Non-invasive characterization of polyurethane-based tissue constructs in a rat abdominal repair model using high frequency ultrasound elasticity imaging

Abstract

The evaluation of candidate materials and designs for soft tissue scaffolds would benefit from the ability to monitor the mechanical remodeling of the implant site without the need for periodic animal sacrifice and explant analysis. Toward this end, the ability of non-invasive ultrasound elasticity imaging (UEI) to assess temporal mechanical property changes in three different types of porous, biodegradable polyurethane scaffolds was evaluated in a rat abdominal wall repair model. The polymers utilized were salt-leached scaffolds of poly(carbonate urethane) urea, poly(ester urethane) urea and poly(ether ester urethane) urea at 85% porosity. A total of 60 scaffolds (20 each type) were implanted in a full thickness muscle wall replacement in the abdomens of 30 rats. The constructs were ultrasonically scanned every 2 weeks and harvested at weeks 4, 8 and 12 for compression testing or histological analysis. UEI demonstrated different temporal stiffness trends among the different scaffold types, while the stiffness of the surrounding native tissue remained unchanged. The changes in average normalized strains developed in the constructs from UEI compared well with the changes of mean compliance from compression tests and histology. The average normalized strains and the compliance for the same sample exhibited a strong linear relationship. The ability of UEI to identify herniation and to characterize the distribution of local tissue in-growth with high resolution was also investigated. In summary, the reported data indicate that UEI may allow tissue engineers to sequentially evaluate the progress of tissue construct mechanical behavior in vivo and in some cases may reduce the need for interim time point animal sacrifice.

Imaging Strategies for Tissue Engineering Applications

“…[70][71][72] In addition, ultrasound elasticity imaging was used for in vivo studies to noninvasively assess temporal mechanical property changes in biodegradable polyurethane scaffolds implanted in the rat muscular abdominal wall for up to 12 weeks, as shown in Figure 6B. 73 In addition to mechanical and morphological properties, functional information can be provided in vivo using Doppler ultrasound imaging because Doppler ultrasound imaging is capable of visualizing local fluid flow noninvasively. Also, exogenous contrast agents, mainly microbubbles, can enhance the sensitivity of Doppler ultrasound imaging, so visualization of microvasculature is possible.…”

“…Reprinted with permission from Gudur et al 61 (B) Normalized strain maps laid over B-mode ultrasound images of various polymer scaffolds implanted in abdominal wall defects. Reprinted with permission from Yu et al 73 (C) Three-dimensional functional ultrasound imaging of three different liver matrix scaffolds following reseeding with hepatoblast-like cells and bioreactor cultivation to evaluate vascular architecture via contrast infusion. Reprinted with permission from Gessner et al 77 Color images available online at www.liebertpub.com/teb 94 NAM ET AL.…”

Noninvasive Quantitative Imaging of Collagen Microstructure in Three-Dimensional Hydrogels Using High-Frequency Ultrasound

“…37 Ultrasound elasticity imaging has been investigated for monitoring the elastic properties of polyurethane-based scaffolds subcutaneously implanted in mice and in a rat abdominal repair model. 38,39 We previously demonstrated the utility of the IBC as a metric for quantifying cell concentration noninvasively within 3D cell-embedded agarose hydrogels, where the ultrasound was backscattered predominantly from cells. 25 In this study, a high-frequency quantitative ultrasound technique was developed to nondestructively and noninvasively characterize the microstructure of 3D acellular collagen scaffolds.…”

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

“…To systematically investigate the correlation of the dynamic, adaptive mechanical and structural property changes with varying rates of scaffold degradation and tissue in-growth, porous scaffolds made from three biodegradable elastomers with different degradation rates were used in a later study: poly(ether ester urethane) urea (PEEUU) for a fast degradation rate, poly(ester urethane) urea (PEUU) for a moderate degradation rate and poly(carbonate urethane) urea (PCUU) for a slow degradation rate. 89 …”