Non-destructive label-free monitoring of collagen gel remodeling using optical coherence tomography

Abstract

Matrix remodeling plays a fundamental role in physiological and pathological processes, as well as in tissue engineering applications. In this paper, optical coherence tomography (OCT), a nondestructive optical imaging technology, was used to image collagen gel remodeling by smooth muscle cells (SMCs). The optical scattering properties of collagen-SMC gels were characterized quantitatively by fitting OCT data to a theoretical model. Matrix remodeling over 5 days produced a 10-fold increase in the reflectivity of the collagen gels, corresponding to a decrease in scattering anisotropy from 0.91 to 0.46. The increase in reflectivity was corroborated in confocal mosaic images. Blocking matrix degradation in collagen-SMC gels with doxycycline, a non-specific matrix metalloproteinases (MMPs) inhibitor, impeded the decrease in scattering anisotropy and resulted in few macroscopic signs of remodeling. Causing matrix degradation in acellular gels with a 3 hr treatment of MMP-8 (collagenase 2) partially mimicked the decrease in anisotropy measured in collagen-SMC gels after 5 days. These results suggest that the decrease in scattering anisotropy in the collagen-SMC gels was due to MMP activity that degrades collagen fibrils into smaller fragments.

Ex Vivo Assessment of Vascular Response to Coronary Stents by Optical Frequency Domain Imaging

“…Stent-related hypersensitivity, although of rare occurrence, is also associated with a thrombogenic milieu that can lead to stent thrombosis (21 attenuation rate in the areas adjacent to the stent struts, as demonstrated in the OFDI signal analysis of this study, may help confirm hypersensitivity and future risk of thrombosis though prospective data is obviously needed to validate this claim. Using collagen-SMC gels studied in vitro, Levitz et al (25,26) recently showed that OCT signal reflection was potentially regulated by modifications of ECM through active matrix metalloproteinases, rather than cell or collagen density. Moreover, other studies involving animals, human atherectomy, and autopsy specimens of coronary stents also demonstrated changes in neointimal ECM over time (27)(28)(29).…”

Evaluation of the marginal fit at implant–abutment interface by optical coherence tomography

“…19 It is a promising imaging modality, which does not require cutting and processing of the specimens and allows the visualization of microstructures of tissue and biomaterials in the real time. 19,20 OCT was developed based on the concept of low-coherence interferometry. In simple words, a laser source is projected over a sample, and the backscattered signal intensity from within the scattering medium reveals depth-resolved information about scattering and reflection of the light in the sample.…”

Non-invasive Assessment of Elastic Modulus of Arterial Constructs during Cell Culture Using Ultrasound Elasticity Imaging

“…Others monitored the growth of biological tissue to indirectly infer the scaffold stiffness, also using optical methods. Levitz et al (2010) showed non-destructive label-free monitoring of collagen gel remodeling by SMC using optical coherence tomography (OCT). Niklason et al (2010) monitored collagen fiber deposition and orientation in SMC-seeded scaffolds cultured in a bioreactor using nonlinear optical microscopic imaging.…”