Local, three-dimensional strain measurements within largely deformed extracellular matrix constructs

The ability to create extracellular matrix (ECM

The influence of extracellular matrix (ECM) micro-structure on the macro- and micro-level biomechanical behavior of tissue constructs and cell-ECM interactions

Cells in vivo reside in a framework known as extracellular matrix (ECM). The ECM guides tissue structure and function by communicating to cells both biochemical and mechanical information about their local micro-environment. It has been well established that mechanical loads applied to tissues influence many fundamental cellular processes; however, pathways that transmit forces from the tissue (macro) to the cellular (micro) level remain to be identified. As such, this dissertation demonstrates new information regarding how ECM microstructure affects the macro- and micro-level biomechanical behavior of tissue constructs and cell-ECM interactions. Since their microstructure can be controlled in vitro, a 3D scaffold of collagen fibrils was used as a model ECM. A tissue construct was then created by seeding fibroblasts, a cell common to connective tissues, inside the collagen ECM. First, the microstructural and macro-level mechanical properties of microstructurally varied collagen ECMs were characterized. To further understand specific mechanisms of the mechanotransduction process, a new experimental system, capable of measuring the three-dimensional (3D) micro-biomechanical behavior of the ECM and cells, was developed. Integrating confocal reflection microscopy with mechanical testing allowed simultaneous 3D visualization of the tissue (macro-level) and of cell and ECM microstructure (micro-level) as measured and controlled mechanical loads were applied to living tissue constructs. Application of a new incremental digital volume correlation algorithm allowed quantification of 3D strains at the micro-level. Combined, these tools allowed study of (1) macro- to micro-level transmission of mechanical strains through tissue constructs and (2) ECM to cell strain transfer inside tissue constructs. Studies revealed that ECM microstructure was a critical determinant in the macro-level stress response, the 3D macro- to micro-level strain transfer properties, and the 3D micro-level strain response of the ECM. Additionally, studies with tissue constructs demonstrated that changes in collagen ECM microstructure altered the transfer of strains from the ECM to resident cells. Applied, this new information will allow the design of microstructurally enhanced ECM constructs for use as functional tissue engineered replacements

Effect of proximal fixation length on complications after endovascular repair of type B aortic dissection.

OBJECTIVE: We evaluated the effect of the achieved proximal seal length on the outcomes after endovascular repair of acute type B aortic dissection (aTBAD). METHODS: A post hoc analysis was performed using data from two prospective, multicenter investigational studies of the Zenith Dissection Endovascular System (STABLE I and II). Patients treated for aTBAD within 14 days of symptom onset were included if complete preoperative and postoperative imaging data were available for review. The patients were divided into four groups according to the length of the achieved proximal seal according to the centerline imaging findings: ≥20 mm, ≥10 to \u3c20 \u3emm, ≥0 to \u3c10 \u3emm, andanalysis. RESULTS: A total of 110 patients were included in the present analysis; 51 were from STABLE I and 59 from STABLE II. Although the study protocol criteria required a ≥20 mm length of nondissected aorta distal to the left common carotid artery to serve as a proximal seal zone, an achieved proximal seal length of ≥20 mm was observed in only 19 of the 110 patients (17.3%) according to the location of stent-graft placement. After a mean follow-up duration of 41.6 ± 21 months, the cumulative rate of the composite device outcome (ie, proximal entry flow, retrograde dissection, transaortic growth, and stent-graft migration) was lowest in patients with an achieved proximal seal length of ≥20 mm (15.8%; 3 of 19). The cumulative rate increased as the seal length decreased (32.0% [8 of 25], 55.6% [20 of 36], and 60.0% [18 of 30] with a proximal seal length of ≥10 to \u3c20 \u3emm, ≥0 to \u3c10 \u3emm, and \u3c0 \u3emm, respectively; P \u3c .01, Cochran-Armitage trend test). CONCLUSIONS: A clear inverse relationship was found between the proximal seal length achieved and associated adverse outcomes. This finding underscores the importance of landing the stent-graft in healthy, nondissected aorta to minimize the risk of complications and provide a durable repair in patients with aTBAD

Role of Pulse Pressure and Geometry of Primary Entry Tear in Acute Type B Dissection Propagation

The hemodynamic and geometric factors leading to propagation of acute Type B dissections are poorly understood. The objective is to elucidate whether geometric and hemodynamic parameters increase the predilection for aortic dissection propagation. A pulse duplicator set-up was used on porcine aorta with a single entry tear. Mean pressures of 100 and 180 mmHg were used, with pulse pressures ranging from 40 to 200 mmHg. The propagation for varying geometric conditions (%circumference of the entry tear: 15–65%, axial length: 0.5–3.2 cm) were tested for two flap thicknesses (1/3rd and 2/3rd of the thickness of vessel wall, respectively). To assess the effect of pulse and mean pressure on flap dynamics, the %true lumen (TL) cross-sectional area of the entry tear were compared. The % circumference for propagation of thin flap (47 ± 1%) was not significantly different (p = 0.14) from thick flap (44 ± 2%). On the contrary, the axial length of propagation for thin flap (2.57 ± 0.15 cm) was significantly different (p < 0.05) from the thick flap (1.56 ± 0.10 cm). TL compression was observed during systolic phase. For a fixed geometry of entry tear (%circumference = 39 ± 2%; axial length = 1.43 ± 0.13 cm), mean pressure did not have significant (p = 0.84) effect on flap movement. Increase in pulse pressure resulted in a significant change (p = 0.02) in %TL area (52 ± 4%). The energy acting on the false lumen immediately before propagation was calculated as 75 ± 9 J/m(2) and was fairly uniform across different specimens. Pulse pressure had a significant effect on the flap movement in contrast to mean pressure. Hence, mitigation of pulse pressure and restriction of flap movement may be beneficial in patients with type B acute dissections

Early experience with a modified preloaded system for fenestrated endovascular aortic repair

Objective Preloaded endovascular delivery systems expand the anatomic eligibility for complex aortic repair by requiring only one iliac access vessel and providing a stable platform for guiding sheaths into challenging target vessels. This article reports the lessons learned and early clinical outcomes using a modified preloaded delivery system for fenestrated endovascular aneurysm repair (FEVAR) in three aortic centers in Europe. Methods From October 2015 to March 2016, consecutive patients presenting with extensive aortic aneurysm treated with a modified preloaded FEVAR were prospectively enrolled from three high volume European aortic centers. The new design is a modification of previous designs of preloaded fenestrated stent grafts and of the p-branch device platform. The technical details of implantation are described and perioperative outcomes, including the learning curve, are collected and reported. Results All patients (30 patients; 80% men; 70.2 years old) presented for nonurgent repair of either a type Ia endoleak (3/30; 10%), a type I-II-III thoracoabdominal (8/30; 27%), or a type IV thoracoabdominal or pararenal (19/30; 63.%) aneurysm repair of a mean size of 64 ± 13 mm using a custom made device. Primary technical success was achieved in 28 of 30 patients (93%) and assisted primary technical success in 29 of 30 patients (97%). The two technical failures included open conversion to repair a ruptured iliac artery and restenting of a dissected superior mesenteric artery which was recognized hours after the index procedure had finished. The mean procedure time was 277 ± 153 minutes, fluoroscopy time 79 ± 36 minutes, dose area product 112 ± 90 Gy cm2, and contrast volume 87 ± 46 mL. All renal fenestrations were successfully stented without type III endoleak on completion angiogram; the preloaded guiding sheaths were used for 53 of 58 renal arteries (91%). Challenges related to learning to the use of the modified preloaded system were experienced early and had no clinical consequences. Major complications occurred in seven cases (23%), including two perioperative deaths because of stroke and sepsis following primary conversion attributable to iliac rupture. There were no target vessel occlusions or type I/III endoleaks found on postoperative imaging. Conclusions Based on early experience, the modified preloaded system can be safely and effectively used during FEVAR, with good technical result and a short period of learning. This device expands treatment to patients with compromised iliac access, thus, additional patients and more follow-up will be required to determine unique risks of operating in this patient population

Validated Computational Model to Compute Re-apposition Pressures for Treating Type-B Aortic Dissections

The use of endovascular treatment in the thoracic aorta has revolutionized the clinical approach for treating Stanford type B aortic dissection. The endograft procedure is a minimally invasive alternative to traditional surgery for the management of complicated type-B patients. The endograft is first deployed to exclude the proximal entry tear to redirect blood flow toward the true lumen and then a stent graft is used to push the intimal flap against the false lumen (FL) wall such that the aorta is reconstituted by sealing the FL. Although endovascular treatment has reduced the mortality rate in patients compared to those undergoing surgical repair, more than 30% of patients who were initially successfully treated require a new endovascular or surgical intervention in the aortic segments distal to the endograft. One reason for failure of the repair is persistent FL perfusion from distal entry tears. This creates a patent FL channel which can be associated with FL growth. Thus, it is necessary to develop stents that can promote full re-apposition of the flap leading to complete closure of the FL. In the current study, we determine the radial pressures required to re-appose the mid and distal ends of a dissected porcine thoracic aorta using a balloon catheter under static inflation pressure. The same analysis is simulated using finite element analysis (FEA) models by incorporating the hyperelastic properties of porcine aortic tissues. It is shown that the FEA models capture the change in the radial pressures required to re-appose the intimal flap as a function of pressure. The predictions from the simulation models match closely the results from the bench experiments. The use of validated computational models can support development of better stents by calculating the proper radial pressures required for complete re-apposition of the intimal flap