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Thiyagarajah, N.

Publications and source records attributed to Thiyagarajah, N..

2 recordsLinked to original sources

The Effects of DMSO Cryopreservation on the Biomechanics and Histology of Human Cerebrovascular Tissue

IntroductionTissue preservation techniques, chiefly cryopreservation, have been demonstrated to alter vascular histology and tissue biomechanics via rapid osmotic change--resulting in collagen fiber rearrangement and internal elastic laminae (IEL) microfractures; however, this has not yet been evaluated in cerebrovascular tissue. As such, we sought to measure the effectiveness of a canonical cryopreservation strategy on the thickness and continuity of human cerebrovascular tissue. With the recent rise in biomechanical analyses of cerebrovascular tissue for the design of novel treatments and optimization of surgical strategies, the importance of designing models with accurate tissue proxies is paramount. MethodsFresh, human cerebrovascular tissue was obtained through the Cleveland Clinic institutional cadaver donation program. Donors with prior craniotomy, intracranial malignancy, or history of cerebrovascular disease were excluded. Cadaveric tissue dissections were completed within fourteen days of patient expiration and sectioned into four specimens. The 164 tissue samples obtained from three donors were then randomized into one of the following experimental conditions: 10% formalin (control), distilled water (dH2O), dimethyl sulfoxide (DMSO), or -80 {degrees}C DMSO cryopreservation. Specimens were then processed into paraffin-embedded sections and treated with Movat pentachrome staining. Vessel layers were measured by two blinded evaluators and discontinuities in internal elastin lamina were tallied. ResultsWe found that DMSO cryopreservation failed to consistently provide a protective effect to cerebrovascular specimens. Tissue stored via this method was reported to occasionally swell in specific vessel tunics of select vessel territories compared to formalin controls. We also observed an increase in the number of transverse elastin breaks with DMSO cryopreservation. ConclusionsThis data demonstrates that conventional tissue preservation methods may fail to preserve layer thicknesses between some vessels and alter biomechanical properties for future testing. Further, with more frequent elastin fractures in the cryopreservation group, recoilability of preserved vessels may vary from in vivo counterparts. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/679363v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1d8cc51org.highwire.dtl.DTLVardef@4ddcd6org.highwire.dtl.DTLVardef@1dd94f1org.highwire.dtl.DTLVardef@5d99bf_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

A Novel Method for the Mechanical Testing of Human Cerebrovascular Tissue: A Validation Study

This study describes and validates a novel mechanical testing apparatus capable of generating a viscoelastic response from which the time-dependent behavior of human cerebrovascular tissue can be derived to inform vessel wall failure prediction and therapeutic device design. Testing involved vascular specimen cannulation, pressurization, and recording dynamic changes in vessel diameter using a three-axis laser micrometer. Device validity and versatility were evaluated via two synthetic microvessel specimen experiments: (I) comparison to an Instron stress-relaxation protocol, and (II) vessel segment length parametric analysis. A standard linear solid (SLS) model was chosen to fit the experimental results, from which the model coefficients (E1, E2, and ) and equilibrium modulus (Ge) were computed. Ge comparisons were made using Bland-Altman analysis and Welchs F-test for experiment I and II, respectively. Device feasibility was evaluated through testing human cadaveric cerebrovascular tissue. The SLS model provided accurate experimental data fits, with overall mean R2 value of 0.99 (SD= 2.4E-3). Ge for inflation-creep and Instron stress-relaxation experiments were statistically comparable, with Bland-Altman mean bias of 1.9% (95% CI: -0.9% - 4.6%, p=.18). Holistically, the vessel segment length parametric analysis revealed inconsistent values for Ge across the complete range of testing lengths, where ad hoc family-wise comparison indicated that the 0.5 cm length cohort was the singular outlier (p < .05). Our device successfully recorded a viscoelastic response from human cadaveric middle cerebral artery tissue (n=12). This study demonstrated that our novel device was both versatile and capable of eliciting an accurate viscoelastic response.

bioengineering↗