Introduction

The medial patellofemoral ligament (MPFL) is the main stabilizer of the patella and therefore mostly reconstructed in the surgical correction of patellofemoral dislocation. Various biomechanical and clinical studies have been conducted on MPFL reconstruction, while the patellofemoral contact pressure (PFCP) which is indicated as one of the predictors of retropatellar osteoarthritis was neglected. Therefore, the aim of this study was to investigate how different MPFL reconstruction approaches affect PFCP.

Introduction

With processing age, meniscus degeneration occurs which is often associated with osteoarthritis. Existing data about the influence of degeneration on the biomechanical properties of the meniscus are still contradictory, or completely unknown regarding the hydraulic permeability. Thus, the aim of this study was to characterise the biomechanical properties and structural composition of the meniscal tissue depending on its degree of degeneration.

Cartilage injury is generally associated with cytokine release and accumulation of reactive oxygen species. These mediators trigger pathologic behaviour of the surviving chondrocytes, which respond by excessive expression of catabolic enzymes, such as matrix metalloproteinase 13 (MMP-13), reduced synthesis of type II collagen (COL2A1) and apoptosis. In the long run, these pathologic conditions can cause a posttraumatic osteoarthritis. With the objective to attenuate the progressive degradation of the extracellular matrix and, what is more, promote chondroanabolic processes, a multidirectional treatment of trauma-induced pathogenesis was tested for the first time. Therefore, we evaluated the combinations of one anabolic growth factor (IGF-1, FGF18 or BMP7) with the antioxidant N-acetyl cysteine (NAC) in a human ex vivo cartilage trauma model and compared the findings with the corresponding monotherapy. Human cartilage tissue was obtained with informed consent from donors undergoing knee joint replacement (n=24). Only macroscopically intact tissue was used to prepare explants. Cartilage explants were subjected to a blunt impact (0.59 J) by a drop-tower and treated by IGF-1 [100 ng/mL], FGF18 [200 ng/mL] or BMP7 [100 ng/mL] and/or NAC [2 mM] for 7 days. Following parameters were analysed: cell viability (live/dead staining), gene expression (qRT-PCR) as well as biosynthesis (ELISA) of type II collagen and MMP-13. For statistical analysisKruskal-Wallis or One-way ANOVA was used. All data were collected in the orthopedic research laboratory of the University of Ulm, Germany.

Trauma-induced cell death was completely prevented by NAC treatment and FGF18 or BMP7 to a large extent, respectively (p<0.0001). IGF-1 exhibited only poor cell protection. Combination of NAC and FGF18 or BMP7 did not result in enhanced effectiveness; however, IGF-1 significantly reduced NAC-mediated cell protection. While IGF-1 or BMP7 induced collagen type II gene expression (p=0.0069 and p<0.0001, respectively) and its biosynthesis (p<0.0001 and p=0.0131, respectively), NAC or FGF18 caused significant suppression of this matrix component (each p<0.001). Although COL2A1 mRNA was significantly increased by NAC plus IGF-1 (p<0.0001), biosynthesis of collagen type II was generally abolished after multidirectional treatment. Except for IGF-1, all tested therapeutics exhibited chondroprotective qualities, as demonstrated by attenuated MMP-13 expression and breakdown of type II collagen. In combination with IGF-1, NAC-mediated chondroprotection was reduced.

Overall, both chondroanabolic and antioxidative therapy had individual advantages. Since adverse interactions were found by simultaneous application of the therapeutics, a sequential approach might improve the efficacy. In support of this strategy current experiments showed that though cell and chondroprotective effects of NAC were maintained after withdrawal of the antioxidant, type II collagen expression recovered by time.