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PubMed2006

Electrospun bioactive nanocomposite scaffolds of polycaprolactone and nanohydroxyapatite for bone tissue engineering.

Nanocomposite scaffolds based on nanofibrous poly(epsilon-caprolactone) (PCL) and nanohydroxyapatite (nanoHA) with different compositions (wt%) were prepared by electrostatic co-spinning to mimic the nano-features of the natural extracellular matrix (ECM). NanoHA was found to be well dispersed in polymers up to the addition of 20 wt%, after ultrasonication. The composite scaffolds were characterized for structure and morphology using XRD, EDX, SEM, and DSC. The scaffolds have a porous nanofibrous morphology with fibers (majority) having diameters in the range of 450-650 nm, depending on composition, and interconnected pore structures. SEM, EDX, and XRD analyses have confirmed the presence of nanoHA in the fibers. As the nanoHA content in the fibers increases, the surface of fibers becomes rougher. The mechanical (tensile) property measurement of the electrospun composites reveals that as the nanoHA content increases, the ultimate strength increases from 1.68 MPa for pure PCL to 2.17, 2.65, 3.91, and 5.49 MPa for PCL/nanoHA composites with the addition of 5, 10, 15, and 20 wt% nanoHA, respectively. Similarly the tensile modulus also increases gradually from 6.12 MPa to 21.05 MPa with the increase of nanoHA content in the PCL/nanoHA fibers, revealing an increase in stiffness of the fibers due to the presence of HA. DSC analysis reveals that as nanoHA in the composite scaffolds increases, the melting point slightly increases due to the good dispersion and interface bonding between PCL and nanoHA.

Biocompatible Materials↗
PubMed2003

Increasing strain and strain rate strengthen transient stiffness but weaken the response to subsequent compression for articular cartilage in unconfined compression.

Strain amplitude and strain rate dependent nonlinear behavior and load-induced mechanical property alterations of full-thickness bovine articular cartilage attached to bone were investigated in unconfined compression. A sequence of test compressions of finite deformation (ranging from 0.9% to 34.5% nominal strain) was performed at strain rates ranging from approximately 0.053%/s to 5.8%/s. Peak and equilibrium loads were analyzed to determine strain amplitude and strain rate dependence of linear versus nonlinear responses. The test protocol was designed to reveal changes in mechanical properties due to these finite deformations by interspersing small-amplitude witness ramps of approximately 1.1% deformation and approximately 0.44%/s strain rate between the test ramps ("witness" meaning to assess any mechanical property changes). We found that peak loads displayed high nonlinearity, stiffening with both increasing compression amplitude and more so with increasing strain rate. The response to witness ramps suggested that mechanical weakening occurred when compression amplitude reached 1.9-2.9% strain and beyond, and that weakening was much more significant at higher strain rate. These findings delineate regimes of linear versus nonlinear behavior of cartilage, and indicate the types of loads which can cause mechanical property alterations. Biological implications of this study are that strain amplitude and strain rate dependent stiffening may be essential to bear physiological loads and to protect cells and matrix from mechanical damage. Structural changes reflected by mechanical weakening at small compression could also initiate remodeling or disease processes.

Animals↗
PubMed1997

A structurally based stress-stretch relationship for tendon and ligament.

We propose a mechanical model for tendon or ligament stress-stretch behavior that includes both microstructural and tissue level aspects of the structural hierarchy in its formulation. At the microstructural scale, a constitutive law for collagen fibers is derived based on a strain-energy formulation. The three-dimensional orientation and deformation of the collagen fibrils that aggregate to form fibers are taken into consideration. Fibril orientation is represented by a probability distribution function that is axisymmetric with respect to the fiber. Fiber deformation is assumed to be incompressible and axisymmetric. The matrix is assumed to contribute to stress only through a constant hydrostatic pressure term. At the tissue level, an average stress versus stretch relation is computed by assuming a statistical distribution for fiber straightening during tissue loading. Fiber straightening stretch is assumed to be distributed according to a Weibull probability distribution function. The resulting comprehensive stress-stretch law includes seven parameters, which represent structural and microstructural organization, fibril elasticity, as well as a failure criterion. The failure criterion is stretch based. It is applied at the fibril level for disorganized tissues but can be applied more simply at a fiber level for well-organized tissues with effectively parallel fibrils. The influence of these seven parameters on tissue stress-stretch response is discussed and a simplified form of the model is shown to characterize the nonlinear experimentally determined response of healing medial collateral ligaments. In addition, microstructural fibril organizational data (Frank et al., 1991, 1992) are used to demonstrate how fibril organization affects material stiffness according to the formulation. A simplified form, assuming a linearly elastic fiber stress versus stretch relationship, is shown to be useful for quantifying experimentally determined nonlinear toe-in and failure behavior of tendons and ligaments. We believe this ligament and tendon stress-stretch law can be useful in the elucidation of the complex relationships between collagen structure, fibril elasticity, and mechanical response.

Animals↗
PubMed2005

Coding SNP in tenascin-C Fn-III-D domain associates with adult asthma.

The extracellular matrix glycoprotein tenascin-C (TNC) has been accepted as a valuable histopathological subepithelial marker for evaluating the severity of asthmatic disease and the therapeutic response to drugs. We found an association between an adult asthma and an SNP encoding TNC fibronectin type III-D (Fn-III-D) domain in a case-control study between a Japanese population including 446 adult asthmatic patients and 658 normal healthy controls. The SNP (44513A/T in exon 17) strongly associates with adult bronchial asthma (chi2 test, P=0.00019, Odds ratio=1.76, 95% confidence interval=1.31-2.36). This coding SNP induces an amino acid substitution (Leu1677Ile) within the Fn-III-D domain of the alternative splicing region. Computer-assisted protein structure modeling suggests that the substituted amino acid locates at the outer edge of the beta-sheet in Fn-III-D domain and causes instability of this beta-sheet. As the TNC fibronectin-III domain has molecular elasticity, the structural change may affect the integrity and stiffness of asthmatic airways. In addition, TNC expression in lung fibroblasts increases with Th2 immune cytokine stimulation. Thus, Leu1677Ile may be valuable marker for evaluating the risk for developing asthma and plays a role in its pathogenesis.

Adult↗
PubMed2004

Physical and biomechanical characteristics of rat cervical ripening are not consistent with increased collagenase activity.

OBJECTIVE: The cervix progressively softens during pregnancy to allow stretch without rupture in labor. Cervical softening is the product of complex modifications that include increased proteoglycan-to-collagen ratio, increased hyaluronic acid and water content, and breakdown of collagen by matrix metalloproteases. The relative contribution of collagen breakdown to cervical ripening is unclear. We sought to identify, discriminate, and quantify the physical characteristics of rat cervix during pregnancy, labor, and both before and after exposure to either prostaglandin (PGE(2)) or the collagenolytic enzyme matrix metalloprotease-1 (MMP-1). STUDY DESIGN: Cervices were collected from nonpregnant rats in diestrus (n=4) and pregnant rats on d10 (n=4), d16 (n=11), d20 (n=5), and d22 (term) nonlabor (NL: n=4) and d22 in term labor (TL: n=7). Cervices were also collected from a separate group in preterm labor induced by RU486 (PTL: n=10). The effect of PGE(2) on cervical characteristics was determined after intravaginal placement of PGE(2) gel (0.5 mg PGE(2): n=3) or placebo metylcellulose gel (CRL(PG) n=6) for 20 hours before euthanasia on d16. The effect of collagen was determined by incubating in vitro cervices from untreated d16 rats with (MMP-1: n=3) and without (CRL(MMP): n=7) activated collagenase before tensile testing. Tensile properties were quantitated by using Shimadzu EZ-test instrumentation (Shimadzu North America, Columbia, Md) with a stretching regimen that mimicked labor contractions while recording the force opposed by the tissue. Parameters such as the slope (a measure of stiffness), yield point (YP; moment the tissue changes its proprieties from elastic to plastic), and break point (BP; a measure of tissue strength) were recorded and analyzed. The plateau was defined as the phase after YP but before BP. RESULTS: Compared with d16, cervical extensibility increased significantly by d20 (slope d16: 0.41 +/- 0.03 N/mm vs d20: 0.19 +/- 0.05 N/mm, P < .01), and during both PTL (slope: 0.17 +/- 0.03 N/mm) and TL (slope: 0.11 +/- 0.02 N/mm). This increase was mimicked by PGE(2) (slope PGE(2): 0.24 +/- 0.03 vs CRL(PG): 0.40 +/- 0.05 N/mm, P=.04), but not by collagenase (slope MMP-1: 0.35 +/- 0.02 vs CRL(MMP): 0.38 +/- 0.05 N/mm, P>.05). YP was significantly reduced as pregnancy advanced, whereas BP increased, suggesting both increased plasticity (compliance) and strength. However, the plateau length increased 3-fold both by d20 and after PGE(2). In contrast, the addition of MMP-1 reduced the plateau. BP occurred significantly earlier in collagenase-treated tissues, but later in PTL-, TL-, and PGE(2)-treated cervices. CONCLUSION: The changes in physical properties of the rat cervix during physiologic ripening are similar to those induced by PGE(2) and RU486, and consist of increased extensibility, compliance, and strength. These changes cannot be attributed to increased collagenase activity, which would decrease tissue compliance and strength.

Animals↗
PubMed1996

The role of the renin-angiotensin system in the pathophysiology of cardiac remodeling.

Cardiac hypertrophy of diverse etiologies is associated with two remodeling events: an increase in cardiac muscle mass, and the abnormal accumulation of fibrillar collagen, which results in increased myocardial stiffness and eventual ventricular dysfunction. Clinical and animal studies have implicated angiotensin II (A II) as a growth promoter of both cardiac myocytes and fibroblasts during the cardiac remodeling that occurs with hypertension and myocardial infarction. The growth-promoting effects of A II occur, in part, independent of effects on hemodynamic load. Tissue culture studies have shown that cardiac myocytes and fibroblasts are targets for the actions of A II. In these cells. A II activates phospholipases C, D, and A2, leading in turn to the activation of multiple, conventional second-messenger pathways. By an undefined process. A II also increases the tyrosine phosphorylation of cytosolic proteins, and activates the STAT family of transcription factors, which may mediate an inflammatory or stress response. A II has been shown to affect gene expression of cultured cardiac myocytes and fibroblasts, induce either cellular hyperplasia or hypertrophy, and increase expression of other growth factors. Cardiac fibroblasts have been shown to respond to A II with increased expression of integrins and the extracellular matrix proteins, collagen and fibronectin. Recently, stretch of cardiac myocytes was shown to induce hypertrophy, through an autocrine release of A II. All of the aforementioned actions of A II are mediated by the AT1 receptor.

Angiotensin II↗
PubMed1994

Cellular mechanisms of captopril-induced matrix remodeling in Syrian hamster cardiomyopathy.

BACKGROUND: Although angiotensin-converting enzyme (ACE) inhibitors have become a mainstay of treatment for chronic congestive heart failure (CHF), it is not known whether the cardiac remodeling effects are a secondary phenomenon, resulting from ACE inhibitors' hemodynamic actions of afterload reduction, or occur through an independent mechanism. METHODS AND RESULTS: We used ultrasonic tissue characterization to define potentially salutary effects of treatment with ACE inhibitors on the material properties of the heart and its potential influence on cardiac remodeling at the cellular level. Ten 1-month-old, cardiomyopathic (CM) Syrian hamsters and 6 normal (NL) hamsters were treated with captopril (2 g/L water ad libitum), and 10 CM hamsters and 10 NL hamsters were maintained untreated for 3 months. Hearts were excised, and backscattered radiofrequency data were acquired from 1200 independent sites from each specimen with a high-resolution 50-MHz acoustic microscope for calculation of integrated backscatter (IB). Treatment with captopril reduced left ventricular mass, calcium concentration, and IB in CM hearts without affecting myofiber size or collagen concentration. The IB from grossly normal regions of myocardium in NL hamsters, treated CM hamsters, and untreated CM hamsters was not significantly different. The IB from the microscopic regions of scar tissue in treated CM hamsters was significantly less (P = .0004) than that from scar tissue in untreated CM hamsters. CONCLUSIONS: The reduced IB from treated scar tissue components reflects specific alterations in the material properties (elastic stiffness, density) of fibrous regions in CM hearts induced by captopril. This is the first report that defines specific cellular effects of ACE inhibitors on the material properties of isolated components of cardiac tissue in experimental cardiomyopathy. These alterations in material properties of scar tissue components represent a potential mechanism for the salutary actions of ACE inhibitors in heart failure.

Animals↗
PubMed2004

Bioabsorbable interbody cages in a sheep cervical spine fusion model.

STUDY DESIGN: An experimental study using a sheep cervical spine interbody fusion model. OBJECTIVES: To compare interbody fusion of an autologous tricortical iliac crest bone graft with two bioabsorbable cages and to determine whether there are differences between the three interbody fusion techniques in 1) the ability to preserve postoperative distraction, 2) the biomechanical stability, and 3) the histologic characteristics of intervertebral bone matrix formation. SUMMARY AND BACKGROUND DATA: Bioabsorbable cages would be beneficial compared with metallic cages; however, currently no suitable bioabsorbable interbody fusion cage is available. METHOD: Twenty-four sheep underwent C3/C4 discectomy and fusion. The following stabilization techniques were used: Group 1) autologous tricortical iliac crest bone graft (n = 8); Group 2) bioabsorbable cage made of 70/30 poly(l-lactide-co-d,l-lactide) (experimental) filled with autologous cancellous bone graft (n = 8); Group 3) bioabsorbable cage made of a polymer-calciumphosphate composite (Biomet Europe, Dordrecht, The Netherlands) filled with autologous cancellous bone graft (n = 8). Radiographic scans to determine disc space height were performed before and after surgery and after 1, 2, 4, 8, and 12 weeks, respectively. After 12 weeks, animals were killed, and fusion sites were evaluated using functional radiographic views in flexion and extension. Quantitative computed tomographic scans were used to assess bone mineral density, bone mineral content, and bony callus volume. Biomechanical testing was performed in flexion, extension, axial rotation, and lateral bending to determine stiffness, ROM, and neutral and elastic zone. Histomorphological and histomorphometrical analysis were performed to evaluate fusion and foreign body reactions associated with the bioabsorbable cages. RESULTS: Over a 12-week period, the polymer-calciumphosphate composite cage showed significantly higher values for disc space height compared with the bone graft and the poly(l-lactide-co-d,l-lactide) cage. Additionally, the polymer-calciumphosphate composite cage demonstrated a significantly higher stiffness and lower ROM, neutral zone, and elastic zone in axial rotation and lateral bending than any other group. However, quantitative computed tomographic scans demonstrated cracks in six of the eight polymer-calciumphosphate composite cages after 12 weeks. Histologically, the highest bone volume/total volume ratio and the highest fusion rate were found in the polymer-calciumphosphate composite cage group. Although the poly(l-lactide-co-d,l-lactide) cage showed grade I through III foreign body reactions in all fusion areas, only two animals developed grade I foreign body reactions with the polymer-calciumphosphate composite cage. CONCLUSION: After 12 weeks, there was no significant difference between the bioabsorbable poly(l-lactide-co-d,l-lactide) cage and the tricortical bone graft. In comparison to the tricortical bone graft, the bioabsorbable polymer-calciumphosphate composite cage showed significantly better distractive properties, a significantly higher biomechanical stiffness, and an advanced interbody fusion; however, six of eight polymer-calciumphosphate composite cages cracked. Although the fate of the foreign body reactions and the cracks is currently unclear for both bioabsorbable cages, the early appearance of large osteolysis associated with use of the poly(l-lactide-co-d,l-lactide) cage allows skepticism regarding the value of this bioabsorbable implant.

Absorbable Implants↗
PubMed1992

Long-term effect of orchidectomy on cortical bone from rat femur: bone mass and mechanical properties.

The study comprised seven groups of intact rats killed at 9, 12, 15, and 24 months of age, and three groups of rats castrated at the age of 9 months and killed together with the intact rats 3, 6, and 15 months after castration. The composition, dimension, and mechanical properties of intact bone as well as the constituent bone collagen from femoral diaphyses were investigated in relation to both age (9-24 months) and castration. Castration had no effect on density and only minor effect on ash and collagen contents. An age-related increase in bone mass, cross-sectional area, and wall thickness of the diaphyses was arrested (bone mass, area) or even reversed (to a decrease in wall thickness) after castration. Therefore, a growing difference, pronounced from 6 months after castration, between intact and castrated rats was observed in bone mass, cross-sectional area, and wall thickness. The compressive mechanical strength of intact bone normalized with regard to cross-sectional area was unaffected by castration, whereas castration tended to increase the stiffness of the bone collagen. When observed in a polarization microscope, two different zones in cross sections of the diaphyses were apparent. The average diameter of the border line separating the two zones was independent of age and castration. By measuring the average thickness of each of the two zones, age-related periosteal bone formation and endosteal bone resorption were demonstrated. After castration, the rate of bone formation was reduced and the rate of bone resorption was accelerated. Castration was thus found to affect the composition and the quality of the cortical bone to a minor extent only.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1998

Definition of the redox states of cobalt-precorrinoids: investigation of the substrate and redox specificity of CbiL from Salmonella typhimurium.

The enzyme CbiL from the facultative anaerobe Salmonella typhimurium exhibits a high degree of homology to CobI from the aerobe Pseudomonas denitrificans (29% identity; 51% conservation obtained by a Blastp search of the ncbi database). As CobI catalyzes the third methylation in the aerobic pathway to vitamin B12 it is proposed that CbiL catalyzes the analogous step in the anaerobic pathway. Potential metallo and metal-free substrates were characterized and their redox states defined by a combination of physicochemical techniques (MALDI-MS, NMR, UV/vis, IR, and EPR) and then used to investigate the function of CbiL. CbiL exhibited an absolute requirement for the presence of a metal ion (Co(II), Ni(II), or Zn(II)) within the tetrapyrrole substrate. CbiL had no preference for the redox state of its cobalt tetrapyrrole substrate, methylating both the reduced form, Co(II) 2, 7-dimethyl-dipyrrocorphin (Co(II)-precorrin-2), and the oxidized form, Co(III) 2,7-dimethyl-isobacterioclorin (Co(III)-factor-II). In contrast CbiL had a marked preference for the oxidized Ni(II) and Zn(II)-2,7-dimethyl-isobacteriochlorin (Ni(II) and Zn(II)-factor-II). Removal of the metal ion from a product of CbiL (Zn(II)-factor-III) allowed characterization by 13C NMR, identifying the tetrapyrrole as 2,7,20-trimethyl-isobacteriochlorin (factor-3), indicating that CbiL methylates at C20, the same site as that methylated by CobI. Competition experiments, utilizing isotopic labeling to distinguish otherwise identical mass substrates and products, revealed that oxidized Co(III) or Ni(II)-factor-II were equally good substrates, whereas Co(II)-precorrin-2 was much preferred over Ni(II)-precorrin-2. Excess Ni(II)-precorrin-2 did not decrease CbiL methylation of Co(II)-precorrin-2, implying that CbiL has a low affinity for Ni(II)-precorrin-2. These results are interpreted on the basis of tetrapyrrole ruffling occurring on the optimization of the metallo-N bond distances. The greater flexibility of the reduced precorrin-2 ring system allows greater deformation on accommodating the bound metal ion, the distortions imposed by bound Ni(II) or Zn(II) ions being larger than Co(II). The resulting distortions imposed on the precorrin ring could then decrease catalysis by causing a departure from the optimal substrate conformation required for CbiL. On oxidation of the Ni(II) or Zn(II)-precorrin-2, the increased stiffness of the ring could then constrain the metallo-factor-II conformation toward that of the usual substrate, allowing greater methylation by CbiL. In contrast to its counterpart CobI in the aerobic pathway of B12 biosynthesis, which methylates the metal-free precorrin-2, these studies show CbiL to be the first methylase unique to the anaerobic pathway, methylating a metallo-precorrin-2 substrate. Implications of CbiL specificity for the mechanism of the anaerobic B12 pathway are discussed.

Bacterial Proteins↗
PubMed1995

Regulation of vascular tone.

The intimal surface of the blood vessel in vivo is subject to shear stress resulting from blood flow, which in most of the circulation, at least at rest, is laminar. Turbulence can occur at bifurcations, especially those of the large arteries, and where vessels curve significantly. Shear stress is a frictional tangential force exerted at the fluid-intimal interface in the long axis of the vessel. It is now known that hemodynamic shear stress can influence a large variety of biological processes in endothelial cells, which vary from those with a short response time, just a few milliseconds, such as the opening of ion channels, to those that change over a period of minutes to several hours, for example, endocytosis and cytoskeleton rearrangement, and those features that alter much more slowly, such as cell shape and stiffness. In addition to these types of changes, there are suggestions that flow acting through shear stress may be responsible for several basic attributes of the vasculature, including the relative size and diameter of the components of a branching vascular system. In this symposium on the flow regulation of the blood vessel, the first presentation dealt with optimality principles that appear to govern the dimensions of the vasculature, in particular the geometry of the arterial branching and the role of shear stress. An optimally designed system is one that requires the least metabolic work to perform its function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Use of the Taguchi method for biomechanical comparison of flexor-tendon-repair techniques to allow immediate active flexion. A new method of analysis and optimization of technique to improve the quality of the repair.

The current trend toward early active flexion after repair of the flexor tendons necessitates a stronger repair than that provided by a modified Kessler technique with use of 4-0 nylon suture. The purpose of the current study was to determine, with use of the Taguchi method of analysis, the strongest and most consistent repair of the flexor tendons. Flexor tendons were obtained from fresh-frozen hands of human cadavera. Eight flexor tendons initially were repaired with the modified Kessler technique with use of 4-0 nylon core suture and 6-0 nylon epitenon suture. A test matrix was used to analyze a total of twenty variables in sixty-four tests. These variables included eight techniques for core-suture repair, four types of core suture, two sizes of core suture, four techniques for suture of the epitenon, and two distances from the repair site for placement of the core suture. After each repair, the specimens were mounted in a servohydraulic mechanical testing machine for tension-testing to failure. The optimum combination of variables was determined, with the Taguchi method, to be an augmented Becker technique with use of 3-0 Mersilene core suture, placed 0.75 centimeter from the cut edge with volar epitenon suture. The four-strand, double modified Kessler technique provided the second strongest repair. Five tendons that had been repaired with use of the optimum combination then were tested and compared with tendons that had been repaired with the standard modified Kessler technique. With the optimum combination of variables, the strength of the repair improved from a mean (and standard deviation) of 17.2 +/- 2.9 to 128 +/- 5.6 newtons, and the stiffness improved from a mean of 4.6 to 16.2 newtons per millimeter.

Biomechanical Phenomena↗
PubMed2005

Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3.

Multiple epiphyseal dysplasia (MED) is a relatively common skeletal dysplasia that can present in childhood with a variable phenotype of short stature and pain and stiffness in the large joints, and often progresses to early-onset osteoarthritis in adulthood. Mutations in the matrilin-3 gene (MATN3) have recently been shown to underlie some forms of autosomal dominant MED. To date all MED mutations in matrilin-3 cluster in the single A-domain, suggesting that they may disrupt the structure and/or function of this important domain. To determine the effects of MATN3 mutations on the structure and function of matrilin-3 we expressed both normal and mutant matrilin-3 in mammalian cells. Wild-type (wt) matrilin-3 was efficiently secreted into conditioned medium, whereas mutant matrilin-3 was retained and accumulated within the cell. Furthermore, when the mutant A-domains were examined individually, they existed primarily in an unfolded conformation. Co-immunoprecipitation experiments demonstrated that the mutant A-domains were specifically associated with ERp72, a chaperone protein known to be involved in mediating disulfide bond formation. Light microscopy of cartilage from an MED patient with a MATN3 mutation showed the presence of intracellular material within the chondrocytes, whilst the overall matrix appeared normal. On electron micrographs, the inclusions noted at the light microscopy level appeared to be dilated cisternae of rough endoplasmic reticulum and immunohistochemical analysis confirmed that the retained protein was matrilin-3. In summary, the data presented in this paper suggest that MED caused by MATN3 mutations is the result of an intracellular retention of the mutant protein.

Animals↗
PubMed2005

Semi-synthetic collagen/poloxamine matrices for tissue engineering.

Collagen-containing poloxamine hydrogels were produced with the aim of overcoming the low stiffness displayed by collagen gels that are not otherwise chemically crosslinked. Matrices were obtained by functionalization of a four-arm PEO-PPO block copolymer (poloxamine, Tetronic) with methcrylate groups and subsequent free radical polymerization of water solutions of the modified polymer in the presence of collagen. The resulting matrices had a sharp increase in stiffness, when compared to pure collagen gels. For example, whereas collagen had a storage modulus (G') around 70 Pa and a loss modulus (G'') of 10 Pa, a crosslinked collagen/poloxamine system containing 8.3% crosslinked poloxamine had G' and G'' values of 7400 and 1000 Pa, respectively. HepG2 cells were seeded within the gels before the crosslinking and the viability levels estimated by AlamarBlue assay were between 65% and 91% for systems containing 0.04-0.09 wt% photoinitiator. HepG2 and endothelial cells also adhered to and spread on the surface of the collagen-containing specimens, suggesting their potential utility in tissue engineering.

Animals↗
PubMed2003

Fibrillin microfibrils are stiff reinforcing fibres in compliant tissues.

Fibrillin-rich microfibrils have endowed tissues with elasticity throughout multicellular evolution. We have used molecular combing techniques to determine Young's modulus for individual microfibrils and X-ray diffraction of zonular filaments of the eye to establish the linearity of microfibril periodic extension. Microfibril periodicity is not altered at physiological zonular tissue extensions and Young's modulus is between 78 MPa and 96 MPa, which is two orders of magnitude stiffer than elastin. We conclude that elasticity in microfibril-containing tissues arises primarily from reversible alterations in supra-microfibrillar arrangements rather than from intrinsic elastic properties of individual microfibrils which, instead, act as reinforcing fibres in fibrous composite tissues.

Aged↗
PubMed1999

Immunohistochemical localization of collagen VI in arthrofibrosis.

Arthrofibrosis is a disabling complication after knee trauma and surgery. Clinically, it is characterized by pain and joint stiffness due to massive connective tissue proliferation. In similar pathological conditions with fibrotic transformation such as lung fibrosis or superficial fibromatoses, an increased expression of collagen type VI has been reported. Collagen VI, which forms a filamentous network, is thought to serve as an anchoring element between collagen I/III fibrils and basement membranes and as a cell binding structure. Collagen VI may also play a contributing role in the pathogenesis of arthrofibrosis. The aim of the present study was therefore to demonstrate the localization and distribution of type VI collagen in arthrofibrotic tissue. Tissue samples from the infrapatellar fat pad and intercondylar synovia of 13 patients suffering from arthrofibrosis were taken at surgery. The expression of type VI collagen was studied immunohistochemically using an immunoperoxidase method for light microscopic visualization. Histologic analysis showed a synovial hyperplasia with inflammatory cell infiltration and vascular proliferation. Compared with normal synovial tissue, type VI collagen was widely distributed as a network subsynovially and around the capillary walls. The results of the present study suggest that dysregulation of collagen VI synthesis could be an important contributing factor in the complex mechanisms of disordered matrix protein deposition leading to arthrofibrosis.

Adolescent↗
PubMed1988

Collagen remodeling of the pressure-overloaded, hypertrophied nonhuman primate myocardium.

Cardiac muscle is tethered within a fibrillar collagen matrix that serves to maximize force generation. In the human pressure-overloaded, hypertrophied left ventricle, collagen concentration is known to be increased; however, the structural and biochemical remodeling of collagen and its relation to cell necrosis and myocardial mechanics is less clear. Accordingly, this study was undertaken in a nonhuman primate model of left ventricular hypertrophy caused by gradual onset experimental hypertension. The amount of collagen, its light microscopic features, and proportions of collagen types I, III, and V were determined together with diastolic and systolic mechanics of the intact ventricle during the evolutionary, early, and late phases of established left ventricular hypertrophy (4, 35, and 88 weeks, respectively). In comparison to controls, we found 1) increased collagen at 4 weeks, as well as a greater proportion of type III, in the absence of myocyte necrosis; 2) collagen septae were thick and dense at 35 weeks, while the proportion of types I and III had converted to control; 3) necrosis was evident at 88 weeks, and the structural remodeling and proportion of collagen types I and III reflected the extent of scar formation; and 4) unlike diastolic myocardial stiffness, which was unchanged at 4, 35, or 88 weeks, the systolic stress-strain relation of the myocardium was altered in either a beneficial or detrimental manner in accordance with structural remodeling of collagen and scar formation. Thus, early in left ventricular hypertrophy, reactive fibrosis and collagen remodeling occur in the absence of necrosis while, later on, reparative fibrosis is present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Disruption of the elastin gene in adult Williams syndrome is accompanied by a paradoxical reduction in arterial stiffness.

Although the aetiology of Williams syndrome (WS) is related to elastin gene disruption, its pathogenesis remains unknown, particularly that of vascular lesions. The aim of the present study was to compare the elastic properties of three WS patients with age- and gender-matched normotensive and hypertensive controls. Common carotid arteries of WS patients had a higher distensibility, a thicker intima-media and a lower elastic modulus. Electron microscopy studies of one WS renal artery showed major abnormalities of the elastic fibres, which displayed a reticular structure and a thickening of the internal elastic lamina, whereas the ultrastructure of elastic fibres was normal in a control subadventitial muscular fibrodysplasia. In this WS arterial stenosis, we studied the expression patterns of several major smooth muscle (SM) phenotypic markers using immunofluorescence and used a normal renal artery as a control. In WS, SM-alpha-actin- and myosin-heavy-chain-positive cells contained low amounts of heavy caldesmon, and laminin-beta1 chain was expressed into the basement membranes, indicating a less differentiated phenotype. In conclusion, in WS patients, the carotid artery wall was abnormally distensible and thick, and major ultrastructural abnormalities of elastic fibres were observed in association with smooth muscle cell de-differentiation. These results indicate that the haplo-insufficiency of the elastin gene in WS patients leads to abnormal elastic fibre assembly within the media. Arterial wall hypertrophy found with a primary defect in elastin may represent a major factor responsible for increased distensibility. We suggest that, in WS, the increased proliferative response and the associated de-differentiation process represent two important mechanisms underlying the matrix accumulation and the development of arterial stenosis.

Adult↗