Biology subjects

MacTaggart, J.

Publications and source records attributed to MacTaggart, J..

4 recordsLinked to original sources

bioRxiv2026

Biomechanical Compatibility With Physiological Limb-Flexion Deformation Reduces Inflammation and Neointimal Hyperplasia After Peripheral Stenting

Introduction: The femoropopliteal artery undergoes substantial axial compression, bending, torsion, and pinching during limb flexion. When an implanted stent does not accommodate these deformations, repetitive biomechanical mismatch may alter the vascular response to implantation and contribute to restenosis. We tested whether designing a peripheral stent to better accommodate physiologic limb-flexion deformation reduces the subsequent inflammatory and neointimal response. Methods: A nitinol stent was developed using multi-objective computational optimization to maintain arterial apposition while reducing wall stress and luminal pinching during physiologic deformation. Sixteen Yucatan minipigs were studied in independent 3- and 6-month cohorts (n=8 each). Each animal received the optimized stent in one limb and a commercial stent with representative biomechanical behavior contralaterally. CTA quantified in vivo limb-flexion deformation, while CT and histology assessed stenosis, neointimal accumulation, inflammatory-cell burden, SMA-positive tissue, and extracellular-matrix composition. Results: The optimized stent accommodated greater axial shortening than the commercial comparator at both 3 months (11.2{+/-}2.7% vs. 6.6{+/-}2.1%, p=0.003) and 6 months (13.7{+/-}4.4% vs. 6.8{+/-}2.3%, p=0.004). Intimal hyperplasia volume was lower with the optimized stent at 3 months (227.5{+/-}85.2 vs. 350.0{+/-}130.5 mm3, p=0.002) and 6 months (183.6{+/-}46.2 vs. 261.2{+/-}60.6 mm3, p=0.001), with significantly lower maximum, mean, and median stenosis at both timepoints. At 3 months, macrophage and total inflammatory-cell counts were 51% and 45% lower, respectively, with the optimized stent. Histologic tissue area was 28% lower at 3 months and 12% lower at 6 months. SMA-positive tissue fraction was higher with the optimized stent at both timepoints, whereas elastin, glycosaminoglycan, and collagen fractions were similar between devices. Discussion: Improved accommodation of limb-flexion deformation was associated with a smaller inflammatory and neointimal response to stent implantation through 6 months, while overall neointimal matrix composition remained largely unchanged. These findings provide in vivo evidence that biomechanical compatibility with the dynamic lower-limb environment can influence vascular healing and should be considered a mechanistic design criterion for peripheral artery stents.

bioengineering↗

bioRxiv2025

BIOMECHANICAL CHARACTERIZATION OF PORCINE LOWER LIMB ARTERIES FOR PRECLINICAL EVALUATION OF PERIPHERAL VASCULAR DEVICES

PurposePeripheral artery disease (PAD) predominantly affects the lower extremities, where complex biomechanical deformations during limb flexion contribute to disease progression and treatment failure. While human and cadaver studies have characterized these deformations, preclinical device testing requires large-animal models that replicate human arterial anatomy and biomechanics. Swine are commonly used, yet their biomechanical comparability to humans remains poorly defined. MethodsWe performed a detailed morphometric and biomechanical analysis of the external iliac (EIA), superficial femoral (SFA), and popliteal (PA) arteries in 20 Yucatan and 16 domestic swine using computed tomography angiography. Arteries were evaluated in straight and flexed limb postures to assess diameters, lengths, axial compression, tortuosity, bending angles, and inscribed sphere radii. Breed-specific effects of age and weight were also analyzed. ResultsPorcine arterial dimensions closely matched human lower extremity vessels. EIA diameters (4.9-7.2 mm) corresponded to human SFA, porcine SFA (4.1-5.9 mm) approximated human PA, and porcine PA (3.0-4.7 mm) resembled human tibial arteries. Segment lengths supported use of multiple devices. Flexion induced 12-33% axial compression, mimicking worst-case human scenarios. Tortuosity increased distally, and bending characteristics in porcine PAs aligned with human data. In Yucatan swine, vessel diameters were stable with age and weight, while domestic swine exhibited greater variability. Flexion-induced compression and tortuosity were not influenced by age or weight. ConclusionSwine are well-suited for modeling the geometry and biomechanics of human lower extremity arteries. Their anatomical compatibility and ability to replicate physiologic deformations make them valuable models for preclinical testing of PAD therapies and vascular devices.

physiology↗

bioRxiv2025

EXPERIMENTAL CHARACTERIZATION OF BALLOON ANGIOPLASTY IN HUMAN FEMOROPOPLITEAL ARTERIES WITH DIFFERENT CALCIUM BURDENS

IntroductionBalloon angioplasty is one of the most common treatments for Peripheral Artery Disease (PAD), but its clinical outcomes continue to disappoint, particularly when managing calcified lesions. We characterized luminal gains and damage after balloon angioplasty using high-resolution imaging, histology, and mechanical testing. MethodsFresh diseased human femoropopliteal arteries (FPA) from n=15 subjects (average age 69 {+/-} 9, range 53-90 years) with different calcium burdens were imaged before, during, and after angioplasty using micro-computed tomography, and luminal gains, calcium fractures, and resulting dissections were quantified. Histology was used to assess structural damage, and biaxial mechanical testing determined damage initiation stretches and stresses. ResultsIn severely calcified FPAs, calcification often manifested as rings or large plate-like deposits. When calcium spanned the entire circumference, angioplasty produced longitudinal cracks but [~]8% luminal area gain. In less calcified arteries, damage manifested primarily as tears along the internal elastic lamina and within the tunica media. Dissections were present in 53% of all FPAs after angioplasty, with a higher prevalence in more calcified vessels and vessels with stenosis (75% each). Damage initiated at lower biaxial stretches (1.11 {+/-} 0.02 vs 1.14-1.15) and lower longitudinal stresses (44 {+/-} 22 kPa vs 57 {+/-} 31 kPa) in severely calcified specimens compared with lightly calcified arteries, but larger calcium burdens generally required more circumferential stress to initiate damage (66 {+/-} 27 kPa). Diabetes mellitus was associated with a higher calcium burden. ConclusionsSevere calcification limits luminal gains after angioplasty. Less calcified arteries accumulate damage to the healthier wall while calcium remains mostly intact. These results may inform clinical strategies and the development of better devices to treat PAD.

bioengineering↗

bioRxiv2025

NITINOL MATERIAL PROPERTIES OF 11 COMMERCIAL PERIPHERAL STENTS DETERMINED USING INVERSE COMPUTATIONAL ANALYSIS

Stent-artery interactions are influenced by the mechanical properties of self-expanding Nitinol stents, but data on these characteristics remain limited. Eleven stents (Absolute Pro, S.M.A.R.T. Control, Misago, Zilver, Complete SE, EverFlex, Innova, Pulsar-18, LifeStent, S.M.A.R.T. Flex, and Supera) used to treat peripheral arterial disease (PAD) were subjected to axial tension, compression, three-point bending, and torsion tests, and the data on reaction forces and moments were compared with finite element simulations of the same experiments. Inverse computational analysis was used to determine austenite and martensite elasticity, transformation stretch, stresses at the start and end of transformation loading, and the start of transformation stress in compression. Uniaxial tensile tests were done on isolated struts from Absolute Pro and Zilver stents to verify the results of the inverse analysis. Our study demonstrate that Nitinol material properties are significantly different across devices. Austenite elasticity ranged 7.5-85 GPa, martensite elasticity 10-47.8 GPa, transformation stretch 1.03-1.08, the start of transformation loading stress 386-465 MPa, the end of transformation loading stress 411-535 MPa, and the start of transformation stress in compression 150-900 MPa. Nitinol of S.M.A.R.T. Control and S.M.A.R.T. Flex devices had the softest response, while Pulsar-18 had the hardest. The presented Nitinol mechanical properties of commonly used PAD stents can improve the fidelity of computational models investigating stent-artery interactions and may help improve clinical outcomes of endovascular PAD repairs through better device design.

bioengineering↗