Porcine hepatocytes culture on biofunctionalized 3D inverted colloidal crystal scaffolds as anin vitromodel for predicting drug hepatotoxicity

Abstract

As drug-induced hepatotoxicity represents one of the most common causes of drug failure, three-dimensional in vitro liver platforms represent a fantastic toolbox to predict drug toxicity and reduce in vivo studies and drug attrition rates.

Recent advances in the development of in vitro liver models for hepatotoxicity testing

“…Scaffold materials generally should have the following characteristics: (1) a 3D porous structure that can facilitate cell growth and timely supply of nutrients and then discharge metabolic waste; (2) good biocompatibility that can promote cells to grow, proliferate, and adhere, and easily degrade in the body; (3) plasticity; (4) the ability to bind to the ECM naturally and better reshape the body [56]. For liver tissue construction, nanofibers [57][58][59], hydrogels [60][61][62], and a decellularized liver matrix [63][64][65][66] have been used as suitable ECMs for hepatocyte culture, maintenance of hepatocyte function, or promotion of liver differentiation of stem cells for drug hepatotoxicity testing (Fig. 3).…”

“…To construct liver extracellular matrix in vitro, biomimetic properties and soft materials are required, and thus hydrogels are a good option [60,61,69]. Moreover, the cells in hydrogels have a 3D environment that is similar to natural tissues.…”

“…Hydrogels are of two types, natural and synthetic. Synthetic hydrogels, such as polyethylene glycol (PEG) [60,69] and polypropylene amine (PAAm) [61], are artificial hydrogels with a defined composition and a strong mechanical structure which are widely used. For example, a biofunctionalized 3D inverted colloidal crystal (ICC) hydrogel platform was used to establish an in vitro liver model for assessment of drug hepatotoxicity (Fig.…”

“…For example, a biofunctionalized 3D inverted colloidal crystal (ICC) hydrogel platform was used to establish an in vitro liver model for assessment of drug hepatotoxicity (Fig. 3b) [60]. Here, poly(ethylene glycol)diacrylate (PEGDA) ICCs were modified with either collagen type I or fibronectin, and then hepatocytes were cultured on this scaffold.…”

Thermoresponsive Inverted Colloidal Crystal Hydrogel Scaffolds for Lymphoid Tissue Engineering

“…Recent studies have considered the liver as a lymphoid tissue as it supports prenatal hematopoiesis and postnatal extramedullary hematopoiesis under the bone marrow stress, in addition to harboring antigen presenting cells and coordinating immune responses . ICC scaffolds have also demonstrated unique advantages to creating liver tissue in vitro . A common anatomical feature across these lymphoid tissues is a stromal network embedded within a microporous 3D ECM meshwork .…”