Engineering 3D Hydrogels for Personalized In Vitro Human Tissue Models

Abstract

There is a growing interest in engineering hydrogels for 3D tissue and disease models. The major motivation is to better mimic the physiological microenvironment of the disease and human condition. 3D tissue models derived from patients' own cells can potentially revolutionize the way treatment and diagnostic alternatives are developed. This requires development of tissue mimetic hydrogels with user defined and tunable properties. In this review article, a recent summary of 3D hydrogel platforms for in vitro tissue and disease modeling is given. Hydrogel design considerations and available hydrogel systems are summarized, followed by the types of currently available hydrogel models, such as bulk hydrogels, porous scaffolds, fibrous scaffolds, hydrogel microspheres, hydrogel sandwich systems, microwells, and 3D bioprinted constructs. Although hydrogels are utilized for a wide range of tissue models, this article focuses on liver and cancer models. This article also provides a detailed section on current challenges and future perspectives of hydrogel-based tissue models.

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

“…Natural hydrogels including polysaccharides, proteins, and animal‐derived mixtures are frequently used for cell culture due to their biodegradability, physiochemical properties, and capability of gelling in mild conditions . They are either ECM‐derived components or ECM analogues, of which the chemical composites and fibrous structure are similar to that of native ECM.…”

“…Polysaccharides with fast gelation properties are appropriate for the fabrication of complex 3D scaffolds with various morphologies, such as microfibers, microspheres, membranes, and defined blocks, thus providing architectural cues for tissue/organ constructs in vitro. The natural proteins used as cell culture matrices are collagen, gelatin, fibrin, silk protein (mainly referring to silk fibroin), poly‐ l ‐lysine (PLL), and soy protein . These proteins can interact with cells and supply physiologically relevant microenvironments to guide cellular behaviors by presenting componential cues .…”

“…The natural proteins used as cell culture matrices are collagen, gelatin, fibrin, silk protein (mainly referring to silk fibroin), poly‐ l ‐lysine (PLL), and soy protein . These proteins can interact with cells and supply physiologically relevant microenvironments to guide cellular behaviors by presenting componential cues . In addition, Matrigel and decellularized extracellular matrices (dECM) are typical animal‐derived mixtures of various polysaccharides (e.g., HA and heparan), proteins (e.g., collagen and laminin), and growth factors.…”

“…These proteins can interact with cells and supply physiologically relevant microenvironments to guide cellular behaviors by presenting componential cues . In addition, Matrigel and decellularized extracellular matrices (dECM) are typical animal‐derived mixtures of various polysaccharides (e.g., HA and heparan), proteins (e.g., collagen and laminin), and growth factors. Usually, they render the biocompatibility and bioactivity of specific tissues that matter in cell survival and growth.…”

“…Hydrogels with high water content can mimic the native ECM microenvironment by spatiotemporal control over biochemical and physical cues due to their high biocompatibility and tunable properties, such as permeability, elasticity, stiffness and chemical reactivity. Various natural and synthetic hydrogels have been utilized to generate tissues by guiding a series of cellular behaviors (e.g., cell adhesion, proliferation, differentiation) in 3D cell culture. Particularly, chemically defined hydrogels can serve as biomimetic matrix or scaffold for instructing 3D tissues formation in organoids and OOC systems.…”