High-resolution elasticity imaging for tissue engineering

Abstract

An elasticity microscope provides high resolution images of tissue elasticity. With this instrument, it may be possible to monitor cell growth and tissue development in tissue engineering. To test this hypothesis, elasticity micrographs were obtained in two model systems commonly used for tissue engineering. In the first, strain images of a tissue-engineered smooth muscle sample clearly identified a several hundred micron thick cell layer from its supporting matrix. Because a one-dimensional mechanical model was appropriate for this system, strain images alone were sufficient to image the elastic properties. In contrast, a second system was investigated in which a simple one-dimensional mechanical model was inadequate. Uncultured collagen microspheres embedded in an otherwise homogeneous gel were imaged with the elasticity microscope. Strain images alone did not clearly depict the elastic properties of the hard spherical cell carriers. However, reconstructed elasticity images could differentiate the hard inclusion from the background gel. These results strongly suggest that the elasticity microscope may be a valuable tool for tissue engineering and other applications requiring the elastic properties of soft tissue at high spatial resolution (75 microm or less).

Application of Elastography for the Noninvasive Assessment of Biomechanics in Engineered Biomaterials and Tissues

“…15,58,157 Despite these challenges, UE has proved to be versatile and of reasonably high resolution for evaluation of strains in both tissues 12,14,50,88,113,114,140,141 and biomaterials for tissue engineering. 1,69,143,162 …”

“…1 Following in vivo culture in rats, the scaffold was examined using a 50 MHz UE elastography. At the resulting 75 μ m resolution, the denser cellularized region of the scaffold previously seeded with SMC showed a higher bulk strain (+4%) compared to that of lower non-cellularized region.…”

“…146 Quasi-static UE has been used to characterize tissues in vivo including skeletal muscle, 12,21,34,157 breast tissue and tumors (where tumors are stiff inclusions in a softer background), 21,50,140,141 tendon, 32,43,92 and the porcine cornea, 59 as well as longitudinal strain monitoring in a cell-seeded collagen substrate 88 and in vascular scaffolds 44 in vitro . A 3D UE strain elastogram obtained from in vitro porcine cornea using a similar setup to Cohn’s “elasticity microscopy” 1 revealed different strain patterns associated with axially heterogeneous micro-anatomical layers, but the elastogram was affected by a high level of noise. While the elastogram achieved high resolution (23.9 × 46.6 μ m), the scanning time was long at 23 min (vs. 1 min in other static UE studies) resulting from numerous cycles of loading/unloading that were required to map a 3D volume of the tissue.…”

Non-invasive and Non-destructive Characterization of Tissue Engineered Constructs Using Ultrasound Imaging Technologies: A Review

“…1 Using the same system, Winterroth et al later monitored changes in the morphology and nonlinear elastic properties of engineered oral mucosal tissues under normal and thermally stressed culture conditions. 84 In vivo, 30 UEI using a commercial array transducer was applied to detect the degradation of the poly(1,8-octanedio-co-citrate) polymer scaffolds subcutaneously implanted in the backs of mice.…”

Quantitative Ultrasound for Nondestructive Characterization of Engineered Tissues and Biomaterials

“…73-76 One study demonstrated the use of a compression elastography technique to compute the relative strain of thin, polyglycolic acid (PGA) scaffolds, embedded with smooth muscle cells. 76 Another study used compression elastography techniques to generate axial strain images for monitoring the degradation of biodegradable, polymer-based scaffolds embedded in gelatin phantoms or implanted subcutaneously in mouse models 74 . Similarly, compression elastography was able to track changes in mechanical stiffness of polyurethane scaffolds implanted in a mouse model over a 12-week period.…”