Engineering in-plane mechanics of electrospun polyurethane scaffolds for cardiovascular tissue applications

Effective cardiovascular tissue surrogates require high control of scaffold structural and mechanical features to match native tissue properties, which are dependent on tissue-specific mechanics, function heterogenicity, and morphology. Bridging scaffold processing variables with native tissue properties is recognized as a priority for advancing biomechanical performance of biomedical materials and, when translated to the clinical practice, their efficacy. Accordingly, this study selected electrospinning on a rotating cylindrical target as an apparatus of broad application and mapped the relationship between key processing variables and scaffold mechanics and structure. This information was…

Physiological Micromechanics of the Anterior Mitral Valve Leaflet

An improved understanding of mitral valve (MV) function remains an important goal for determining mechanisms underlying valve disease and for developing novel therapies. Critical to heart valve tissue homeostasis is the valvular interstitial cells (VICs), which reside in the interstitium and maintain the extracellular matrix (ECM) through both protein synthesis and enzymatic degradation [1]. There is scant experimental data on the alterations of the MV fiber network reorganization as a function of load, which is critical for implementation of computational strategies that attempt to link this meso-micro scale phenomenon. The observed large scale deformations experienced by VICs could be imp…

Fiber Micro-Architecture in the Longitudinal-Radial and Circumferential-Radial Planes of Ascending Thoracic Aortic Aneurysm Media.

It was recently demonstrated by our group that the delamination strength of ascending thoracic aortic aneurysms (ATAA) was lower than that of control (CTRL, non-aneurysmal) ascending thoracic aorta (ATA), and the reduced strength was more pronounced among bicuspid (BAV) vs. tricuspid aortic valve (TAV) patients, suggesting a different risk of aortic dissection for BAV patients. We hypothesized that aortic valve morphologic phenotype predicts fiber micro-architectural anomalies in ATA. To test the hypothesis, we characterized the micro-architecture in the longitudinal-radial (Z-RAD) and circumferential-radial (Θ-RAD) planes of human ATA tissue that was artificially dissected medially. The ou…

On the biomechanical function of scaffolds for engineering load-bearing soft tissues

Replacement or regeneration of load-bearing soft tissues has long been the impetus for the development of bioactive materials. While maturing, current efforts continue to be confounded by our lack of understanding of the intricate multi-scale hierarchical arrangements and interactions typically found in native tissues. The current state of the art in biomaterial processing enables a degree of controllable microstructure that can be used for the development of model systems to deduce fundamental biological implications of matrix morphologies on cell function. Furthermore, the development of computational frameworks which allow for the simulation of experimentally derived observations represe…

Micro - Architectural Data Extraction for Electrospun Poly (Ester Urethane) Urea Scaffolds for Biomechanical Modeling.

Problem: Soft tissue engineered applications have raised the need for accurate descriptions of tissue microstructure and their contributions to global mechanical behavior [1]. Accurate material image analysis is crucial to model engineered tissue biomechanics. The present study proposes a novel method to automatically collect micro-architectural data from electron micrographs (SEM) of electrospun poly (ester urethane) urea (PEUU). Methods: Sets of contiguous SEM images for electrospun PEUU scaffolds made using three mandrel collection tangential velocities (1.5, 4.5, 9.0 m/s) were analyzed. A combination of thresholding and morphological procedures enabled overlaps of fibers to be detected.…

A Method to Extract the Complete Fiber Network Topology of Planar Fibrous Tissues and Scaffolds

Improving fabrication protocols and design strategies, investigating on how fibrous ECM and synthetic architectures affect cell morphology, metabolism and phenotypic expression, predicting mechanical behaviors, have increasingly become crucial goals in the understanding of native tissues and in the development of engineered tissue. In the present study, an image-based analysis approach that provides an automatic tool to fully characterize engineered tissue fiber network topology was developed. The following micro architectural features were detected: fiber angle distribution, fiber connectivity, fiber overlap spatial density, and fiber diameter. In order to demonstrate the potential of this…

A novel approach to fully characterize fiber network morphology of planar fibrous tissues and scaffolds

Understanding how scaffold structure influences cell morphology, metabolism, phenotypic expression, and predicting mechanical behaviors have increasingly become crucial goals in the development of engineered tissue scaffolds. A novel image-based analysis algorithm that provides an automatic tool to characterize engineered tissue fiber network topology is presented. Micro architectural descriptors that unambiguously define the fiber network topology were detected, which include fiber orientation distribution, connectivity, intersection spatial density, and diameter. Algorithm performance was tested using actual sample scanning electron microscopy (SEM) images of (1) electrospun poly(ester ur…

Large strain stimulation promotes extracellular matrix production and stiffness in an elastomeric scaffold model

Mechanical conditioning of engineered tissue constructs is widely recognized as one of the most relevant methods to enhance tissue accretion and microstructure, leading to improved mechanical behaviors. The understanding of the underlying mechanisms remains rather limited, restricting the development of in silico models of these phenomena, and the translation of engineered tissues into clinical application. In the present study, we examined the role of large strip-biaxial strains (up to 50%) on ECM synthesis by vascular smooth muscle cells (VSMCs) micro-integrated into electrospun polyester urethane urea (PEUU) constructs over the course of 3 weeks. Experimental results indicated that VSMC …

Micro Scale Based Mechanical Models for Electrospun Poly (Ester Urethane) Urea Scaffolds.

Micro scale based mechanical models can provide a tool to guide tissue engineering scaffold design and to investigate on how the cellular mechanical and metabolic response are related to local micro-structural deformations. The present study proposes a novel approach to automatically collect micro-architectural data from SEM images of electrospun poly (ester urethane) urea (PEUU) and to recreate statistically equivalent scaffold mechanical models. Sets of contiguous SEM images for each of the three mandrel velocities (1.5, 4.5, 9.0 m/s) were analyzed. A combination of thresholding and morphological procedures enabled fibers overlaps to be detected. The algorithm precision was tested on regu…

Systems level approach reveals the correlation of endoderm differentiation of mouse embryonic stem cells with specific microstructural cues of fibrin gels

Stem cells receive numerous cues from their associated substrate that help to govern their behaviour. However, identification of influential substrate characteristics poses difficulties because of their complex nature. In this study, we developed an integrated experimental and systems level modelling approach to investigate and identify specific substrate features influencing differentiation of mouse embryonic stem cells (mESCs) on a model fibrous substrate, fibrin. We synthesized a range of fibrin gels by varying fibrinogen and thrombin concentrations, which led to a range of substrate stiffness and microstructure. mESCs were cultured on each of these gels, and characterization of the diff…

Continuous Microfiber Wire Mandrel‐Less Biofabrication for Soft Tissue Engineering Applications

Suture materials are the most common bioimplants in surgical and clinical practice, playing a crucial role in wound healing and tendon and ligament repair. Despite the assortment available on the market, sutures are still affected by significant disadvantages, including failure in mimicking the mechanical properties of the tissue, excessive fibrosis, and inflammation. This study introduces a mandrel-less electrodeposition apparatus to fabricate continuous microfiber wires of indefinite length. The mandrel-less biofabrication produces wires, potentially used as medical fibers, with different microfiber bundles, that imitate the hierarchical organization of native tissues, and tailored mechan…

Arsenic promotes NF-Κb-mediated fibroblast dysfunction and matrix remodeling to impair muscle stem cell function

Abstract Arsenic is a global health hazard that impacts over 140 million individuals worldwide. Epidemiological studies reveal prominent muscle dysfunction and mobility declines following arsenic exposure; yet, mechanisms underlying such declines are unknown. The objective of this study was to test the novel hypothesis that arsenic drives a maladaptive fibroblast phenotype to promote pathogenic myomatrix remodeling and compromise the muscle stem (satellite) cell (MuSC) niche. Mice were exposed to environmentally relevant levels of arsenic in drinking water before receiving a local muscle injury. Arsenic-exposed muscles displayed pathogenic matrix remodeling, defective myofiber regeneration …

Tailoring Electrospinning Fabrication for Scaffolds for Heart Valve Tissue Engineering

Previous work in controlling mechanical properties of electrospun scaffolds has largely been limited to altering the orientation of the fibrous network by either large rotational velocity or by altering the electric field during fabrication. Our lab has previously developed a technique to analyze the complete microstructural topology of electrospun scaffolds and extract key descriptors. In this project, we translated the target mandrel at varying speeds along its rotational axis in order to modify the microarchitecture without altering the fiber orientation angle. Using the algorithm mentioned above, we determined that increasing the translation speed resulted in a decrease in fiber interse…

A MICRO-ARCHITECTURAL BASED STRUCTURAL MODEL FOR ELASTOMERIC ELECTROSPUN SCAFFOLDS FOR HEART VALVE TISSUE ENGINEERING

BACKGROUND. Improving how scaffold architectures affect cell morphology, metabolism, phenotypic expression, and predicting mechanical behaviors, are crucial goals in the development of engineered heart valve scaffolds. Studies are required to elucidate how the fibrous microstructure translates into specific tissue (or meso-scale) level mechanical behavior. Deterministic structural models can quantify how key structures contribute to the mechanical response as a function of bulk deformation across multiple scales, as well as provide a better understanding of cellular mechanical response to local micro-structural deformations. An appropriate representative volume element (RVE) size was determ…

From single fiber to macro-level mechanics: A structural finite-element model for elastomeric fibrous biomaterials

In the present work, we demonstrate that the mesoscopic in-plane mechanical behavior of membrane elastomeric scaffolds can be simulated by replication of actual quantified fibrous geometries. Elastomeric electrospun polyurethane (ES-PEUU) scaffolds, with and without particulate inclusions, were utilized. Simulations were developed from experimentally-derived fiber network geometries, based on a range of scaffold isotropic and anisotropic behaviors. These were chosen to evaluate the effects on macro-mechanics based on measurable geometric parameters such as fiber intersections, connectivity, orientation, and diameter. Simulations were conducted with only the fiber material model parameters a…

Micro-Meso Scale Model of Electrospun Poly (Ester Urethane) Urea Scaffolds

Soft tissue engineering applications require accurate descriptions of native and engineered tissue microstructure and their contributions to global mechanical behavior [1–6]. Moreover, micro scale based mechanical models can be used to: (1) guide tissue engineering scaffold design, (2) provide a better understanding of cellular mechanical and metabolic response to local micro-structural deformations, and (3) investigate structural changes as a function of deformation across multiple scales. We present a novel approach to automatically collect micro-architectural data (fibers overlaps, fiber connectivity, and fiber orientation) from SEM images of electrospun poly (ester urethane) urea (PEUU)…

A custom image-based analysis tool for quantifying elastin and collagen micro-architecture in the wall of the human aorta from multi-photon microscopy

The aorta possesses a micro-architecture that imparts and supports a high degree of compliance and mechanical strength. Alteration of the quantity and/or arrangement of the main load-bearing components of this micro-architecture - the elastin and collagen fibers - leads to mechanical, and hence functional, changes associated with aortic disease and aging. Therefore, in the future, the ability to rigorously characterize the wall fiber micro-architecture could provide insight into the complicated mechanisms of aortic wall remodeling in aging and disease. Elastin and collagen fibers can be observed using state-of-the-art multi-photon microscopy. Image-analysis algorithms have been effective at…

Evaluation of the stromal vascular fraction of adipose tissue as the basis for a stem cell-based tissue-engineered vascular graft

Abstract Objective One of the rate-limiting barriers within the field of vascular tissue engineering is the lengthy fabrication time associated with expanding appropriate cell types in culture. One particularly attractive cell type for this purpose is the adipose-derived mesenchymal stem cell (AD-MSC), which is abundant and easily harvested from liposuction procedures. Even this cell type has its drawbacks, however, including the required culture period for expansion, which could pose risks of cellular transformation or contamination. Eliminating culture entirely would be ideal to avoid these concerns. In this study, we used the raw population of cells obtained after digestion of human lipo…

Preparation and characterization of a biologic scaffold from esophageal mucosa

Biologic scaffolds composed of extracellular matrix (ECM) are commonly used to facilitate a constructive remodeling response in several types of tissue, including the esophagus. Surgical manipulation of the esophagus is often complicated by stricture, but preclinical and clinical studies have shown that the use of an ECM scaffold can mitigate stricture and promote a constructive outcome after resection of full circumference esophageal mucosa. Recognizing the potential benefits of ECM derived from homologous tissue (i.e., site-specific ECM), the objective of the present study was to prepare, characterize, and assess the in-vivo remodeling properties of ECM from porcine esophageal mucosa. The…

Elastomeric Electrospun Polyurethane Scaffolds: The Interrelationship Between Fabrication Conditions, Fiber Topology, and Mechanical Properties

Electrospinning has been gaining increasing popularity in the fabrication of engineered tissue scaffolds due to its ability to produce nano to micro scale fibrous sheets. Many investigators have attempted to apply various degrees of control to this process in order to produce fiber meshes with more predictable patterns. These attempts have largely been limited to controlling fiber alignment and have fallen into two categories: physical manipulation of the fibers by pulling them into alignment using a rapidly spinning mandrel[1–3] or manipulation of the electric field during fabrication.[4, 5]

A microstructure based mechanical model for planar fibrous scaffolds.

Cardiac valve and myocardium tissue regeneration has consistently raised interest for cell-seeded/microintegrated planar fibrous scaffolds. Electrospun constructs, decellularized tissues and collagen/fibrin gels often show a similar microstructure mainly characterized by the fibrous network topology. Microstructure based mechanical modeling enable fabrication parameters and scaffolds morphology to be related to mesomacro mechanical response. A novel approach to (1) characterize the material fibers network microarchitecture, (2) reproduce stochastically equivalent fiber network models, and (3) predict the mechanical response at meso-macro level is presented in this work. Electron micrographs…

Correlations between transmural mechanical and morphological properties in porcine thoracic descending aorta.

Determination of correlations between transmural mechanical and morphological properties of aorta would provide a quantitative baseline for assessment of preventive and therapeutic strategies for aortic injuries and diseases. A multimodal and multidisciplinary approach was adopted to characterize the transmural morphological properties of descending porcine aorta. Histology and multi-photon microscopy were used for describing the media layer micro-architecture in the circumferential-radial plane, and Fourier Transform infrared imaging spectroscopy was utilized for determining structural protein, and total protein content. The distributions of these quantified properties across the media thi…

Extracellular matrix fiber microarchitecture is region-specific in bicuspid aortic valve-associated ascending aortopathy

Abstract Objective Ascending thoracic aortic aneurysm (ATAA) in patients with bicuspid aortic valve (BAV) commonly dilate asymmetrically compared with patients with tricuspid aortic valve (TAV). This discrepancy in aneurysm geometry led us to hypothesize that microarchitectural differences underlie the observed asymmetric dilatation pattern. The purpose of this study was to characterize the microarchitectural distinctions of the extracellular matrix of the 2 phenotypes with a focus on the proportion of radially oriented elastin and collagen fibers in different circumferential aortic regions. Methods Aortic tissue rings were obtained just distal to the sinotubular junction from patients with…

Nonthrombogenic, Biodegradable Elastomeric Polyurethanes with Variable Sulfobetaine Content

For applications where degradable polymers are likely to have extended blood contact, it is often important for these materials to exhibit high levels of thromboresistance. This can be achieved with surface modification approaches, but such modifications may be transient with degradation. Alternatively, polymer design can be altered such that the bulk polymer is thromboresistant and this is maintained with degradation. Toward this end a series of biodegradable, elastic polyurethanes (PESBUUs) containing different zwitterionic sulfobetaine (SB) content were synthesized from a polycaprolactone-diol (PCL-diol):SB-diol mixture (100:0, 75:25, 50:50, 25:75 and 0:100) reacted with diisocyanatobuta…

Micro – Meso scale based biomechanical models to assist the design and fabrication of scaffolds for Cardiac Tissue Regeneration

Questo lavoro presenta una strategia di modellazione strutturale basata su dati di micro-architettura finalizzata a: (A) guidare fabbricazione e progetto di scaffold per ingegneria di tessuto, (B) studiare la risposta cellulare meccanica alle deformazioni strutturali. Applicazioni cliniche ideali per la metodologia proposta sono le valvole cardiache e il patch di miocardio. Custom software di analisi d’immagine e’ stato utilizzato per caratterizzare la morfologia dei campioni. Le topologie dei materiali individuate sono state impiegate per generare equivalenti modelli a rete. Il comportamento meccanico alla macro scala e’ stato studiato mediante prove di carico biassiale. Questa messe speri…

Fabrication Techniques for Electrospun Polyurethane Scaffolds that Generate Valve Leaflet Mechanical Properties.

In Vivo Functional Evaluation of Tissue-Engineered Vascular Grafts Fabricated Using Human Adipose-Derived Stem Cells from High Cardiovascular Risk Populations

Many preclinical evaluations of autologous small-diameter tissue-engineered vascular grafts (TEVGs) utilize cells from healthy humans or animals. However, these models hold minimal relevance for clinical translation, as the main targeted demographic is patients at high cardiovascular risk such as individuals with diabetes mellitus or the elderly. Stem cells such as adipose-derived mesenchymal stem cells (AD-MSCs) represent a clinically ideal cell type for TEVGs, as these can be easily and plentifully harvested and offer regenerative potential. To understand whether AD-MSCs sourced from diabetic and elderly donors are as effective as those from young nondiabetics (i.e., healthy) in the conte…

Comprehensive Biomaterials, Chapter 94 “The Mechanics of Native and Engineered Cardiac Soft Tissue”.

Abdominal wall reconstruction by a regionally distinct biocomposite of extracellular matrix digest and a biodegradable elastomer.

Current extracellular matrix (ECM) derived scaffolds offer promising regenerative responses in many settings, however in some applications there may be a desire for more robust and long lasting mechanical properties. A biohybrid composite material that offers both strength and bioactivity for optimal healing towards native tissue behavior may offer a solution to this problem. A regionally distinct biocomposite scaffold composed of a biodegradable elastomer (poly(ester urethane)urea) and porcine dermal ECM gel was generated to meet this need by a concurrent polymer electrospinning/ECM gel electrospraying technique where the electrosprayed component was varied temporally during the processing…

STRUCTURAL DETERMINISTIC MODELING DESIGN AND FABRICATION OF ELECTROSPUN SCAFFOLDS FOR SOFT TISSUE ENGINEERING

The research fields of tissue engineering, biomechanics and regenerative medicine continue to evolve in response to the ever growing need for tissue replacement options. These fields aim to restore, maintain, or improve tissue or whole organ function. This doctoral studies focus on the development and experimental validation of a structural deterministic modeling strategy to: A) guide tissue engineering scaffold design, B) provide a better understanding of cellular mechanical and metabolic response to local micro-structural deformations. Targeted clinical application was the pulmonary heart valve. Electrospinning was selected as the optimal platform technology to implement, validate and tes…

Micro-Architecture Based Structural Model for Elastomeric Electrospun Scaffolds.

Controlling micro-structure to enhance de novo extracellular matrix deposition in elastomeric scaffolds for cardiac tissue regeneration

Characterization of the complete fiber network topology of planar fibrous tissues and scaffolds

Understanding how engineered tissue scaffold architecture affects cell morphology, metabolism, phenotypic expression, as well as predicting material mechanical behavior has recently received increased attention. In the present study, an image-based analysis approach that provides an automated tool to characterize engineered tissue fiber network topology is presented. Micro-architectural features that fully defined fiber network topology were detected and quantified, which include fiber orientation, connectivity, intersection spatial density, and diameter. Algorithm performance was tested using scanning electron microscopy (SEM) images of electrospun poly(ester urethane)urea (ES-PEUU) scaffo…

Association of Fiber Orientation and Dissection Properties of Ascending Thoracic Aortic Aneurysms With Aortic Valve Morphology

Type A aortic dissection (AoD) of an ascending thoracic aortic aneurysm (ATAA) is a life-threatening cardiovascular emergency with a high potential for death. Despite improved surgical techniques, the morbidity risk for emergent surgery remains 24% worldwide according to data from the International Registry of Acute Aortic Dissection [1].Copyright © 2011 by ASME

Effects of Rastering Velocity on Electrospun Polyeurthane Structure and Mechanical Properties

The effect of detergents on the basement membrane complex of a biologic scaffold material

The basement membrane complex (BMC) is a critical component of the extracellular matrix (ECM) that supports and facilitates the growth of cells. This study investigates four detergents commonly used in the process of tissue decellularization and their effect upon the BMC. The BMC of porcine urinary bladder was subjected to 3% Triton-X 100, 8 mM 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS), 4% sodium deoxycholate or 1% sodium dodecyl sulfate (SDS) for 24 h. The BMC structure for each treatment group was assessed by immunolabeling, scanning electron microscopy (SEM) and second harmonic generation (SHG) imaging of the fiber network. The composition was assessed by quantif…

Bi-layered polyurethane – Extracellular matrix cardiac patch improves ischemic ventricular wall remodeling in a rat model

As an intervention to abrogate ischemic cardiomyopathy, the concept of applying a temporary, local patch to the surface of the recently infarcted ventricle has been explored from a number of design perspectives. Two important features considered for such a cardiac patch include the provision of appropriate mechanical support and the capacity to influence the remodeling pathway by providing cellular or biomolecule delivery. The objective of this report was to focus on these two features by first evaluating the incorporation of a cardiac extracellular matrix (ECM) component, and second by evaluating the impact of patch anisotropy on the pathological remodeling process initiated by myocardial …

Unseeded Elastomeric Single Leaflets Retain Function and Remodel After Implant In Ovine Pulmonary Outflow Tract

Current materials for heart valve replacement and repair are limited by the inability to grow or remodel. Tissue engineered valves offer the potential to overcome these disadvantages by creating living structures, but is limited by the availability of biocompatible scaffold materials with desirable biomechanical properties. We assessed the in vivo performance of a novel scaffold poly(carbonate urethane) urea (PCUU), fabricated by electrospinning and implanted in the pulmonary outflow tract of sheep. PCUU was electrospun into elastomeric sheets of thickness ranging from 120-180 μm. Using cardiopulmonary bypass we replaced the native anterior pulmonary leaflet with an acellular PCUU leaflet. …

A mechanistic model on the role of “radially-running” collagen fibers on dissection properties of human ascending thoracic aorta.

Aortic dissection (AoD) is a common condition that often leads to life-threatening cardiovascular emergency. From a biomechanics viewpoint, AoD involves failure of load-bearing microstructural components of the aortic wall, mainly elastin and collagen fibers. Delamination strength of the aortic wall depends on the load-bearing capacity and local micro-architecture of these fibers, which may vary with age, disease and aortic location. Therefore, quantifying the role of fiber micro-architecture on the delamination strength of the aortic wall may lead to improved understanding of AoD. We present an experimentally-driven modeling paradigm towards this goal. Specifically, we utilize collagen fib…

Alterations in the Microstructure of the Anterior Mitral Valve Leaflet Under Physiological Stress

An improved understanding of mitral valve (MV) function remains an important goal for determining mechanisms underlying valve disease and for developing novel therapies. Critical to heart valve tissue homeostasis is the valvular interstitial cells (VICs), which reside in the interstitium and maintain the extracellular matrix (ECM) through both protein synthesis and enzymatic degradation [1]. There is scant quantitative experimental data on the alterations of the MV fiber network reorganization as a function of load, which is critical for implementation of computational strategies that attempt to link this meso-micro scale phenomenon. The observed large scale deformations experienced by VICs…

Positive effects of an extracellular matrix hydrogel on rat anterior cruciate ligament fibroblast proliferation and collagen mRNA expression

Summary Background/Objective We have previously shown that an extracellular matrix (ECM) bioscaffold derived from porcine small intestine submucosa (SIS) enhanced the healing of a gap injury of the medial collateral ligament as well as the central third defect of the patellar tendon. With the addition of a hydrogel form of SIS, we found that a transected goat anterior cruciate ligament (ACL) could also be healed. The result begs the research question of whether SIS hydrogel has positive effects on ACL fibroblasts (ACLFs) and thus facilitates ACL healing. Methods In the study, ECM-SIS hydrogel was fabricated from the digestion of decellularised and sterilised sheets of SIS derived from αGal-…

Meso-scale topological cues influence extracellular matrix production in a large deformation, elastomeric scaffold model

Physical cues are decisive factors in extracellular matrix (ECM) formation and elaboration. Their transduction across scale lengths is an inherently symbiotic phenomenon that while influencing ECM fate is also mediated by the ECM structure itself. This study investigates the possibility of enhancing ECM elaboration by topological cues that, while not modifying the substrate macro scale mechanics, can affect the meso-scale strain range acting on cells incorporated within the scaffold. Vascular smooth muscle cell micro-integrated, electrospun scaffolds were fabricated with comparable macroscopic biaxial mechanical response, but different meso-scale topology. Seeded scaffolds were conditioned …

FIBER DISTRIBUTION OF ASCENDING THORACIC AORTIC ANEURYSMS ASSOCIATED WITH VALVE MORPHOLOGY

Analysis of Electrospun Scaffolds Micro - Architectural Data.

Effect of Physiologic Oscillatory Fluid Shear Stress on Engineered Heart Valve Tissue Formation.

It was previously demonstrated that combined flexure and flow in vitro conditioning augments engineered heart valve tissue formation using bone marrow-derived mesenchymal stem cells (MSC) seeded on polyglycolic acid (PGA)/poly-L-lactic acid (PLLA) blend nonwoven fibrous scaffolds (Engelmayr, et al., Biomaterials 2006; vol. 27 pp. 6083-95). Additionally, seeded scaffolds incorporated into a tissue engineered valve construct experienced significant increases in tissue formation rates with media supplementation (basic fibroblast growth factor [bFGF] and ascorbic acid-2-phosphate [AA2P]) and dynamic conditioning approximating pulmonary valve levels (Ramaswamy, et al., Biomaterials 2010; vol. 31…

Constitutive modeling of ascending thoracic aortic aneurysms using microstructural parameters.

Ascending thoracic aortic aneurysm (ATAA) has been associated with diminished biomechanical strength and disruption in the collagen fiber microarchitecture. Additionally, the congenital bicuspid aortic valve (BAV) leads to a distinct extracellular matrix structure that may be related to ATAA development at an earlier age than degenerative aneurysms arising in patients with the morphological normal tricuspid aortic valve (TAV). The purpose of this study was to model the fiber-reinforced mechanical response of ATAA specimens from patients with either BAV or TAV. This was achieved by combining image-analysis derived parameters of collagen fiber dispersion and alignment with tensile testing dat…

A Method to Extract the Complete Fiber Network Topology of Planar Fibrous Tissues and Scaffolds.

Improving fabrication protocols and design strategies, investigating on how scaffold architecture affects cell morphology, metabolism and phenotypic expression, predicting mechanical behaviors, have increasingly become crucial goals in the development of engineered tissue scaffolds. In the present study, an image-based analysis approach that provides an automatic tool to fully characterize engineered tissues fiber network topology was developed. The following micro architectural features are detected: fiber angle distribution, fiber connectivity, fiber overlap spatial density, fiber diameter. In order to demonstrate the potential of this approach Electrospun poly(ester urethane)urea (ES-PEU…

Microstructural manipulation of electrospun scaffolds for specific bending stiffness for heart valve tissue engineering

Biodegradable thermoplastic elastomers are attractive for application in cardiovascular tissue construct development due to their amenability to a wide range of physical property tuning. For heart valve leaflets, while low flexural stiffness is a key design feature, control of this parameter has been largely neglected in the scaffold literature where electrospinning is being utilized. This study evaluated the effect of processing variables and secondary fiber populations on the microstructure, tensile and bending mechanics of electrospun biodegradable polyurethane scaffolds for heart valve tissue engineering. Scaffolds were fabricated from poly(ester urethane) urea (PEUU) and the deposition…

A Hydrogel Derived From Decellularized Dermal Extracellular Matrix. Biomaterials

The ECM of mammalian tissues has been used as a scaffold to facilitate the repair and reconstruction of numerous tissues. Such scaffolds are prepared in many forms including sheets, powders, and hydrogels. ECM hydrogels provide advantages such as injectability, the ability to fill an irregularly shaped space, and the inherent bioactivity of native matrix. However, material properties of ECM hydrogels and the effect of these properties upon cell behavior are neither well understood nor controlled. The objective of this study was to prepare and determine the structure, mechanics, and the cell response in vitro and in vivo of ECM hydrogels prepared from decellularized porcine dermis and urinar…

Solubilized liver extracellular matrix maintains primary rat hepatocyte phenotype in-vitro.

Whole organ engineering and cell-based regenerative medicine approaches are being investigated as potential therapeutic options for end-stage liver failure. However, a major challenge of these strategies is the loss of hepatic specific function after hepatocytes are removed from their native microenvironment. The objective of the present study was to determine if solubilized liver extracellular matrix (ECM), when used as a media supplement, can better maintain hepatocyte phenotype compared to type I collagen alone or solubilized ECM harvested from a non-liver tissue source. Liver extracellular matrix (LECM) from four different species was isolated via liver tissue decellularization, solubil…

Micro-Meso Scale Models of Electrosun Poly (Ester Urethane) Urea Scaffolds.

A NOVEL APPROACH TO FULLY CHARACTERIZE FIBER NETWORK MORPHOLOGY OF PLANAR FIBROUS TISSUES AND SCAFFOLDS

Comprendere come la struttura di uno scaffold influenzi la morfologia cellulare e predirne il comportamento meccanico sono divenuti obiettivi fondamentali nello sviluppo dei tessuti ingegnerizzati. In questo studio si presenta un algoritmo innovativo basato su analisi d’immagine. Vengono introdotti descrittori di micro architettura che identificano univocamente la topologia della rete di fibre: orientamento delle fibre, connettività, densità spaziale delle intersezioni e diametro. Le prestazioni dell’algoritmo sono state valutate utilizzando immagini di microscopio a scansione elettronica (SEM) di (1) scaffolds in poliestere uretano-urea prodotti per elettrospinning, (2) gel di collagene se…

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction

Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infar…

Geometric characterization and simulation of planar layered elastomeric fibrous biomaterials

An important class of biomaterials is composed of layered networks of elastomeric fibers. While there is a growing interest in modeling and simulation of the mechanical response of these biomaterials, a theoretical foundation for such simulations has yet to be firmly established. The present work addresses this issue in two ways. First, using methods of geometric probability we develop theoretical estimates for the linear and areal fiber intersection densities for two-dimensional fibrous networks. These are expressed in terms of the fiber density and orientation distribution function, both of which are relatively easy to measure properties. Secondly, we develop a random walk algorithm for g…

A Structural Deterministic Model for Electrospun Scaffolds.

Biomaterials Science: An Introduction to Materials in Medicine, 3rd ed., Chapter I.1.4 Finite Element Analysis in Biomechanics