Prospective Mid-Term Results of a Completely Metal-Free Ceramic Total Knee Endoprosthesis: A Concise Follow-Up of a Previous Report.

BACKGROUND: Hypersensitivity reactions are suspected to cause premature aseptic loosening in susceptible patients after total knee arthroplasty. In response, metal-free implants have been developed. The aim of this prospective, observational midterm study was the assessment of a completely metal-free ceramic knee replacement system as a concise follow-up of a previous report. METHODS: Thirty-eight patients, with anamnestic suspected or documented allergy to the metal used in prosthetic alloys, participated in this 4-year follow-up of the metal-free BPK-S (Peter Brehm) total knee replacement system with ceramic femoral and tibial components. Clinical assessment included Knee Society Score (KSS), Oxford Knee Score, Euro Quol-5D-Visual Analogue Scale (EQ-5D-VAS), and perioperative or postoperative complications and need for revision. The position of the implant, signs of loosening, and leg alignment were assessed radiographically. RESULTS: All postoperative clinical scores improved significantly from baseline to 48-month follow-up examination. The Oxford Knee Score improved from 39 to 15 points. The KSS improved from 99 to 195 points (the KSS knee score 42.5 to 96 and the KSS function score 60 to 100). The EQ-5D improved from 12 to 7 points; the EQ-VAS improved from 52.5 to 97 points. No allergic reactions could be detected. Radiologically, a median preoperative varus deformity of 5° improved to 0° at 4-year follow-up. Radiolucent lines appeared around uncemented areas with no clinical symptoms. CONCLUSION: The fully metal-free BPK-S Integration ceramic knee replacement system exhibits excellent immuno-allergological compatibility, offering a safe option for patients with prior hypersensitivity reactions to metallic materials. Full cementation of all components is recommended to avoid radiolucent lines around the implant.

Is percutaneous suturing superior to open fibrin gluing in acute Achilles tendon rupture?

PURPOSE: Open fibrin gluing is reported to enable anatomical reconstruction with less soft tissue compromise than suture repair. Our main objective was to compare the complication rate, function, pain and disability of the two operative approaches of percutaneous suture using the Paessler technique and open fibrin gluing. METHODS: Sixty-four patients (two centres, retrospective cohort study, 2000-2009) who had undergone acute Achilles tendon repair with either percutaneous suture (n = 27; 44 years) or open fibrin glue (n = 37; 45 years) took part in a follow-up examination after a median of 63 months (range, six to 180). Ankle range of motion, calf and ankle circumferences and return to work and sports activities were evaluated. Isokinetic und sonographic evaluation results were retrieved. RESULTS: Complications were noted in 22 patients (34 %). Delayed wound healing without evidence of surgical site infection was found in three patients in the fibrin group and two patients in the suture group. Postoperative scar tenderness described as pain at the rim of the shoe was significantly more frequent in the suture group (p = 0.03). Re-rupture requiring re-operation occurred in one patient. Transient paresthesia of the heel occurred in 12 patients. No sural nerve lesions were reported. There was no significant difference between groups regarding lower leg circumference, disability, or function. Ultrasound and isokinetic measurements did not reveal a significant difference between the two methods. CONCLUSIONS: The present study suggests that open fibrin gluing is a reasonable alternative to percutaneous repair of acute ruptures of the Achilles tendon and both techniques can yield reliably good results.

The Biomechanics of Cartilage-An Overview.

Articular cartilage (AC) sheathes joint surfaces and minimizes friction in diarthrosis. The resident cell population, chondrocytes, are surrounded by an extracellular matrix and a multitude of proteins, which bestow their unique characteristics. AC is characterized by a zonal composition (superficial (tangential) zone, middle (transitional) zone, deep zone, calcified zone) with different mechanical properties. An overview is given about different testing (load tests) methods as well as different modeling approaches. The widely accepted biomechanical test methods, e.g., the indentation analysis, are summarized and discussed. A description of the biphasic theory is also shown. This is required to understand how interstitial water contributes toward the viscoelastic behavior of AC. Furthermore, a short introduction to a more complex model is given.

Arterial anatomy of the hallucal sesamoids.

The aim of this study was to analyze the arterial supply of the sesamoid bones of the hallux. Twenty-two feet from adult cadavers were injected with epoxide resin or an acrylic polymer in methyl methacrylate (Acrifix) and subsequently processed by two slice plastination methods and the enzyme maceration technique. Afterwards, the arterial supply of the sesamoid bones was studied. The first plantar metatarsal artery provided a medial branch to the medial sesamoid bone. The main branch of the first plantar metatarsal artery continued its course distally along the lateral side of the lateral sesamoid and supplied it. The supplying arteries penetrated the sesamoid bones on the proximal, plantar, and distal sides. The analysis and cataloging of the microvascular anatomy of the sesamoids revealed the first plantar metatarsal artery as the main arterial source to the medial and lateral sesamoid bones. In addition, the first plantar metatarsal artery ran along the lateral plantar side of the lateral sesamoid bone, suggesting that this artery is at increased risk during soft-tissue procedures such as hallux valgus surgery.

Compressive forces induce osteogenic gene expression in calvarial osteoblasts.

Bone cells and their precursors are sensitive to changes in their biomechanical environment. The importance of mechanical stimuli has been observed in bone homeostasis and osteogenesis, but the mechanisms responsible for osteogenic induction in response to mechanical signals are poorly understood. We hypothesized that compressive forces could exert an osteogenic effect on osteoblasts and act in a dose-dependent manner. To test our hypothesis, electrospun poly(epsilon-caprolactone) (PCL) scaffolds were used as a 3-D microenvironment for osteoblast culture. The scaffolds provided a substrate allowing cell exposure to levels of externally applied compressive force. Pre-osteoblasts adhered, proliferated and differentiated in the scaffolds and showed extensive matrix synthesis by scanning electron microscopy (SEM) and increased Young's modulus (136.45+/-9.15 kPa) compared with acellular scaffolds (24.55+/-8.5 kPa). Exposure of cells to 10% compressive strain (11.81+/-0.42 kPa) resulted in a rapid induction of bone morphogenic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), and MAD homolog 5 (Smad5). These effects further enhanced the expression of genes and proteins required for extracellular matrix (ECM) production, such as alkaline phosphatase (Akp2), collagen type I (Col1a1), osteocalcin/bone gamma carboxyglutamate protein (OC/Bglap), osteonectin/secreted acidic cysteine-rich glycoprotein (ON/Sparc) and osteopontin/secreted phosphoprotein 1 (OPN/Spp1). Exposure of cell-scaffold constructs to 20% compressive strain (30.96+/-2.82 kPa) demonstrated that these signals are not osteogenic. These findings provide the molecular basis for the experimental and clinical observations that appropriate physical activities or microscale compressive loading can enhance fracture healing due in part to the anabolic osteogenic effects.

Dynamic regulation of bone morphogenetic proteins in engineered osteochondral constructs by biomechanical stimulation.

Osteochondral tissue-engineered grafts are proposed to hold greater potential to repair/regenerate damaged cartilage through enhanced biochemical and mechanical interactions with underlying subchondral bone as compared to simple engineered cartilage. Additionally, biomechanical stimulation of articular chondrocytes (ACs) or osteoblasts (OBs) was shown to induce greater morphogenesis of the engineered tissues composed of these cells. In this report, to define the advantages of biomechanical stimulation to osteochondral grafts for tissue engineering, we examined whether (1) ACs and OBs in three-dimensional (3D) osteochondral constructs support functional development of each other at the molecular level, and (2) biomechanical stimulation of osteochondral constructs further promotes the regenerative potential of such grafts. Various configurations of cell/scaffold assemblies, including chondral, osseous, and osteochondral constructs, were engineered with mechano-responsive electrospun poly(ɛ-caprolactone) scaffolds. These constructs were subjected to either static or dynamic (10% cyclic compressive strain at 1 Hz for 3 h/day) culture conditions for 2 weeks. The expression of bone morphogenetic proteins (BMPs) was examined to assess the regenerative potential of each treatment on the cells. Biomechanical stimulation augmented a marked upregulation of Bmp2, Bmp6, and Bmp7 as well as downregulation of BMP antagonist, Bmp3, in a time-specific manner in the ACs and OBs of 3D osteochondral constructs. More importantly, the presence of biomechanically stimulated OBs was especially crucial for the induction of Bmp6 in ACs, a BMP required for chondrocytic growth and differentiation. Biomechanical stimulation led to enhanced tissue morphogenesis possibly through this BMP regulation, evident by the improved effective compressive modulus of the osteochondral constructs (710 kPa of dynamic culture vs. 280 kPa of static culture). Similar BMP regulation was observed in the femoral cartilages of the rats subjected to gentle exercise, demonstrating the physiological relevance of in vitro biomechanical stimulation of osteochondral constructs. Overall, our findings show that biomechanical stimulation may be critical for cross signaling between ACs and OBs to support chondrocytic growth in 3D osteochondral tissues.

Hepatocyte growth factor-loaded biomaterials for mesenchymal stem cell recruitment.

Human adult mesenchymal stem cells (MSC) can be readily harvested from bone marrow through aspiration. MSC are involved in tissue regeneration and repair, particularly in wound healing. Due to their high self-renewal capacity and excellent differentiation potential in vitro, MSC are ideally suited for regenerative medicine. The complex interactions of MSC with their environment and their influence on the molecular and functional levels are widely studied but not completely understood. MSC secrete, for example, hepatocyte growth factor (HGF), whose concentration is enhanced in wounded areas and which is shown to act as a chemoattractant for MSC. We produced HGF-loaded biomaterials based on collagen and fibrin gels to develop a recruitment system for endogenous MSC to improve wound healing. Here, we report that HGF incorporated into collagen or fibrin gels leads to enhanced and directed MSC migration in vitro. HGF-loaded biomaterials might be potentially used as in vivo wound dressings to recruit endogenous MSC from tissue-specific niches towards the wounded area. This novel approach may help to reduce costly multistep procedures of cell isolation, in vitro culture, and transplantation usually used in tissue engineering.

Evaluation of implant position and knee alignment after patient-specific unicompartmental knee arthroplasty.

Implant positioning and knee alignment are two primary goals of successful unicompartmental knee arthroplasty. This prospective study outlines the radiographic results following 32 patient-specific unicompartmental medial resurfacing knee arthroplasties. By means of standardized pre- and postoperative radiographs of the knee in strictly AP and lateral view, AP weight bearing long leg images as well as preoperative CT-based planning drawings an analysis of implant positioning and leg axis correction was performed.The mean preoperative coronal femoro-tibial angle was corrected from 7° to 1° (p<0.001). The preoperative medial proximal tibial angle of 87° was corrected to 89° (p<0.001). The preoperative tibial slope of 5° could be maintained. The extent of the dorsal femoral cut was equivalent to the desired value of 5mm given by the CT-based planning guide. The mean accuracy of the tibial component fit was 0mm in antero-posterior and +1mm in medio-lateral projection. Patient-specific fixed bearing unicompartmental knee arthroplasty can restore leg axis reliably, obtain a medial proximal tibial angle of 90°, avoid an implant mal-positioning and ensure maximal tibial coverage.

Sequential alterations in catabolic and anabolic gene expression parallel pathological changes during progression of monoiodoacetate-induced arthritis.

Chronic inflammation is one of the major causes of cartilage destruction in osteoarthritis. Here, we systematically analyzed the changes in gene expression associated with the progression of cartilage destruction in monoiodoacetate-induced arthritis (MIA) of the rat knee. Sprague Dawley female rats were given intra-articular injection of monoiodoacetate in the knee. The progression of MIA was monitored macroscopically, microscopically and by micro-computed tomography. Grade 1 damage was observed by day 5 post-monoiodoacetate injection, progressively increasing to Grade 2 by day 9, and to Grade 3-3.5 by day 21. Affymetrix GeneChip was utilized to analyze the transcriptome-wide changes in gene expression, and the expression of salient genes was confirmed by real-time-PCR. Functional networks generated by Ingenuity Pathways Analysis (IPA) from the microarray data correlated the macroscopic/histologic findings with molecular interactions of genes/gene products. Temporal changes in gene expression during the progression of MIA were categorized into five major gene clusters. IPA revealed that Grade 1 damage was associated with upregulation of acute/innate inflammatory responsive genes (Cluster I) and suppression of genes associated with musculoskeletal development and function (Cluster IV). Grade 2 damage was associated with upregulation of chronic inflammatory and immune trafficking genes (Cluster II) and downregulation of genes associated with musculoskeletal disorders (Cluster IV). The Grade 3 to 3.5 cartilage damage was associated with chronic inflammatory and immune adaptation genes (Cluster III). These findings suggest that temporal regulation of discrete gene clusters involving inflammatory mediators, receptors, and proteases may control the progression of cartilage destruction. In this process, IL-1ß, TNF-α, IL-15, IL-12, chemokines, and NF-κB act as central nodes of the inflammatory networks, regulating catabolic processes. Simultaneously, upregulation of asporin, and downregulation of TGF-ß complex, SOX-9, IGF and CTGF may be central to suppress matrix synthesis and chondrocytic anabolic activities, collectively contributing to the progression of cartilage destruction in MIA.

Mechanical signals control SOX-9, VEGF, and c-Myc expression and cell proliferation during inflammation via integrin-linked kinase, B-Raf, and ERK1/2-dependent signaling in articular chondrocytes.

INTRODUCTION: The importance of mechanical signals in normal and inflamed cartilage is well established. Chondrocytes respond to changes in the levels of proinflammatory cytokines and mechanical signals during inflammation. Cytokines like interleukin (IL)-1beta suppress homeostatic mechanisms and inhibit cartilage repair and cell proliferation. However, matrix synthesis and chondrocyte (AC) proliferation are upregulated by the physiological levels of mechanical forces. In this study, we investigated intracellular mechanisms underlying reparative actions of mechanical signals during inflammation. METHODS: ACs isolated from articular cartilage were exposed to low/physiologic levels of dynamic strain in the presence of IL-1beta. The cell extracts were probed for differential activation/inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling cascade. The regulation of gene transcription was examined by real-time polymerase chain reaction. RESULTS: Mechanoactivation, but not IL-1beta treatment, of ACs initiated integrin-linked kinase activation. Mechanical signals induced activation and subsequent C-Raf-mediated activation of MAP kinases (MEK1/2). However, IL-1beta activated B-Raf kinase activity. Dynamic strain did not induce B-Raf activation but instead inhibited IL-1beta-induced B-Raf activation. Both mechanical signals and IL-1beta induced ERK1/2 phosphorylation but discrete gene expression. ERK1/2 activation by mechanical forces induced SRY-related protein-9 (SOX-9), vascular endothelial cell growth factor (VEGF), and c-Myc mRNA expression and AC proliferation. However, IL-1beta did not induce SOX-9, VEGF, and c-Myc gene expression and inhibited AC cell proliferation. More importantly, SOX-9, VEGF, and Myc gene transcription and AC proliferation induced by mechanical signals were sustained in the presence of IL-1beta. CONCLUSIONS: The findings suggest that mechanical signals may sustain their effects in proinflammatory environments by regulating key molecules in the MAP kinase signaling cascade. Furthermore, the findings point to the potential of mechanosignaling in cartilage repair during inflammation.

Novel electrospun scaffolds for the molecular analysis of chondrocytes under dynamic compression.

Mechanical training of engineered tissue constructs is believed necessary to improve regeneration of cartilaginous grafts. Nevertheless, molecular mechanisms underlying mechanical activation are not clear. This is partly due to unavailability of appropriate scaffolds allowing exposure of cells to dynamic compressive strains (DCS) in vitro while permitting subsequent molecular analyses. We demonstrate that three-dimensional macroporous electrospun poly(epsilon-caprolactone) scaffolds can be fabricated that are suitable for the functional and molecular analysis of dynamically loaded chondrocytes. These scaffolds encourage chondrocytic proliferation promoting expression of collagen type II, aggrecan, and Sox9 while retaining mechanical strength after prolonged dynamic compression. Further, they exhibit superior infiltration of exogenous agents into the cells and permit easy retrieval of cellular components postcompression to allow exploration of molecular mechanisms of DCS. Using these scaffolds, we observed that chondrocytes responded to DCS in a magnitude-dependent manner exhibiting antiinflammatory and proanabolic responses at low physiological magnitudes. Proinflammatory responses and decreased cellular viability were observed at hyperphysiological magnitudes. These scaffolds provide a means of unraveling the mechanotransduction-induced transcriptional and posttranslational activities involved in cartilage regeneration and repair.

Biomechanical thresholds regulate inflammation through the NF-kappaB pathway: experiments and modeling.

BACKGROUND: During normal physical activities cartilage experiences dynamic compressive forces that are essential to maintain cartilage integrity. However, at non-physiologic levels these signals can induce inflammation and initiate cartilage destruction. Here, by examining the pro-inflammatory signaling networks, we developed a mathematical model to show the magnitude-dependent regulation of chondrocytic responses by compressive forces. METHODOLOGY/PRINCIPAL FINDINGS: Chondrocytic cells grown in 3-D scaffolds were subjected to various magnitudes of dynamic compressive strain (DCS), and the regulation of pro-inflammatory gene expression via activation of nuclear factor-kappa B (NF-kappaB) signaling cascade examined. Experimental evidences provide the existence of a threshold in the magnitude of DCS that regulates the mRNA expression of nitric oxide synthase (NOS2), an inducible pro-inflammatory enzyme. Interestingly, below this threshold, DCS inhibits the interleukin-1beta (IL-1beta)-induced pro-inflammatory gene expression, with the degree of suppression depending on the magnitude of DCS. This suppression of NOS2 by DCS correlates with the attenuation of the NF-kappaB signaling pathway as measured by IL-1beta-induced phosphorylation of the inhibitor of kappa B (IkappaB)-alpha, degradation of IkappaB-alpha and IkappaB-beta, and subsequent nuclear translocation of NF-kappaB p65. A mathematical model developed to understand the complex dynamics of the system predicts two thresholds in the magnitudes of DCS, one for the inhibition of IL-1beta-induced expression of NOS2 by DCS at low magnitudes, and second for the DCS-induced expression of NOS2 at higher magnitudes. CONCLUSIONS/SIGNIFICANCE: Experimental and computational results indicate that biomechanical signals suppress and induce inflammation at critical thresholds through activation/suppression of the NF-kappaB signaling pathway. These thresholds arise due to the bistable behavior of the networks originating from the positive feedback loop between NF-kappaB and its target genes. These findings lay initial groundwork for the identification of the thresholds in physical activities that can differentiate its favorable actions from its unfavorable consequences on joints.