SciCombinator

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Concept: Articular cartilage repair

169

Articular cartilage maturation is the postnatal development process that adapts joint surfaces to their site-specific biomechanical demands. Maturation involves gross morphological changes that occur through a process of synchronised growth and resorption of cartilage and generally ends at sexual maturity. The inability to induce maturation in biomaterial constructs designed for cartilage repair has been cited as a major cause for their failure in producing persistent cell-based repair of joint lesions. The combination of growth factors FGF2 and TGFβ1 induces accelerated articular cartilage maturation in vitro such that many molecular and morphological characteristics of tissue maturation are observable. We hypothesised that experimental growth factor-induced maturation of immature cartilage would result in a biophysical and biochemical composition consistent with a mature phenotype. Using native immature and mature cartilage as reference, we observed that growth factor-treated immature cartilages displayed increased nano-compressive stiffness, decreased surface adhesion, decreased water content, increased collagen content and smoother surfaces, correlating with a convergence to the mature cartilage phenotype. Furthermore, increased gene expression of surface structural protein collagen type I in growth factor-treated explants compared to reference cartilages demonstrates that they are still in the dynamic phase of the postnatal developmental transition. These data provide a basis for understanding the regulation of postnatal maturation of articular cartilage and the application of growth factor-induced maturation in vitro and in vivo in order to repair and regenerate cartilage defects.

Concepts: Bone, Gene, Molecular biology, Collagen, Cartilage, Knee, Biochemistry, Articular cartilage repair

167

OBJECTIVE: The 1-34 amino acid segment of the parathyroid hormone (PTH [1-34]) mediates anabolic effects in chondrocytes and osteocytes. The aim of this study was to investigate whether systemic application of PTH [1-34] improves the repair of non-osteoarthritic, focal osteochondral defects in vivo. DESIGN: Standardized cylindrical osteochondral defects were bilaterally created in the femoral trochlea of rabbits (n = 8). Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to the treatment group (n = 4) for 6 weeks, controls (n = 4) received saline. Articular cartilage repair was evaluated by macroscopic, biochemical, histological and immunohistochemical analyses. Reconstitution of the subchondral bone was assessed by micro-computed tomography. Effects of PTH [1-34] on synovial membrane, apoptosis, and expression of the PTH receptor (PTH1R) were determined. RESULTS: Systemic PTH [1-34] increased PTH1R expression on both, chondrocytes and osteocytes within the repair tissue. PTH [1-34] ameliorated the macro- and microscopic aspect of the cartilaginous repair tissue. It also enhanced the thickness of the subchondral bone plate and the microarchitecture of the subarticular spongiosa within the defects. No significant correlations were established between these coexistent processes. Apoptotic levels, synovial membrane, biochemical composition of the repair tissue, and type-I/II collagen immunoreactivity remained unaffected. CONCLUSIONS: PTH [1-34] emerges as a promising agent in the treatment of focal osteochondral defects as its systemic administration simultaneously stimulates articular cartilage and subchondral bone repair. Importantly, both time-dependent mechanisms of repair did not correlate significantly at this early time point and need to be followed over prolonged observation periods.

Concepts: Bone, Calcitonin, Collagen, Extracellular matrix, Parathyroid hormone, Cartilage, Autologous chondrocyte implantation, Articular cartilage repair

151

Untreated articular cartilage defects may lead to chronic joint degeneration and functional disability. In the past decade, several cartilage repair techniques have emerged for the treatment of cartilage lesions. Among these techniques, mosaicplasty was introduced by the senior author into the clinical practice in 1992. This article does not intend to give a review or a comparison of currently existing surgical techniques which aim to repair symptomatic focal defects; however, it focuses on the procedures used in the everyday practice in the authors' institute, namely microfracture, mosaicplasty, autologous chondrocyte implantation (ACI), osteochondral allograft transplantation and biodegradable osteochondral scaffolds. It gives a brief summary of these well-described techniques, summarizes the authors' clinical experience and available data on the clinical outcome, and the rehabilitation protocol following different procedures, with a special emphasis on mosaicplasty.

Concepts: Cartilage, Knee, Organ transplant, Knee cartilage replacement therapy, Autologous chondrocyte implantation, Chondrocyte, Articular cartilage damage, Articular cartilage repair

29

Surgical options for cartilage resurfacing may be significantly improved by advances and application of biomaterials that direct tissue repair. A poly(ethylene glycol) diacrylate (PEGDA) hydrogel was designed to support cartilage matrix production, with easy surgical application. A model in vitro system demonstrated deposition of cartilage-specific extracellular matrix in the hydrogel biomaterial and stimulation of adjacent cartilage tissue development by mesenchymal stem cells. For translation to the joint environment, a chondroitin sulfate adhesive was applied to covalently bond and adhere the hydrogel to cartilage and bone tissue in articular defects. After preclinical testing in a caprine model, a pilot clinical study was initiated where the biomaterials system was combined with standard microfracture surgery in 15 patients with focal cartilage defects on the medial femoral condyle. Control patients were treated with microfracture alone. Magnetic resonance imaging showed that treated patients achieved significantly higher levels of tissue fill compared to controls. Magnetic resonance spin-spin relaxation times (T(2)) showed decreasing water content and increased tissue organization over time. Treated patients had less pain compared with controls, whereas knee function [International Knee Documentation Committee (IKDC)] scores increased to similar levels between the groups over the 6 months evaluated. No major adverse events were observed over the study period. With further clinical testing, this practical biomaterials strategy has the potential to improve the treatment of articular cartilage defects.

Concepts: Bone, Chondroitin sulfate, Extracellular matrix, Mesenchymal stem cell, Proteoglycan, Nuclear magnetic resonance, Cartilage, Articular cartilage repair

28

SYNOPSIS: Ice hockey goaltenders are a specialized population of athletes because of the unique physical demand that the position, especially those who employ the butterfly technique, places on their lower extremities, specifically at the hip. It is no surprise that hip injuries are a common occurrence among goalies. A review of the biomechanical literature has demonstrated that stressing the hip in flexion and end-range internal rotation, the position goaltenders commonly use, puts the hip in an “at risk” position for injury and is likely a major contributing factor to overuse hip injuries. The stress on a goaltender’s hip is further intensified by the presence of bony deformities, such as cam or pincer type femoroacetabular impingement (FAI), which can lead to chondrolabral junction and articular cartilage injuries. There have been few published reports of goaltenders functional outcomes following FAI surgery and to our knowledge no studies have yet identified the specific challenges presented in the rehabilitation of goaltenders post FAI surgery. Here we present a 6-phase return to skating program as part of the rehabilitation protocol that was developed to aid hockey goaltenders recovering from surgery. LEVEL OF EVIDENCE: Therapy, level 5. J Orthop Sports Phys Ther. Epub 12 February 2013. doi:10.2519/jospt.2013.4430.

Concepts: Ice, Knee, Ice hockey, Articular cartilage repair, Kingston, Ontario, Hockey, Goaltender, Ice hockey goaltenders

28

Cartilage therapy for focal articular lesions of the knee has been implemented for more than a decade, and it is becoming increasingly available. What do we know on the healing response of cartilage lesions? What do we know on the treatment of focal cartilage lesions of the knee and the prognostic factors involved? PubMed articles related to articular cartilage regeneration of the knee in clinical studies were searched from January 2006 to November 2012, using the following key words: articular cartilage, regeneration, clinical studies, and knee. A total of 44 reports were found. They showed the following possibilities for the treatment of focal lesions of the articular cartilage of the knee: cartilage regeneration and repair including cartilage reparation with gene-activated matrices, autologous chondrocyte implantation (ACI) and matrix-induced ACI (MACI), microfracture, osteochondral autograft transfer (mosaicplasty), biological approaches (scaffolds, mesenchymal stem cells-MSCs, platelet-rich plasma, growing factors-GF, bone morphogenetic proteins-BMPs, magnetically labeled synovium-derived cells-M-SDCs, and elastic-like polypeptide gels), osteotomies, stem-cell-coated titanium implants, and chondroprotection with pulsed electromagnetic fields. Untreated cartilage lesions on the femoral condyles had a superior healing response compared to those on the tibial plateaus, and in the patellofemoral joint. Clinical outcome regarding the treatment of medial defects is better than that of the lateral defects. Improvement from baseline was better for patients < or = 30 years compared with patients > or = 30 years. ACI, MACI, and mosaicplasty have shown similar results. The results of comparative clinical studies using ACI have shown some superiority over conventional microfracturing in medium or large defects and in long-term durability. Some biological methods such as scaffolds, MSCs, GF, M-SDCs, BMPs, and elastic-like polypeptide gels still need more research.

Concepts: Bone, Collagen, Cartilage, Knee, Knee cartilage replacement therapy, Autologous chondrocyte implantation, Chondrocyte, Articular cartilage repair

26

Concomitant unloading procedures, such as high tibial osteotomy (HTO), are increasingly recognized as an important part of cartilage repair. This study presents survival rate, functional outcome, complication rate, and return to work following combined single-stage autologous chondrocyte implantation (ACI) and HTO.

Concepts: Cartilage, Orthopedic surgery, Knee cartilage replacement therapy, Osteotomy, Autologous chondrocyte implantation, Articular cartilage repair

25

Articular cartilage, together with skin, was predicted to be one of the first tissues to be successfully engineered. However cartilage repair remains nowadays still elusive, as we are still not able to overcome the hurdles of creating biomaterials corresponding to the native properties of the tissue, and which operate in joints environment that is not favorable for regeneration. In this review, we give an overview of the outcome of current cartilage treatment techniques. Furthermore we present current research strategies for improving cartilage tissue engineering.

Concepts: Bone, Extracellular matrix, Future, Cartilage, Tissues, Knee, Tissue, Articular cartilage repair

25

Articular cartilage repair remains challenging, because most clinical failures are due to the lack of subchondral bone regeneration. We report an innovative approach improving cartilage repair by regenerating a robust subchondral bone, supporting articular cartilage.

Concepts: Bone, Bone marrow, Skeletal system, Regeneration, Cartilage, Articular cartilage damage, Articular cartilage repair

24

While numerous randomized controlled trials have compared surgical treatments for cartilage defects of the knee, the comparative efficacy of these treatments is still poorly understood. The goal of this network meta-analysis was to synthesize these randomized data into a comprehensive model allowing pairwise comparisons of all treatment options and treatment rankings based on multiple measures of efficacy. We hypothesized that advanced chondral procedures would have improved outcomes when compared to microfracture.

Concepts: Epidemiology, Randomized controlled trial, Cartilage, Knee, Efficacy, Articular cartilage repair, Pairwise comparison, Microfracture surgery