correction of gene defects prior to cell transplantation [ 43 ].…”

Suture Fiber Reinforcement of a 3D Printed Gelatin Scaffold for Its Potential Application in Soft Tissue Engineering

“…In order to satisfy these issues, the concept of a "biofabrication window" was introduced [11]. Based on this biofabrication window concept (for improving the physical and biological properties of biomaterial ink), various natural polymer biomaterial inks have been studied [12][13][14][15]. Gelatin, one of these natural polymers, is a powerful candidate material for biomaterial ink because it has a chemical structure and biological properties resembling those of collagen and includes a cell adhesion motif (Arg-Gly-Asp) [16,17].…”