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COMMENTARY
HIGHLIGHTED TOPICS
Biomechanics and Mechanotransduction in Cells and Tissues
Titanium is currently the gold standard for implants that restore function to failed skeletal structures such as bone and teeth. Despite the extensive use of these implants, little is known about how the bone-implant interface responds to mechanical loading. In the first featured article, entitled "Modulation of bone ingrowth of rabbit femur titanium implants by in vivo axial micromechanical loading," Dr. P. A. Clark and colleagues (1) applied micromechanical loading to transcortical titanium implants in femurs of New Zealand White rabbits. At both the tissue and cellular levels, cyclic loading induced an anabolic response at the bone-implant interface, increasing bone volume, bone formation rate, and numbers of osteoblast-like cells lining endocortical surfaces. Double-fluorescent labeling revealed that mechanical stimulation of the implants also led to significantly greater bone apposition rate. The presence of chondrocyte-like cells suggested that the mechanical forces applied to the implants were transduced to peri-implant bone and induced endochondral ossification. Whether these observed short-term increases might lead to stronger bonding at the bone-implant interface and greater implant stability remains to be seen. Such a model could be used to investigate how cells and tissues respond to mechanical loading of titanium implants in vivo, as many in vitro studies have shown that stimuli, such as growth factors, induce very different cellular responses on titanium compared with other substrates such as tissue culture plastic. Clinically, this approach, in conjunction with methods such as surface modification, could be used to accelerate and increase initial bone ingrowth and, possibly, stimulate osteogenesis to ensure long-term functionality of implants.
Tissue structure and function are often attributed to the cells that make them up. In the second featured article, entitled "Extracellular matrix (ECM) microstructural composition regulates local cell-ECM biomechanics and fundamental fibroblast behavior: a multidimensional perspective," Dr. A. M. Pizzo and colleagues (2) examined the signaling and communication potential of the ECM component of tissues as a means of predictably controlling cell fate and thereby tissue properties. These investigators seeded fibroblasts within collagen ECM, in which the three-dimensional (3D) microstructural composition was systematically varied to yield low and high fibril densities. Multidimensional imaging allowed qualitative and quantitative comparisons of properties such as 3D cell morphometry, local strain state of the cell and surrounding ECM, and spatial distribution of cell-matrix adhesion molecules. Fibroblasts grown in low fibril-density matrices exhibited greater length-to-height ratios, decreased 3D surface areas, and fewer cytoplasmic projections than cells in high fibril-density matrices. Temporal and spatial changes in 3D local strain state also showed that these cells more extensively remodeled their surrounding ECM. The 3D microstructure of ECM regulated not only cell spreading and shape but also fundamental responses such as proliferation. This study provides new insight into how ECM microstructure regulates fundamental cell behavior and tissue remodeling, thus enhancing our understanding of the tissue repair process and providing fundamental design information for engineering functional biomaterials to improve or accelerate restoration of lost tissue function.
In the third and final featured article, entitled "Mechanical deformation of neutrophils into the narrow channels induces pseudopod projection and changes biomechanical properties," Drs. B. Yap and R. D. Kamm (3) explored the influence of mechanical forces to alter the structure and behavior of human neutrophils. These investigators imposed forces and deformations comparable to those naturally encountered by a neutrophil during its passage through the pulmonary microvasculature. They examined the cellular response by measuring the rheological properties of stiffness and viscosity and by observing morphological changes in the cell. The primary finding was that mechanical forces induce neutrophils to undergo a remodeling process that results in changes in viscoelastic properties and, as evidenced by the formation of pseudopods, activation of the cell. Such viscoelastic changes occur within a remarkably short time frame. Some take place within a matter of seconds, and similar to the recirculation time of blood, recovery or activation occurs in less than 1 min. These observations highlight the importance of considering the neutrophil not as a passive cell but as one capable of actively sensing and rapidly responding to mechanical stimuli.
Journal of Applied Physiology
May 2005, Volume 98
REFERENCES
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