Combinatorial screen of dynamic mechanical stimuli for predictive control of MSC mechano-responsiveness

Abstract

Mechanobiological-based control of mesenchymal stromal cells (MSCs) to facilitate engineering and regeneration of load-bearing tissues requires systematic investigations of specific dynamic mechanical stimulation protocols. Using deformable membrane microdevice arrays paired with combinatorial experimental design and modeling, we probed the individual and integrative effects of mechanical stimulation parameters (strain magnitude, rate at which strain is changed, and duty period) on myofibrogenesis and matrix production of MSCs in three-dimensional hydrogels. These functions were found to be dominantly influenced by a previously unidentified, higher-order interactive effect between strain magnitude and duty period. Empirical models based on our combinatorial cue-response data predicted an optimal loading regime in which strain magnitude and duty period were increased synchronously over time, which was validated to most effectively promote MSC matrix production. These findings inform the design of loading regimes for MSC-based engineered tissues and validate a broadly applicable approach to probe multifactorial regulating effects of mechanobiological cues.

An oral hydrogel carrier for delivering resveratrol into intestine-specific target released with high encapsulation efficiency and loading capacity based on structure-selected alginate and pectin

“…Multivariate optimization methods were employed to obtain the optimal conditions. 26 Firstly, different types of ALG and pectin must be selected, which might influence the physical and chemical properties of the produced hydrogel carrier. The results are shown in Fig.…”

Advanced Robotics to Address the Translational Gap in Tendon Engineering

“…While several recent studies have provided alternative approaches to actuating their bioreactors, the constructs lack physiologic relevance given that these systems largely rely on uniaxial loading, involve tissue constructs that are not representative of an anatomic location for the tissue construct to be used in and offer inadequate mechanical load to tissue constructs. The diaphragm pump and pressure regulator system used in Liu et al's study allowed for the tissue construct to receive compressive mechanical stimulation by cyclic bulging and deformation of the membrane the tissue was cultured upon [ 64 ]. Raimondi et al proposed a bioreactor which provided pulsatile shear stress and uniaxial tensile loading using an electromagnetic actuator.…”

“…With longer experiments, it would also be beneficial to explore the effect of incrementally increasing loading throughout the culture. It has been shown that incremental loading is necessary for sustained improvement in the mechanical properties of MSK tissues [ 64 ]. The capability of the humanoid robot presented in Mouthuy et al's study to offer multiple force loading regimes consistent with estimated quantities of force in human tendon during abduction is promising for the eventual development of physiologically relevant tissue constructs [ 87 – 90 ].…”

Bidirectional Differentiation of Human-Derived Stem Cells Induced by Biomimetic Calcium Silicate-Reinforced Gelatin Methacrylate Bioink for Odontogenic Regeneration

“…It was hypothesized that the increase in stress-strain was due to the increased covalent bonds provided by CS, as shown in the results above. The mechanical properties of scaffolds are known to affect cellular functions, extracellular matrix remodeling, and cellular differentiation [39]. In addition, the increase in tensile stress-strain allows for better manipulation during surgery and for better adaptation to native pressures.…”