Dynamically tunable cell culture platforms for tissue engineering and mechanobiology

Abstract

Human tissues are sophisticated ensembles of many distinct cell types embedded in the complex, but well-defined, structures of the extracellular matrix (ECM). Dynamic biochemical, physicochemical, and mechano-structural changes in the ECM define and regulate tissue-specific cell behaviors. To recapitulate this complex environment in vitro, dynamic polymer-based biomaterials have emerged as powerful tools to probe and direct active changes in cell function. The rapid evolution of polymerization chemistries, structural modulation, and processing technologies, as well as the incorporation of stimuli-responsiveness, now permit synthetic microenvironments to capture much of the dynamic complexity of native tissue. These platforms are comprised not only of natural polymers chemically and molecularly similar to ECM, but those fully synthetic in origin. Here, we review recent in vitro efforts to mimic the dynamic microenvironment comprising native tissue ECM from the viewpoint of material design. We also discuss how these dynamic polymer-based biomaterials are being used in fundamental cell mechanobiology studies, as well as towards efforts in tissue engineering and regenerative medicine.

A biomaterial approach to cell reprogramming and differentiation

“…This type of research has shown the possibility for different approaches to activate cellular pathways by enabling proper cell organization and exposure to bioactive surface molecules that can enhance differentiation. By tuning nanotopographical cues, cell behavior can be studied in a dynamic medium that further represents the matrix in which these cells could be applied [82, 83, 84]. …”

Tailored Combinatorial Microcompartments through the Self‐Organization of Microobjects: Assembly, Characterization, and Cell Studies

“…Anunderstanding of the interaction of individual cells and cell clusters with their surrounding and in particular with biomaterials is regarded as key for the development of advanced therapies and approaches not limited to regenerative medicine. [1] In this context, it has been established that cell behavior may differ,f or example,i nt erms of cell adhesion, differentiation, and apoptosis,o nf lat 2D surfaces versus in 3D microwells. [2] Fors creening purposes,a dvanced 3D microarray fabrication techniques have been exploited, for instance in well-based formats for the study of cell-surface topography interactions.These studies revealed the impact of micro-and nanotopographies on metabolic activity,disclosed the mechanisms of biomaterials-induced mechano-transduction, [3] or helped to assess and rationalize the impact of topography on stem cell differentiation.…”

Switchable phase transition behavior of thermoresponsive substrates for cell sheet engineering

“…Hence, maintenance of membrane proteins and ECM integrity is the most obvious advantages of thermoresponsive tissue culture dishes. This generally occurs because of disruption of adhesive junctions between basal side of cultured cells and grafted PNIPAAm layer by temperate trigger …”