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Objective: Fibrin sealants are routinely used for intra-articular surgical fixation of cartilage fragments and implants. However, the mechanical properties of fibrin sealants in the context of cartilage repair are unknown. The purpose of this study was to characterize the adhesive and frictional properties of fibrin sealants using an ex vivo model., Design: Native bovine cartilage-bone composites were assembled with a single application of Tisseel or Vistaseal. Composites were tested in tension and lap shear. In addition, the coefficient of friction (COF) was measured in a native cartilage annulus model alone and with minced cartilage. Finally, the effect of a double application of fibrin sealant was evaluated., Results: There were no significant differences in tensile modulus, ultimate tensile strength (UTS), shear modulus, or ultimate shear strength (USS) between the 2 fibrin sealants. Both fibrin sealants demonstrated a UTS and USS of <8 and <30 kPa, respectively. There were no differences in COF between the sealants when tested alone or with minced cartilage. A double application of fibrin sealant did not alter the mechanical properties compared with a single application of fibrin sealant., Conclusions: Fibrin sealant adhesive properties are not affected by the sealant type studied or the number of applications in a bovine cartilage-bone model. Fibrin sealant tribological properties are not affected by sealant type or the addition of minced cartilage. The adhesive properties of Tisseel and Vistaseal were less than those desired for the in vivo fixation of cartilage repair implants. These findings motivate the development of an improved cartilage-specific adhesive for cartilage repair applications., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The purpose of this study was to determine the in vitro effects of a single exposure of bupivacaine on the mechanical properties of bovine cartilage explants at 3 weeks., Design: Femoral condyle articular cartilage explants were aseptically harvested from juvenile bovine stifle joints before being exposed to chondrogenic medium containing 0.50% (wt/vol) bupivacaine, 0.25% (wt/vol) bupivacaine, or no medication (control) for 1 hour. Explants were then washed and maintained in culture in vitro for 3 weeks before testing. Cell viability, tensile and compressive mechanical properties, histological properties, and biochemical properties were then assessed., Results: Explants exhibited a dose-dependent decrease in mean tensile Young's modulus with increasing bupivacaine concentration (9.86 MPa in the controls, 6.48 MPa in the 0.25% bupivacaine group [ P = 0.048], and 4.72 MPa in the 0.50% bupivacaine group [ P = 0.005]). Consistent with these results, collagen content and collagen crosslinking decreased with bupivacaine exposure as measured by mass spectrometry. Compressive properties of the explants were unaffected by bupivacaine exposure. Explants also exhibited a trend toward dose-dependent decreases in viability (51.2% for the controls, 47.3% for the 0.25% bupivacaine-exposed group, and 37.0% for the 0.50% bupivacaine-exposed group [ P = 0.072])., Conclusions: Three weeks after 1-hour bupivacaine exposure, the tensile properties of bovine cartilage explants were significantly decreased, while the compressive properties remained unaffected. These decreases in tensile properties corresponded with reductions in collagen content and crosslinking of collagen fibers. Physicians should be judicious regarding the intra-articular administration of bupivacaine in native joints., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KTC: Stock in Abbott Laboratories. GO: Nothing to disclose. WEB: Research support: L’Oreal/AAAS, NIH, NSF; Cofounder: Cartilage Inc. KAA: Research support: NIH, NSF; Cofounder: Cartilage Inc. DW: Research support: NIH, NSF, Vericel; Consultant: Newclip Technics, Mitek Sports Medicine, Vericel; Cofounder: Cartilage Inc.

Objective: The use of porcine animal models for cartilage injury has increased recently due to their similarity with humans with regard to cartilage thickness, limited intrinsic healing of chondral defects, and joint loading biomechanics. However, variations in the mechanical and biochemical properties of porcine hip articular cartilage among various tissue ages and weightbearing (WB) regions are still unknown. This study's aim was to characterize the mechanical and biochemical properties of porcine hip articular cartilage across various ages and WB regions., Methods: Articular cartilage explants were harvested from WB and non-weightbearing (NWB) surfaces of the femoral head and acetabulum of domesticated pigs ( Sus scrofa domesticus ) at fetal (gestational age: 80 days), juvenile (6 months), and adult (2 years) ages. Explants underwent compressive stress-relaxation mechanical testing, biochemical analysis for total collagen and glycosaminoglycan (GAG) content, and histological staining., Results: Juvenile animals consistently had the highest mechanical properties, with 2.2- to 7.6-time increases in relaxation modulus, 1.3- to 2.3-time increases in instantaneous modulus, and 4.1- to 14.2-time increases in viscosity compared with fetal cartilage. Mechanical properties did not significantly differ between the WB and NWB regions. Collagen content was highest in the NWB regions of the juvenile acetabulum (65.3%/dry weight [DW]) and femoral head (75.4%/DW) cartilages. GAG content was highest in the WB region of the juvenile acetabulum (23.7%/DW) and the WB region of the fetal femoral head (27.5%/DW) cartilages. Histological staining for GAG and total collagen content followed the trends from the quantitative biochemical assays., Conclusion: This study provides a benchmark for the development and validation of preclinical porcine models for hip cartilage pathologies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dean Wang is an orthopedic surgery consultant for Cartilage Inc, Vericel Corp, Newclip Technics, and Mitek Sports Medicine. Ryan P. Donahue, Kyriacos A. Athanasiou, and Jerry C. Hu are scientific consultants for Cartilage Inc.

Objective: The medial femoral condyle of the knee exhibits some of the highest incidences of chondral degeneration. However, a dearth of healthy human tissues has rendered it difficult to ascertain whether cartilage in this compartment possesses properties that predispose it to injuries. Assessment of young, healthy tissue would be most representative of the tissue's intrinsic properties., Design: This work examined the topographical differences in tribological, tensile, and compressive properties of young (n = 5, 26.2 ± 5.6 years old), healthy, human medial femoral condyles, obtained from viable allograft specimens. Corresponding to clinical incidences of pathology, it was hypothesized that the lowest mechanical properties would be found in the posterior region of the medial condyle, and that tissue composition would correspond to the established structure-function relationships of cartilage., Results: Young's modulus, ultimate tensile strength, aggregate modulus, and shear modulus in the posterior region were 1.0-, 2.8-, 1.1-, and 1.0-fold less than the values in the anterior region, respectively. Surprisingly, although glycosaminoglycan content is thought to correlate with compressive properties, in this study, the aggregate and shear moduli correlated more robustly to the amount of pyridinoline crosslinks per collagen. Also, the coefficient of friction was anisotropic and ranged 0.22-0.26 throughout the condyle., Conclusion: This work showed that the posteromedial condyle displays lower tensile and compressive properties, which correlate to collagen crosslinks and may play a role in this region's predisposition to injuries. Furthermore, new structure-function relationships may need to be developed to account for the role of collagen crosslinks in compressive properties.

Objective: Tissue-engineered cartilage implants must withstand the potential inflammatory and joint loading environment for successful long-term repair of defects. The work's objectives were to develop a novel, direct cartilage-macrophage co-culture system and to characterize interactions between self-assembled neocartilage and differentially stimulated macrophages., Design: In study 1, it was hypothesized that the proinflammatory response of macrophages would intensify with increasing construct stiffness; it was expected that the neocartilage would display a decrease in mechanical properties after co-culture. In study 2, it was hypothesized that bioactive factors would protect neocartilage properties during macrophage co-culture. Also, it was hypothesized that interleukin 10 (IL-10)-stimulated macrophages would improve neocartilage mechanical properties compared to lipopolysaccharide (LPS)-stimulated macrophages., Results: As hypothesized, stiffer neocartilage elicited a heightened proinflammatory macrophage response, increasing tumor necrosis factor alpha (TNF-α) secretion by 5.47 times when LPS-stimulated compared to construct-only controls. Interestingly, this response did not adversely affect construct properties for the stiffest neocartilage but did correspond to a significant decrease in aggregate modulus for soft and medium stiffness constructs. In addition, bioactive factor-treated constructs were protected from macrophage challenge compared to chondrogenic medium-treated constructs, but IL-10 did not improve neocartilage properties, although stiff constructs appeared to bolster the anti-inflammatory nature of IL-10-stimulated macrophages. However, co-culture of bioactive factor-treated constructs with LPS-treated macrophages reduced TNF-α secretion by over 4 times compared to macrophage-only controls., Conclusions: In conclusion, neocartilage stiffness can mediate macrophage behavior, but stiffness and bioactive factors prevent macrophage-induced degradation. Ultimately, this co-culture system could be utilized for additional studies to develop the burgeoning field of cartilage mechano-immunology.

Objective: To enhance the in vitro integration of self-assembled articular cartilage to native articular cartilage using chondroitinase ABC., Design: To examine the hypothesis that chondroitinase ABC (C-ABC) integration treatment (C-ABC int ) would enhance integration of neocartilage of different maturity levels, this study was conducted in 2 phases. In phase I, the impact on integration of 2 treatments, TCL (TGF-β1, C-ABC, and lysyl oxidase like 2) and C-ABC int , was examined via a 2-factor, full factorial design. In phase II, construct maturity (2 levels) and C-ABC int concentration (3 levels) were the factors in a full factorial design to determine whether the effective C-ABC int dose was dependent on neocartilage maturity level. Neocartilages formed or treated per the factors above were placed into native cartilage rings, cultured for 2 weeks, and, then, integration was studied histologically and mechanically. Prior to integration, in phase II, a set of treated constructs were also assayed to provide a baseline of properties., Results: In phase I, C-ABC int and TCL treatments synergistically enhanced interface Young's modulus by 6.2-fold ( P = 0.004) and increased interface tensile strength by 3.8-fold ( P = 0.02) compared with control. In phase II, the interaction of the factors C-ABC int and construct maturity was significant ( P = 0.0004), indicating that the effective C-ABC int dose to improve interface Young's modulus is dependent on construct maturity. Construct mechanical properties were preserved regardless of C-ABC int dose., Conclusions: Applying C-ABC int to neocartilage is an effective integration strategy with translational potential, provided its dose is calibrated appropriately based on implant maturity, that also preserves implant biomechanical properties.

Introduction: This study develops assays to quantify collagen subtypes and crosslinks with liquid chromatography-mass spectrometry (LC-MS) and characterizes the cartilages in the Yucatan minipig., Methods: For collagen subtyping, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was performed on tissues digested in trypsin. For collagen crosslinks, LC-MS analysis was performed on hydrolysates. Samples were also examined histologically and with bottom-up proteomics. Ten cartilages (femoral condyle, femoral head, facet joint, floating rib, true rib, auricular cartilage, annulus fibrosus, 2 meniscus locations, and temporomandibular joint disc) were analyzed., Results: The collagen subtyping assay quantified collagen types I and II. The collagen crosslinks assay quantified mature and immature crosslinks. Collagen subtyping revealed that collagen type I predominates in fibrocartilages and collagen type II in hyaline cartilages, as expected. Elastic cartilage and fibrocartilages had more mature collagen crosslink profiles than hyaline cartilages. Bottom-up proteomics revealed a spectrum of ratios between collagen types I and II, and quantified 42 proteins, including 24 collagen alpha-chains and 12 minor collagen types., Discussion: The novel assays developed in this work are sensitive, inexpensive, and use a low operator time relative to other collagen analysis methods. Unlike the current collagen assays, these assays quantify collagen subtypes and crosslinks without an antibody-based approach or lengthy chromatography. They apply to any collagenous tissue, with broad applications in tissue characterization and tissue engineering. For example, a novel finding of this work was the presence of a large quantity of collagen type III in the white-white knee meniscus and a spectrum of hyaline and fibrous cartilages.

Objective: Pathology of the facet and sacroiliac (SI) joints contributes to 15% to 45% and 10% to 27% of lower back pain cases, respectively. Although tissue engineering may offer novel treatment options to patients suffering from cartilage degeneration in these joints, the tribological characteristics of the facet and SI joints have not been studied in either the human or relevant large animal models, which hinders the development of joint-specific cartilage implants., Design: Cartilage was isolated from the knee, cervical facet, thoracic facet, lumbar facet, and SI joints of 6 skeletally mature Yucatan minipigs ( Sus scrofa ). Tribological characteristics were assessed via coefficient of friction testing, interferometry, and immunohistochemistry for lubricin organization., Results: Compared with the knee, the coefficient of friction was higher by 43% in the cervical facet, 77% in the thoracic facet, 37% in the lumbar facet, and 28% in the SI joint. Likewise, topographical features of the facet and SI joints varied significantly, ranging from a 114% to 384% increase and a 48% to 107% increase in global and local surface roughness measures, respectively, compared with the knee. Additionally, the amount of lubricin in the SI joint was substantially greater than in the knee. Statistical correlations among the various tribological parameters revealed that there was a significant correlation between local roughness and coefficient of friction, but not global roughness or the presence of lubricin., Conclusion: These location-specific tribological characteristics of the articular cartilages of the spine will need to be taken into consideration during the development of physiologically relevant, functional, and durable tissue-engineered replacements for these joints.

Meniscus tissue deficiency resulting from primary meniscectomy or meniscectomy after failed repair is a clinical challenge because the meniscus has little to no capacity for regeneration. Loss of meniscus tissue has been associated with early-onset knee osteoarthritis due to an increase in joint contact pressures in meniscectomized knees. Clinically available replacement strategies range from allograft transplantation to synthetic implants, including the collagen meniscus implant, ACTIfit, and NUSurface. Although short-term efficacy has been demonstrated with some of these treatments, factors such as long-term durability, chondroprotective efficacy, and return to sport activities in young patients remain unpredictable. Investigations of cell-based and tissue-engineered strategies to treat meniscus tissue deficiency are ongoing.

Objective: Previous work has shown that increasing the production of boundary lubricant, superficial zone protein (SZP), did not reduce the friction coefficient of self-assembled articular cartilage constructs and was possibly due to poor retention of the lubricant. The aim of this investigation was to reduce the friction coefficient of self-assembled articular cartilage constructs through enhancing SZP retention by the exogenous addition of extracellular matrix (ECM) extracted from the superficial zone of native articular cartilage., Design: Superficial zone cartilage was shaved from juvenile bovine femoral condyles using a dermatome, minced finely with razor blades, extracted with 4 M guanidine-hydrochloride, buffer exchanged with culture medium, and added directly to the culture medium of self-assembled articular cartilage constructs at low (10 µg/mL) and high (100 µg/mL) concentrations for 4 weeks. Biochemical and biomechanical properties were determined at the conclusion of 4 weeks culture., Results: ECM treatment increased compressive and tensile stiffness of self-assembled articular cartilage constructs and decreased the friction coefficient. Glycosaminoglycan content decreased and collagen content increased significantly in self-assembled constructs by the ECM treatment., Conclusions: Friction coefficients of self-assembled articular cartilage constructs were reduced by adding extracted superficial zone ECM into the culture medium of self-assembled articular cartilage constructs.

The frequency and impact of temporomandibular joint (TMJ) disorders necessitate research in characterizing the joint's function. The 6 discal attachments have not yet been systematically characterized under tension. Understanding their role in joint function may guide our study of TMJ pathologies, including disc displacement. In the present study, a porcine model was used to characterize the attachments in tension anteroposteriorly and mediolaterally, based on previously identified similarities in the porcine and human masticatory behaviors and discal properties. Tensile stiffness, strength, toughness, and maximum strain were quantified. Collagen alignment was characterized via polarized light and scanning electron microscopy. Anisotropy was demonstrated in all attachments, with the exception of the anterior inferior attachment. Anteroposteriorly, the lateral attachment was stiffest (8.3 MPa) and the anterior superior was least stiff (1.4 MPa). Mediolaterally, the posterior superior attachment was stiffest (16.3 MPa) and the medial was least stiff (1.4 MPa). The greatest strain was observed in the lateral attachment in the mediolateral direction and the posterior superior attachment in the anteroposterior direction. With greatest strains in the most commonly observed directions of disc displacement, it is suggested that compromise in the posterior and lateral attachments contributes to partial lateral and anterior disc displacement.

The temporomandibular joint (TMJ) disc plays a critical role in normal function of the joint, and many disorders of the TMJ are a result of disc dysfunction. Previous quantitative TMJ characterization studies examined either the human or a specific animal model, but no single study has compared different species, in the belief that differences in joint morphology, function, and diet would be reflected in the material properties of the disc. In this study, we examined topographical biochemical (collagen, glycosaminoglycan, and DNA content) and biomechanical (tensile and compressive) properties of the human TMJ disc, and also discs from the cow, goat, pig, and rabbit. Regional and interspecies variations were identified in all parameters measured, and certain disc characteristics were observed across all species, such as a weak intermediate zone under mediolateral tension. While human discs possessed properties distinct from those of the other species, pig discs were most similar to the human, suggesting that the pig may be a suitable animal model for TMJ bioengineering efforts.

Bovine articular chondrocytes were seeded on either polyglycolic acid (PGA) non-woven mesh scaffolds or a biomatrix from the species Porites lutea (POR). These constructs were cultured for 6 weeks in the presence of insulin-like growth factor (IGF)-I (10 ng/ml or 100 ng/ml) or transforming growth factor (TGF)-beta 1 (5 ng/ml or 30 ng/ml) to determine the in-vitro articular cartilage regeneration capacity of each. Histology, deoxyribonucleic acid content, collagen I and II (immunohistochemistry and enzyme-linked immunosorbent assay), and glycosaminoglycan (GAG) contents were measured at 0 weeks, 2 weeks, and 6 weeks to assess the characteristics of chondrogenesis. Both scaffolds supported the maintenance of the chondrocytic phenotype, as evidenced by the predominance of collagen II and the presence of rounded chondrocytes embedded in lacunae. Regardless of growth factor treatment, cells cultured on PGA scaffolds produced more collagen type II than those cultured on POR. Conversely, by 6 weeks, cells cultured on POR scaffolds produced more GAG than those cultured on PGA scaffolds, again regardless of the growth factor used. Across the two groups, 100 ng/ml of IGF-I had the greatest overall effect in GAG content. This work indicates that PGA and the POR scaffolds are both effective growth matrices for articular cartilage, with each scaffold exhibiting different yet desirable profiles of articular cartilage growth.

Tissue-engineering of the temporomandibular joint (TMJ) disc aims to provide patients with TMJ disorders an option to replace diseased tissue with autologous, functional tissue. This study examined clinically relevant cell sources by comparing costal chondrocytes, dermal fibroblasts, a mixture of the two, and TMJ disc cells in a scaffoldless tissue-engineering approach. It was hypothesized that all constructs would produce matrix relevant to the TMJ disc, but the mixture constructs were expected to appear most like the TMJ disc constructs. Costal chondrocyte and mixture constructs were morphologically and biochemically superior to the TMJ disc and dermal fibroblast constructs, and their compressive properties were not significantly different. Costal chondrocyte constructs produced almost 40 times more collagen and 800 times more glycosaminoglycans than did TMJ constructs. This study demonstrates the ability of costal chondrocytes to produce extracellular matrix that may function in a TMJ disc replacement.

Temporomandibular joint disc tissue-engineering studies commonly fail to produce significant matrix before construct contraction. We hypothesized that poly-L-lactic acid (PLLA) non-woven meshes would limit contraction, allow for comprehensive mechanical evaluation, and maintain viability relative to polyglycolic acid (PGA) non-woven mesh controls. Additionally, we proposed that growth factor stimulation, while limiting contraction, would increase construct properties relative to previous reports. After 4 wks, cell proliferation and matrix deposition were similar between the two meshes, but PGA constructs had contracted significantly. Furthermore, only PLLA constructs could be tested in tension and compression. Additional PLLA constructs were formed, then treated with insulin-like growth factor-1 (10 ng/mL), transforming growth factor-beta 1 (5 ng/mL), or transforming growth factor-beta 3 (5 ng/mL). Transforming growth factor-beta 1 yielded the most cells, collagen, and glycosaminoglycans at 6 wks; these constructs also demonstrated improved mechanics. Analysis of these data demonstrated significant temporomandibular joint disc-engineering potential for PLLA and transforming growth factor-beta 1.

Tissue engineering of chondrocytic or fibroblastic musculoskeletal tissues has been relatively well studied compared with that of the temporomandibular joint (TMJ) disc. Early attempts at tissue engineering the disc have been misguided owing to a lack of understanding of the composition and function of the TMJ disc. The objective of this review is to compare the TMJ disc with a chondrocytic tissue (hyaline articular cartilage) and a fibroblastic tissue (tendon) to understand better the properties of this fibrocartilaginous tissue. The TMJ disc has 25 times more glycosaminoglycan (GAG) per dry weight than tendon but half that of articular cartilage. The disc's tensile modulus is six times more than cartilage but orders less than tendon. The GAG content and tensile modulus suggest that the TMJ disc is characterized as a tissue between hyaline cartilage and tendon, but the disc appears more tendon like when considering its collagen make-up and cell content. Like tendon, the TMJ disc contains primarily collagen type I at 85 per cent per dry weight, while articular cartilage has 30 per cent less collagen, which is type II. Knowledge of quantitative comparisons between joint tissues can give extensive insight into how to improve tissue engineering of the TMJ disc.

This paper describes the development and use of an instrument mechanically to impact bovine articular cartilage and record the event using a piezoelectric accelerometer, as well as to carry out post-impact characterization of the tissue. Two levels of impact (low: 6 cm drop height, 18.4 N tup; high: 10 cm drop height, 27.8 N tup) were chosen such that the former did not show gross damage upon inspection, while the latter showed substantial gross damage. Peak stress, time to peak stress, and impact duration were taken from data recorded by the instrument. Three cartilage biomechanical properties (aggregate modulus, Poisson's ratio, and permeability) were acquired by creep indentation, and tissue morphology rated on a standardized scale was also determined. When subjected to the high level of impact, articular cartilage showed statistically significant (p < 0.05) differences in all three impact metrics and morphology. This high level of impact also resulted in a 37 per cent decrease in the aggregate modulus of the tissue. Lower drop heights resulted in more consistent impact curves, demonstrated less standard deviation, and did not change the biomechanical properties of the tissues. With the instrument and techniques described in this study, articular cartilage can be subjected to specific levels of impact in order to study injury biomechanics of the tissue at specific levels of mechanical damage.

The temporomandibular joint (TMJ) disc is a specialized fibrocartilaginous tissue. When the disc becomes an obstacle and becomes damaged, surgeons have no choice but to perform a discectomy. Tissue engineering may provide a novel treatment modality for TMJ disorder patients who undergo discectomy. No studies have been conducted on the most favourable media for TMJ disc cells. The objective of the current study was to examine the effects on biochemical and biomechanical properties of varying ascorbic acid concentrations (0, 25, or 50 microg/ml) on TMJ disc cells seeded on non-woven PGA scaffolds. The ascorbic acid concentration of the 25 microg/ml group resulted in more effective cell seeding of the scaffolds, with 1.53 million cells per construct, by comparison with the 0 and 50 microg/ml groups which had 1.20 million and 1.32 million cells per scaffold respectively. At week 4, the 25 microg/ml group had a higher collagen content than the 0 microg/ml group, with 30.4 +/- 2.7 and 24.9 +/- 3.3 microg of collagen per construct respectively. The 25 microg/ml group had a higher aggregate modulus than the 50 microg/ml group, with values of 6.1 +/- 1.3 and 4.0 +/- 0.9 kPa respectively at week 4. The results of this study indicate that the use of 25 microg/ml of ascorbic acid in culture media is effective for the tissue engineering of the TMJ disc, significantly outperforming media without or with 50 microg/ml of ascorbic acid.

Quantification of the material properties of the meniscus is of paramount importance, creating a 'gold-standard' reference for future tissue engineering research. The purpose of this study was to determine the compressive and circumferential tensile properties in the rabbit meniscus. Creep and recovery indentation experiments were performed on the meniscus using a creep indentation apparatus and analysed via a finite element optimization method to determine the compressive material properties at six topographical locations. Tensile properties of samples taken circumferentially from the rabbit meniscus were also examined. Results show that the femoral side of the anterior portion exhibits the highest aggregate modulus (510 +/- 100 kPa) and shear modulus (240 +/- 40 kPa), while the lowest aggregate modulus (120 +/- 30 kPa) and shear modulus (60 +/- 20 kPa) were found on the femoral side of the posterior location. Values of 156.6 +/- 48.9 MPa for Young's modulus and of 21.6 +/- 7.0 MPa for the ultimate tensile strength of were found from the tensile samples, which are similar to the values found in other animal models. These baseline values of material properties will be of help in future tissue engineering efforts.

The purpose of this investigation was to examine the compressive properties of the porcine meniscus at a variety of topographical locations using a creep indentation experiment. Three different solution techniques were used to analyse the creep response of the tissue. Specifically, the indentation stiffness, aggregate modulus, permeability, Poisson's ratio, and shear modulus were determined at six different testing locations (anterior, central, and posterior regions; femoral and tibial sides) of both the medial and lateral porcine menisci. Results indicate topographical variations among the testing locations, with the femoral-anterior portion of the medial meniscus having the highest indentation stiffness (350+/-110 kPa), aggregate modulus (270+/-90 kPa), and shear modulus (140+/-40 kPa). The tibial-posterior region of the medial meniscus exhibited the lowest indentation stiffness (170+/-40 kPa), aggregate modulus (130+/-30 kPa), and shear modulus (60+/-20 kPa). No statistical differences were found at the six tested locations of the lateral meniscus.