Which risk factors determine cartilage thickness and composition change in radiographically normal knees? - Data from the Osteoarthritis Initiative.

Objective: Therapy for osteoarthritis ideally aims at preserving structure before radiographic change occurs. This study tests: a) whether longitudinal deterioration in cartilage thickness and composition (transverse relaxation-time T2) are greater in radiographically normal knees "at risk" of incident osteoarthritis than in those without risk factors; and b) which risk factors may be associated with these deteriorations. Design: 755 knees from the Osteoarthritis Initiative were studied; all were bilaterally Kellgren Lawrence grade [KLG] 0 initially, and had magnetic resonance images available at 12- and 48-month follow-up. 678 knees were "at risk", whereas 77 were not (i.e., non-exposed reference). Cartilage thickness and composition change was determined in 16 femorotibial subregions, with deep and superficial T2 being analyzed in a subset (n â€‹= â€‹59/52). Subregion values were used to compute location-independent change scores. Results: In KLG0 knees "at risk", the femorotibial cartilage thinning score (-634 â€‹± â€‹516 â€‹µm) over 3 years exceeded the thickening score by approximately 20%, and was 27% greater (p â€‹< â€‹0.01; Cohen D -0.27) than the thinning score in "non-exposed" knees (-501 â€‹± â€‹319 â€‹µm). Superficial and deep cartilage T2 change, however, did not differ significantly between both groups (p â€‹≥ â€‹0.38). Age, sex, body mass index, knee trauma/surgery history, family history of joint replacement, presence of Heberden's nodes, repetitive knee bending were not significantly associated with cartilage thinning (r2<1%), with only knee pain reaching statistical significance. Conclusions: Knees "at risk" of incident knee OA displayed greater cartilage thinning scores than those "non-exposed". Except for knee pain, the greater cartilage loss was not significantly associated with demographic or clinical risk factors.

The specialist in regeneration-the Axolotl-a suitable model to study bone healing?

While the axolotl's ability to completely regenerate amputated limbs is well known and studied, the mechanism of axolotl bone fracture healing remains poorly understood. One reason might be the lack of a standardized fracture fixation in axolotl. We present a surgical technique to stabilize the osteotomized axolotl femur with a fixator plate and compare it to a non-stabilized osteotomy and to limb amputation. The healing outcome was evaluated 3 weeks, 3, 6 and 9 months post-surgery by microcomputer tomography, histology and immunohistochemistry. Plate-fixated femurs regained bone integrity more efficiently in comparison to the non-fixated osteotomized bone, where larger callus formed, possibly to compensate for the bone fragment misalignment. The healing of a non-critical osteotomy in axolotl was incomplete after 9 months, while amputated limbs efficiently restored bone length and structure. In axolotl amputated limbs, plate-fixated and non-fixated fractures, we observed accumulation of PCNA+ proliferating cells at 3 weeks post-injury similar to mouse. Additionally, as in mouse, SOX9-expressing cells appeared in the early phase of fracture healing and amputated limb regeneration in axolotl, preceding cartilage formation. This implicates endochondral ossification to be the probable mechanism of bone healing in axolotls. Altogether, the surgery with a standardized fixation technique demonstrated here allows for controlled axolotl bone healing experiments, facilitating their comparison to mammals (mice).

T1 and T2* mapping of the human quadriceps and patellar tendons using ultra-short echo-time (UTE) imaging and bivariate relaxation parameter-based volumetric visualization.

Quantification of magnetic resonance (MR)-based relaxation parameters of tendons and ligaments is challenging due to their very short transverse relaxation times, requiring application of ultra-short echo-time (UTE) imaging sequences. We quantify both T1 and T2* in the quadriceps and patellar tendons of healthy volunteers at a field strength of 3 T and visualize the results based on 3D segmentation by using bivariate histogram analysis. We applied a 3D ultra-short echo-time imaging sequence with either variable repetition times (VTR) or variable flip angles (VFA) for T1 quantification in combination with multi-echo acquisition for extracting T2*. The values of both relaxation parameters were subsequently binned for bivariate histogram analysis and corresponding cluster identification, which were subsequently visualized. Based on manually-drawn regions of interest in the tendons on the relaxation parameter maps, T1 and T2* boundaries were selected in the bivariate histogram to segment the quadriceps and patellar tendons and visualize the relaxation times by 3D volumetric rendering. Segmentation of bone marrow, fat, muscle and tendons was successfully performed based on the bivariate histogram analysis. Based on the segmentation results mean T2* relaxation times, over the entire tendon volumes averaged over all subjects, were 1.8 ms ±â€¯0.1 ms and 1.4 ms ±â€¯0.2 ms for the patellar and quadriceps tendons, respectively. The mean T1 value of the patellar tendon, averaged over all subjects, was 527 ms ±â€¯42 ms and 476 ms ±â€¯40 ms for the VFA and VTR acquisitions, respectively. The quadriceps tendon had higher mean T1 values of 662 ms ±â€¯97 ms (VFA method) and 637 ms ±â€¯40 ms (VTR method) compared to the patellar tendon. 3D volumetric visualization of the relaxation times revealed that T1 values are not constant over the volume of both tendons, but vary locally. This work provided additional data to build upon the scarce literature available on relaxation times in the quadriceps and patellar tendons. We were able to segment both tendons and to visualize the relaxation parameter distributions over the entire tendon volumes.

From macroscopic mechanics to cell-effective stiffness within highly aligned macroporous collagen scaffolds.

In the design of macroporous biomaterial scaffolds, attention is payed predominantly to the readily accessible macroscopic mechanical properties rather than to the mechanical properties experienced by the cells adhering to the material. However, the direct cell mechanical environment has been shown to be of special relevance for biological processes such as proliferation, differentiation and extracellular matrix formation both in vitro and in vivo. In this study we investigated how individual architectural features of highly aligned macroporous collagen scaffolds contribute to its mechanical properties on the macroscopic vs. the microscopic scale. Scaffolds were produced by controlled freezing and freeze-drying, a method frequently used for manufacturing of macroporous biomaterials. The individual architectural features of the biomaterial were carefully characterized to develop a finite element model (FE-model) that finally provided insights in the relation between the biomaterial's mechanical properties on the macro-scale and the properties on the micro-scale, as experienced by adhering cells. FE-models were validated by experimental characterization of the scaffolds, both on the macroscopic and the microscopic level, using mechanical compression testing and atomic force microscopy. As a result, a so-called cell-effective stiffness of these non-trivial scaffold architectures could be predicted for the first time. A linear dependency between the macroscopic scaffold stiffness and the cell-effective stiffness was found, with the latter being consistently higher by a factor of 6.4 ±â€¯0.6. The relevance of the cell-effective stiffness in controlling progenitor cell differentiation was confirmed in vitro. The obtained information about the cell-effective stiffness is of particular relevance for the early stages of tissue regeneration, when the cells first populate and interact with the biomaterial. Beyond the specific biomaterial investigated here, the introduced method is transferable to other complex biomaterial architectures. Design-optimization in 3D macroporous scaffolds that are based on a deeper understanding of the mechanical environment provided to the cells will help to enhance biomaterial-based tissue regeneration approaches.

Radiographically normal knees with contralateral joint space narrowing display greater change in cartilage transverse relaxation time than those with normal contralateral knees: a model of early OA? - data from the Osteoarthritis Initiative (OAI).

OBJECTIVE: To develop a model of early osteoarthritis, by examining whether radiographically normal knees with contralateral joint space narrowing (JSN), but without contralateral trauma history, display greater longitudinal cartilage composition change (transverse relaxation time; T2) than subjects with bilaterally normal knees. METHODS: 120 radiographically normal knees (Kellgren Lawrence grade [KLG] 0) from the Osteoarthritis Initiative were studied. 60 case knees displayed definite contralateral radiographic knee osteoarthritis (KLG ≥ 2) whereas 60 reference subjects were bilaterally KLG0, and were matched 1:1 to cases based on age, sex, and BMI. All had multi-echo spin-echo MRI acquired at year (Y) 1 and 4 follow-up, with cartilage T2 being determined in superficial and deep cartilage layers across 16 femorotibial subregions. T2 across all regions was considered the primary analytic focus. RESULTS: Of 60 KLG0 case knees (30 female, age: 65.0 ± 8.8 y, BMI: 27.6 ± 4.4 kg/m2), 21/22/13/4 displayed contralateral JSN 0/1/2/3, respectively. The longitudinal increase in the deep layer cartilage T2 between Y1 and Y4 was significantly greater (P = 0.03; Cohen's D 0.50) in the 39 KLG0 case knees with contralateral JSN (1.2 ms; 95% confidence interval [CI] [0.4, 2.0]) than in matched KLG0 reference knees (0.1 ms; 95% CI [-0.5, 0.7]). No significant differences were identified in superficial T2 change. T2 at Y1 was significantly greater in case than in reference knees, particularly in the superficial layer of the medial compartment. CONCLUSIONS: Radiographically normal knees with contralateral, non-traumatic JSN represent an applicable model of early osteoarthritis, with deep layer cartilage composition (T2) changing more rapidly than in bilaterally normal knees. CLINICALTRIALS. GOV IDENTIFICATION: NCT00080171.

Author Correction: Tibio-Femoral Contact Force Distribution is Not the Only Factor Governing Pivot Location after Total Knee Arthroplasty.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Tibio-Femoral Contact Force Distribution is Not the Only Factor Governing Pivot Location after Total Knee Arthroplasty.

Total knee arthroplasty aims to mimic the natural knee kinematics by optimizing implant geometry, but it is not clear how loading relates to tibio-femoral anterior-posterior translation or internal-external pivoting. We hypothesised that the point of pivot in the transverse plane is governed by the location of the highest axial force. Tibio-femoral loading was measured using an instrumented tibial component in six total knee arthroplasty patients (aged 65-80y, 5-7y post-op) during 5-6 squat repetitions, while knee kinematics were captured using a mobile video-fluoroscope. In the range of congruent tibio-femoral contact the medial femoral condyle remained approximately static while the lateral condyle translated posteriorly by 4.1 mm (median). Beyond the congruent range, the medial and lateral condyle motions both abruptly changed to anterior sliding by 4.6 mm, and 2.6 mm respectively. On average, both the axial loading and pivot position were more medial near extension, and transferred to the lateral side in flexion. However, no consistent relationship between pivoting and load distribution was found across all patients throughout flexion, with R2 values ranging from 0.00 to 0.65. Tibio-femoral kinematics is not related to the load distribution alone: medial loading of the knee does not necessarily imply a medial pivot location.

Cartilage loss in radiographically normal knees depends on radiographic status of the contralateral knee - data from the Osteoarthritis Initiative.

OBJECTIVE: To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis (OA), but without contralateral trauma history, display greater cartilage thickness loss than knees from subjects with bilaterally radiographically normal knees. METHODS: 828 radiographically normal knees (Kellgren Lawrence grade [KLG] 0) from the Osteoarthritis Initiative [OAI] were studied; 150 case knees displayed definite radiographic knee OA (KLG ≥ 2) contralaterally, and had MRI double echo steady state (DESS) images available at 12 and 48 month follow-up. 678 reference knees displayed KLG0 at the contralateral side. Cartilage thickness change was determined in femorotibial subregions and location-independent cartilage thinning scores were computed. Case and reference knees were compared using ANCOVA. RESULTS: Of the 150 KLG0 case knees, 108 had a contralateral KLG2 knee (50 without, and 58 with joint space narrowing [JSN]), 31 a KLG3 and 11 a KLG4 knee. The cartilage thinning score tended to be greater in case than reference knees; the cartilage thinning score in KLG0 case knees with contralateral radiographic JSN (-858 µm; [95% confidence interval -1016, -701 µm]) was significantly greater (P = 0.0012) than that in bilaterally KLG0 reference knees (-634 µm; [-673, -596 µm]), whereas KLG0 knees with contralateral KLG2 without JSN only showed relatively small thinning scores (-530 µm, [-631, -428 µm]). Region-specific analysis suggested greater rates of cartilage loss in case than in reference knees in the lateral, rather than medial, femorotibial compartment. CONCLUSIONS: Radiographically normal knees with contralateral JSN may serve as a human model of early OA, for testing disease modifying drugs in clinical trials designed to prevent cartilage loss before the onset of radiographic change. CLINICALTRIALS. GOV IDENTIFICATION: NCT00080171.

A biomaterial with a channel-like pore architecture induces endochondral healing of bone defects.

Biomaterials developed to treat bone defects have classically focused on bone healing via direct, intramembranous ossification. In contrast, most bones in our body develop from a cartilage template via a second pathway called endochondral ossification. The unsolved clinical challenge to regenerate large bone defects has brought endochondral ossification into discussion as an alternative approach for bone healing. However, a biomaterial strategy for the regeneration of large bone defects via endochondral ossification is missing. Here we report on a biomaterial with a channel-like pore architecture to control cell recruitment and tissue patterning in the early phase of healing. In consequence of extracellular matrix alignment, CD146+ progenitor cell accumulation and restrained vascularization, a highly organized endochondral ossification process is induced in rats. Our findings demonstrate that a pure biomaterial approach has the potential to recapitulate a developmental bone growth process for bone healing. This might motivate future strategies for biomaterial-based tissue regeneration.

A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge.

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232-243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1.

Mechanosensation across borders: fibroblasts inside a macroporous scaffold sense and respond to the mechanical environment beyond the scaffold walls.

In tissue defects, cells face distinct mechanical boundary conditions, but how this influences early stages of tissue regeneration remains largely unknown. Biomaterials are used to fill defects but also to provide specific mechanical or geometrical signals. However, they might at the same time shield mechanical information from surrounding tissues that is relevant for tissue functionalisation. This study investigated how fibroblasts in a soft macroporous biomaterial scaffold respond to distinct mechanical environments while they form microtissues. Different boundary stiffnesses counteracting scaffold contraction were provided via a newly developed in vitro setup. Online monitoring over 14 days revealed 3.0 times lower microtissue contraction but 1.6 times higher contraction force for high vs. low stiffness. This difference was significant already after 48 h, a very early stage of microtissue growth. The microtissue's mechanical and geometrical adaptation indicated a collective cellular behaviour and mechanical communication across scaffold pore walls. Surprisingly, the stiffness of the environment influenced cell behaviour even inside macroporous scaffolds where direct cell-cell contacts are hindered. Mechanical communication between cells via traction forces is essential for tissue adaptation to the environment and should not be blocked by rigid biomaterials. Copyright © 2017 John Wiley & Sons, Ltd.

The haematoma and its role in bone healing.

Fracture treatment is an old endeavour intended to promote bone healing and to also enable early loading and regain of function in the injured limb. However, in today's clinical routine the healing potential of the initial fracture haematoma is still not fully recognized. The Arbeitsgemeinschaft für Osteosynthesefragen (AO) formed in Switzerland in 1956 formulated four AO principles of fracture treatment which are still valid today. Fracture treatment strategies have continued to evolve further, as for example the relatively new concept of minimally invasive plate osteosynthesis (MIPO). This MIPO treatment strategy harbours the benefit of an undisturbed original fracture haematoma that supports the healing process. The extent of the supportive effect of this haematoma for the bone healing process has not been considered in clinical practice so far. The rising importance of osteoimmunological aspects in bone healing supports the essential role of the initial haematoma as a source for inflammatory cells that release the cytokine pattern that directs cell recruitment towards the injured tissue. In reviewing the potential benefits of the fracture haematoma, the early development of angiogenic and osteogenic potentials within the haematoma are striking. Removing the haematoma during surgery could negatively influence the fracture healing process. In an ovine open tibial fracture model the haematoma was removed 4 or 7 days after injury and the bone that formed during the first two weeks of healing was significantly reduced in comparison with an undisturbed control. These findings indicate that whenever possible the original haematoma formed upon injury should be conserved during clinical fracture treatment to benefit from the inherent healing potential.

[Steel or titanium for osteosynthesis : A mechanobiological perspective]. / Stahl oder Titan bei der Osteosynthese : Eine mechanobiologische Perspektive.

BACKGROUND: An implant used for stabilizing a fracture creates a mechanical construct, which directly determines the biology of bone healing. The stabilization of fractures places high mechanical demands on implants and therefore steel and titanium are currently almost exclusively used as the materials of choice. OBJECTIVES: The possible range of attainable mechanobiological stimulation for mechanotherapy as a function of plate stiffness depending on the selection of the plate material and the physical and mechanical properties of the material options are discussed. MATERIAL AND METHODS: An overview of the material properties of steel and titanium is given. For dynamically fixed long bone fractures as examples, various finite element models of plate osteosynthesis (steel/titanium) are created and the plate working length (PWL, screw configuration close to fracture) is varied. The interfragmentary movement (IFM) as a measure of mechanobiological stimulation is evaluated. RESULTS: Stimulation in the form of IFM varies across the fracture and also as a function of the osteosynthesis material and the configuration. The influence of the material appears to be notably smaller than the influence of PWL but both lose their influence largely over a bridged fracture situation (contact). With a flexible titanium plate and large PSS, a greater mechanobiological stimulation is produced. CONCLUSION: An essential prerequisite for the secondary fracture healing is an appropriate mechanobiological environment, which can be controlled by the osteosynthesis material and the configuration and is also affected by the type of fracture and load.

Muscle and tendon adaptation in adolescent athletes: A longitudinal study.

There is evidence that a non-uniform adaptation of muscle and tendon in young athletes results in increased tendon stress during mid-adolescence. The present longitudinal study investigated the development of the morphological and mechanical properties of muscle and tendon of volleyball athletes in a time period of 2 years from mid-adolescence to late adolescence. Eighteen elite volleyball athletes participated in magnetic resonance imaging and ultrasound-dynamometry sessions to determine quadriceps femoris muscle strength, vastus lateralis, medialis and intermedius morphology, and patellar tendon mechanical and morphological properties in mid-adolescence (16 ± 1 years) and late adolescence (18 ± 1 years). Muscle strength, anatomical cross-sectional area (CSA), and volume showed significant (P < 0.05) but moderate increases of 13%, 6%, and 6%, respectively. The increase of patellar tendon CSA (P < 0.05) was substantially greater (27%) and went in line with increased stiffness (P < 0.05; 25%) and reduced stress (P < 0.05; 9%). During late adolescence, a pronounced hypertrophy of the patellar tendon led to a mechanical strengthening of the tendon in relation to the functional and morphological development of the muscle. These adaptive processes may compensate the unfavorable relation of muscle strength and tendon loading capacity in mid-adolescence and might have implications on athletic performance and tendon injury risk.

Immunological characterization of the early human fracture hematoma.

The initial inflammatory phase of fracture healing is of great importance for the clinical outcome. We aimed to develop a detailed time-dependent analysis of the initial fracture hematoma. We analyzed the composition of immune cell subpopulations by flow cytometry and the concentration of cytokines and chemokines by bioplex in 42 samples from human fractures of long bones <72 h post-trauma. The early human fracture hematoma is characterized by maturation of granulocytes and migration of monocytes/macrophages and hematopoietic stem cells. Both T helper cells and cytotoxic T cells proliferate within the fracture hematoma and/or migrate to the fracture site. Humoral immunity characteristics comprise high concentration of pro-inflammatory cytokines such as IL-6, IL-8, IFNγ and TNFα, but also elevated concentration of anti-inflammatory cytokines, e.g., IL-1 receptor antagonist and IL-10. Furthermore, we found that cells of the fracture hematoma represent a source for key chemokines. Even under the bioenergetically restricted conditions that exist in the initial fracture hematoma, immune cells are not only present, but also survive, mature, function and migrate. They secrete a cytokine/chemokine cocktail that contributes to the onset of regeneration. We hypothesize that this specific microenvironment of the initial fracture hematoma is among the crucial factors that determine fracture healing.

BMP delivery complements the guiding effect of scaffold architecture without altering bone microstructure in critical-sized long bone defects: A multiscale analysis.

Scaffold architecture guides bone formation. However, in critical-sized long bone defects additional BMP-mediated osteogenic stimulation is needed to form clinically relevant volumes of new bone. The hierarchical structure of bone determines its mechanical properties. Yet, the micro- and nanostructure of BMP-mediated fast-forming bone has not been compared with slower regenerating bone without BMP. We investigated the combined effects of scaffold architecture (physical cue) and BMP stimulation (biological cue) on bone regeneration. It was hypothesized that a structured scaffold directs tissue organization through structural guidance and load transfer, while BMP stimulation accelerates bone formation without altering the microstructure at different length scales. BMP-loaded medical grade polycaprolactone-tricalcium phosphate scaffolds were implanted in 30mm tibial defects in sheep. BMP-mediated bone formation after 3 and 12 months was compared with slower bone formation with a scaffold alone after 12 months. A multiscale analysis based on microcomputed tomography, histology, polarized light microscopy, backscattered electron microscopy, small angle X-ray scattering and nanoindentation was used to characterize bone volume, collagen fiber orientation, mineral particle thickness and orientation, and local mechanical properties. Despite different observed kinetics in bone formation, similar structural properties on a microscopic and sub-micron level seem to emerge in both BMP-treated and scaffold only groups. The guiding effect of the scaffold architecture is illustrated through structural differences in bone across different regions. In the vicinity of the scaffold increased tissue organization is observed at 3 months. Loading along the long bone axis transferred through the scaffold defines bone micro- and nanostructure after 12 months.

Increased unilateral tendon stiffness and its effect on gait 2-6 years after Achilles tendon rupture.

Achilles tendon rupture (ATR) alters tissue composition, which may affect long-term tendon mechanics and ankle function during movement. However, a relationship between Achilles tendon (AT) properties and ankle joint function during gait remains unclear. The primary hypotheses were that (a) post-ATR tendon stiffness and length differ from the noninjured contralateral side and that (b) intra-patient asymmetries in AT properties correlate to ankle function asymmetries during gait, determined by ankle angles and moments. Ultrasonography and dynamometry were used to assess AT tendon stiffness, strain, elongation, and rest length in both limbs of 20 ATR patients 2-6 years after repair. Three-dimensional ankle angles and moments were determined using gait analysis. Injured tendons exhibited increased stiffness, rest length, and altered kinematics, with higher dorsiflexion and eversion, and lower plantarflexion and inversion. Intra-patient tendon stiffness and tendon length ratios were negatively correlated to intra-patient ratios of the maximum plantarflexion moment and maximum dorsiflexion angle, respectively. These results suggest that after surgical ATR repair, higher AT stiffness, but not a longer AT, may contribute to deficits in plantarflexion moment generation. These data further support the claim that post-ATR tendon regeneration results in the production of a tissue that is functionally different than noninjured tendon.

Longitudinal analysis of MR spin-spin relaxation times (T2) in medial femorotibial cartilage of adolescent vs mature athletes: dependence of deep and superficial zone properties on sex and age.

OBJECTIVE: Cartilage spin-spin magnetic resonance imaging (MRI) relaxation time (T2) represents a promising imaging biomarker of "early" osteoarthritis (OA) known to be associated with cartilage composition (collagen integrity, orientation, and hydration). However, no longitudinal imaging studies have been conducted to examine cartilage maturation in healthy subjects thus far. Therefore, we explore T2 change in the deep and superficial cartilage layers at the end of adolescence. METHODS: Twenty adolescent and 20 mature volleyball athletes were studied (each 10 men and 10 women). Multi-echo spin-echo (MESE) images were acquired at baseline and 2-year follow-up. After segmentation, cartilage T2 was calculated in the deep and superficial cartilage layers of the medial tibial (MT) and the central, weight-bearing part of the medial femoral condyle (cMF), using five echoes (TE 19.4-58.2 ms). RESULTS: 16 adolescent (6 men, 10 women, baseline age 15.8 ± 0.5 years) and 17 mature (nine men, eight women, age 46.5 ± 5.2 years) athletes had complete baseline and follow-up images of sufficient quality to compute T2. In adolescents, a longitudinal decrease in T2 was observed in the deep layers of MT (-2.0 ms; 95% confidence interval (CI): [-3.4, -0.6] ms; P < 0.01) and cMF (-1.3 ms; [-2.4, -0.3] ms; P < 0.05), without obvious differences between males and females. No significant change was observed in the superficial layers, or in the deep or superficial layers of the mature athletes. CONCLUSION: In this first pilot study on quantitative imaging of cartilage maturation in healthy, athletic subjects, we find evidence of cartilage compositional change in deep cartilage layers of the medial femorotibial compartment in adolescents, most likely related to organizational changes in the collagen matrix.