Static and Dynamic Biomaterial Engineering for Cell Modulation

Abstract

In the biological microenvironment, cells are surrounded by an extracellular matrix (ECM), with which they dynamically interact during various biological processes. Specifically, the physical and chemical properties of the ECM work cooperatively to influence the behavior and fate of cells directly and indirectly, which invokes various physiological responses in the body. Hence, efficient strategies to modulate cellular responses for a specific purpose have become important for various scientific fields such as biology, pharmacy, and medicine. Among many approaches, the utilization of biomaterials has been studied the most because they can be meticulously engineered to mimic cellular modulatory behavior. For such careful engineering, studies on physical modulation (e.g., ECM topography, stiffness, and wettability) and chemical manipulation (e.g., composition and soluble and surface biosignals) have been actively conducted. At present, the scope of research is being shifted from static (considering only the initial environment and the effects of each element) to biomimetic dynamic (including the concepts of time and gradient) modulation in both physical and chemical manipulations. This review provides an overall perspective on how the static and dynamic biomaterials are actively engineered to modulate targeted cellular responses while highlighting the importance and advance from static modulation to biomimetic dynamic modulation for biomedical applications.

Keywords: biomaterial engineering; biomedical engineering; cell modulation; dynamic modulation; static modulation.

Figure 1

Trends in biomaterials research. Biomaterials can be largely divided into three generations. First-generation biomaterials are bioinert materials, and the focus is on the biocompatibility of the materials themselves. Second-generation biomaterials are bioactive materials that, in addition to being harmless to the body, have specific functions through the physical and chemical modification of the material surface and drug release. Third-generation biomaterials are bio-responsive materials that can organically react with living organisms to surroundings or specific stimuli. In particular, the concept of stimulation or viewpoint control is introduced, dynamic control is possible, and biomedical materials are moving toward those with two-way rather than one-way functionality. The processing scale of biomaterials decreases to the nano level, the complexity gradually increases, and the functionality becomes complex.

Figure 2

Methods of controlling biomaterials for cell modulation. Biomaterials can be classified as physical-oriented or chemical-oriented depending on their effects on cells. They can then be further classified as static or dynamic. Typical examples of static-physical modulation include static topology, static stability, and static environment (e.g., temperature, electrical/magnetic field), while examples of static-chemical modulation include chemical composition, solid biosignals, and surface-immobilized biosignals. Dynamic modulation enables surface property change, dynamic release, dynamic interaction, and dynamic stimulation through additional cues, such as light, electric/magnetic fields, ultrasonic, and deformation, based on static modulation.

Figure 3

Complex interactions during cellular behavior modulation. (A) The physical and chemical properties of the ECM determine cell fates through a variety of mechanisms, such as direct interaction, intracellular signaling, direct nuclear signaling, and mechano-sensitivity signaling. (B) Example of dynamic modulation using magnetic stimuli. Schematic of genetic encoding of Piezo1 by Ad-Piezo1 with human cytomegalovirus (CMV) promotor and its magnetomechanical gating with specifically targeted m-Torquer with Myc antibody. Reproduced with permission from [92]. Copyright Nature Materials, 2021. (C) Confocal microscope images of Piezo1-expressing neuron (DAPI, nucleus; CellTracker, cytosol; Myc, Piezo1, m-Torquer (red); neuron). (1) and (2) are Z-sectioned images. Reproduced with permission from [92]. Copyright Nature Materials, 2021.