Dieter Van Assche

Autologous Chondrocyte Implantation Postoperative Care and Rehabilitation Science and Practice

Autologous chondrocyte implantation is an advanced, cell-based orthobiological technology used for the treatment of chondral defects of the knee. It has been in clinical use since 1987 and has been performed on 12 000 patients internationally; but despite having been in clinical use for more than 15 years, the evidence base for rehabilitation after autologous chondrocyte implantation is notably deficient. The authors review current clinical practice and present an overview of the principles behind autologous chondrocyte implantation rehabilitation practices. They examine the main rehabilitation components and discuss their practical applications within the overall treatment program, with the aim of facilitating the formulation of appropriate, individualized patient rehabilitation protocols for autologous chondrocyte implantation.

Characterized Chondrocyte Implantation in the Patellofemoral Joint An Up to 4-Year Follow-up of a Prospective Cohort of 38 Patients

Background: Autologous chondrocyte implantation (ACI) is an accepted treatment option for selected condylar cartilage defects in the knee. Results for patellofemoral chondral defects have been less favorable. Hypothesis: Autologous chondrocyte implantation with characterized chondrocytes will result in clinically relevant improvement in patellofemoral lesions. Study Design: Case series; Level of evidence, 4. Methods: Patients with symptomatic patellofemoral full-thickness cartilage lesions were treated with ACI using characterized chondrocytes (ChondroCelect) covered with a collagen type I membrane. Clinical outcome was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and a visual analog scale (VAS) for pain. Responders were defined using 5 categories (≥10 points and ≥20%, 30%, 50%, 70%) based on the KOOS and VAS. Treatment failure was defined as partial loosening of more than 20% of the graft with subsequent procedures to the subchondral bone. Results: Thirty-eight patients, with a mean defect size of 4.89 cm2 (range, 1.5-11 cm2), were treated for a patellar defect (n = 28), trochlear defect (n = 7), or a kissing lesion (trochlea and patella; n = 3). The minimum follow-up period was 24 months (mean, 37 months; range, 24-72 months). Treated patients showed statistically significant improvements in the KOOS (at 12, 18, 24, 36, and 48 months) and VAS (at the same time points) compared with pretreatment for each time point. Responder analysis identified approximately 84% of patients with a clinically relevant improvement greater than 10 points at 3 years. Treatment failure was observed in 5 patients. The most commonly reported adverse events were joint crepitation (n = 18) and arthrofibrosis (n = 7). No relationship could be found between clinical outcome and anatomic characteristics of the patellofemoral joint, lesion size and site, time since onset, or age. Nine patients required additional surgery: 6 because of persistent symptoms and 3 for hardware removal. Conclusion: Characterized chondrocyte implantation resulted in statistically significant and clinically relevant improvement over time. These results add to the evidence demonstrating that ACI is a valuable cartilage repair technique for patellofemoral lesions.

Physical Activity Levels After Characterized Chondrocyte Implantation Versus Microfracture in the Knee and the Relationship to Objective Functional Outcome With 2-year Follow-up

Background Characterized chondrocyte implantation results in superior structural repair compared with microfracture, but may be associated with a slower recovery of physical activity levels due to the arthrotomy. Hypotheses Our hypotheses were that (1) microfracture results in increased activity levels over 2 years after surgery compared with characterized chondrocyte implantation, (2) patients with high preinjury activity levels have a better functional outcome, and (3) high levels of low-load activities after surgery improve functional outcome. Study Design Cohort study; Level of evidence, 2. Methods Sixty-seven patients with local cartilage defects (mean size, 2.4 cm2; standard deviation, 1.5 cm2) of the femoral condyle underwent characterized chondrocyte implantation (n = 33) or microfracture (n = 34), followed by an identical rehabilitation protocol. Activity levels (assessed using the Activity Rating Scale) and functional outcome were determined at baseline, and 1 and 2 years after surgery. Functional outcome was based on the pooled symmetry index (derived from isokinetic knee extension strength and 3 one-legged hop tests). Patients’ participation in low-load activities during the first 3 months after surgery was assessed using rehabilitation data. Mixed linear model analyses and Wilcoxon rank sum tests were used. Results Activity levels in patients treated with characterized chondrocyte implantation and microfracture were comparable at 1 and 2 years after surgery. Preinjury activity levels showed no relationship to functional outcome. Lack of postoperative low-load activities resulted in a significantly worse functional outcome (mean pooled symmetry index 78.2%) compared with high levels of postoperative surgery low-load activities (mean pooled symmetry index 92.4%). Conclusion Despite differences between the characterized chondrocyte implantation and microfracture procedures, patients’ activity levels were comparable at 2 years after surgery. Lack of low-load activities after surgery adversely affected functional outcome.

Non-surgical treatments for the management of early osteoarthritis

AbstractNon-surgical treatments are usually the first choice for the management of knee degeneration, especially in the early osteoarthritis (OA) phase when no clear lesions or combined abnormalities need to be addressed surgically. Early OA may be addressed by a wide range of non-surgical approaches, from non-pharmacological modalities to dietary supplements and pharmacological therapies, as well as physical therapies and novel biological minimally invasive procedures involving injections of various substances to obtain a clinical improvement and possibly a disease-modifying effect. Numerous pharmaceutical agents are able to provide clinical benefit, but no one has shown all the characteristic of an ideal treatment, and side effects have been reported at both systemic and local level. Patients and physicians should have realistic outcome goals in pharmacological treatment, which should be considered together with other conservative measures. Among these, exercise is an effective conservative approach, while physical therapies lack literature support. Even though a combination of these therapeutic options might be the most suitable strategy, there is a paucity of studies focusing on combining treatments, which is the most common clinical scenario. Further studies are needed to increase the limited evidence on non-surgical treatments and their combination, to optimize indications, application modalities, and results with particular focus on early OA. In fact, most of the available evidence regards established OA. Increased knowledge about degeneration mechanisms will help to better target the available treatments and develop new biological options, where preliminary results are promising, especially concerning early disease phases. Specific treatments aimed at improving joint homoeostasis, or even counteracting tissue damage by inducing regenerative processes, might be successful in early OA, where tissue loss and anatomical changes are still at very initial stages. Level of evidence IV.

Are personal characteristics associated with exercise participation in patients with rheumatoid arthritis? A cross-sectional explorative survey.

BACKGROUND Organized exercise programs for patients with rheumatoid arthritis (RA) are useful to enhance physical activity and fitness. However, participation and adherence rates of these programs are low. This study aimed to identify demographic, personal and disease-related factors interfering with implementing an exercise program for RA. METHODS A random sample of ambulatory RA patients from a single centre was divided into two groups, depending on their willingness to participate in an exercise program. Subsequently, demographic data (gender, age, disease duration and educational level) and disease-related and personal factors were obtained (Disease Activity Score; Short Form 36 [SF-36]; Health Assessment Questionnaire; Global Disease Activity; and also the Utrecht Coping List [UCL], Illness Cognition Questionnaire; TAMPA scale and modified Baecke questionnaire). RESULTS Of the 154 people completing the survey, 113 (73%) indicated that they were willing to participate in an exercise program. These positive responders (PR) were more often female (p<0.05), and had a higher educational level (p<0.05). In the negative responders (NR), higher scores were found in the general health perception (54.7; [SD 18.3] versus 47.4; [SD 20.8]) and vitality (61.6 [SD 19.8] versus 53.7 [SD 20.1] sections of the SF-36, and a lower score was found on the reassuring thoughts subscale of the UCL (11.9 [SD 2.7] versus 12.9 [SD 2.7]) compared with the PR (all p<0.05). CONCLUSIONS Although few differences were found between the groups, some insights regarding pitfalls in implementing an exercise program were highlighted. Further insights into external and personal motivators for patients are needed.

Towards secondary prevention of early knee osteoarthritis

Osteoarthritis (OA) of the knee is the most common arthritic disease, yet a convincing drug treatment is not available. The current narrative review focuses on integration of scientific evidence and professional experience to illustrate which management approaches can be taken for prototypical individual patient profiles with early knee OA. Animal models suggest that: (1) OA can progress even in the presence of fully recovered movement kinetics, kinematics and muscle activation patterns; (2) muscle weakness is an independent risk factor for the onset and possibly the rate of progression of knee OA; (3) onset and progression of OA are not related to body weight but appear to depend on the percentage of body fat. From studies in the human model, one could postulate that risk factors associated with progression of knee OA include genetic traits, preceding traumatic events, obesity, intensity of pain at baseline, static and dynamic joint malalignment and reduced muscle strength. Taken this into account, an individual can be identified as early knee OA at high risk for disease progression. A holistic patient-tailored management including education, supportive medication, weight loss, exercise therapy (aerobic, strengthening and neuromuscular) and behavioural approaches to improve self-management of early knee OA is discussed in individual prototypic patients. Secondary prevention of early knee OA provides a window of opportunity to slow down or even reverse the disease process. Yet, as the sheer number of patients early in the OA disease process is probably large, a more structured approach is needed to provide appropriate care depending on the patient’s individual risk profile.

Recent advances in cartilage repair (ICL 3)

Articular cartilage possesses low intrinsic healing property due to its lack of vascularity and progenitor cells. Thus, damage to the hyaline cartilage may lead to a progressive degeneration of the joint and eventually to osteoarthritis (OA). In the last years, different surgical techniques have been introduced in the clinical practice to overcome this issue. Bone marrow stimulation, for example, is a widely known method to allow cell invasion from the bloodstream to the site of damage. However, the reparative tissue has different morphological and biomechanical properties when compared to the native cartilage. In particular, the newly formed fibrocartilage has a low amount of proteoglycans and a higher concentration of type I collagen. This different matrix composition leads to a decrease in the mechanical strength and to a poor integration of the reparative tissue with the native cartilage.

Chapter 22 – Clinical Translation

With recent developments in the field of tissue engineering (TE), innovative products are seeking access to the market to be applied in patients. Therefore, a framework has to be defined in which tissue-engineered products can prove their safety and effectiveness. For these products, the challenge to live up to the standards of drug development arises, not only with respect to practical implementation but also with respect to legislation and ethics. Within this chapter, an overview is given on the development of the standards for this new class of products and on the current status of regulation and legislation in this rapidly changing field.