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ABSTRACT: The engineering foundation for novel approaches for the repair of congenital defects that involve the main pulmonary artery (PA) must rest on an understanding of changes in the structure-function relationship that occur during postnatal maturation. In the present study, we quantified the postnatal growth patterns in structural and biomechanical behavior in the ovine PA in the juvenile and adult stages. The biaxial mechanical properties and collagen and elastin fiber architecture were studied in four regions of the PA wall, with the collagen recruitment of the medial region analyzed using a custom biaxial mechanical-multiphoton microscopy system. Circumferential residual strain was also quantified at the sinotubular junction and bifurcation locations, which delimit the PA. The PA wall demonstrated significant mechanical anisotropy, except in the posterior region where it was nearly isotropic. Overall, we observed only moderate changes in regional mechanical properties with growth. We did observe that the medial and lateral locations experience a moderate increase in anisotropy. There was an average of about 24% circumferential residual stain present at the luminal surface in the juvenile stage that decreased to 16% in the adult stage with a significant decrease at the bifurcation, implying that the PA wall remodels toward the bifurcation with growth. There were no measurable changes in collagen and elastin content of the tunica media with growth. On average, the collagen fiber recruited more rapidly with strain in the adult compared to the juvenile. Interestingly, the PA thickness remained constant with growth. When this fact is combined with the observed stable overall mechanical behavior and increase in vessel diameter with growth, a simple Laplace Law wall stress estimate suggests an increase in effective PA wall stress with postnatal maturation. This observation is contrary to the accepted theory of maintenance of homeostatic stress levels in the regulation of vascular function and suggests alternative mechanisms regulate postnatal somatic growth. Understanding the underlying mechanisms, incorporating important structural features during growth, will help to improve our understanding of congenital defects of the PA and lay the basis for functional duplication in their repair and replacement.
Journal of Biomechanical Engineering 02/2013; 135(2):021022. · 1.90 Impact Factor
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ABSTRACT: Surgical replacement of the pulmonary valve (PV) is a common treatment option for congenital pulmonary valve defects. Engineered tissue approaches to develop novel PV replacements are intrinsically complex, and will require methodical approaches for their development. Single leaflet replacement utilizing an ovine model is an attractive approach in that candidate materials can be evaluated under valve level stresses in blood contact without the confounding effects of a particular valve design. In the present study an approach for optimal leaflet shape design based on finite element (FE) simulation of a mechanically anisotropic, elastomeric scaffold for PV replacement is presented. The scaffold was modeled as an orthotropic hyperelastic material using a generalized Fung-type constitutive model. The optimal shape of the fully loaded PV replacement leaflet was systematically determined by minimizing the difference between the deformed shape obtained from FE simulation and an ex-vivo microCT scan of a native ovine PV leaflet. Effects of material anisotropy, dimensional changes of PV root, and fiber orientation on the resulting leaflet deformation were investigated. In-situ validation demonstrated that the approach could guide the design of the leaflet shape for PV replacement surgery.
Journal of biomechanics 01/2013; · 2.66 Impact Factor
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ABSTRACT: While the role of collagen and elastin fibrous components in heart valve valvular biomechanics has been extensively investigated, the biomechanical role of the glycosaminoglycan (GAG) gelatinous-like material phase remains unclear. In the present study, we investigated the biomechanical role of GAGs in porcine aortic valve (AV) leaflets under tension utilizing enzymatic removal. Tissue specimens were removed from the belly region of porcine AVs and subsequently treated with either an enzyme solution for GAG removal or a control (buffer with no enzyme) solution. A dual stress level test methodology was used to determine the effects at low and high (physiological) stress levels. In addition, planar biaxial tests were conducted both on-axis (i.e. aligned to the circumferential and radial axes) and at 45° off-axis to induce maximum shear, to explore the effects of augmented fiber rotations on the fiber-fiber interactions. Changes in hysteresis were used as the primary metric of GAG functional assessment. A simulation of the low-force experimental setup was also conducted to clarify the internal stress system and provide viscoelastic model parameters foR this loading range. Results indicated that under planar tension the removal of GAGs had no measureable affect extensional mechanical properties (either on- or 45° off-axis), including peak stretch, hysteresis and creep. Interestingly, in the low-force range, hysteresis was markedly reduced, from 35.96±2.65% in control group to 25.00±1.64% (p<0.001) as a result of GAG removal. Collectively, these results suggest that GAGs do not play a direct role in modulating the time-dependent tensile properties of valvular tissues. Rather, they appear to be strongly connected with fiber-fiber and fiber-matrix interactions at low force levels. Thus, we speculate that GAGs may be important in providing a damping mechanism to reduce leaflet flutter when the leaflet is not under high tensile stress.
Acta biomaterialia 10/2012; · 3.98 Impact Factor
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ABSTRACT: The semilunar (aortic and pulmonary) heart valves function under dramatically different hemodynamic environments, and have been shown to exhibit differences in mechanical properties, extracellular matrix (ECM) structure, and valve interstitial cell (VIC) biosynthetic activity. However, the relationship between VIC function and the unique micromechanical environment in each semilunar heart valve remains unclear. In the present study, we quantitatively compared porcine semilunar mRNA expression of primary ECM constituents, and layer- and valve-specific VIC-collagen mechanical interactions under increasing transvalvular pressure (TVP). Results indicated that the aortic valve (AV) had a higher fibrillar collagen mRNA expression level compared to the pulmonary valve (PV). We further noted that VICs exhibited larger deformations with increasing TVP in the collagen rich fibrosa layer, with substantially smaller changes in the spongiosa and ventricularis layers. While the VIC-collagen micro-mechanical coupling varied considerably between the semilunar valves, we observed that the VIC deformations in the fibrosa layer were similar at each valve's respective peak TVP. This result suggests that each semilunar heart valve's collagen fiber microstructure is organized to induce a consistent VIC deformation under its respective diastolic TVP. Collectively, our results are consistent with higher collagen biosynthetic demands for the AV compared to the PV, and that the valvular collagen microenvironment may play a significant role in regulating VIC function.
Cellular and Molecular Bioengineering 09/2012; 5(3):254-265. · 1.95 Impact Factor
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ABSTRACT: 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 mandrel was translated at varying rates in order to modify fiber intersection density. Scaffolds were also fabricated in conjunction with secondary fiber populations designed either for mechanical reinforcement or to be selectively removed following fabrication. It was determined that increasing fiber intersection densities within PEUU scaffolds was associated with lower bending moduli. Further, constructs fabricated with stiff secondary fiber populations had higher bending moduli whereas constructs with secondary fiber populations which were selectively removed had noticeably lower bending moduli. Insights gained from this work will be directly applicable to the fabrication of soft tissue constructs, specifically in the development of cardiac valve tissue constructs.
Acta biomaterialia 08/2012; · 3.98 Impact Factor
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ABSTRACT: The intimal and medial linings of the pulmonary artery consist largely of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), respectively. The migration of these cell types to a potential tissue-engineered pulmonary valve (TEPV) implant process is therefore of interest in understanding the valve remodeling process. Visualization and cell tracking by MRI, which employs hypointense contrast achievable through the use of superparamagnetic iron oxide (SPIO) microparticles to label cells, provides a method in which this can be studied. We investigated the SPIO labeling efficiency of human VECs and VSMCs, and used two- and three-dimensional gradient echo sequences to track the migration of these cells in agar gel constructs. Protamine sulfate (4.5 µg/mL) was used to enhance SPIO uptake and was found to have no influence on cell viability or proliferation. MRI experiments were initially performed using a 9.4-T scanner. The results demonstrated that the spatial positions of hypointense spots were relatively unchanged over 12 days. Subsequent MR experiments performed at 7 T demonstrated that three-dimensional imaging provided the best spatial resolution to assess cell fate. R(2)* maps were bright in SPIO cell-encapsulated gels in comparison with unlabeled counterparts. Signal voids were ruled out as hypointense regions owing to the smooth exponential decay of T(2)* in these voxels. As a next step, we intend to use the SPIO cell labeling and MR protocols established in this study to assess whether hemodynamic stresses will alter the vascular cell migratory patterns. These studies will shed light on the mechanisms of vascular remodeling after TEPV implantation.
NMR in Biomedicine 03/2012; 25(3):410-7. · 3.21 Impact Factor
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ABSTRACT: Decellularized aortic valves (AV) are promising scaffolds for tissue engineered heart valve (TEHV) application; however, it is not known what the intrinsic fatigue mechanism of the AV extracellular matrix (ECM) is and how this relates to decellularized AV functional limits when tissue remodeling does not take place. In this study, decellularized AVs were subjected to in vitro cardiac exercising and the exercised leaflets were characterized to assess the structural and mechanical alterations. A flow-loop cardiac exerciser was designed to allow for pulsatile flow conditions while maintaining sterility. The acellular valve conduits were sutured into a silicone root with the Valsalva sinus design and subjected to cardiac cycling for 2 weeks (1.0 million cycles) and 4 weeks (2.0 million cycles). Following exercising, thorough structural and mechanical characterizations were then performed. The overall morphology was maintained and the exercised leaflets were able to coapt and support load; however, the leaflets
exhibited an unfolded and thinned morphology. The straightening of the locally wavy collagen fiber structure was confirmed by histology and small angle light scattering; the disruption of elastin network was also observed. Biaxial mechanical testing showed that the leaflet extensibility was largely reduced by cardiac exercising. In the absence of cellular maintenance, decellularized leaflets experience structural
fatigue due to lack of exogenous stabilizing crosslinks, and the structural disruption is irreversible and cumulative. Although not being a means to predict the durability of the acellular valve implants, this mechanistic study reveals the fatigue pattern of the acellular leaflets and implies the importance of recellularization in developing a TEHV, in which long term durability will likely be better achieved by
continual remodeling and repair of the valvular ECM.
Cardiovascular Engineering and Technology 03/2012; 3(1):62-72.
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ABSTRACT: Alteration of the native mitral valve (MV) shape has been hypothesized to have a profound effect on the local tissue stress distribution, and is potentially linked to limitations in repair durability. The present study was undertaken to elucidate the relation between MV annular shape and central mitral valve anterior leaflet (MVAL) strain history, using flat annuloplasty in an ovine model. In addition, we report for the first time the presence of residual in vivo leaflet strains. In vivo leaflet deformations were measured using sonocrystal transducers sutured to the MVAL (n = 10), with the 3D positions acquired over the full cardiac cycle. In six animals a flat ring was sutured to the annulus and the transducer positions recorded, while in the remaining four the MV was excised from the exsanguinated heart and the stress-free transducer positions obtained. In the central region of the MVAL the peak stretch values, referenced to the minimum left ventricular pressure (LVP), were 1.10 ± 0.01 and 1.31 ± 0.03 (mean ± standard error) in the circumferential and radial directions, respectively. Following flat ring annuloplasty, the central MVAL contracted 28% circumferentially and elongated 16% radially at minimum LVP, and the circumferential direction was under a negative strain state during the entire cardiac cycle. After valve excision from the exsanguinated heart, the MVAL contracted significantly (18 and 30% in the circumferential and radial directions, respectively), indicating the presence of substantial in vivo residual strains. While the physiological function of the residual strains (and their associated stresses) are at present unknown, accounting for their presence is clearly necessary for accurate computational simulations of MV function. Moreover, we demonstrated that changes in annular geometry dramatically alter valvular functional strains in vivo. As levels of homeostatic strains are related to tissue remodeling and homeostasis, our results suggest that surgically introduced alterations in MV shape could lead to the long term MV mechanobiological and microstructural alterations that could ultimately affect MV repair durability.
Annals of biomedical engineering 02/2012; 40(7):1455-67. · 2.41 Impact Factor
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ABSTRACT: Infarct expansion after myocardial infarction (MI) is an important phenomenon that initiates and sustains adverse left ventricular (LV) remodeling. We tested the hypothesis that infarct modification by material-induced infarct stiffening and thickening limits infarct expansion and LV remodeling.
Anteroapical infarction was induced in 21 sheep. Sheep were randomized to injection of saline (2.6 mL) or tissue filler material (2.6 mL) into the infarct within 3 hours of MI. Animals were monitored for 8 weeks with echocardiography to assess infarct expansion and global LV remodeling. Morphometric measurements were performed of excised hearts to quantify infarct thickness. Regional blood flow was assessed with colored microspheres. Infarct material properties were measured using biaxial tensile testing.
Compared with controls at 8 weeks, treatment animals had less infarct expansion, reduced LV dilatation (LV systolic volumes: 60.8±4.3 vs 80.3±6.9 mL; p<0.05), greater ejection fraction (0.310±0.026 vs 0.276±0.013; p<0.05), thicker infarcts (5.5±0.2 vs 2.2±0.3 mm; p<0.05), and greater infarct blood flow (0.22±0.04 vs 0.11±0.03 mL/min/g; p<0.05). The longitudinal peak strain in the treatment group was less (0.05014±0.0141) than the control group (0.1024±0.0101), indicating increased stiffness of the treated infarcts.
Durable infarct thickening and stiffening can be achieved by infarct biomaterial injection, resulting in the amelioration of infarct expansion and global LV remodeling. Further material optimization will allow for clinical translation of this novel treatment paradigm.
The Annals of thoracic surgery 08/2011; 92(2):617-24. · 3.74 Impact Factor
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ABSTRACT: Glutaraldehyde (GLUT) crosslinked porcine aortic heart valves are continued to be extensively used in heart valve replacement surgeries. GLUT does not crosslink glycosaminoglycans in the tissue and we have demonstrated that GAG loss is associated with tissue degeneration. In this study, we examined the ability of neomycin to enhance GLUT crosslinking to stabilize GAGs, as well as provide evidence of improved functional integrity. Neomycin enhanced GLUT crosslinked (NG) leaflets exposed to collagenase and elastase enzymes exhibited an increased resistance to proteolytic degradation. Furthermore, NG leaflets exhibited small but significant increases in collagen denaturation temperatures when compared to that of standard GLUT crosslinked BHVs. NG leaflets subjected to storage, accelerated cyclic fatigue, and in vitro enzyme mediated GAG degradation revealed improved GAG stabilization versus standard GLUT crosslinked valves, which sustained substantial decreases in GAG content. Ultrastructural analysis using transmission electron microscopy qualitatively confirmed NG leaflets preserved GAGs after enzymatic degradation. Biomechanical analyses demonstrated that NG leaflets were functionally similar to GLUT tissues but were slightly stiffer under both planar biaxial tension and under flexure. Interestingly, after GAGase treatment, GLUT tissues showed increased areal compliance and reduced hysteresis, while NG leaflets were unchanged. Collectively, NG cross-linking functionally insulated the tissue from GAG digestion, and imparted modest additional matrix stiffness but maintained tissue hysteresis properties.
Journal of Biomedical Materials Research Part B Applied Biomaterials 06/2011; 99(2):217-29. · 2.15 Impact Factor
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ABSTRACT: Mechanical cues that trigger pathological remodeling in smooth muscle tissues remain largely unknown and are thought to be pivotal triggers for strain-induced remodeling. Thus, an understanding of the effects mechanical stimulation is important to elucidate underlying mechanisms of disease states and in the development of methods for smooth muscle tissue regeneration. For example, the urinary bladder wall (UBW) adaptation to spinal cord injury (SCI) includes extensive hypertrophy as well as increased collagen and elastin, all of which profoundly alter its mechanical response. In addition, the pro-fibrotic growth factor TGF-β1 is upregulated in pathologies of other smooth muscle tissues and may contribute to pathological remodeling outcomes. In the present study, we utilized an ex vivo organ culture system to investigate the response of UBW tissue under various strain-based mechanical stimuli and exogenous TGF-β1 to assess extracellular matrix (ECM) synthesis, mechanical responses, and bladder smooth muscle cell (BSMC) phenotype. Results indicated that a 0.5-Hz strain frequency triangular waveform stimulation at 15% strain resulted in fibrillar elastin production, collagen turnover, and a more compliant ECM. Further, this stretch regime induced changes in cell phenotype while the addition of TGF-β1 altered this phenotype. This phenotypic shift was further confirmed by passive strip biomechanical testing, whereby the bladder groups treated with TGF-β1 were more compliant than all other groups. TGF-β1 increased soluble collagen production in the cultured bladders. Overall, the 0.5-Hz strain-induced remodeling caused increased compliance due to elastogenesis, similar to that seen in early SCI bladders. Thus, organ culture of bladder strips can be used as an experimental model to examine ECM remodeling and cellular phenotypic shift and potentially elucidate BMSCs ability to produce fibrillar elastin using mechanical stretch either alone or in combination with growth factors.
Biomechanics and Modeling in Mechanobiology 03/2011; 11(1-2):131-45. · 3.19 Impact Factor
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ABSTRACT: The aim of the study was to assess the effect of geometric variations on the stresses developed in the leaflets of congenital bicuspid aortic valves (CBAV). We developed a model for the human tri-leaflet aortic valve based on the geometry and dimensions published in the literature. We also developed simulated CBAV geometry based on the most common geometry present in patients with CBAV that is published in the literature. We employed a constitutive relationship for the leaflet material from the previously published experimental data of fresh porcine aortic valve leaflet specimens for the analysis. We performed dynamic finite element (FE) structural analysis of the valves in the aortic position in order to compute the strain and stress distribution on the leaflets of the tri-leaflet valve and the CBAV models. Our results showed that large changes in the computed in-plane leaflet strain and stress occurred with variations in the geometry of the simulated CBAV whereas changes due to alterations in material constants were correspondingly less. The valve orifice area in the fully open position was significantly reduced in CBAV compared to that for the tri-leaflet valve. The changes in geometry of CBAV resulted in large changes in in-plane strain and stress and our results suggest that geometrical variations may be a potential risk factor inducing calcific aortic stenosis frequently present in patients with CBAV.
Cardiovascular Engineering and Technology 03/2011; 2(1):48-56.
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ABSTRACT: There is a significant gap in our knowledge of engineered heart valve tissue (EHVT) development regarding detailed three-dimensional (3D) tissue formation and remodeling from the point of in vitro culturing to full in vivo function. As a step toward understanding the complexities of EHVT formation and remodeling, a novel serial confocal microscopy technique was employed to obtain 3D microstructural information of pre-implant (PRI) and post-implant for 12 weeks (POI) EHVT fabricated from PGA:PLLA scaffolds and seeded with ovine bone-marrow-derived mesenchymal stem cells. Custom scaffold fiber tracking software was developed to quantify scaffold fiber architectural features such as length, tortuosity, and minimum scaffold fiber-fiber separation distance and scaffold fiber orientation was quantified utilizing a 3D fabric tensor. In addition, collagen and cellular density of ovine pulmonary valve leaflet tissue were also analyzed for baseline comparisons. Results indicated that in the unseeded state, scaffold fibers formed a continuous, oriented network. In the PRI state, the scaffold showed some fragmentation with a scaffold volume fraction of 7.79%. In the POI specimen, the scaffold became highly fragmented, forming a randomly distributed short fibrous network (volume fraction of 2.03%) within a contiguous, dense collagenous matrix. Both PGA and PLLA scaffold fibers were observed in the PRI and POI specimens. Collagen density remained similar in both PRI and POI specimens (74.2 and 71.5%, respectively), though the distributions in the transmural direction appeared slightly more homogenous in the POI specimen. Finally, to guide future 2D histological studies for large-scale studies (since acquisition of high-resolution volumetric data is not practical for all specimens), we investigated changes in relevant collagen and scaffold metrics (collagen density and scaffold fiber orientation) with varying section spacing. It was found that a sectioning spacing up to 25 μm (for scaffold morphology) and 50 μm (for collagen density) in both PRI and POI tissues did not result in loss of information fidelity, and that sectioning in the circumferential or radial direction provides the greatest preservation of information. This is the first known work to investigate EHVT microstructure over a large volume with high resolution and to investigate time evolving in vivo EHVT morphology. The important scaffold fiber structural changes observed provide morphological information crucial for guiding future structurally based constitutive modeling efforts focused on better understanding EHVT tissue formation and remodeling.
Annals of biomedical engineering 01/2011; 39(1):205-22. · 2.41 Impact Factor
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Advanced Materials 10/2010; 23(1):106-11. · 13.88 Impact Factor
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ABSTRACT: Interest in developing durable mitral valve repair methods is growing, underscoring the need to better understand the native mitral valve mechanics. In this study, the authors investigate the dynamic deformation of the mitral valve strut chordae-to-anterior leaflet transition zone using a novel stretch mapping method and report the complex mechanics of this region for the first time. Eight structurally normal porcine mitral valves were studied in a pulsatile left heart simulator under physiological hemodynamic conditions -120 mm peak transvalvular pressure, 5 l/min cardiac output at 70 bpm. The chordal insertion region was marked with a structured array of 31 miniature markers, and their motions throughout the cardiac cycle were tracked using two high speed cameras. 3D marker coordinates were calculated using direct linear transformation, and a second order continuous surface was fit to the marker cloud at each time frame. Average areal stretch, principal stretch magnitudes and directions, and stretch rates were computed, and temporal changes in each parameter were mapped over the insertion region. Stretch distribution was heterogeneous over the entire strut chordae insertion region, with the highest magnitudes along the edges of the chordal insertion region and the least along the axis of the strut chordae. At early systole, radial stretch was predominant, but by mid systole, significant stretch was observed in both radial and circumferential directions. The compressive stretches measured during systole indicate a strong coupling between the two principal directions, explaining the small magnitude of the systolic areal stretch. This study for the first time provides the dynamic kinematics of the strut chordae insertion region in the functioning mitral valve. A heterogeneous stretch pattern was measured, with the mechanics of this region governed by the complex underlying collagen architecture. The insertion region seemed to be under stretch during both systole and diastole, indicating a transfer of forces from the leaflets to the chordae and vice versa throughout the cardiac cycle, and demonstrating its role in optimal valve function.
Journal of Biomechanical Engineering 08/2010; 132(8):081004. · 1.90 Impact Factor
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ABSTRACT: 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) scaffolds. SEM images of rabbit mesenchymal stem cell (MSC) seeded collagen gel scaffolds and decellularized rat carotid arteries were also analyzed to further evaluate the ability of the algorithm to capture fiber network morphology regardless of scaffold type and the evaluated size scale. The image analysis procedure was validated qualitatively and quantitatively, comparing fiber network topology manually detected by human operators (n = 5) with that automatically detected by the algorithm. Correlation values between manual detected and algorithm detected results for the fiber angle distribution and for the fiber connectivity distribution were 0.86 and 0.93 respectively. Algorithm detected fiber intersections and fiber diameter values were comparable (within the mean +/- standard deviation) with those detected by human operators. This automated approach identifies and quantifies fiber network morphology as demonstrated for three relevant scaffold types and provides a means to: (1) guarantee objectivity, (2) significantly reduce analysis time, and (3) potentiate broader analysis of scaffold architecture effects on cell behavior and tissue development both in vitro and in vivo.
Biomaterials 07/2010; 31(20):5345-54. · 7.40 Impact Factor
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ABSTRACT: 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 represents a positive departure from what has mostly been an empirically driven field, enabling a deeper understanding of the highly complex biological mechanisms we wish to ultimately emulate. Ongoing research is actively pursuing new materials and processing methods to control material structure down to the micro-scale to sustain or improve cell viability, guide tissue growth, and provide mechanical integrity, all while exhibiting the capacity to degrade in a controlled manner. The purpose of this review is not to focus solely on material processing but to assess the ability of these techniques to produce mechanically sound tissue surrogates, highlight the unique structural characteristics produced in these materials, and discuss how this translates to distinct macroscopic biomechanical behaviors.
Acta biomaterialia 07/2010; 6(7):2365-81. · 3.98 Impact Factor
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ABSTRACT: As the complete understanding of urinary bladder function requires knowledge of organ level deformations, we conducted ex vivo studies of surface strains of whole bladders during controlled filling. The surface strains derived from displacements of surface markers applied to the posterior surface of excised rat bladders were tracked under slow filling with pressure and volume simultaneously recorded in the passive and completely inactivated states (i.e. with and without smooth muscle tone, respectively). Bladders evaluated in the passive state exhibited spontaneous contractions and larger average peak pressures (16.7 mm Hg compared to 6.4 mm Hg in the inactive state). Overall, the bladders exhibited anisotropic deformations and were stiffer in the circumferential direction, with average peak stretch values of approximately 2.3 and approximately 1.9 in the longitudinal and circumferential directions, respectively, for both states. Although bladders in the passive state were stiffer, they had similar average peak areal stretches of 4.3 in both states. However, differences early in the filling process as a result of a loss in smooth muscle tone in the inactive state resulted in longitudinal lengthening of 36%. Idealizing the bladder as a prolate spheroid, we estimated the wall stress-strain relation during filling and demonstrated that the intact bladder exhibited the classic stress-stretch relation, with a significantly protracted low stress region and peak stresses of 36 and 51 kPa in the longitudinal and circumferential directions, respectively. The present study fills a major gap in the urinary bladder biomechanics literature, wherein knowledge of the pressure-volume-wall stress-wall strain relation was explored for the first time in a functioning organ ex vivo.
Journal of biomechanics 06/2010; 43(9):1708-16. · 2.66 Impact Factor
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Danielle Gottlieb,
Tandon Kunal,
Sitaram Emani,
Elena Aikawa,
David W Brown,
Andrew J Powell,
Arthur Nedder,
George C Engelmayr,
Juan M Melero-Martin, Michael S Sacks,
John E Mayer
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ABSTRACT: Clinical translation of tissue-engineered heart valves requires valve competency and lack of stenosis in the short and long term. Early studies of engineered valves showed promise, although lacked complete definition of valve function. Building on prior experiments, we sought to define the in vivo changes in structure and function of autologous engineered pulmonary valved conduits.
Mesenchymal stem cells were isolated from neonatal sheep bone marrow and seeded onto a bioresorbable scaffold. After 4 weeks of culture, valved conduits were implanted. Valve function, cusp, and conduit dimensions were evaluated at implantation (echocardiography), at the experimental midpoint (magnetic resonance imaging), and at explant, at 1 day, and 1, 6, 12, or 20 weeks postoperatively (direct measurement, echocardiography). Histologic evaluation was performed.
Nineteen animals underwent autologous tissue-engineered valved conduit replacement. At implantation, valved conduit function was excellent; maximum transvalvular pressure gradient by Doppler echocardiography was 17 mm Hg; most valved conduits showed trivial pulmonary regurgitation. At 6 postoperative weeks, valve cusps appeared less mobile; pulmonary regurgitation was mild to moderate. At 12 weeks or more, valved conduit cusps were increasingly attenuated and regurgitant. Valved conduit diameter remained unchanged over 20 weeks. Dimensional measurements by magnetic resonance imaging correlated with direct measurement at explant.
We demonstrate autologous engineered tissue valved conduits that function well at implantation, with subsequent monitoring of dimensions and function in real time by magnetic resonance imaging. In vivo valves undergo structural and functional remodeling without stenosis, but with worsening pulmonary regurgitation after 6 weeks. Insights into mechanisms of in vivo remodeling are valuable for future iterations of engineered heart valves.
The Journal of thoracic and cardiovascular surgery 03/2010; 139(3):723-31. · 3.41 Impact Factor
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ABSTRACT: Although bioprosthetic heart valves (BHV) remain the primary treatment modality for adult heart valve replacement, continued problems with durability remain. Several studies have implicated flexure as a major damage mode in porcine-derived heterograft biomaterials used in BHV fabrication. Although conventional accelerated wear testing can provide valuable insights into BHV damage phenomena, the constituent tissues are subjected to complex, time-varying deformation modes (i.e., tension and flexure) that do not allow for the control of the amount, direction, and location of flexure. Thus, in this study, customized fatigue testing devices were developed to subject circumferentially oriented porcine BHV tissue strips to controlled cyclic flexural loading. By using this approach, we were able to study layer-specific structural damage induced by cyclic flexural tensile and compressive stresses alone. Cycle levels of 10 x 10(6), 25 x 10(6), and 50 x 10(6) were used, with resulting changes in flexural stiffness and collagen structure assessed. Results indicated that flexural rigidity was markedly reduced after only 10 x 10(6) cycles, and progressively decayed at a lower rate with cycle number thereafter. Moreover, the against-curvature fatigue direction induced the most damage, suggesting that the ventricularis and fibrosa layers have low resistance to cyclic flexural compressive and tensile loads, respectively. The histological analyses indicated progressive collagen fiber delamination as early as 10 x 10(6) cycles but otherwise no change in gross collagen orientation. Our results underscore that porcine-derived heterograft biomaterials are very sensitive to flexural fatigue, with delamination of the tissue layers the primary underlying mechanism. This appears to be in contrast to pericardial BHV, wherein high tensile stresses are considered to be the major cause of structural failure. These findings point toward the need for the development of chemical fixation technologies that minimize flexure-induced damage to extend porcine heterograft biomaterial durability. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.
Journal of Biomedical Materials Research Part A 02/2010; 94(1):205-13. · 2.63 Impact Factor
