A method of assessing peripheral stent abrasiveness under cyclic deformations experienced during limb movement

Poor outcomes of peripheral arterial disease stenting are often attributed to the inability of stents to accommodate the complex biomechanics of the flexed lower limb. Abrasion damage caused by rubbing of the stent against the artery wall during limb movement plays a significant role in reconstruction failure but has not been characterized. Our goals were to develop a method of assessing the abrasiveness of peripheral nitinol stents and apply it to several commercial devices. Misago, AbsolutePro, Innova, Zilver, SmartControl, SmartFlex, and Supera stents were deployed inside electrospun nanofibrillar tubes with femoropopliteal artery-mimicking mechanical properties and subjected to cyclic axial compression (25%), bending (90°), and torsion (26°/cm) equivalent to five life-years of severe limb flexions. Abrasion was assessed using an abrasion damage score (ADS, range 1–7) for each deformation mode. Misago produced the least abrasion and no stent fractures (ADS 3). Innova caused small abrasion under compression and torsion but large damage under bending (ADS 7). Supera performed well under bending and compression but caused damage under torsion (ADS 8). AbsolutePro produced significant abrasion under bending and compression but less damage under torsion (ADS 12). Zilver fractured under all three deformations and severely abraded the tube under bending and compression (ADS 15). SmartControl and SmartFlex fractured under all three deformations and produced significant abrasion due to strut penetration (ADS 20 and 21). ADS strongly correlated with clinical 12- month primary patency and target lesion revascularization rates, and the described method of assessing peripheral stent abrasiveness can guide device selection and development

Non-Destructive Characterization of Peripheral Arteries using Intravascular Ultrasound

Peripheral Artery Disease (PAD) is the chronic obstruction of blood flow to the extremities caused by plaque buildup. Poor circulation results in exertional pain, numbness, and weakness, and in severe cases, can manifest critical conditions, including gangrene and limb loss. PAD affects approximately 8.5 million Americans and costs the United States $21 billion annually in direct medical expenses. High expenditures are attributed to operation and intervention failures resulting in frequent need for revascularization. Treatment of PAD typically involves lifestyle/diet adjustments, bypass surgery, or angioplasty/stenting. Unfortunately, repeated limb deformation during locomotion often results in adverse repair device-artery interactions, which hinder the long-term efficacy of endovascular therapies. Patient and lesion-specific device selection guided by computational modeling can help improve clinical outcomes, but these models rely heavily on accurately recorded three-dimensional arterial geometry and plaque composition. Intravascular ultrasound (IVUS) is a minimally invasive method of endovascular imaging that allows evaluation of the geometry and composition of the arterial wall, but its two-dimensional nature is often insufficient to capture complex three-dimensional plaques. We have developed a method of obtaining three-dimensional arterial geometry from two-dimensional IVUS images to build Computer-Aided Design models of calcified human femoropopliteal arteries. Our imaging method will allow for the characterization of calcium, necrotic core, fibrofatty, and fibrous tissue using IVUS. Correlation of IVUS images with conventional histology, micro-CT imaging, and clinical CTA data will help inform computational models.https://digitalcommons.unmc.edu/surp2021/1025/thumbnail.jp

Towards precision nanomanufacturing for mechanical design: From individual nanofibers to mechanically biomimetic nanofibrillary vascular grafts

Electrospun nanofibers have high potential to improve properties and performance of biomedical materials due to their biomimetic structure and unique mechanical properties. Despite their potential, use of polymer nanofibers has been limited due to poor control over nanofiber structure and properties and due to lack of advanced design and nanomanufacturing methods. The objective of this work was to improve the understanding of process parameter-structure-property relationships in individual biomedical nanofibers, and to develop an advanced method for mechanically and structurally biomimetic nanofiber-based vascular graft material manufacturing. Mechanical tests of individual biomedical DNA nanofibers show ultrahigh mechanical properties and atypical size-effects, indicating on high molecular orientation and possible fundamentally different molecular alignment mechanisms from synthetic polymer nanofibers. Novel structural characterization methods were developed to study molecular structure and its size-effects in individual DNA nanofibers. The results reveal high molecular orientation in DNA nanofibers, which decreases gradually with increase of diameter. These results are in good agreement with observed mechanical properties and with proposed bottom-up molecular alignment mechanisms during DNA electrospinning. Based on mechanical analysis of individual nanofibers, an advanced method was developed for manufacturing of mechanically biomimetic nanofibrillary vascular graft materials. Different process parameter-property relationships were established to induce biaxial non-linearity and anisotropy. These relationships were studied parametrically and used to mimic the mechanical properties of human carotid artery and pig iliac artery. In-vivo tests of pig iliac artery-mimetic nanofibrillary graft material show improved surgical and biomechanical characteristics compared to the state-of-the-art control material. Histology results reveal that developed biomimetic nanofibrillary vascular graft material also possesses improved healing response manifested by smooth muscle cell infiltration within the graft material and by endothelial cell coverage on the grafted lumen. The results of this study provide new knowledge of manufacturing, structure, and properties of individual nanofibers and nanofibrillary membranes. These results can be used to develop new and improve existing mechanical design principles of nanofibrillary materials for biomedical and other applications

Mechanical Properties and Structure of DNA and Collagen Nanofilaments

DNA is used as self-assembling multifunctional building material for novel technologies, such as nanostructured sensing materials and field-effect transistors, or nanosized computers and functioning devices. While having the unique advantage of forming complex structures, the self-assembly process is hard to control. Electrospinning is an alternative top-down nanomanufacturing method, by which polymer nanofibers can be produced in high electric fields. Unlike self-assembly, electrospinning can provide continuous nanofibers, with ability to bridge the nano and micro scales. This study presents the first systematic investigation of continuous electrospun DNA nanofibers. Two types of fibers from single stranded (ss) and double stranded (ds) DNA solutions with wide range of diameters were produced by electrospinning. Tensile tests of single DNA nanofibers were performed for the first time, revealing very high mechanical properties – exceeding 1GPa strength and 300MPa toughness for the best results. Mechanical tests also showed size effects on strain at failure and toughness which increase significantly as fiber diameters decrease. Based on mechanical response the differences of molecular networks were proposed. Structural studies using Raman spectroscopy, X-ray diffraction (XRD) and other methods provided additional insight on DNA nanofiber structure. Electrospun collagen scaffolds are widely used in tissue engineering, with aim to replicate natural environment of the extracellular matrix (ECM). However, due to organic solvents used in production, the artificial collagen scaffolds are unable to mimic the mechanical properties and structure of the natural ECM. Fibers from collagen-DNA hybrid solutions were made to enhance the processing, structure, and properties of tissue engineering fibers. It was found that as little as 0.2% of DNA enabled electrospininning collagen fibers from aqueous solutions. XRD and thermogravimetric analyses exhibited close correspondence to natural collagen fiber results, unlike the results from conventionally produced fibers. Moreover, higher DNA concentrations produced extraordinary increases in ultimate strain and toughness up to three orders of magnitude in the hybrid nanofibers. The results of this study show that continuous DNA and collagen-DNA nanofibers can serve as building blocks for novel high-performance biodegradable and biocompatible materials for tissue engineering and other bionanotechnology devices and applications

Mechanical Properties and Structure of DNA and Collagen Nanofilaments

DNA is used as self-assembling multifunctional building material for novel technologies, such as nanostructured sensing materials and field-effect transistors, or nanosized computers and functioning devices. While having the unique advantage of forming complex structures, the self-assembly process is hard to control. Electrospinning is an alternative top-down nanomanufacturing method, by which polymer nanofibers can be produced in high electric fields. Unlike self-assembly, electrospinning can provide continuous nanofibers, with ability to bridge the nano and micro scales. This study presents the first systematic investigation of continuous electrospun DNA nanofibers. Two types of fibers from single stranded (ss) and double stranded (ds) DNA solutions with wide range of diameters were produced by electrospinning. Tensile tests of single DNA nanofibers were performed for the first time, revealing very high mechanical properties – exceeding 1GPa strength and 300MPa toughness for the best results. Mechanical tests also showed size effects on strain at failure and toughness which increase significantly as fiber diameters decrease. Based on mechanical response the differences of molecular networks were proposed. Structural studies using Raman spectroscopy, X-ray diffraction (XRD) and other methods provided additional insight on DNA nanofiber structure. Electrospun collagen scaffolds are widely used in tissue engineering, with aim to replicate natural environment of the extracellular matrix (ECM). However, due to organic solvents used in production, the artificial collagen scaffolds are unable to mimic the mechanical properties and structure of the natural ECM. Fibers from collagen-DNA hybrid solutions were made to enhance the processing, structure, and properties of tissue engineering fibers. It was found that as little as 0.2% of DNA enabled electrospininning collagen fibers from aqueous solutions. XRD and thermogravimetric analyses exhibited close correspondence to natural collagen fiber results, unlike the results from conventionally produced fibers. Moreover, higher DNA concentrations produced extraordinary increases in ultimate strain and toughness up to three orders of magnitude in the hybrid nanofibers. The results of this study show that continuous DNA and collagen-DNA nanofibers can serve as building blocks for novel high-performance biodegradable and biocompatible materials for tissue engineering and other bionanotechnology devices and applications

Quantifying polymer chain orientation in strong and tough nanofibers with low crystallinity : towards next generation nanostructured superfibers

Advanced fibers revolutionized structural materials in the second half of the 20th century. However, all high-strength fibers developed to date are brittle. Recently, pioneering simultaneous ultrahigh strength and toughness were discovered in fine (<250 nm) individual electrospun polymer nanofibers (NFs). This highly desirable combination of properties was attributed to high macromolecular chain alignment coupled with low crystallinity. Quantitative analysis of the degree of preferred chain orientation will be crucial for control of NF mechanical properties. However, quantification of supramolecular nanoarchitecture in NFs with low crystallinity in the ultrafine diameter range is highly challenging. Here, we discuss the applicability of traditional as well as emerging methods for quantification of polymer chain orientation in nanoscale one-dimensional samples. Advantages and limitations of different techniques are critically evaluated on experimental examples. It is shown that straightforward application of some of the techniques to sub-wavelength-diameter NFs can lead to severe quantitative and even qualitative artifacts. Sources of such size-related artifacts, stemming from instrumental, materials, and geometric phenomena at the nanoscale, are analyzed on the example of polarized Raman method but are relevant to other spectroscopic techniques. A proposed modified, artifact-free method is demonstrated. Outstanding issues and their proposed solutions are discussed. The results provide guidance for accurate nanofiber characterization to improve fundamental understanding and accelerate development of nanofibers and related nanostructured materials produced by electrospinning or other methods. We expect that the discussion in this review will also be useful to studies of many biological systems that exhibit nanofilamentary architectures and combinations of high strength and toughness

Quantifying Polymer Chain Orientation in Strong and Tough Nanofibers with Low Crystallinity: Toward Next Generation Nanostructured Superfibers

International audienceAdvanced fibers revolutionized structural materials in the second half of the 20th century. However, all high-strength fibers developed to date are brittle. Recently, pioneering simultaneous ultrahigh strength and toughness were discovered in fine (<250 nm) individual electrospun polymer nanofibers (NFs). This highly desirable combination of properties was attributed to high macromolecular chain alignment coupled with low crystallinity. Quantitative analysis of the degree of preferred chain orientation will be crucial for control of NF mechanical properties. However, quantification of supramolecular nanoarchitecture in NFs with low crystallinity in the ultrafine diameter range is highly challenging. Here, we discuss the applicability of traditional as well as emerging methods for quantification of polymer chain orientation in nanoscale one-dimensional samples. Advantages and limitations of different techniques are critically evaluated on experimental examples. It is shown that straightforward application of some of the techniques to sub-wavelength-diameter NFs can lead to severe quantitative and even qualitative artifacts. Sources of such size-related artifacts, stemming from instrumental, materials, and geometric phenomena at the nanoscale, are analyzed on the example of polarized Raman method but are relevant to other spectroscopic techniques. A proposed modified, artifact-free method is demonstrated. Outstanding issues and their proposed solutions are discussed. The results provide guidance for accurate nanofiber characterization to improve fundamental understanding and accelerate development of nanofibers and related nanostructured materials produced by electrospinning or other methods. We expect that the discussion in this review will also be useful to studies of many biological systems that exhibit nanofilamentary architectures and combinations of high strength and toughness