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Mechanical interlocking of engineered cartilage to an underlying polymeric substrate: towards a biohybrid tissue equivalent.

This study investigates the feasibility of engineering a biohybrid cartilage equivalent (BCE) with the long-term goal of restoring the mechanical integrity and interfacial characteristics of severely damaged cartilage. The BCE depends on the successful adhesion, via mechanical interlocking, of a cartilage layer to a nondegradable composite scaffold or prosthesis. The model scaffold, consisting of a nonwoven mesh bonded to a solid core, was seeded with bovine articular chondrocytes. High molecular weight poly(L-lactic acid), which has a slow degradation time, was used to model the nondegradable polymer. Biochemical and histological analysis demonstrate that the BCE can support the growth of a cartilaginous matrix for at least 6 weeks in culture. Mechanical testing of the BCE showed cartilage adhesion strength increased from 19.27+/-1.62 to 43.79+/-3.88 kPa between 35 and 50 days in culture. Nonmechanically interlocked cartilage achieved less than 5% of this adhesion strength. For the first time, atomic force microscopy (AFM) was used to characterize surface topography of tissue-engineered cartilage. Surface roughness of constructs after 8 and 10 weeks ranged from 153 to 171 nm, falling within the range of native cartilage (100-600 nm). This study demonstrates the feasibility of creating a biohybrid cartilage equivalent by mechanically interlocking a cartilaginous layer to an underlying polymeric matrix.

Animals↗

Age-related changes in the expression of gelatinase and tissue inhibitor of metalloproteinase genes in mandibular condylar, growth plate, and articular cartilage in rats.

Mandibular condylar cartilage acts as both articular and growth plate cartilage during growth, and then becomes articular cartilage after growth is complete. Cartilaginous extracellular matrix is remodeled continuously via a combination of production, degradation by matrix metalloproteinases (MMPs), and inhibition of MMP activity by tissue inhibitors of metalloproteinases (TIMPs). This study attempted to clarify the age-related changes in the mRNA expression patterns of MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 in mandibular condylar cartilage in comparison to tibial growth plate and articular cartilage using an in situ hybridization method in growing and adult rats. MMP-2 and MMP-9 were expressed in a wide range of condylar cartilage cells during growth, and their expression domains became limited to mature chondrocytes in adults. The patterns of TIMP-1 and TIMP-2 expression were similar to those of MMP-2 and MMP-9 during growth, and were maintained until adulthood. TIMP-3 was localized to hypertrophic chondrocytes throughout the growth stage. Therefore, we concluded that TIMP-1 and TIMP-2 were general inhibitors of MMP-2 and MMP-9 in condylar cartilage, while TIMP-3 regulates the collagenolytic degradation of the hypertrophic cartilage matrix.

Aging↗

Analysis of cartilage differentiation from skeletal muscle grown on bone matrix. III. Environmental regulation of glycosaminoglycan and proteoglycan synthesis.

The ability of numerous nutritional and topographic factors to influence differentiation of embryonic mesenchyme has given rise to several theories which attempt to explain the development of muscle and cartilage from these similar-appearing cells. Some theories are challenged by the observation that a substratum of demineralized bone is capable of supporting the transformation of skeletal muscle into cartilage in vitro and that the potential to form cartilage still resides within cloned myoblasts and fibroblasts of skeletal muscle. In the present study, culture media CMRL-1066, minimal essential medium (MEM), and F-12 provide varied nutritional environments and are tested for their ability to support the morphological and biochemical transformation of skeletal muscle into cartilage. Morphologically, CMRL-1066 reproducibly supports hyaline cartilage formation, whereas MEM does so in only one out of three explants onto demineralized bone, and F-12 is incapable of supporting formation of a hyaline matrix. Biochemically, each medium is sufficient to elicit synthesis of cartilage-like patterns of sulfated glycosaminoglycans and proteoglycan monomer. Synthesis of hyaluronic acid (HA) initially increases in explants grown in CMRL-1066, but decreases prior to chondrogenesis. MEM elicits a similar increase in HA synthesis, but the subsequent decrease is not as rapid. In F-12, synthesis remains depressed throughout the experiment. The data show that increases in HA synthesis occur concurrent with the appearance of fibroblast-like cells, which normally precede chondroblasts. Decreases in HA synthesis correlate well with the onset of chondrogenesis. Explants grown in CMRL-1066 reproducibly from cartilage and synthesize the greatest amounts of proteoglycan aggregate. Those grown in MEM form cartilage infrequently, synthesize reduced amounts of proteoglycan aggregate-like material, and contain greater amounts of HA, of low molecular weight. The data demonstrate that chondrogenesis can be subtly regulated by environmental factors, and such factors regulate both the morphological and biochemical expression of the phenotype through HA synthesis.

Animals↗

Immunological evidence for two distinct chondroitin sulfate proteoglycan core proteins: differential expression in cartilage matrix deficient mice.

The expression and core protein structure of two proteoglycans, the major cartilage proteoglycan isolated from a rat chondrosarcoma and a small molecular weight chondroitin sulfate proteoglycan isolated from a rat yolk sac tumor, have been compared. The cartilage proteoglycan was not detectable in the cartilage tissue of cartilage matrix deficient (cmd/cmd) neonatal mice by immunofluorescence, but the cmd cartilage did react with antibodies against the core protein of the yolk sac tumor proteoglycan. Radioimmunoassays showed that the core proteins of these proteoglycans are not cross-reactive with each other. Analysis of the core proteins by sodium dodecyl sulfate/polyacrylamide gel electrophoresis after chondroitinase ABC treatment of the proteoglycan revealed a large difference in their sizes. The cartilage proteoglycan core protein had a molecular weight of about 200,000 while the yolk sac tumor proteoglycan core protein migrated with an apparent molecular weight of about 20,000. In addition, the cultured yolk sac tumor cells that make the small proteoglycan did not react with antiserum against the cartilage proteoglycan. These results indicate that the proteoglycan isolated from the yolk sac tumor is similar to the small chondroitin sulfate proteoglycan species found in cartilage and support the existence of at least two dissimilar and genetically independent chondroitin sulfate proteoglycan core proteins.

Animals↗

An asymptotic solution for the contact of two biphasic cartilage layers.

This study addresses the hypothesis that interstitial fluid plays a major role in the load support mechanism of articular cartilage. An asymptotic solution is presented for two contacting biphasic cartilage layers under compression. This solution is valid for identical thin (i.e. epsilon = h'/a'0 << 1), frictionless cartilage layers, and for the 'early' time response (i.e. t' << (h')2/HAk) after the application of a step load. An equilibrium asymptotic solution is also presented (i.e.t'-->infinity). Here h' is the thickness, a'0 is a characteristic contact radius, HA is the aggregate modulus and k is the permeability of the cartilage layer. A main conclusion from this analysis is that the fluid phase of cartilage plays a major role in providing load support during the first 100-200 s after contact loading. Further, the largest component of stress in cartilage is the hydrostatic pressure developed in the interstitial fluid. For tissue fluid volume fraction (porosity) in the range 0.6 < or = phi f < or = 0.8, k = O(10(-15) m4/Ns) and HA = O(1 MPa), the peak magnitude of the principal effective (or elastic) stress may be as low as 14% of the peak hydrostatic pressure within the tissue, or the contact stress at the surface. In effect, the interstitial fluid shields the solid matrix from high normal stresses and strains. The asymptotic solution also shows that pressure-sensitive film measurements of intra-articular contact stress do not measure the elastic stress at the surface, but they rather provide a measure of the interstitial fluid pressure. Finally, this analysis provides strong support for the hypothesis that, if sudden loading causes shear failure within the cartilage-bone layer structure, this failure would take place at the cartilage-bone interface, and the plane of failure would be either parallel or perpendicular to this interface.

Adhesiveness↗

Age-related decrease in the activity of UDP-xylose:core protein xylosyltransferase in rat costal cartilage.

The activity of UDP-xylose:core protein xylosyltransferase (EC 2.4.2.26) in costal cartilage of young rats (3 months) and old rats (36 months) was measured. The enzyme activity in cartilage of young rats (mean +/- S.D.) is 3370 +/- 1440 Bq h-1 mg-1 DNA, which is about three times higher than that determined in cartilage of old rats (1090 +/- 520 Bq h-1 mg-1 protein). The amount of galactosamine-containing proteoglycosaminoglycans that are extractable with 4 M guanidinium chloride from cartilage is significantly higher in young rats (29.1 +/- 4.8 nmol GalN per mg cartilage wet weight) than in old animals (5.8 +/- 3.0 nmol GalN per mg cartilage wet weight). Thus, if xylosyltransferase activity is referred to the amount of galactosamine-containing proteoglycans in cartilage, nearly identical values are obtained (young rats, 80 +/- 30 Bq h-1 mumol-1 GalN; old rats, 85 +/- 35 Bq h-1 mumol-1 GalN). The results support the assumption that the synthesis of proteochondroitin sulfate is diminished in costal cartilage of old rats by a mechanism involving a reduced activity of xylosyltransferase.

Aging↗

Comparative analysis of collagens solubilized from human foetal, and normal and osteoarthritic adult articular cartilage, with emphasis on type VI collagen.

The different collagen types were extracted sequentially, by 4 M guanidinium chloride and pepsin, from human foetal and normal and osteoarthritic adult articular cartilage. They were characterized by electrophoresis and immunoblotting. Most of the collagenous proteins present in articular cartilage from young human foetuses were solubilized: almost 40% of the total collagen was extracted in the native form with 4 M guanidinium chloride. Type VI collagen was detected in this fraction as high-molecular-mass chains (185-220 kDa) and a low-molecular-mass chain (140 kDa). Type II, IX and XI collagens were also present, but were extracted more extensively by pepsin digestion. Comparative analysis of normal and osteoarthritic cartilage from adults reveals some major differences: an increase in the solubility of the collagen and modifications of soluble collagen types in osteoarthritic cartilage. Furthermore, type VI collagen was present at a higher concentration in guanidinium chloride extracts of osteoarthritic cartilage than those of normal tissue. This finding was corroborated by electron microscopic observations of the same samples: abundant (100 nm) periodic fibrils were observed in the disorganized pericellular capsule of cloned cells in osteoarthritic cartilage. In normal tissues the pericellular zone was more compact and contained only a few such banded fibrils. The differences in the collagen types solubilized from normal and osteoarthritic cartilage, although corresponding to a minor proportion of the total collagen, demonstrate that important modifications in chondrocyte metabolism and in the collagenous network do occur in degenerated cartilage.

Aged↗

Laser shaping of composite cartilage grafts.

INTRODUCTION: The restoration of malformations of different etiology in the head and neck area continue to be a problem to the reconstructive surgeon. Many of these problems are created by the destruction of cartilage. The success of the reconstructive effort very often depends on the selection of a composite cartilage graft of proper size, shape, and thickness, which has to replace the missing cartilage. Despite the best of surgeon's intentions, the postoperative result is not always satisfactory due to the difficulty in obtaining a cartilage of the proper shape. Using a carbon dioxide laser, composite cartilage samples 0.4 to 1 mm thick taken from rabbits ears were irradiated. METHODS: Rabbit ear cartilage with covering epithelium was used. The thickness of the composite graft measured 0.4 to 1 mm. Specimens were reshaped, treated with a carbon dioxide laser, then immersed in saline. CONCLUSION: It was observed that it was possible to change the shape of the cartilage, which then had the tendency to retain its new form for several days. Thicker composite grafts retained the new shape more satisfactorily. The significance of this experiment for future corrective surgery in various parts of the head and neck area is evident. We anticipate that this technique may be useful to mold grafted cartilage for use in complex reconstructions such as nasal, auricular, and tracheal deformities.

Animals↗

Accumulation of procollagen in the degenerative articular cartilage of dogs with osteoarthritis.

Collagen metabolism was studied in degenerative articular cartilage of dogs with spontaneous, early onset osteoarthritis. A fraction of collagen which represented about 1.5% of the total was extracted from cartilage samples with dilute phosphate buffer (pH 7.4) containing 0.2% sodium dodecyl sulfate. Agarose gel filtration in the presence of sodium dodecyl sulfate revealed that extracts of degenerative cartilage had about 24% procollagen whereas extracts of normal samples had only 3%. The isolated procollagen fraction was rechromatographed on agarose columns in the presence of mercaptoethanol. This resulted in the identification of a collagen species which migrated between marker beta and alpha collagen chains. The molecular weight of this collagen was estimated to be 150,000. Based on incorporation of [14C]proline, its ratio of hydroxy[14C]proline to total 14C was 0.32. Procollagen was not found after limited pepsin digestion (pH 3, 4 degrees C, 16 h) of degenerative cartilage samples. Since the total collagen content (microgram hydroxyproline/mg cartilage), hydroxy-[14C]proline/mg cartilage, specific radioactivity of hydroxyproline in the extractable collagen fraction were similar for normal and degenerative cartilage we propose that procollagen accumulated in the degenerative cartilage due to a partial defect in conversion of procollagen to collagen.

Animals↗

The distribution of proteoglycans of high electrophoretic mobility in cartilages from different species and of different ages.

The distribution of small proteoglycans of high relative electrophoretic mobility in cartilage of various species and of different ages was studied. Proteoglycans extracted by 4 M guanidinium chloride were purified by ion-exchange chromatography and assessed by gel electrophoresis. Proteoglycans fractionated by equilibrium density gradient centrifugation under 'dissociative' conditions were similarly purified and assessed. A rapid migrating population was found in articular cartilages of young humans, baboons, calves, pigs, rabbits, rats, chickens and in mandibular and vertebral cartilages of dog-fish. It was not detected in unfractionated proteoglycans extracted from fetal rat, pig, calf, baboon and human cartilages. In baboon and human fetal cartilages of advanced gestational age, however, small amounts of the rapid population were present being detected in the low density fractions of dissociative gradients. The rapid migrating population was not found either in unfractionated or in fractionated proteoglycans obtained from articular cartilages of humans aged over 40. It was also absent from human osteoarthritic cartilages but was detected even at advanced age in cartilages covering osteophytes.

Adult↗

Recombinant human interleukin-1 stimulates human articular cartilage to undergo resorption and human chondrocytes to produce both tissue- and urokinase-type plasminogen activator.

Cytokines capable of stimulating cartilage resorption have frequently been identified as 'interleukin-1 (IL-1)-like' peptides. In this study for the first time we have employed homogeneous recombinant IL-1 alpha and IL-1 beta in an all-human culture system to define the effects of IL-1 on articular cartilage and chondrocytes in culture. Recombinant IL-1 (10-100 U/ml) could stimulate cartilage resorption, although the maximum degree of tissue breakdown rarely reached the levels obtained when cartilage was treated with crude mononuclear-cell conditioned medium or all-trans retinoic acid (1 microM) over a similar time course. Levels of plasminogen activator (PA) activity, a neutral proteinase which may contribute to cartilage destruction in arthritis, increased markedly in the cartilage/chondrocyte culture supernatants and in the chondrocyte cell layers in response to the stimulation of cultures with recombinant IL-1 (1-100 U/ml). Elevated levels of PA activity were detectable after 4-8 h stimulation of the chondrocytes with IL-1 while characterization of the PA activities indicated that both types of PA activity were expressed, viz. urokinase-type PA (u-PA) and tissue-type PA (t-PA). Both IL-1 alpha and IL-1 beta could elicit these responses and their effects were comparable for a given dose. These studies show definitively that pure IL-1, free from contaminating cytokines, is capable of inducing human cartilage resorption and stimulating the expression of two types of PA activity by chondrocytes. In contrast to IL-1, retinoic acid increased the detectable levels of only u-PA in the chondrocyte cell layers. Chondrocyte u-PA may have an important role in cartilage degradative processes since it is one of the few neutral proteinases now known to be increased in activity in retinoid-stimulated cartilage.

Adult↗

Indentation instrument for the measurement of cartilage stiffness under arthroscopic control.

Changes in the biomechanical properties of articular cartilage are one of the first signs of the tissue degeneration. We have developed a small size indentation instrument for the quantification of cartilage stiffness under arthroscopic control. During measurement, the indenter imposes a constant deformation on the cartilage and the maximal indenter force, by which the cartilage resists the deformation, is used as a measure for cartilage stiffness. The instrument has been tested in laboratory conditions with elastomer and cadaver knee joint cartilage samples. A linear relationship was found between indenter force and elastomer stiffness (r = 0.990, n = 14) as well as between indenter force and cartilage shear modulus obtained by a reference device (r = 0.879, n = 22). Also, the correlation between two repeated measurements at the measurement sites, used to evaluate the reproducibility, was linear (r = 0.953, n = 16). Quantitative detection of cartilage stiffness is possible with the instrument.

Arthroscopes↗

Cartilage volume quantification via Live Wire segmentation.

RATIONALE AND OBJECTIVES: A reduction in cartilage volume is characteristic of osteoarthritis and hence there exists a need for an accurate and reproducible method to measure in vivo cartilage volume. Quantification of cartilage volume from magnetic resonance (MR) images requires a segmentation technique such as the user-driven "Live Wire" strategy that can reliably delineate object volumes in a time-efficient manner. In the present work, the accuracy and reproducibility of the Live Wire method for the quantification of cartilage volume in MR images is evaluated. MATERIALS AND METHODS: The accuracy of the Live Wire method was assessed by comparing the MR-based volume measurement of a patellar cartilage-shaped phantom versus data calculated via water displacement. The inter- and intra-operator reproducibility of the technique was evaluated from Live Wire segmentation of the patellar cartilage volume from fat-suppressed 3-dimensional spoiled-gradient-echo images of five healthy human volunteers performed by three operators. To provide data for analysis of inter-scan reproducibility, the human scans were repeated five times with the aid of a leg-restraining jig to minimize repositioning error. RESULTS: The volume of the patellar cartilage-shaped phantom measured via Live Wire segmentation of MR images was within 97.8% of its true volume. The average inter- and intra-operator coefficients of variation of three operators were 3.0% and 0.4%, respectively. The average inter-scan coefficient of variation of five repeated scans of each volunteer was 2.7%. CONCLUSION: The data suggest that the Live Wire strategy is an accurate, reproducible, and efficient technique to measure cartilage volume in vivo in a feasible amount of operator time.

Adult↗

Increased MIG-6 mRNA transcripts in osteoarthritic cartilage.

The biochemical mechanism for initiation of cartilage destruction in osteoarthritis (OA) is unknown but may involve as yet unidentified cartilage genes. The first evidence that MIG-6, a protein involved in signal transduction, is expressed in articular cartilage came from our recent in vitro microarray experiments using the Affymetrix canine GeneChip. Quantitative RT-PCR (q RT-PCR) confirmed a fourfold increase in MIG-6 mRNA in cartilage in response to mechanical impact in vitro. Our goal is to determine if MIG-6, which responds to mechanical impact, could have a role in the initiation of OA. We determined that mRNA transcript levels of MIG-6 were fourfold higher in degenerated cartilage from dogs with hip osteoarthritis than in disease-free cartilage from unaffected dogs and twofold higher than in the cartilage surrounding the lesion. This is the first report associating MIG-6 with OA. Additional studies will determine what role MIG-6 has in the origin of cartilage degeneration.

Adaptor Proteins, Signal Transducing↗

Long-term maintenance of human articular cartilage in culture for biomaterial testing.

Cartilage is a tissue that derives its unique mechanical and biological properties from the combination of relatively few cells and a large amount of a complex extracellular matrix. Furthermore, cartilage tissue is comparatively slow to respond to changes or harmful influences. To date, the optimal generation and long-term maintenance of cultured human articular cartilage for in vitro testing of biomaterials, poses an experimental difficulty. Experiments using cultured isolated chondrocytes in combination with scaffolds often fail to yield results comparable to the in-vivo situation. Consequently, our aim was to develop a culture method that allows in vitro maintenance of human hyaline cartilage explants in an optimal quality over an extended period of time. Such a culture could, for example, be used to determine the long-term effect of a new scaffold on intact cartilage, as an in vitro model for repair processes and to investigate biomaterial integration. In this study we compared conventional static cultures with and without serum supplementation to a serum-free perfusion culture for the ability to maintain human articular cartilage explants in a morphologically intact and differentiated state over an extended period of time of up to 56 days. Results were evaluated and compared by morphological, histochemical and immunohistochemical methods. The experiments showed that short-term maintenance of cartilage in a differentiated state for up to 14 days is possible under all culture conditions tested. However, best long-term culture results for up to 56 days were obtained with perfusion culture under serum-free conditions. Such a perfusion culture system can be used to perform biocompatabilty tests in vitro by long-term coculture of biomaterial and intact human articular cartilage.

Adult↗

Cartilage abnormalities are associated with abnormal Phex expression and with altered matrix protein and MMP-9 localization in Hyp mice.

X-linked hypophosphatemic rickets (HYP) in humans is caused by mutations in the PHEX gene. This gene mutation is also found in Hyp mice, the murine homologue of the human disease. At present, it is unknown why loss of Phex function leads to cartilage abnormalities in Hyp mice. In the present study, we compared in wild-type and Hyp mice Phex protein localization in cartilage of developing long bone as well as localization of skeletal matrix proteins and matrix metalloproteinase-9 (MMP-9). Also compared were chondrocyte apoptosis in the growth plate, mineralization and cartilage remnant retention in the metaphysis, and chondroclast/osteoclast characteristics in the primary spongiosa. Phex protein was detected in proliferating and hypertrophic chondrocytes in growth plate cartilage of wild-type mice, but not in Hyp mice. Hyp mice exhibited a widened and irregular hypertrophic zone in growth plate cartilage showing hypomineralization, increased cartilage remnants from the growth plate in both metaphyseal trabecular and cortical bone, and fewer and smaller chondroclasts/osteoclasts in the primary spongiosa. Increased link protein and C-propeptide of type II procollagen of Hyp mice reflected the increase in chondrocytes and matrix in the cartilaginous growth plate and in bone. In addition, growth plate osteocalcin and bone sialoprotein levels were decreased, while osteonectin was increased, in hypertrophic chondrocytes and cartilage matrix in Hyp mice. MMP-9 in hypertrophic chondrocytes was also reduced in Hyp mice and fewer apoptotic hypertrophic chondrocytes were detected. These findings suggest that Phex may control mineralization and removal of hypertrophic chondrocytes and cartilage matrix in growth plate by regulating the synthesis and deposition of certain bone matrix proteins and proteases such as MMP-9.

Animals↗

Consolidation responses of delipidized articular cartilage.

OBJECTIVE: To determine the role of articular cartilage lipids in its load-bearing function. DESIGN: Normal and delipidised, bovine articular cartilage specimens were statically loaded and both the hydrostatic excess pore pressure and creep strain were measured. From this the compression stiffness of the skeletal structures of both types of matrices was determined. BACKGROUND: It has been hypothesized that surfactant injection could relief osteoarthritis, but there is no study in the literature relating to the influence of lipids, the main ingredients of such products, on cartilage load-carriage. METHODS: Articular cartilage specimens were obtained from the patellar grooves of 2-3 year old bovine animals. When required specimen delipidization was carried out using chloroform/methanol rinsing. Both normal and delipidised samples were loaded in the consolidometer and the hydrostatic excess pore pressure and strain were measured. RESULTS: The transient patterns of the hydrostatic excess pore pressure were similar for both types of tissue, with a relatively insignificant increase of 2% in the maximum hydrostatic excess pore pressure of the delipidized samples relative to the normal intact specimens. The maximum creep strain of the delipidised specimens decreased by 10% on average relative to their normal intact counterparts, thereby indicating that delipidization causes stiffening of the cartilage matrix. CONCLUSION: The delipidized fluid-saturated articular cartilage is stiffer than its intact counterpart with consequence for cartilage compliance during function. RELEVANCE: Because osteoarthritis can be accompanied by lipid loss in cartilage, this study contributes to the further understanding of the disease with potential benefit for treatment.

Adaptation, Physiological↗

Arthroscopic evaluation of cartilage degeneration using indentation testing--influence of indenter geometry.

BACKGROUND: It has been suggested that the early onset of cartilage degeneration might be detected with a handheld indentation probe during knee arthroscopy, prior to any visible change on the articular surface. Collagen degradation has been considered as the first sign of cartilage degeneration. Therefore, it is important to consider the collagen network as a distinct constituent in the study of arthroscopic evaluation of cartilage degeneration. METHODS: The tip of an arthroscopic probe (indenter) was modeled as rigid and in contact with a cartilage/bone disk of sufficiently large radius to simulate an indentation in a joint. A fibril-reinforced model of cartilage, including streaming potentials and distinct constitutive laws for the proteoglycan matrix and collagen network, was used to determine the contact mechanics of indenter and cartilage. The finite element package ABAQUS was employed to obtain numerical solutions. FINDINGS: A spherical indenter produces a relatively uniform deformation in cartilage, but can easily slide on the articular surface. In contrast, a cylindrical indenter produces great deformation gradients for quick compression rates, but does not slide as easily on the articular surface as the spherical indenter. Small porous and large solid indenters should be used to evaluate the properties of the proteoglycan matrix and collagen network, respectively, in order to minimize or maximize the fluid pressure in the corresponding case. When the collagen network is substantially degraded, the gradients of fluid pressure and deformation are greatly reduced regardless of indenter geometry. INTERPRETATION: The indenter geometry including its porosity is important to the material safety of articular cartilage in indentation and precise evaluation of cartilage degeneration.

Arthroscopy↗