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

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

22

Chondral injuries are short of self-healing ability and need to surgical repair after articular cartilage injury. Conventional treatment includes debridement and drainage under arthroscope, micro-fracture, osteochondral autograft transplantation (OATS), mosaiplasty and osteochondral allografts (OCA), autologous chondrocyte implantation (ACI). Debridement and drainage could remove pain factor, and has advantages of simple operation, wide clinical application and early clinical effect. Micro-fracture and osteochondral autograft transplantation is suitable for small area of cartilage repair, while the further effect showed that fibrous cartilage permeated by drill could decrease postoperative clinical effect. Osteochondral autograft transplantation has better advantages for reconstruction complete of wear-bearing joint. Autologous chondrocyte implantation and allogeneic cartilage transplantation are suitable for large area of cartilage defect, postoperative survival of allogeneic cartilage transplantation is effected by local rejection reaction and decrease further clinical effect. Cartilage tissue engineering technology could improve repair quality of autologous chondrocyte implantation, and make repair tissue close to transparent cartilage, but has limit to combined subchondral bone plate, reactive bone edema, bone loss and bad axis of lower limb. New technology is applied to cartilage injury, and has advantages of less trauma, simple operation, rapid recover, good clinical effect and less cost;and could be main method for treat cartilage injury with surgical repair technology. How to improve repair quality with compression resistance and abrasive resistance are expected to be solved.

Concepts: Bone, Extracellular matrix, Cartilage, Knee, Organ transplant, Knee cartilage replacement therapy, Autologous chondrocyte implantation, Articular cartilage repair

7

In embryonic models and stem cell systems, mesenchymal cells derived from the neuroectoderm can be distinguished from mesoderm-derived cells by their Hox-negative profile-a phenotype associated with enhanced capacity of tissue regeneration. We investigated whether developmental origin and Hox negativity correlated with self-renewal and environmental plasticity also in differentiated cells from adults. Using hyaline cartilage as a model, we showed that adult human neuroectoderm-derived nasal chondrocytes (NCs) can be constitutively distinguished from mesoderm-derived articular chondrocytes (ACs) by lack of expression of specific HOX genes, including HOXC4 and HOXD8. In contrast to ACs, serially cloned NCs could be continuously reverted from differentiated to dedifferentiated states, conserving the ability to form cartilage tissue in vitro and in vivo. NCs could also be reprogrammed to stably express Hox genes typical of ACs upon implantation into goat articular cartilage defects, directly contributing to cartilage repair. Our findings identify previously unrecognized regenerative properties of HOX-negative differentiated neuroectoderm cells in adults, implying a role for NCs in the unmet clinical challenge of articular cartilage repair. An ongoing phase 1 clinical trial preliminarily indicated the safety and feasibility of autologous NC-based engineered tissues for the treatment of traumatic articular cartilage lesions.

Concepts: Gene, Developmental biology, Cellular differentiation, Cartilage, Tissues, Mesenchyme, Autologous chondrocyte implantation, Articular cartilage repair