We evaluated the durability of autologous chondrocyte transplantation grafts in 61 patients treated for isolated cartilage defects on the femoral condyle or the patella and followed up for a mean of 7.4 years (range, 5 to 11). Durability was determined by comparing the clinical status at the long-term follow-up with that found 2 years after the transplantation. After 2 years, 50 of the 61 patients had good or excellent clinical results, and 51 of 61 had good or excellent results at 5 to 11 years later. Grafted areas from 11 of the patients were evaluated with an electromechanical indentation probe during a second-look arthroscopy procedure (mean follow-up, 54.3 months; range, 33 to 84); stiffness measurements were 90% or more of those of normal cartilage in eight patients. Eight of twelve 2-mm biopsy samples taken from these patients showed hyaline characteristics with safranin O staining and a homogeneous appearance in polarized light. Three fibrous and eight hyaline biopsy specimens stained positive to aggrecan and to cartilage oligomeric matrix protein. Hyaline-like specimens stained positive for type II collagen, and fibrous, for type I collagen. Autologous chondrocyte transplantation for the treatment of articular cartilage injuries has a durable outcome for as long as 11 years.

Autologous Chondrocyte Transplantation Biomechanics and Long-Term Durability

The in vivo pathomechanics of osteoarthritis (OA) at the knee is described in a framework that is based on an analysis of studies describing assays of biomarkers, cartilage morphology, and human function (gait analysis). The framework is divided into an Initiation Phase and a Progression Phase. The Initiation Phase is associated with kinematic changes that shift load bearing to infrequently loaded regions of the cartilage that cannot accommodate the loads. The Progression Phase is defined following cartilage breakdown. During the Progression Phase, the disease progresses more rapidly with increased load. While this framework was developed from an analysis of in vivo pathomechanics, it also explains how the convergence of biological, morphological, and neuromuscular changes to the musculoskeletal system during aging or during menopause lead to the increased rate of idiopathic OA with aging. Understanding the in vivo response of articular cartilage to its physical environment requires an integrated view of the problem that considers functional, anatomical, and biological interactions. The integrated in vivo framework presented here will be helpful for the interpretation of laboratory experiments as well as for the development of new methods for the evaluation of OA at the knee.

A framework for the in vivo pathomechanics of osteoarthritis at the knee

"Tissue engineering" uses implanted cells, scaffolds, DNA, protein, and/or protein fragments to replace or repair injured or diseased tissues and organs. Despite its early success, tissue engineers have faced challenges in repairing or replacing tissues that serve a predominantly biomechanical function. An evolving discipline called "functional tissue engineering" (FTE) seeks to address these challenges. In this paper, the authors present principles of functional tissue engineering that should be addressed when engineering repairs and replacements for load-bearing structures. First, in vivo stress/strain histories need to be measured for a variety of activities. These in vivo data provide mechanical thresholds that tissue repairs/replacements will likely encounter after surgery. Second, the mechanical properties of the native tissues must be established for subfailure and failure conditions. These "baseline data" provide parameters within the expected thresholds for different in vivo activities and beyond these levels if safety factors are to be incorporated. Third, a subset of these mechanical properties must be selected and prioritized. This subset is important, given that the mechanical properties of the designs are not expected to completely duplicate the properties of the native tissues. Fourth, standards must be set when evaluating the repairs/replacements after surgery so as to determine, "how good is good enough?" Some aspects of the repair outcome may be inferior, but other mechanical characteristics of the repairs and replacements might be suitable. New and improved methods must also be developed for assessing the function of engineered tissues. Fifth, the effects of physical factors on cellular activity must be determined in engineered tissues. Knowing these signals may shorten the iterations required to replace a tissue successfully and direct cellular activity and phenotype toward a desired end goal. Finally, to effect a better repair outcome, cell-matrix implants may benefit from being mechanically stimulated using in vitro "bioreactors" prior to implantation. Increasing evidence suggests that mechanical stress, as well as other physical factors, may significantly increase the biosynthetic activity of cells in bioartificial matrices. Incorporating each of these principles of functional tissue engineering should result in safer and more efficacious repairs and replacements for the surgeon and patient.

Functional Tissue Engineering: The Role of Biomechanics

Importance Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity. Objective To determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone. Design, Setting, and Participants Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27-41) with pain and radiographic knee OA. Interventions Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise. Main Outcomes and Measures Mechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100). Results Three hundred ninety-nine participants (88%) completed the study. Mean weight loss for diet + exercise participants was 10.6 kg (11.4%); for the diet group, 8.9 kg (9.5%); and for the exercise group, 1.8 kg (2.0%). After 18 months, knee compressive forces were lower in diet participants (mean, 2487 N; 95% CI, 2393 to 2581) compared with exercise participants (2687 N; 95% CI, 2590 to 2784, pairwise difference [Δ] exercise vs diet  = 200 N; 95% CI, 55 to 345; P  = .007). Concentrations of IL-6 were lower in diet + exercise (2.7 pg/mL; 95% CI, 2.5 to 3.0) and diet participants (2.7 pg/mL; 95% CI, 2.4 to 3.0) compared with exercise participants (3.1 pg/mL; 95% CI, 2.9 to 3.4; Δ exercise vs diet + exercise  = 0.39 pg/mL; 95% CI, −0.03 to 0.81; P  = .007; Δ exercise vs diet  = 0.43 pg/mL; 95% CI, 0.01 to 0.85, P  = .006). The diet + exercise group had less pain (3.6; 95% CI, 3.2 to 4.1) and better function (14.1; 95% CI, 12.6 to 15.6) than both the diet group (4.8; 95% CI, 4.3 to 5.2) and exercise group (4.7; 95% CI, 4.2 to 5.1, Δ exercise vs diet + exercise  = 1.02; 95% CI, 0.33 to 1.71; P pain  = .004; 18.4; 95% CI, 16.9 to 19.9; Δ exercise vs diet + exercise , 4.29; 95% CI, 2.07 to 6.50; P function exercise vs diet + exercise  = −2.81; 95% CI, −4.76 to −0.86; P  = .005). Conclusions and Relevance Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group. Trial Registration clinicaltrials.gov Identifier:NCT00381290

https://jamanetwork.com/journals/jama/articlepdf/1741824/jpc130008.pdf

Effects of Intensive Diet and Exercise on Knee Joint Loads, Inflammation, and Clinical Outcomes Among Overweight and Obese Adults With Knee Osteoarthritis: The IDEA Randomized Clinical Trial

http://www.liralab.it/IIT_school/files/Papers/BPhJ%2086.04%20-%20IT-AFM.pdf

Dynamic Elastic Modulus of Porcine Articular Cartilage Determined at Two Different Levels of Tissue Organization by Indentation-Type Atomic Force Microscopy

Joints are functional units that transmit mechanical loads between contacting bones during normal daily or specialized activities, e.g., sports. All components of the joint, i.e. articular cartilage, bone, muscles, ligaments/tendons and nerves, participate in load transmission. Failure in any of these components can cause joint malfunction, which, in turn, may lead to accumulation of damage in other joint components. Mechanical forces have great influence on the synthesis and rate of turnover of articular cartilage molecules, such as proteoglycans (PGs). Regular cyclic loading of the joint enhances PG synthesis and makes cartilage stiff. On the other hand, loading appears to have less evident effects on the articular cartilage collagen fibril network. Continuous compression of the cartilage diminishes PG synthesis and causes damage of the tissue through necrosis. The prevailing view is that osteoarthrosis (OA) starts from the cartilage surface through PG depletion and fibrillation of the superficial collagen network. It has also been suggested that the initial structural changes take place in the subchondral bone, especially when the joint is exposed to an impact type of loading. This in turn would create an altered stress pattern on joint surfaces, which leads to structural damage and mechanical failure of articular cartilage. The importance of the neuromuscular system to the initiation and progression of OA is still poorly understood. Many surgical extra- and intra-articular procedures have been used for the treatment of OA. Although some of the new methods, such as autologous chondrocyte transplantation and mosaicplasty, have given good clinical results, it is reasonable to emphasize that the methods still are experimental and more controlled studies are needed.

U. Väätäinen

Papers

Normal and pathological adaptations of articular cartilage to joint loading.

Indentation instrument for the measurement of cartilage stiffness under arthroscopic control