Extracellular matrix (ECM) is a complex cellular environment consisting of proteins, proteoglycans, and other soluble molecules. ECM provides structural support to mammalian cells and a regulatory milieu with a variety of important cell functions, including assembling cells into various tissues and organs, regulating growth and cell-cell communication. Developing a tailored in vitro cell culture environment that mimics the intricate and organized nanoscale meshwork of native ECM is desirable. Recent studies have shown the potential of hydrogels to mimic native ECM. Such an engineered native-like ECM is more likely to provide cells with rational cues for diagnostic and therapeutic studies. The research for novel biomaterials has led to an extension of the scope and techniques used to fabricate biomimetic hydrogel scaffolds for tissue engineering and regenerative medicine applications. In this article, we detail the progress of the current state-of-the-art engineering methods to create cell-encapsulating hydrogel tissue constructs as well as their applications in in vitro models in biomedicine. Keywordsbiopatterning; cell-encapsulating microfluidic hydrogels; cell microenvironment; extracellular matrix; tissue engineering Mimicking the extracellular matrixCells and tissues are routinely cultured in vitro on 2D substrates [1][2][3]. However, it has been demonstrated that cells or tissues cultured on 2D substrates (e.g., tissue culture plates or flasks) do not mimic cell growth in vivo, and fail to express certain tissue-specific genes and proteins at levels comparable to those found in vivo. For instance, it has been found that cell-drug interactions in a 2D culture system do not represent the actual working mechanism in vivo. Thus, 2D culture is not appropriate to be used in in vitro drug testing models. This is due to the fact that cells and tissues in vivo are immersed within a 3D network constituting a complex extracellular environment with a highly porous nanotopography, while a 2D culture system is too simple to mimic the native environment (Table 1).From a tissue engineering (TE) standpoint, constructing a culture environment that closely mimicks the native tissue, which is composed of the extracellular matrix (ECM), soluble bioactive factors, and products of homo-and hetero-typical cell-cell interactions, is desirable to replicate tissue functions in vitro. However, this remains as one of the major challenges in TE, given the complexity of cell-ECM interactions as well as multicellular architectural features such as repeating tissue units and proper vascular structure. Cells commit to their fate by deriving a vast amount of information from this environment. As a part of the cell environment, ECM has been the most emulated component in TE studies. In native tissue, ECM is mainly a mixture of two classes of macromolecules, glycosaminoglycans and fibrous proteins (e.g., collagen, elastin, fibronectin and laminin), which self-assemble into nanofibrillar supramolecular networks that fill the extracellul...

As representative soft materials with widespread applications, gels with various functions have been developed. However, traditional gels are vulnerable to stress-induced formation of cracks. The propagation of these cracks may affect the integrity of network structures of gels, resulting in the loss of functionality and limiting the service life of the gels. To address this challenge, self-healing gels that can restore their functionalities and structures after damage have been developed as "smart" soft materials. In this paper, we present an overview of the current strategies for synthesizing self-healing gels based on the concept of constitutional dynamic chemistry, which involves molecular structures capable of establishing dynamic networks based upon physical interactions or chemical reactions. The characterization methods of self-healing gels and the key factors that affect self-healing properties are analyzed. We also illustrate the emerging applications of self-healing gels, with emphasis on their usage in industry (coatings, sealants) and biomedicine (tissue adhesives, agents for drug or cell delivery). We conclude with a perspective on challenges facing the field, along with prospects for future development.

The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell-microenvironment interactions continue to overturn much early progress in the field. Key challenges continue to be dissecting the roles of chemistry, structure, mechanics, and electrophysiology in the cell microenvironment, and understanding and harnessing the roles of periodicity and drift in these factors. This review encapsulates where recent advances appear to leave the ever-shifting state of the art, and it highlights areas in which substantial potential and uncertainty remain.

Hydrogels find widespread applications in biomedical engineering due to their hydrated environment and tunable properties (e.g., mechanical, chemical, biocompatible) similar to the native extracellular matrix (ECM). However, challenges still exist regarding utilizing hydrogels in applications such as engineering 3D tissue constructs and active targeting in drug delivery, due to the lack of controllability, actuation, and quick‐response properties. Recently, magnetic hydrogels have emerged as a novel biocomposite for their active response properties and extended applications. In this review, the state‐of‐the‐art methods for magnetic hydrogel preparation are presented and their advantages and drawbacks in applications are discussed. The applications of magnetic hydrogels in biomedical engineering are also reviewed, including tissue engineering, drug delivery and release, enzyme immobilization, cancer therapy, and soft actuators. Concluding remarks and perspectives for the future development of magnetic hydrogels are addressed.

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