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PubMed1995

Oral heparin in the treatment of rheumatoid arthritis.

Heparin was administered orally in 10 patients with rheumatoid arthritis. The treatment resulted in clinical improvement in all cases (significant reduction in the number of tender and swollen joints and morning stiffness). This was associated with a decrease in erythrocyte sedimentation rate (8/10 patients) and cholesterol in all patients, although the differences were not significant. Recent data indicate that heparin can bind cytokines with potent immune modulatory action (e.g. TNF-alpha, interferon gamma etc.). Thus, neutralization of their action on target cells could be partially responsible for the beneficial effects reported. Moreover, heparin inhibits T cell traffic to a site of antigen by blocking enzymes digesting the extracellular matrix and interfering with selection activity. The results of our preliminary study suggest that heparin, given per os, may have immunomodulatory properties with potential application in human disease.

Administration, Oral↗
PubMed2005

Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer.

PURPOSE: Matrix metalloproteinases (MMPs) degrade extracellular proteins and facilitate tumor growth, invasion, metastasis, and angiogenesis. This trial was undertaken to determine the effect of prinomastat, an inhibitor of selected MMPs, on the survival of patients with advanced non-small-cell lung cancer (NSCLC), when given in combination with gemcitabine-cisplatin chemotherapy. PATIENTS AND METHODS: Chemotherapy-naive patients were randomly assigned to receive prinomastat 15 mg or placebo twice daily orally continuously, in combination with gemcitabine 1,250 mg/m2 days 1 and 8 plus cisplatin 75 mg/m2 day 1, every 21 days for up to six cycles. The planned sample size was 420 patients. RESULTS: Study results at an interim analysis and lack of efficacy in another phase III trial prompted early closure of this study. There were 362 patients randomized (181 on prinomastat and 181 on placebo). One hundred thirty-four patients had stage IIIB disease with T4 primary tumor, 193 had stage IV disease, and 34 had recurrent disease (one enrolled patient was ineligible with stage IIIA disease). Overall response rates for the two treatment arms were similar (27% for prinomastat v 26% for placebo; P = .81). There was no difference in overall survival or time to progression; for prinomastat versus placebo patients, the median overall survival times were 11.5 versus 10.8 months (P = .82), 1-year survival rates were 43% v 38% (P = .45), and progression-free survival times were 6.1 v 5.5 months (P = .11), respectively. The toxicities of prinomastat were arthralgia, stiffness, and joint swelling. Treatment interruption was required in 38% of prinomastat patients and 12% of placebo patients. CONCLUSION: Prinomastat does not improve the outcome of chemotherapy in advanced NSCLC.

Adult↗
PubMed1993

Achilles tendon healing: a correlation between functional and mechanical performance in the rat.

The pathogenesis and treatment of rupture of the Achilles tendon remain a source of controversy. This study presents the results of a biomechanical, functional, and morphological evaluation of a group of rats that had division and repair of the Achilles tendon. A total of 46 rats were used: 18 for biomechanical testing, 18 for functional evaluation, and 10 for histology. Morphological examination revealed an early inflammatory response with loose connective tissue formation that was replaced gradually by fibroblasts and a collagenous matrix. The functional evaluation (Achilles functional index [AFI]) was made from measurements of the hind pawprints of walking rats. Division and repair of the Achilles tendon produced a significant functional impairment (mean [+/- SEM] AFI = -87 +/- 8; p < 0.001), which gradually improved with healing time. The load to failure for the repaired tendons consistently improved with healing time, in a manner similar to the functional recovery. The average deformation (repair/control) varied considerably and was not related to healing time. The stiffness of the repaired tendons increased with healing time and was 60% of the corresponding control side by day 15. The major finding of this study was a strong correlation between the AFI and the failure load of the healing tendon-bone constructs (250-300 g group, r = 0.97, p < 0.001; 325-375 g group, r = 0.96, p < 0.001).

Achilles Tendon↗
PubMed1997

Effect of MMA-g-UHMWPE grafted fiber on mechanical properties of acrylic bone cement.

Ultrahigh molecular weight polyethylene (UHMWPE) fibers were treated with argon plasma for 5 min, followed by uv irradiation in methyl methacrylate (MMA)-chloroform solution for 5 h to obtain MMA-g-UHMWPE grafted fiber. The grafting content was estimated by the titration of esterification method. The grafting amount of 5280 nmol/g was the largest for the MMA concentration at 18.75 vol%. To improve the mechanical properties of acrylic bone cement, pure UHMWPE fiber and MMA-g-UHMWPE fiber were added to the surgical Simplex. P radiopaque bone cement. The mechanical properties including tensile strength, tensile modulus, compressive strength, bending strength, and bending stiffness were measured. Dynamic mechanical analysis was also performed. By comparing the effect of the pure UHMWPE fiber and MMA-g-UHMWPE grafted fiber on the mechanical properties of acrylic bone cement, it was found that the acrylic bone cement with MMA-g-UHMWPE grafted fiber had a more significant reinforcing effect than that with untreated UHMWPE fiber. This might be due to the improvement of the interfacial bonding between the grafted fibers and the acrylic bone cement matrix.

Acrylates↗
PubMed1984

The glutaraldehyde-stabilized porcine aortic valve xenograft. II. Effect of fixation with or without pressure on the tensile viscoelastic properties of the leaflet material.

We have examined the tensile viscoelastic properties of circumferential and radial strips of porcine aortic valve leaflets following fixation in glutaraldehyde and formaldehyde, with or without pressure. After aldehyde treatment, the radial strips remained weaker and less stiff than circumferential strips and responded slightly differently to the treatment. After fixation, with or without pressure, the radial strips showed large changes in stress-strain and hysteresis responses due to initial loading, and there was a twofold reduction in tensile strength and final stiffness. For strips in both directions, fixation without pressure produced doubled extensibility and a ramping stress-strain curve. Permanent (plastic) deformation of 5-20% occurred as a result of cyclic loading, stress relaxation, and creep experiments. Pressure fixation, however, produced little change in stress-strain results other than a simple shift to lower strain and produced no plasticity. Both methods of fixation reduced stress relaxation and creep. Mechanical test results are consistent with a loss of ground substance matrix during fixation. Reductions in tensile strength after fixation may be due to "riveting" of collagen geometry, producing local stress concentrations.

Animals↗
PubMed2004

The role of the cytoskeleton in the viscoelastic properties of human articular chondrocytes.

Biomechanical factors are believed to play an important role in regulating the metabolic activity of chondrocytes in articular cartilage. Previous studies suggest that cytoskeletal proteins such as actin, vimentin, and tubulin influence cellular mechanical properties, and may therefore influence the mechanical interactions between the chondrocyte and the surrounding tissue matrix. In this study, we investigated the role of specific cytoskeletal components on the mechanical properties of individual chondrocytes isolated from normal or osteoarthritic hip articular cartilage. Chondrocytes were exposed to a range of concentrations of chemical agents that disrupt the primary cytoskeletal elements (cytochalasin D for F-actin microfilaments, acrylamide for vimentin intermediate filaments, and colchicine for microtubules). Chondrocyte mechanical properties were determined using the micropipette aspiration technique coupled with a viscoelastic solid model of the cell. Chondrocyte stiffness (elastic modulus) was significantly increased with osteoarthritis. With increasing cytochalasin D treatment, chondrocyte stiffness decreased by up to 90% and apparent viscosity decreased by up to 80%. The effect of cytochalasin D was greater on normal chondrocytes than those isolated from osteoarthritic cartilage. Treatment with acrylamide also decreased the moduli and viscosity, but only at the highest concentration tested. No consistent changes in cell mechanical properties were observed with colchicine treatment. These findings suggest that microfilaments and possibly intermediate filaments provide the viscoelastic properties of the chondrocyte, and changes in the structure and properties of these cytoskeletal elements may reflect changes in the chondrocyte with osteoarthritis.

Acrylamide↗
PubMed1997

Relationship between passive tissue strain and collagen uncoiling during healing of infarcted myocardium.

OBJECTIVE: The structure of the collagen scar during healing of a myocardial infarction is a determinant of the function of the remodeled tissue. We hypothesize that the passive deformations of both scar and normal tissue are related to the underlying collagen uncoiling as the tissue stretches, and that the unloaded tortuosity of the collagen may be a determinant of tissue stiffness at low ventricular pressure. Hence collagen uncoiling and tissue strain were measured during passive loading in normal tissue, and in healing infarct tissue. METHODS: Left ventricles of rats were infarcted by ligation of the left anterior descending artery for 2 weeks. Surface strains were measured during passive inflation in the scar region in one set of excised hearts, and other arrested hearts were fixed at different ventricular pressures, after which collagen tortuosity was measured in the infarcted and normal tissue. RESULTS: Passive loading strains were smaller in the scar in both the fiber and cross-fiber directions. Tortuosity decreased with load in normal and infarcted tissue, with fibrils tending to straighten more in the scar tissue at higher pressures (1.056 +/- 0.009 vs. 1.024 +/- 0.009 at P = 20 mmHg) with similar tortuosities at zero pressure (1.110 +/- 0.012 vs. 1.098 +/- 0.019). The decrease in tortuosity with strain was greater for the infarcted tissue. CONCLUSIONS: The greater stiffness of infarcted tissue at low pressure is not due to 'straightened' collagen fibers, and there may be a different three-dimensional structure of infarct vs. normal coiled collagen fibers which can affect the material properties of these tissues.

Animals↗
PubMed2005

Mitral valve stiffening in end-stage heart failure: evidence of an organic contribution to functional mitral regurgitation.

OBJECTIVE: Mitral regurgitation is a complication for many patients with congestive heart failure. Although this regurgitation is considered purely functional, we hypothesize that the alterations in cardiac geometry and function induce dysfunctional remodeling of the mitral valve, which can be demonstrated by alterations in the material behavior of the leaflets and chordae. METHODS: Mitral leaflets and chordae from 23 valves from transplant recipient hearts (11 with dilated and 12 with ischemic cardiomyopathy) and from 21 normal valves (from autopsy) were mechanically tested. RESULTS: Radially oriented anterior mitral leaflet strips from failing hearts were 61% stiffer and 23% less viscous on average than those from autopsy control hearts. The mean stiffness of circumferentially oriented anterior leaflet strips was 50% higher than that of control hearts. Leaflet extensibility was reduced 35% overall. Likewise, the failing heart chordae were an average of 16% stiffer (all P < or = .05). CONCLUSIONS: Mitral valves in congestive heart failure have significantly altered mechanics that suggest that the tissue is permanently distended and fibrotic and might be unable to stretch sufficiently to cover the valve orifice. These material changes in the valve tissues accompany the biochemical alterations in extracellular matrix composition that we have previously reported. Our finding of leaflet and chordal remodeling suggests that mitral regurgitation in patients experiencing heart failure might not be purely functional and that these mitral valves should not be considered normal. Moreover, there are implications for strategies of mitral valve surgery or percutaneous approaches in this patient population.

Chordae Tendineae↗
PubMed1992

Composition and mechanics of mesenteric resistance arteries from pregnant rats.

We tested the hypothesis that the systemic resistance vasculature of the rat is remodeled during pregnancy as evidenced by significant alterations in the passive mechanical properties and extracellular matrix proteins in mesenteric arteries. Mechanical characteristics were determined for arteries from 20-day pregnant rats (n = 6) and age-matched controls (n = 5). Lumen diameter and wall thickness were measured in pressurized arteries (250-microns diameter) using a dimension analyzing system. Distensibility (the relative change in diameter per unit change in pressure) was less in the arteries from the pregnant rats (P less than 0.01). The calculated stress-strain relationships and elastic moduli indicated that the arteries were less stiff by late gestation (P less than 0.05). Ultramicro amino acid analysis and radioimmunoassay were used to measure hydroxyproline, desmosine, and leucine as indicators of collagen, elastin, and total protein, respectively, in similar-sized arteries. Hydroxyproline/leucine (index of collagen) and desmosine/leucine (elastin concentration) decreased 19 and 15% by late gestation (P less than 0.05). The significant alterations in passive mechanics and in extracellular protein content support the concept that arterial wall remodeling in the peripheral vasculature may be one component of the cardiovascular adaptations during pregnancy.

Animals↗
PubMed1992

On the relationship between the microstructure of bone and its mechanical stiffness.

A recent study of bone structure shows that the plate-shaped carbonate apatite crystals in individual lamellae are arranged in layers across the lamellae, and that the orientation of these layers are different in alternate lamellae. Based on these findings, a new micromechanical model for the Young's modulus of bone is proposed, which accounts for the anisotropy and geometrical characteristics of the material. The model incorporates the platelet-like geometry of the basic reinforcing unit, the presence of alternating thin and thick lamellae, and the orientations of the crystal platelets in the lamellae. The thin and thick lamellae are modeled as orthotropic composite layers made up of thin rectangular apatite platelets within a collagen matrix, and classical orthotropic elasticity theory is used to calculate the Young's modulus of the lamellae. Bone is viewed as an assembly of such orthotropic lamellae bent into cylindrical structures, and having a constant, alternating angle between successive lamellae. The micromechanical model employs a modified rule-of-mixtures to account for the two types of lamellae. The model provides a curve similar to the published experimental data on the angular dependence of Young's modulus, including a local maximum at an angle between 0 and 90 degrees. A rigorous testing of the model awaits additional experimental data.

Animals↗
PubMed1985

Effect of filler content and size on properties of composites.

Two series of dental composites, along with the unfilled resin matrix, were examined to determine the effects of filler level and size on selected properties. Both series were prepared by incorporating a silanated barium borosilicate filler into a visible-light-activated polyphenylene polymethacrylate resin matrix. One series had a filler particle size of 2 microns, with filler levels of 20, 40, 45, 50, and 53% (vol). The second series contained a 15-microns filler in amounts of 20, 40, 50, 60, and 65% (vol). Tests conducted included: depth of cure as evaluated by hardness, water sorption, compressive strength, stress-strain behavior under slow compression, toothbrush abrasion, and wear by hydroxyapatite. Analysis of the data indicated that increased filler levels resulted in increased hardness, compressive strength and stiffness, and decreased water sorption. Also, there was a slight trend toward improved depth of cure. Incorporation of the 2-microns filler decreased the abrasion resistance of the resins to toothbrushing as compared with the unfilled resin, while addition of the 15-microns filler improved resistance. All filled resins exhibited a significant improvement in resistance to wear by hydroxyapatite as compared with the unfilled resin. There was a trend for increased wear with increased filler level. The particle size of the filler appeared to have a moderate influence on the properties. When compared with 15-microns filled resins of the same filler levels, the 2-micron filled series appeared to have inferior properties in terms of depth of cure, compressive strength, water sorption, and resistance to toothbrush abrasion. Properties which were less affected by particle size were hardness, stiffness, and wear resistance to hydroxyapatite.

Chemical Phenomena↗
PubMed2000

A novel injectable bioactive bone cement for spinal surgery: a developmental and preclinical study.

The injection of bone cement by minimally invasive techniques for the treatment of vertebral body fractures or for stabilization of an osteoporotic vertebral body is regarded as promising in spinal surgery. The purpose of this study was to develop a novel injectable bioactive bone cement to address such concerns. The cement was composed mainly of strontium-containing hydroxyapatite (Sr-HA) filler and Bisphenol A Diglycidylether Dimethacrylate (D-GMA) resin. The Sr-HA filler was prepared by precipitation and calcination, then analyzed with Fourier transform infrared (FTIR) spectra and X-ray diffraction (XRD) patterns. Samples of strontium-containing hydroxyapatite cement (SrHAC) were formed by a combination of powder filler and resin matrix, with the setting time and peak temperature recorded. Cell relative growth rate (RGR), Tetrazolium bromide (MTT), and haemolysis tests were used to detect initial in vitro biocompatibility of the new cement. In vitro spinal biomechanical testing and morphological observation after bone cement injection were performed on pig spines. Results indicate that the setting time and peak temperature of the cement was 15 min and 55 degrees C, respectively. Cytotoxicity of the cement was class 1 (no cytotoxicity) and haemolysis was 1% (no haemolysis). Stiffness after cement injection and fatigue loading were 112% and 95% of the intact bone, respectively, which is similar to that of natural bone. Radiopacity of SrHAC allowed easy radiographic imaging. The use of SrHAC cement is, thus, promising in spinal surgery.

Animals↗
PubMed1981

Mechanical properties of model synthetic tendons.

Model synthetic tendons consisting of 20 vol % of texturized poly(ethylene terephthalate) fibers and of the water-swollen poly(2-hydroxyethyl methacrylate) matrix have the tensile modulus E = 1.5 +/- 0.1 GPa, strength and strain-at-break sigma b = 85 +/- 10 MPa and epsilon b = 0.08 +/- 0.02. The force required for breaking tendons with the diameters 2, 3, 4 mm is, respectively, 300, 500, and 960 N. By these properties model synthetic tendons closely imitate the properties of natural tendons. Long-term (100 min) and repeated short-term (30 times 1 min) creep shows that on loading model tendons lose some 10% of their stiffness, but that the whole deformation is reversible. The shape of the compliance vs. time dependence of synthetic tendons closely resembles the dependence determined for the parent fiber. The stiffness and strength of a tendon are given by those of the fiber bundle used; by varying fiber volume fraction, it is possible to adjust the required mechanical properties of tendons.

Animals↗
PubMed1997

Synthesis of BISGMA derivatives, properties of their polymers and composites.

2,2-Bis[4-(2 hydroxy-3-methacryloyloxy propoxy) phenyl] propane (BisGMA) is commonly the main component of the organic matrix of dental filling materials. Derivatives of BisGMA were synthesized from the diglycidyl ether of Bisphenol A (DGEBA) by the parallel reaction with methacrylic acid (MAA) and isophthalic acid as well as mixtures of methacrylic anhydride with palmitic acid and acetic anhydride, respectively, whereby MAA was partially substituted by the latter components. By this technique the structure of BisGMA monomer could be varied with regard to weight content of C=C double bonds, the hydrophilicity of the molecule as well as its flexibility or stiffness. Free-radical initiated homopolymerization of the monomers was carried out at 80 degrees C. Composites, prepared from mixtures of monomers with triethylene glycol dimethacrylate (TEGDMA) filled with 76% silica were room temperature polymerized using both redox and photoinitiated techniques. The polymerization shrinkage, diffusion coefficients of water in the crosslinked polymer, and some thermal properties of the homopolymers were determined. Mechanical properties of the resulting polymers and composites are compared to those of BisGMA itself.

Journal Article↗
PubMed2003

Chemical and biomechanical characterization of hyperhomocysteinemic bone disease in an animal model.

BACKGROUND: Classical homocystinuria is an autosomal recessive disorder caused by cystathionine beta-synthase (CBS) deficiency and characterized by distinctive alterations of bone growth and skeletal development. Skeletal changes include a reduction in bone density, making it a potentially attractive model for the study of idiopathic osteoporosis. METHODS: To investigate this aspect of hyperhomocysteinemia, we supplemented developing chicks (n = 8) with 0.6% dl-homocysteine (hCySH) for the first 8 weeks of life in comparison to controls (n = 10), and studied biochemical, biomechanical and morphologic effects of this nutritional intervention. RESULTS: hCySH-fed animals grew faster and had longer tibiae at the end of the study. Plasma levels of hCySH, methionine, cystathionine, and inorganic sulfate were higher, but calcium, phosphate, and other indices of osteoblast metabolism were not different. Radiographs of the lower limbs showed generalized osteopenia and accelerated epiphyseal ossification with distinct metaphyseal and suprametaphyseal lucencies similar to those found in human homocystinurics. Although biomechanical testing of the tibiae, including maximal load to failure and bone stiffness, indicated stronger bone, strength was proportional to the increased length and cortical thickness in the hCySH-supplemented group. Bone ash weights and IR-spectroscopy of cortical bone showed no difference in mineral content, but there were higher Ca2+/PO4(3-) and lower Ca2+/CO3(2-) molar ratios than in controls. Mineral crystallization was unchanged. CONCLUSION: In this chick model, hyperhomocysteinemia causes greater radial and longitudinal bone growth, despite normal indices of bone formation. Although there is also evidence for an abnormal matrix and altered bone composition, our finding of normal biomechanical bone strength, once corrected for altered morphometry, suggests that any increase in the risk of long bone fracture in human hyperhomocysteinemic disease is small. We also conclude that the hCySH-supplemented chick is a promising model for study of the connective tissue abnormalities associated with homocystinuria and an important alternative model to the CBS knock-out mouse.

Animals↗
PubMed1999

Angiotensin-converting enzyme and matrix metalloproteinase inhibition with developing heart failure: comparative effects on left ventricular function and geometry.

The progression of congestive heart failure (CHF) is left ventricular (LV) myocardial remodeling. The matrix metalloproteinases (MMPs) contribute to tissue remodeling and therefore MMP inhibition may serve as a useful therapeutic target in CHF. Angiotensin converting enzyme (ACE) inhibition favorably affects LV myocardial remodeling in CHF. This study examined the effects of specific MMP inhibition, ACE inhibition, and combined treatment on LV systolic and diastolic function in a model of CHF. Pigs were randomly assigned to five groups: 1) rapid atrial pacing (240 beats/min) for 3 weeks (n = 8); 2) ACE inhibition (fosinopril, 2.5 mg/kg b.i.d. orally) and rapid pacing (n = 8); 3) MMP inhibition (PD166793 2 mg/kg/day p.o.) and rapid pacing (n = 8); 4) combined ACE and MMP inhibition (2.5 mg/kg b.i.d. and 2 mg/kg/day, respectively) and rapid pacing (n = 8); and 5) controls (n = 9). LV peak wall stress increased by 2-fold with rapid pacing and was reduced in all treatment groups. LV fractional shortening fell by nearly 2-fold with rapid pacing and increased in all treatment groups. The circumferential fiber shortening-systolic stress relation was reduced with rapid pacing and increased in the ACE inhibition and combination groups. LV myocardial stiffness constant was unchanged in the rapid pacing group, increased nearly 2-fold in the MMP inhibition group, and was normalized in the ACE inhibition and combination treatment groups. Increased MMP activation contributes to the LV dilation and increased wall stress with pacing CHF and a contributory downstream mechanism of ACE inhibition is an effect on MMP activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Drug release properties of a gel bead prepared with pectin and hydrolysate.

A calcium-induced pectin gel bead (PB) containing pectin hydrolysate was prepared, and the drug release profiles and degradation properties of the PB were investigated in aqueous media. The stiff PB swelled in physiological saline and its drug release rate decreased with exposure to increasing concentrations of CaCl2 during preparation. And erosion of the PB was not observed in physiological saline. However, the PB did disintegrate in phosphate buffer (pH 6.8) and the rate of disintegration depended on the calcium chloride concentration used to prepare the PB. In addition, the drug release rate of the PB in buffer solution decreased as the rate of gel erosion declined. Consequently, it appears that the PB gel matrix is an effective medium by which to control the release of drug within the gastrointestinal tract.

Calcium Chloride↗
PubMedDate not supplied

Effect of passage number and collagen type on the proliferative, biosynthetic, and contractile activity of adult canine articular chondrocytes in type I and II collagen-glycosaminoglycan matrices in vitro.

One tissue-engineering approach being investigated for the treatment of defects in articular cartilage involves the implantation of autologous chondrocyte-seeded absorbable scaffolds. The present study evaluated the effects of passage number (freshly isolated and passages 1 and 2) and collagen type on the proliferative, biosynthetic, and contractile activity of adult canine articular chondrocytes grown in type I and II collagen-glycosaminoglycan (GAG) matrices that were cross-linked by dehydrothermal/carbodiimide treatment. P0, P1, and P2 cells seeded in the type II matrices continued to proliferate over a 4-week period, but thereafter the P0 and P1 cells continued to increase in number and the P2 cells decreased. At 4 weeks the DNA contents of the type I and II matrices seeded with P1 and P2 cells were comparable, and higher than the values for matrices seeded with freshly isolated chondrocytes. The rates of protein and GAG synthesis by the P1 and P2 cells were comparable, and higher than the rates for the P0 chondrocytes, after 1 week, and the rates were generally higher in the type II than in the type I collagen scaffolds. Western blot analysis demonstrated the presence of newly synthesized type II collagen in type II matrices in which P1 and P2 cells were grown. The cross-linking treatment imparted a sufficient degree of mechanical stiffness to both types of matrices to resist cell-mediated contraction. This study demonstrated that adult articular chondrocytes expanded in number through two passages in monolayer culture can be expected to provide behavior comparable to or better than freshly isolated cells with respect to proliferation and biosynthesis through 4 weeks of culture in collagen-GAG matrices, and these cells retain the capability to synthesize type II collagen. The results of this investigation further commend the use of a type II collagen-GAG matrix, based on the higher biosynthetic rates of the cells grown in the matrices, for the preparation of chondrocyte-seeded scaffolds for articular cartilage tissue engineering.

Animals↗