Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell-Extracellular Matrix Interactions.

In bone tissue engineering, the design of in vitro models able to recreate both the chemical composition, the structural architecture, and the overall mechanical environment of the native tissue is still often neglected. In this study, we apply a bioreactor system where human bone-marrow hMSCs are seeded in human femoral head-derived decellularized bone scaffolds and subjected to dynamic culture, i.e., shear stress induced by continuous cell culture medium perfusion at 1.7 mL/min flow rate and compressive stress by 10% uniaxial load at 1 Hz for 1 h per day. In silico modeling revealed that continuous medium flow generates a mean shear stress of 8.5 mPa sensed by hMSCs seeded on 3D bone scaffolds. Experimentally, both dynamic conditions improved cell repopulation within the scaffold and boosted ECM production compared with static controls. Early response of hMSCs to mechanical stimuli comprises evident cell shape changes and stronger integrin-mediated adhesion to the matrix. Stress-induced Col6 and SPP1 gene expression suggests an early hMSC commitment towards osteogenic lineage independent of Runx2 signaling. This study provides a foundation for exploring the early effects of external mechanical stimuli on hMSC behavior in a biologically meaningful in vitro environment, opening new opportunities to study bone development, remodeling, and pathologies.

Shape-Morphing Fibrous Hydrogel/Elastomer Bilayers Fabricated by a Combination of 3D Printing and Melt Electrowriting for Muscle Tissue Regeneration.

This paper reports an approach for the fabrication of shape-changing bilayered scaffolds, which allow the growth of aligned skeletal muscle cells, using a combination of 3D printing of hyaluronic acid hydrogel, melt electrowriting of thermoplastic polycaprolactone-polyurethane elastomer, and shape transformation. The combination of the selected materials and fabrication methods allows a number of important advantages such as biocompatibility, biodegradability, and suitable mechanical properties (elasticity and softness of the fibers) similar to those of important components of extracellular matrix (ECM), which allow proper cell alignment and shape transformation. Myoblasts demonstrate excellent viability on the surface of the shape-changing bilayer, where they occupy space between fibers and align along them, allowing efficient cell patterning inside folded structures. The bilayer scaffold is able to undergo a controlled shape transformation and form multilayer scroll-like structures with cells encapsulated inside. Overall, the importance of this approach is the fabrication of tubular constructs with a patterned interior that can support the proliferation and alignment of muscle cells for muscle tissue regeneration.

A bioartificial rat heart tissue: Perfusion decellularization and characterization.

Despite remarkable advancement in the past decades, heart-related defects are still prone to progress irreversibly and can eventually lead to heart failure. A personalized extracellular matrix-based bioartificial heart created by allografts/xenografts emerges as an alternative as it can retain the original three-dimensional architecture combined with a preserved natural heart extracellular matrix. This study aimed at developing a procedure for decellularizing heart tissue harvested from rats and evaluating decellularization efficiency in terms of residual nuclear content and structural properties. Tissue sections showed no or little visible cell nuclei in decellularized heart, whereas the native heart showed dense cellularity. In addition, there was no significant variation in the alignment of muscle fibers upon decellularization. Furthermore, no significant difference was detected between native and decellularized hearts in terms of fiber diameter. Our findings demonstrate that fiber alignment and diameter can serve as additional parameters in the characterization of biological heart scaffolds as these provide valuable input for evaluating structural preservation of decellularized heart. The bioartificial scaffold formed here can be functionalized with patient's own material and utilized in regenerative engineering.