Introduction

Biological cells are fundamental building blocks of tissues and organs of living organisms.1 Over their lifetimes, cells are responsible for the development, programmed remodeling, and regeneration of tissues and organs. In addition, cells play crucial physiological roles, such as transport of oxygen and carbon dioxide, signal transduction, muscle contraction/ relaxation, homeostasis, immune response, and metabolic activities. In addition, a number of chronic and malignant diseases result from a wide range of genetic abnormalities and the conversion of normal cells to cancer cells.

Therefore, cells have been studied extensively as biomarkers for early detection, therapeutic targets, and even as sources for regenerative medicine that can take current levels of diagnosis and disease treatment to the next level.2–7 In these efforts, cells are typically isolated from tissues of interest and cultured in vitro. Alternatively, various pluripotent and multipotent stem cells are being studied to generate specific cell types for use both in understanding their diverse emergent behavior and for treating disease and tissue defects via their in vivo transplantation.8–10 Efforts to directly convert fibroblasts (main component of connective tissue) to neuronal cells (i.e., nerve cells) are also under way.11, 12 Additionally, these cells are actively being used to assemble in vitro platforms, such as “body-on-a chip” that can screen newly designed drug molecules, including recombinant proteins and genes.13, 14 From these studies, there is a growing consensus that the successful use of cells in fundamental studies and translational clinical treatments greatly depends on the ability to retain cell viability and to regulate cellular activities in a controllable and predictable manner.

It is well understood that the diverse activities of cells, including growth, gene expression, migration, differentiation, and even programmed death, are regulated by multifaceted extracellular microenvironmental factors and genetic influences (Figure 1). The characteristics of the microenvironment include various soluble biochemical factors, biochemical and biomechanical properties of the surrounding extracellular matrix, and intercellular adhesion.15–22 These factors also influence cellular binding and uptake of drug molecules and subsequent therapeutic activities.23, 24 Major goals in the regenerative medicine field have been to recapitulate the extracellular microenvironment in vitro for specific diagnostic applications. In addition, a major goal for in vivo applications to regenerate damaged or diseased tissue has been to recapitulate specific tissue functions in vivo by first developing proper in vitro cell culture and subsequent in vivo transplantation tools and biomolecular carriers.21, 25–27 Aligned with these efforts, various materials, either alone or integrated with other engineering devices such as microelectromechanical systems, are also being explored to analyze and control chemical, mechanical, and biological interactions inside and between cells.28–34

Figure 1
figure 1

Cross-talk between a cell and its extracellular microenvironment including soluble ligands (e.g., growth factors, cytokines), extracellular matrix (ECM), and external mechanical force. Various soluble ligands in biological fluids and insoluble ligands of the ECM activate or deactivate cellular signaling responsible for force generation, secretion of enzymes (e.g., metalloproteinase to soften ECM and transglutaminase to stiffen ECM), and secretion of other soluble ligands.

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Interactive biological materials

For the last few decades, there has been significant growth in designing such interactive biological materials by introducing or creating novel materials chemistry, characterization, and processing techniques. For instance, materials designed to present cell adhesion ligands found in the native extracellular matrix with mechanical properties similar to specific tissues were found to improve viability, modulate cellular adhesion machinery, and further stimulate or inhibit diverse cellular activities of various normal and pathologic cells.35–37 Additionally, various nanoscale materials (e.g., bioconjugated quantum dots, superparamagnetic iron oxide nanoparticles, carbon nanotubes) with unique photonic activities, as well as microfabricated materials coupled with electromechanical sensors were proposed to analyze cellular mechanics and signaling.31, 38–43 To this end, nano-sized biomolecular carriers were developed to facilitate binding to target cells and subsequent intracellular drug transport (Figure 2).44–47However, there are still significant grand challenges in assembling such material systems that interface with biological cells. These challenges include overcoming both the difficulty of assembling multifunctional materials at varied length scales and the limited controllability of the feedback mechanism between cells and materials, and realizing the ability to sense and detect cellular near- to mid-term activities in vivo.

Figure 2
figure 2

Multifunctional nanoparticles devised to image and treat target cells and tissues. Particles are loaded with image contrast agents and drugs or interests and their surfaces are engineered to present peptides or proteins that can specifically bind with proteins overexpressed by target cells and tissues. Note: MRI, magnetic resonance imaging; CT, computed tomography.

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This issue of MRS Bulletin addresses these scientific and engineering challenges. The articles in this issue first critically explore the design of materials that have proved capable of reporting biological activities of cells, and second, identify challenges that are currently being faced. In addition, recent work that incorporates molecular and cellular biology techniques, specifically genetic engineering and strategies that harness the immune system into materials design, is described. The articles also include a discussion of opportunities for the future development of multifunctional materials for sensing and therapies. Finally, clinical perspectives and opportunities for the future development of these materials are discussed.

Overview of the articles

Kuo and Smith discuss perspectives on natural tissues as materials and also discuss how to develop novel synthetic materials that guide cell function. Next, Lewis et al. introduce efforts to design materials capable of modulating the immune response: (1) materials capable of suppressing immune response and (2) materials capable of activating or enhancing immune response. Then, Mastria and Chilkoti present a body of work based on genetically encoded elastin-like polypeptides that offer a route to modular, multifunctional drug delivery systems. Hwang et al. discuss the area of nanotheranostics and give examples of their recent work on genetic modification of cells and molecular imaging. Lee et al. introduce material considerations for vascularized organs-on-a chip, which is rapidly emerging as a promising tool for fundamental and applied biological studies. Finally, Gomes et al. present their perspective on the potential barriers for translating gene therapies into clinical practice and what must be overcome for clinical translation.