Macrophages serve to maintain organ homeostasis in response to challenges from injury, inflammation, malignancy, particulate exposure, or infection. Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. Using macrophages of different origins and species, we report that macrophage elasticity is a major determinant of innate macrophage function. Macrophage elasticity is modulated not only by classical biologic activators such as LPS and IFN-γ, but to an equal extent by substrate rigidity and substrate stretch. Macrophage elasticity is dependent upon actin polymerization and small rhoGTPase activation, but functional effects of elasticity are not predicted by examination of gene expression profiles alone. Taken together, these data demonstrate an unanticipated role for cell elasticity as a common pathway by which mechanical and biologic factors determine macrophage function.

Cartilage tissue engineering is a promising approach for repairing and regenerating cartilage tissue. To date, attempts have been made to construct zonal cartilage that mimics the cartilaginous matrix in different zones. However, little attention has been paid to the chondrocyte density gradient within the articular cartilage. We hypothesized that the chondrocyte density gradient plays an important role in forming the zonal distribution of extracellular matrix (ECM). In this study, collagen type II hydrogel/chondrocyte constructs were fabricated using a bioprinter. Three groups were created according to the total cell seeding density in collagen type II pre-gel: Group A, 2 × 107 cells/mL; Group B, 1 × 107 cells/mL; and Group C, 0.5 × 107 cells/mL. Each group included two types of construct: one with a biomimetic chondrocyte density gradient and the other with a single cell density. The constructs were cultured in vitro and harvested at 0, 1, 2, and 3 weeks for cell viability testing, reverse-transcription quantitative PCR (RT-qPCR), biochemical assays, and histological analysis. We found that total ECM production was positively correlated with the total cell density in the early culture stage, that the cell density gradient distribution resulted in a gradient distribution of ECM, and that the chondrocytes’ biosynthetic ability was affected by both the total cell density and the cell distribution pattern. Our results suggested that zonal engineered cartilage could be fabricated by bioprinting collagen type II hydrogel constructs with a biomimetic cell density gradient. Both the total cell density and the cell distribution pattern should be optimized to achieve synergistic biological effects.

Methacrylated gelatin (GelMA)/bacterial cellulose (BC) composite hydrogels have been successfully prepared by immersing BC particles in GelMA solution followed by photo-crosslinking. The morphology of GelMA/BC hydrogel was examined by scanning electron microscopy and compared with pure GelMA. The hydrogels had very well interconnected porous network structure, and the pore size decreased from 200 to 10 µm with the increase of BC content. The composite hydrogels were also characterized by swelling experiment, X-ray diffraction, thermogravimetric analysis, rheology experiment and compressive test. The composite hydrogels showed significantly improved mechanical properties compared with pure GelMA. In addition, the biocompatility of composite hydrogels were preliminarily evaluated using human articular chondrocytes. The cells encapsulated within the composite hydrogels for 7 days proliferated and maintained the chondrocytic phenotype. Thus, the GelMA/BC composite hydrogels might be useful for cartilage tissue engineering.

To withstand physiological loading over a lifetime, human synovial joints are covered and protected by articular cartilage, a layer of low-friction, load-bearing tissue. The unique mechanical function of articular cartilage largely depends on the composition and structural integrity of the cartilage matrix. The matrix is produced by highly specialized resident cells called chondrocytes. Under physiological loading, chondrocytes maintain the balance between degradation and synthesis of matrix macromolecules. Under excessive loading or injury, however, degradation exceeds synthesis, causing joint degeneration and, eventually, osteoarthritis (OA). Hence, the mechanoresponses of chondrocytes play an important role in the development of OA. Despite its clear importance, the mechanobiology of articular chondrocytes is not well understood. To summarize our current understanding, here we review studies of the effect of mechanical forces on mechanical and biological properties of articular chondrocytes. First, we present the viscoelastic properties of the cell nucleus, chondrocyte, pericellular matrix, and chondron. Then we discuss how these properties change in OA. Finally, we discuss the responses of normal and osteoarthritic chondrocytes to a variety of mechanical stimuli. Studies reviewed here may provide novel insights into the pathogenesis of OA and may help in development of effective biophysical treatment.

Cells resident in certain hollow organs are subjected routinely to large transient stretches, including every adherent cell resident in lungs, heart, great vessels, gut, and bladder. We have shown recently that in response to a transient stretch the adherent eukaryotic cell promptly fluidizes and then gradually resolidifies, but mechanism is not yet understood. In the isolated human bladder smooth muscle cell, here we applied a 10% transient stretch while measuring cell traction forces, elastic modulus, F-actin imaging and the F-actin/G-actin ratio. Immediately after a transient stretch, F-actin levels and cell stiffness were lower by about 50%, and traction forces were lower by about 70%, both indicative of prompt fluidization. Within 5min, F-actin levels recovered completely, cell stiffness recovered by about 90%, and traction forces recovered by about 60%, all indicative of resolidification. The extent of the fluidization response was uninfluenced by a variety of signaling inhibitors, and, surprisingly, was localized to the unstretch phase of the stretch-unstretch maneuver in a manner suggestive of cytoskeletal catch bonds. When we applied an “unstretch-restretch” (transient compression), rather than a “stretch-unstretch” (transient stretch), the cell did not fluidize and the actin network did not depolymerize. Taken together, these results implicate extremely rapid actin disassembly in the fluidization response, and slow actin reassembly in the resolidification response. In the bladder smooth muscle cell, the fluidization response to transient stretch occurs not through signaling pathways, but rather through release of increased tensile forces that drive acute disassociation of actin.