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Strain Concentrations Surrounding an Ellipsoid Model of Lacunae and Osteocytes.

Direct cell sensing of tissue matrix strains is one possible signaling mechanism for mechanically mediated bone adaptation. We utilized homogenization theory to estimate bone tissue matrix strains surrounding osteocytes using two sets of models. The first set of models estimated the strain levels surrounding the lacunae and canaliculi, taking into account variations in lamellar properties. The second set estimated strain levels in the osteocyte and the surrounding matrix for different cellular mechanical properties. The results showed that the strain levels found in and surrounding osteocytes, 1700 to 2700 microstrain (denoted as µe; 1 µe =.0001% strain), were significantly greater than the trabecular tissue level strains of {1325 µe, 287 µe, 87 µe} used for model input. Variation in lamellar properties did not affect strain levels, except at lamellar boundaries. Strain in and surrounding the osteocyte was not significantly affected by cellular stiffness ranging between 28 and 28, 000 Pascals (Pa). Strain levels surrounding lacunae and canaliculi were approximately equivalent.

Journal Article↗

Biomechanical and biochemical changes in lumbar vertebrae of rapidly growing rats.

Although growth-related biochemical, morphological, and biomechanical properties of rat cortical bone have been investigated, similar properties of immature rat vertebral bone have not been well characterized. Information about these properties is necessary, however, for comparative analyses of rat vertebral bone adaptation. Thus a method was developed to characterize growth-related differences in immature rat vertebral bone. The centra of sixth lumbar vertebrae (L6) of 44-day-old and 54-day-old male Sprague-Dawley rats were compressed to 50% of their initial height at a 50%/s strain rate while immersed in a potassium phosphate buffer solution (pH 7.4, 37 degrees C). Structural and material properties for the 54-day-old group that were significantly greater than those for the 44-day-old group included load, stress, and energy at the proportional limit; initial maximum load and stress; and load and energy at 50% strain. The structural stiffness of L6, as well as its elastic modulus, was significantly greater in the older animals. The calcium concentrations and calcium-to-collagen ratios in 54-day-old vertebrae were significantly greater than in younger animals. These results indicated that the specimen preparation and testing protocol developed for rat vertebrae produced reliable biomechanical results, even with the relatively small size of rat vertebrae bodies, and that the quantity and quality of the matrix of immature rat vertebral bone changed significantly during this period of rapid growth. Our test protocol will be useful for investigating the responses of rat vertebral bone to exercise, disease, and spaceflight.

Animals↗

Novel biopolymers as implant matrix for the delivery of ciprofloxacin: biocompatibility, degradation, and in vitro antibiotic release.

The purpose of this study was to investigate the in vitro-in vivo degradation and tissue compatibility of three novel biopolymers viz. polymerized rosin (PR), glycerol ester of polymerized rosin (GPR) and pentaerythritol ester of polymerized rosin (PPR) and study their potential as implant matrix for the delivery of ciprofloxacin hydrochloride. Free films of polymers were used for in vitro degradation in PBS (pH 7.4) and in vivo in rat subcutaneous model. Sample weight loss, molecular weight decline, and morphological changes were analyzed after periodic intervals (30, 60, and 90 days) to monitor the degradation profile. Biocompatibility was evaluated by examination of the inflammatory tissue response to the implanted films on postoperative days 7, 14, 21, and 28. Furthermore, direct compression of dry blends of various polymer matrices with 20%, 30%, and 40% w/w drug loading was performed to investigate their potential for implant systems. The implants were characterized in terms of porosity and ciprofloxacin release. Biopolymer films showed slow rate of degradation, in vivo rate being faster on comparative basis. Heterogeneous bulk degradation was evident with the esterified products showing faster rates than PR. Morphologically all the films were stiff and intact with no significant difference in their appearance. The percent weight remaining in vivo was 90.70 +/- 6.2, 85.59 +/- 5.8, and 75.56 +/- 4.8 for PR, GPR, and PPR films respectively. Initial rapid drop in Mw was demonstrated with nearly 20.0% and 30.0% decline within 30 days followed by a steady decline to nearly 40.0% and 50.0% within 90 days following in vitro and in vivo degradation respectively. Biocompatibility demonstrated by acute and subacute tissue reactions showed minimal inflammatory reactions with prominent fibrous encapsulation and absence of necrosis demonstrating good tissue compatibility to the extent evaluated. All implants showed erosion and increase in porosity that affected the drug release. Increase in drug loading significantly altered the ciprofloxacin release in extended dissolution studies. PPR produced drug release >90% over a period of 90 days promising its utility in implant systems. The results demonstrated the utility of novel film forming biopolymers as implant matrix for controlled/sustained drug delivery with excellent biocompatibility characteristics.

Animals↗

Esophageal reconstruction with ECM and muscle tissue in a dog model.

An in vivo study was conducted to determine if an extracellular matrix (ECM) scaffold co-localized with autologous muscle tissue could achieve constructive remodeling of esophageal tissue without stricture. ECM derived from the porcine urinary bladder was processed, decellularized, configured into a tube shape, and terminally sterilized for use as a bioscaffold for esophageal reconstruction in a dog model. Twenty-two dogs were divided into four groups, three groups of five and one group of seven. Groups 1 and 2 were repaired with either ECM alone or muscle tissue alone, respectively. Groups 3 and 4 were repaired with ECM plus either a partial (30%) covering with muscle tissue or a complete (100%) covering with muscle tissue, respectively. Animals in groups 1 and 2 were sacrificed within approximately 3 weeks because of the formation of intractable esophageal stricture. Four of five dogs in group 3 and six of seven dogs in group 4 were survived for 26 days to 230 days and showed constructive remodeling of esophageal tissue with the formation of well organized esophageal tissue layers, minimal stricture, esophageal motility, and a normal clinical outcome. Mechanical testing of a subset of the remodeled esophageal tissue from animals in groups 3 and 4 showed progressive remodeling from a relatively stiff, non-compliant ECM tube structure toward a tissue with near normal biomechanical properties. We conclude that ECM bioscaffolds plus autologous muscle tissue, but not ECM scaffolds or muscle tissue alone, can facilitate the in situ reconstitution of structurally and functionally acceptable esophageal tissue.

Animals↗

Surface treatment of injectable strontium-containing bioactive bone cement for vertebroplasty.

A novel injectable bioactive bone-bonding cement (SrHAC) composed of strontium-containing hydroxyapatite (Sr-HA) as the inorganic filler and bisphenol A diglycidylether dimethacrylate (Bis-GMA) as the organic matrix for vertebroplasty was developed previously. In this study, the Sr-HA powders were surface treated with methyl methacrylate (MMA) to improve the interface integration of the two phases. After surface treatment, the compression strength and Young's modulus, which were tested after immersion in distilled water at 37 degrees C for 24 h according to ISO 5833, were increased by 68.65 % (p <.001) and 31.02% (p <.001), respectively. The bending strength and bending stiffness of the bioactive bone cement were significantly improved by 54.44% (p <.001) and 83.90% (p <.001). In addition, the handling property of the cement was also enhanced. In vitro biomechanical testing showed that the stiffness of the fractured spine recovered to 82.5% (p <.01) of the intact condition after cementation with surface-treated SrHAC. The failure load of the spine cemented with original and MMA-treated SrHAC improved by 14.25% (p <.05) and 46.91% (p <.05) in comparison with the fractured spines. Results from this study revealed that the MMA-treated SrHAC has a better mechanical effect for orthopedic applications.

Animals↗

Development of the gerbil inner ear observed in the hemicochlea.

A frequency-dependent change in hearing sensitivity occurs during maturation in the basal gerbil cochlea. This change takes place during the first week after the onset of hearing. It has been argued that the mass of a given cochlear segment decreases during development and thus increases the best frequency. Changes in mass during cochlear maturation have been estimated previously by measuring the changes in cochlear dimensions. Fixed, dehydrated, embedded, or sputter-coated tissues were used in such work. However, dehydration of the tissue, a part of most histological techniques, results in severe distortion of some aspects of cochlear morphology. The present experiments, using a novel preparation, the hemicochlea, show that hydrated structures, such as the tectorial membrane and the basilar membrane hyaline matrix, are up to 100% larger than estimated previous studies. Therefore, the hemicochlea was used to study the development of cochlear morphology in the gerbil between the day of birth and postnatal day 19. We used no protocols that would have resulted in severe distortion of cochlear elements. Consequently, a detailed study of cochlear morphology yields several measures that differ from previously published data. Our experiments confirm growth patterns of the cochlea that include a period of remarkably rapid change between postnatal day 6 and 8. The accelerated growth starts in the middle of the cochlea and progresses toward the base and the apex. In particular, the increase in height of Deiters' cells dominated the change, "pushing" the tectorial membrane toward scala vestibuli. This resulted in a shape change of the tectorial membrane and the organ of Corti. The tectorial membrane was properly extended above the outer hair cells by postnatal day 12. This time coincides with the onset of hearing. The basilar membrane hyaline matrix increased in thickness, whereas the multilayered tympanic cover layer cells decreased to a single band of cells by postnatal day 19. Before and after the period of rapid growth, the observed gross morphological changes are rather small. It is unlikely that dimensional changes of cochlear structures between postnatal days 12 and 19 contribute significantly in the remapping of the frequency-place code in the base of the cochlea. Instead, structural changes affecting the stiffness of the cochlear partition might be responsible for the shift in best frequency.

Animals↗

Pretreatment with platelet derived growth factor-BB modulates the ability of costochondral resting zone chondrocytes incorporated into PLA/PGA scaffolds to form new cartilage in vivo.

Optimal repair of chondral defects is likely to require both a suitable population of chondrogenic cells and a biodegradable matrix to provide a space-filling structural support during the early stages of cartilage formation. This study examined the ability of chondrocytes to support cartilage formation when incorporated into biodegradable scaffolds constructed from copolymers (PLG) of polylactic acid (PLA) and polyglycolic acid (PGA) and implanted in the calf muscle of nude mice. Scaffolds were fabricated to be more hydrophilic (PLG-H) or were reinforced with 10% PGA fibers (PLG-FR), increasing the stiffness of the implant by 20-fold. Confluent primary cultures of rat costochondral resting zone chondrocytes (RC) were loaded into PLG-H foams and implanted intramuscularly. To determine if growth factor pretreatment could modulate the ability of the cells to form new cartilage, RC cells were pretreated with recombinant human platelet derived growth factor-BB IPDGF-BB) for 4 or 24 h prior to implantation. To assess whether scaffold material properties could affect the ability of chondrogenic cells to form cartilage, RC cells were also loaded into PLG-FR scaffolds. To determine if the scaffolds or treatment with PDGF-BB affected the rate of chondrogenesis, tissue at the implant site was harvested at four and eight weeks post-operatively, fixed, decalcified and embedded in paraffin. Sections were obtained along the transverse plane of the lower leg, stained with haematoxylin and eosin, and then assessed by morphometric analysis for area of cartilage, area of residual implant, and area of fibrous connective tissue formation (fibrosis). Whether or not the cartilage contained hypertrophic cells was also assessed. The amount of residual implant did not change with time in any of the implanted tissues. The area occupied by PLG-FR implants was greater than that occupied by PLG-H implants at both time points. All implants were surrounded by fibrous connective tissue, whether they were seeded with RC cells or not. The amount of fibrosis was reduced at eight weeks for both implant types. When RC cells were present, the amount of fibrosis was less than seen in cell-free scaffolds. Pretreatment with PDGF-BB caused a slightly greater degree of fibrosis at four weeks than was seen if untreated cells were used in the implants. However, at eight weeks, if the cells had been exposed to PDGF-BB for 24 h, fibrosis was comparable to that seen associated with cell-free scaffolds. The cells supported an equivalent area of cartilage formation in both scaffolds. PDGF-BB caused a time-dependent decrease in cartilage formation at four weeks, but at eight weeks, there was a marked increase in cartilage formation in PDGF-BB-treated cells that was greatest in cells exposed for 4 h compared to those exposed for 24 h. Moreover, PDGF-BB decreased the formation of hypertrophic cells. The results indicate that in this model, RC cells produce cartilage; pretreatment of the RC cells with PDGF-BB promotes retention of a hyaline-like chondrogenic phenotype; and the material properties of the implant do not negatively impact on the ability of the cells to support chondrogenesis.

Animals↗

Adapting the Lagrangian speckle model estimator for endovascular elastography: theory and validation with simulated radio-frequency data.

Intravascular ultrasound (IVUS) is known to be the reference tool for preoperative vessel lesion assessments and for endovascular therapy planning. Nevertheless, IVUS echograms only provide subjective information about vessel wall lesions. Since changes in the vascular tissue stiffness are characteristic of vessel pathologies, catheter-based endovascular ultrasound elastography (EVE) has been proposed in the literature as a method for outlining the elastic properties of vessel walls. In this paper, the Lagrangian Speckle Model Estimator (LSME) is formulated for investigations in EVE, i.e., using a polar coordinate system. The method was implemented through an adapted version of the Levenberg-Marquardt minimization algorithm, using the optical flow equations to compute the Jacobbian matrix. The theoretical framework was validated with simulated ultrasound rf data of mechanically complex vessel wall pathologies. The results, corroborated with Ansys finite element software, demonstrated the potential of EVE to provide useful information about the heterogeneous nature of atherosclerotic plaques.

Animals↗

The changes caused by modification of biomechanical properties of a bone.

The paper presents the distribution of the parameters of mechanical stiffness in a sample of animal bone. The parameters are measured at different distances from the cortical bone. As it is widely known, bone properties vary significantly depending on the length of the bone. Additionally, the properties of trabecular bone also depend on its distance from the cortical bone. The study presents the results for both samples of normal bone tissue and samples of bone tissue with chemically modified biomechanical properties. For each sample a matrix of measurement points was defined. For each measurement point, a micro hardness test was performed in order to define hardness of the micro volume and to measure the Young's modulus. This test was carried out using Micro-Combi-Tester equipment. Micro hardness was measured with Vickers diamond, and the analysis of deformation properties was realized by the Olivier and Pharr method. The application of Oliver and Pharr method enabled the calculation of Young's modulus directly from the unloading curve. Additionally, mineral density for all samples was measured using Dual Energy X-ray Absorptiometry method. This study allowed for comparison of bone mineral density parameter with Young's modulus. The aim of this comparison was to demonstrate changes caused by modification of biomechanical properties of bone.

Absorptiometry, Photon↗

Statistical physics models for nacre fracture simulation.

Natural biological materials such as nacre (or mother-of-pearl), exhibit phenomenal fracture strength and toughness properties despite the brittle nature of their constituents. For example, nacre's work of fracture is three orders of magnitude greater than that of a single crystal of its constituent mineral. This study investigates the fracture properties of nacre using a simple discrete lattice model based on continuous damage random thresholds fuse network. The discrete lattice topology of the proposed model is based on nacre's unique brick and mortar microarchitecture, and the mechanical behavior of each of the bonds in the discrete lattice model is governed by the characteristic modular damage evolution of the organic matrix that includes the mineral bridges between the aragonite platelets. The analysis indicates that the excellent fracture properties of nacre are a result of their unique microarchitecture, repeated unfolding of protein molecules (modular damage evolution) in the organic polymer, and the presence of fiber bundle of mineral bridges between the aragonite platelets. The numerical results obtained using this simple discrete lattice model are in excellent agreement with the previously obtained experimental results, such as nacre's stiffness, tensile strength, and work of fracture.

Animals↗

Force heterogeneity in a two-dimensional network model of lung tissue elasticity.

We have developed a model of forces developed in lung tissue in which the stress-bearing units are heterogeneous. Each element of the fiber network is composed of an idealized elastin and collagen element in parallel. Elastin is represented by linear springs and collagen by stiff strings that extend without resistance until taut. The model can quantitatively account for the nonlinear shape of the length-tension curve of lung tissue strips when the knee lengths of the collagen fibers are distributed according to an inverse power law. The novel feature of this model is that as macroscopic strain increases the load is carried by progressively fewer elements with progressively higher forces, and preferential pathways of force transmission emerge within the matrix. The topology of these self-organizing pathways of force transmission takes the rough appearance of cracks, but, unlike real cracks, they represent the locus of force concentration rather than force release.

Collagen↗

[Esophageal scintigraphy in patients with systemic sclerosis: clinical symptoms correlated with the esophagus noted by the patients].

Systemic sclerosis (SSc) is a multisystem connective tissue disorder characterized by excessive accumulation of the extracellular matrix. About 90% of the patients with SSc have detectable gastrointestinal tract involvement, 50% of these patients have clinically important manifestations. The aim of the study was estimation of the connection between subjective symptoms from the esophagus and results of the esophageal scintigraphy. 30 patients with systemic sclerosis were comprised to the study. Esophageal scintigraphy was performed in each patients, as well as questionnaire about type, intensity and frequency of esophageal dysmotility. Also it estimated was stiffness of the skin according to modified Rodnan score. Independent of esophageal dysmotility symptoms which were noted by patients, esophageal scintigraphy registered changes in 97% of the patients. The most often esophageal dysmotility was observed in lower part of the esophagus. Statistically Dysmolity of the central portion of the esophagus was observed more often in patients with diagnosed ISSc.

Adult↗

[The effect of a phorbol ester on the aortic wall].

Changes in the muscle tissue stiffness are important and necessary signs of the contractile process. The work is devoted to the study of this parameter of the smooth muscle tissue reaction during the action of phorbol esters, (namely, phorbol 12-myristate 13-acetate (PMA)), synthetic imitators of diacylglycerole. The experiments were carried out on isolated native preparations of aorta thoracic area of guinea pig under isometric conditions. Contraction induced by PMA or by the temperature was not accompanied by the stiffness changes. Potassium contraction (its development, amplitude, relaxation) evoked on the plateau of the PMA-induced contraction was similar in all respects to that in control: the stiffness increased significantly. These findings prove independent development of these two types of contractile processes. At the same time, the stiffness invariability and similar ratios of optical density to mechanical strength changes in the contractions induced by PMA action or by temperature show the likeness of the force generation mechanisms in these mechano-chemical reactions. The results obtained cannot be explained in terms of the generally accepted hypothesis of actomyosin interaction. The conclusion is made that phorbolic esters during the action on the smooth muscle tissue activate the mechanical strength generation by the connective tissue matrix.

Animals↗

Effect of beta-aminopropionitrile on bone mechanical properties.

In vivo beta-aminopropionitrile treatment caused significant changes in the mechanical properties of rat femora. In femora treated with beta-aminopropinitrile as compared with controls, there was a 44 per cent decrease in bone stiffness and a 47 per cent increase in bone deformation to failure. Bone ash was decreased 5 per cent in the treated group. It is likely that the decrease in bone ash was secondary to impaired intermolecular bone-collagen cross-linking, which is a well established consequence of treatment with beta-aminopropionitrile. Thus, beta-aminopropionitrile influences bone mechanical properties directly by impairing collagen cross-linking and indirectly by altering bone-matrix mineralization.

Aminopropionitrile↗

Histamine effects on endothelial cell fibronectin interaction studied by atomic force microscopy.

Atomic force microscopy was used to investigate the cellular response to histamine, one of the major inflammatory mediators that cause endothelial hyperpermeability and vascular leakage. AFM probes were labeled with fibronectin and used to measure binding strength between alpha5beta1 integrin and fibronectin by quantifying the force required to break single fibronectin-integrin bonds. The cytoskeletal changes, binding probability, and adhesion force before and after histamine treatment on endothelial cells were monitored. Cell topography measurements indicated that histamine induces cell shrinkage. Local cell stiffness and binding probability increased twofold after histamine treatment. The force necessary to rupture single alpha5beta1-fibronectin bond increased from 34.0 +/- 0.5 pN in control cells to 39 +/- 1 pN after histamine treatment. Experiments were also conducted to confirm the specificity of the alpha5beta1-fibronectin interaction. In the presence of soluble GRGDdSP the probability of adhesion events decreased >50% whereas the adhesion force between alpha5beta1 and fibronectin remained unchanged. These data indicate that extracellular matrix-integrin interactions play an important role in the endothelial cell response to changes of external chemical mediators. These changes can be recorded as direct measurements on live endothelial cells by using atomic force microscopy.

Animals↗

The use of poly(ethylene glycol) hydrogels to investigate the impact of ECM chemistry and mechanics on smooth muscle cells.

Hydrogels based on poly(ethylene glycol) (PEG) are of increasing interest for regenerative medicine applications and are ideal materials to direct cell function due to the ability to confer key functionalities of native extracellular matrix (ECM) on PEG's otherwise inert backbone. Given extensive recent evidence that ECM compliance influences a variety of cell functions, PEG-based hydrogels are also attractive due to the ease with which their mechanical properties can be controlled. In these studies, we exploited the chemical and mechanical tunability of PEG-based gels to study the impact of ECM chemistry and mechanics on smooth muscle cells (SMCs) in both 2-D and 3-D model systems. First, by controlling the extent of crosslinking and therefore the mechanical properties of PEG-based hydrogels (tensile moduli from 13.7 to 423.9kPa), we report here that the assembly of F-actin stress fibers and focal adhesions, indicative of the state of actin contractility, were influenced by the compliance of 2-D PEG gels functionalized with either short adhesive peptides or full-length ECM proteins. Varying ECM ligand density and identity independent of gel compliance affected the physical properties of the focal adhesions, and also influenced SMC spreading in 2-D. Furthermore, SMCs proliferated to a greater extent as gel stiffness was increased. In contrast, the degree of SMC differentiation, which was qualitatively assessed by the extent of smooth muscle alpha-actin bundling and the association of calponin and caldesmon with the alpha-actin fibrils, was found to decrease with substrate stiffness in 2-D cultures. In 3-D, despite the fact that their viability and degree of spreading were greatly reduced, SMCs did express some contractile markers indicative of their differentiated phenotype when cultured within PEG-RGDS constructs. Combined, these data suggest that the mechanical and chemical properties of PEG hydrogels can be tuned to influence SMC phenotype in both 2-D and 3-D.

Actins↗

Myocardial fibrosis in transforming growth factor beta(1)heterozygous mice.

Aging is associated with an increase in myocardial extracellular matrix components and contractile dysfunction. Transforming growth factor- beta(1)(TGF- beta(1)) has been shown to regulate expression of collagen genes and extracellular matrix component synthesis in the heart, and may contribute to the increase in myocardial fibrosis with aging. Therefore, we examined whether TGF- beta(1)heterozygous mutant mice would exhibit less age-associated myocardial fibrosis than normal mice. Twelve heterozygous TGF- beta(1)(+/-) deficient mice and 26 wild-type controls were examined to determine if there was a difference in development of myocardial fibrosis or mortality at 24 months of age due to the loss of one TGF- beta(1)allele. Animals which survived to 24 months of age were killed, and morphometric and functional studies were performed in isolated perfused hearts and in hearts from 6 month old control mice. Pressure-volume relations of the LV were assessed in the isovolumic (balloon in LV) Langendorff preparation. Eleven of 12 (92%) TGF- beta(1)deficient mice survived to 24 months of age in comparison to 66% (12/18) age-matched controls (P<0.05). Hearts from the 24 month old TGF- beta(1)deficient mice exhibited a decrease in myocardial fibrosis (4+/-1 v. 10+/-1% average LV fibrosis in TGF- beta(1)(+/-) and age-matched controls, respectively (P<0.05) and greater compliance (i.e.,lower LV end-diastolic pressure at a given balloon volume), decreased myocardial stiffness, and shorter contractile duration in comparison to 24-month-old wild-type controls. This suggests that modulation of collagen production and/or degradation by TGF- beta(1)may contribute to changes in myocardial structure and function with age. Thus, loss of one TGF- beta(1)allele appears to ameliorate age associated myocardial fibrosis and improve LV compliance, which may contribute to increased survival over the life span of these mice.

Aging↗

Fibrin-polyurethane composites for articular cartilage tissue engineering: a preliminary analysis.

In this study we investigated the use of a fibrin hydrogel to improve the potential of a polyurethane (PU) scaffold-based system for articular cartilage tissue engineering. PU-only ("no-fibrin") and PU-fibrin ("fibrin") composites were cultured for up to 28 days and analyzed for DNA content, glycosaminoglycan (GAG) content, type II collagen content, GAG release, and gene expression of aggrecan, collagen I, and collagen II. The use of fibrin allowed for higher viable cell-seeding efficiency (10% higher DNA content on day 2 in fibrin versus no-fibrin composites) and more even cell distribution on seeding, a more than 3-fold increase in the percentage of newly synthesized GAG retained in the constructs, and 2- to 6-fold higher levels of type II collagen and aggrecan gene expression through day 14. Addition of aprotinin to the medium inhibited fibrin degradation, most noticeably in the center of the constructs, but had little effect on biochemical composition or gene expression. Short-term mechanical compression (0-10% sinusoidal strain at 0.1 Hz for 1 h, applied twice daily for 3 days) doubled the rate of GAG release from the constructs, but had little effect on gene expression, regardless of the presence of fibrin. Although further work is needed to optimize this system, the addition of fibrin hydrogel to encapsulate cells in the stiff, macroporous PU scaffold is a step forward in our approach to articular cartilage tissue engineering.

Aggrecans↗