Comparison of biological augmentation in rotator cuff repair using inflamed versus non-inflamed bursal tissue in rats.

PURPOSE: To examine how augmentation of a rotator cuff repair with inflamed versus non-inflamed bursal tissue affects tendon-to-bone healing in a rat model of rotator cuff repair. METHODS: 136 Sprague-Dawley rats were randomly assigned to an inflamed or non-inflamed bursal tissue application group. After detachment the supraspinatus tendon was re-attached with bursal tissue sewn onto the tendon-to-bone interface. The specimens were analysed biomechanically 6 and at 7 weeks and immunohistologically at 1 and at 7 weeks after surgery. RESULTS: Immunohistological results showed no significant difference in the percentage of collagen type II in the tendon-to-bone interface at 1 (p = 0.97) and 7 weeks (p = 0.42) when utilising autologous non-inflamed bursal tissue in comparison to inflamed bursal tissue specimens. The inflamed bursa group also showed no significant difference in collagen I to III quotient (p= 0.14) after surgery in comparison to post-surgery non-inflamed bursa groups. Biomechanical assessment showed that tendon stiffness (p = 0.87 resp. p = 0.1) and the tendon viscoelasticity (p = 0.12 resp. p = 0.07) was the same after 6 and 7 weeks comparing inflamed bursa to the non-inflamed bursa group. There was no significant difference (p = 0.8 resp. p = 0.97) in load to failure between in both inflamed and non-inflamed bursa groups after 6 and 7 weeks. CONCLUSION: Autologous inflamed bursal tissue derived from the Achilles bursa and implanted to the tendon-to-bone interface after rotator cuff repair facilitates the same histological and biomechanical healing response as using a non-inflamed bursa interposition in rats. CLINICAL RELEVANCE: During augmentation of a rotator cuff repair, it is irrelevant whether the bursa tissue is inflamed or not.

Influence of kinematic alignment on femorotibial kinematics in medial stabilized TKA design compared to mechanical alignment.

INTRODUCTION: Worldwide more and more primary knee replacements are being performed. Kinematic alignment (KA) as one of many methods of surgical alignment has been shown to have a significant impact on kinematics and function. The aim of the present study was to compare KA and mechanical alignment (MA) with regard to femorotibial kinematics. MATERIALS AND METHODS: Eight fresh frozen human specimens were tested on a knee rig during active knee flexion from 30 to 130°. Within the same specimen a medial stabilized (MS) implant design was used first with KA and then with MA. RESULTS: The femorotibial kinematics showed more internal rotation of the tibia in KA compared to MA. At the same time, there was a larger medial rotation point in KA. Both alignment methods showed femoral rollback over the knee bend. CONCLUSION: Relating to an increased internal rotation and a more precise medial pivot point, it can be concluded that KA combined with a MS implant design may partially support the reproduction of physiological knee joint mechanics.

[Treatment of Osteochondral Lesions in the Ankle: A Guideline from the Group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU)]. / Behandlung osteochondraler Läsionen des Sprunggelenks: Empfehlungen der Arbeitsgemeinschaft Klinische Geweberegeneration der DGOU.

Background: Osteochondral lesions (OCL) of the ankle are a common cause of ankle pain. Although the precise pathophysiology has not been fully elucidated, it can be assumed that a variety of factors are responsible, mainly including traumatic events such as ankle sprains. Advances in arthroscopy and imaging techniques, in particular magnetic resonance imaging (MRI), have improved the possibilities for the diagnosis of OCLs of the ankle. Moreover, these technologies aim at developing new classification systems and modern treatment strategies. Material and Methods: This article is a review of the literature. Recommendations of the group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) for the treatment of OCLs of the ankle are presented. The review gives a concise overview on the results of clinical studies and discusses advantages and disadvantages of different treatment strategies. Results: Non-operative treatment shows good results for selected indications in children and adolescents, especially in early stages of osteochondritis dissecans (OCD). However, surgical treatment is usually indicated in OCLs in adolescents and adults, depending on the size and location of the lesion. Various arthroscopic and open procedures are frequently employed, including reattachment of the fragment, local debridement of the lesion with fragment removal and curettage of the lesion, bone marrow-stimulation by microfracture or microdrilling (antegrade or retrograde), and autologous matrix-induced chondrogenesis (AMIC®) - with or without reconstruction of a subchondral bone defect or cyst by autologous cancellous bone grafting. Isolated subchondral cysts with an intact cartilage surface can be treated by retrograde drilling and possibly additional retrograde bone grafting. For larger defects or as salvage procedure, osteochondral cylinder transplantation (OATS® or Mosaicplasty®) or matrix-induced autologous chondrocyte transplantation (MACT) are recommended. Transplantation of so-called (osteochondral) mega grafts, such as autologous bone grafts or allografts, are used for very large osteochondral defects that cannot be reconstructed otherwise. Implantation of the so-called "small metal implants" - such as HemiCAP Talus® - is reserved for selected cases after failed primary reconstruction. Corrective osteotomies are indicated in accompanying axial malalignments. Conclusions: There are several different treatment strategies for OCLs, but clinical studies are rare and evidence is limited. Therefore, interventional studies, e.g. randomised controlled trials (RCTs), but also observational studies, e.g. based on data of the Cartilage Registry of the German Society of Orthopaedics and Traumatology (www.knorpelregister-dgou.de), are needed and are recommended by the authors.

Periodontal ligament cells as alternative source for cell-based therapy of tendon injuries: in vivo study of full-size Achilles tendon defect in a rat model.

Tendon's natural healing potential is extremely low and inefficient, with significant dysfunction and disability due to hypocellularity and hypovascularity of tendon tissues. The application of stem cells can aid in significantly enhanced repair of tendon rupture; therefore, the main aim of this study is to assess the potential of using periodontal ligament cells (PDL), usually obtained from patients undergoing orthodontic treatment, as a novel cell source for cell-based therapy for tendon injuries in a clinically relevant rat full-size Achilles tendon defect. In addition, the study compares the differences between the healing effects of Achilles tendon-derived cells (AT) versus PDL and, hence, comprises of four experimental groups, native tendon (NT), empty defect (ED), PDL and human AT (hAT). The tendon healing in each group was assessed in the late remodelling phase at 16 weeks after surgery using a combination of methods, including evaluation of gross morphological appearance; various histological and immunohistological stainings; and detailed analyses of cell morphometry. Based on these outcome measures, PDL cell-implanted tendons exhibited not only advanced tissue maturation, less ectopic fibrocartilage formation, more organised collagen fibres, tendon matrix expression corresponding to the final healing stage, and better cell-morphometry parameters when compared with the ED group, but were also very similar to the tendons treated with hAT-derived cells. Taken together, our study clearly demonstrates the feasibility of using PDL cells as a novel cell source for tendon repair and strongly recommends this cell type for the future development of innovative regenerative applications for treatment of different tendon or ligament pathologies.

Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: A guideline by the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU).

BACKGROUND: Autologous chondrocyte implantation (ACI) is an established and well-accepted procedure for the treatment of localised full-thickness cartilage defects of the knee. METHODS: The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning therapeutic consequences of primary cartilage lesions and the suitable indication for ACI. RESULTS: Based on best available scientific evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than three to four square centimetres; in the case of young and active sports patients at 2.5cm(2), while advanced degenerative joint disease needs to be considered as the most important contraindication. CONCLUSION: The present review gives a concise overview on important scientific background and the results of clinical studies and discusses the advantages and disadvantages of ACI. LEVEL OF EVIDENCE: Non-systematic Review.

[Clinical management of rotator cuff tears. Current concepts in cell-based therapy strategies]. / Klinische Versorgung von Rupturen der Rotatorenmanschette. Aktueller Stand der Zelltherapie.

Due to the increasing demand for functionality in an aging yet physically active society, the treatment of rotator cuff tears is of ever-growing importance. Despite intensive research efforts, the treatment of degenerative rotator cuff tears, in particular their long-term outcome, is still a challenge. While in recent years the focus was on biomechanics and the technical aspects of rotator cuff reconstruction, attention has now turned to the biological considerations of tendon regeneration. This article highlights the current state of biological rotator cuff augmentation in a clinical setting and provides an insight into and an outlook on the experimental procedures.

Development and validation of a weight-bearing finite element model for total knee replacement.

Total knee arthroplasty (TKA) is a successful procedure for osteoarthritis. However, some patients (19%) do have pain after surgery. A finite element model was developed based on boundary conditions of a knee rig. A 3D-model of an anatomical full leg was generated from magnetic resonance image data and a total knee prosthesis was implanted without patella resurfacing. In the finite element model, a restarting procedure was programmed in order to hold the ground reaction force constant with an adapted quadriceps muscle force during a squat from 20° to 105° of flexion. Knee rig experimental data were used to validate the numerical model in the patellofemoral and femorotibial joint. Furthermore, sensitivity analyses of Young's modulus of the patella cartilage, posterior cruciate ligament (PCL) stiffness, and patella tendon origin were performed. Pearson's correlations for retropatellar contact area, pressure, patella flexion, and femorotibial ap-movement were near to 1. Lowest root mean square error for retropatellar pressure, patella flexion, and femorotibial ap-movement were found for the baseline model setup with Young's modulus of 5 MPa for patella cartilage, a downscaled PCL stiffness of 25% compared to the literature given value and an anatomical origin of the patella tendon. The results of the conducted finite element model are comparable with the experimental results. Therefore, the finite element model developed in this study can be used for further clinical investigations and will help to better understand the clinical aspects after TKA with an unresurfaced patella.

[The German Cartilage Registry (KnorpelRegister DGOU) for evaluation of surgical treatment for cartilage defects: experience after six months including first demographic data]. / Das KnorpelRegister DGOU zur Erfassung von Behandlungsergebnissen nach Knorpeloperationen: Erfahrungen nach 6 Monaten und erste epidemiologische Daten.

The German Cartilage Registry (KnorpelRegister DGOU) has been introduced in October 2013 and aims on the evaluation of patients who underwent cartilage repair for symptomatic cartilage defects. It represents a nation-wide cohort study which has been introduced by the working group "Tissue Regeneration" of the Germany Society of Orthopaedic Surgery and Traumatology and is technically based upon a web-based remote data entry (RDE) system. The present article describes first experiences with the registry including patient and treatment characteristics. Between October 2013 and April 2014, a total of 230 patients who had undergone surgical cartilage repair for symptomatic full-thickness cartilage defects of the knee has been included in the German Cartilage Registry from 23 cartilage repair centres. Mean age was 37.11 years (SD 13.61) and mean defect size was 3.68 cm(2) (SD 0.23). Since the introduction of the KnorpelRegister DGOU the total number of registered patients has increased steadily up to the most recent figure of 72 patients within one month. Patients were treated mainly according to the recommended therapies. The highest percentage in therapy is represented by the bone marrow stimulation techniques (55.02 %) as well as by the autologous chondrocyte transplantation (34.92 %). Unlike the patient collective in the majority of prospective randomised controlled trials, the patient population within the registry shows a high proportion of patients with accompanying pathologies, with an age of more than 50 years at the time of treatment and with unfavourably assessed accompanying pathologies such as an affection of the opposite cartilage surface or a previously resected meniscus. In summary, the technical platform and forms of documentation of the KnorpelRegister DGOU have proved to be very promising within the first six months. Unlike data from other clinical trials, the previous analysis of the patients' data and therapies reflects successfully the actual medical care situation of patients with cartilage defects of the knee joint. This analysis also provides new information on subgroups of patients that have not yet been recorded in the scientific literature. This will be part of the first analysis of clinical treatment data. An expansion of the KnorpelRegister DGOU to patients with cartilage defects of the ankle and hip joints is already decided upon and initialised.

Stress-shielding induced bone remodeling in cementless shoulder resurfacing arthroplasty: a finite element analysis and in vivo results.

Cementless surface replacement arthroplasty (CSRA) of the shoulder was designed to preserve the individual anatomy and humeral bone stock. A matter of concern in resurfacing implants remains the stress shielding and bone remodeling processes. The bone remodeling processes of two different CSRA fixation designs, conical-crown (Epoca RH) and central-stem (Copeland), were studied by three-dimensional (3-D) finite element analysis (FEA) as well as evaluation of contact radiographs from human CSRA retrievals. FEA included one native humerus model with a normal and one with a reduced bone stock quality. Compressive strains were evaluated before and after virtual CSRA implantation and the results were then compared to the bone remodeling and stress-shielding pattern of eight human CSRA retrievals (Epoca RH n=4 and Copeland n=4). FEA revealed for both bone stock models increased compressive strains at the stem and outer implant rim for both CSRA designs indicating an increased bone formation at those locations. Unloading of the bone was seen for both designs under the central implant shell (conical-crown 50-85%, central-stem 31-93%) indicating high bone resorption. Those effects appeared more pronounced for the reduced than for the normal bone stock model. The assumptions of the FEA were confirmed in the CSRA retrieval analysis which showed bone apposition at the outer implant rim and stems with highly reduced bone stock below the central implant shell. Overall, clear signs of stress shielding were observed for both CSRAs designs in the in vitro FEA and human retrieval analysis. Especially in the central part of both implant designs the bone stock was highly resorbed. The impact of these bone remodeling processes on the clinical outcome as well as long-term stability requires further evaluation.

[Experience with medial unicompartmental prostheses with a mobile plateau]. / Erfahrungen mit medialen monokondylären Prothesen mit mobilem Plateau.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) has become an accepted therapy for medial osteoarthritis. The main reasons for its popularity are the minimally invasive surgical technique and the reports of excellent long-term results including high patient satisfaction and good knee joint function especially in younger patients. OBJECTIVES: The purpose of our retrospective study was to evaluate the physical activities of patients who had undergone an Oxford III medial UKA. Special attention was paid to implant positioning and osteoarthritis of the patellofemoral joint. MATERIALS AND METHODS: Of 181 implanted Oxford III prosthesis, 136 (75.1%) could be followed up. The mean age at time of surgery was 65.2 years; the average time of follow-up was 4.2 years. In addition to a physical examination and x-ray, the following scores were obtained: WOMAC (Western Ontario and McMaster Osteoarthritis Index), OKS (Oxford Knee Score), KSS (Knee Society Score), UCLA activity and the Turba score. RESULTS: The majority of the patients (81%) returned to their sporting activity following knee surgery. Higher complication rates or progression of osteoarthritis associated with sporting activities were not observed. The active patients had significantly higher scores for the OKS, KSS, WOMAC, and UCLA scores. The correct implant position, especially avoiding overcorrection to valgus malalignment, is important for good clinical outcome. CONCLUSION: Our results demonstrate that a high degree of patient satisfaction in terms of physical and sporting activity can be achieved using the Oxford III UKA for medial osteoarthritis without an increased risk for complications.

Tissue characteristics in tendon-to-bone healing change after rotator cuff repair using botulinumneurotoxin A for temporary paralysis of the supraspinatus muscle in rats.

We hypothesized that botulinumneurotoxin A (BoNtA) positively influences tissue characteristics at the re-insertion site when used as an adjuvant prior to rotator cuff repair. One hundred and sixty Sprague-Dawley rats were randomly assigned to either a BoNtA or saline-injected control group. BoNtA or saline solution was injected into the supraspinatus muscle one week prior to repair of an artificially created supraspinatus tendon defect. Post-operatively, one subgroup was immobilized using a cast on the operated shoulder while the other had immediate mobilization. Histologically, the fibrocartilage transition zone was more prominent and better organized in the BoNtA groups when compared to the saline control group. In the immediately mobilized BoNtA groups significantly more collagen 2 at the insertion was detected than in the control groups (p<0.05). Fiber orientation of all BoNtA groups was better organized and more perpendicular to the epiphysis compared with control groups. Tendon stiffness differed significantly (p<0.05) between casted BoNtA and casted saline groups. Tendon viscoelasticity was significantly higher (p<0.05) in the immobilized saline groups no matter if repaired with increased or normal repair load. The results of this study suggest that reduction of load at the healing tendon-to-bone interface leads to improved repair tissue properties.

[Post-treatment rehabilitation after autologous chondrocyte implantation: State of the art and recommendations of the Clinical Tissue Regeneration Study Group of the German Society for Accident Surgery and the German Society for Orthopedics and Orthopedic Surgery]. / Nachbehandlung bei der autologen Chondrozytentransplantation: Eine Bestandsaufnahme und Empfehlung der AG Klinische Geweberegeneration der DGU/DGOOC.

BACKGROUND: Over the course of the past two decades autologous chondrocyte implantation (ACI) has become an important surgical technique for treating large cartilage defects. The original method using a periostal flap has been improved by using cell-seeded scaffolds for implantation, the matrix-based autologous chondrocyte implantation (mb-ACI) procedure. MATERIAL AND METHODS: Uniform nationwide guidelines for post-ACI rehabilitation do not exist. A survey was conducted among the members of the clinical tissue regeneration study group concerning the current rehabilitation protocols and the members of the study group published recommendations for postoperative rehabilitation and treatment after ACI based on the results of this survey. RESULTS: There was agreement on fundamentals concerning a location-specific rehabilitation protocol (femoral condyle vs. patellofemoral joint). With regard to weight bearing and range of motion a variety of different protocols exist. Similar to this total agreement on the role of magnetic resonance imaging (MRI) for postsurgical care was found but again a great variety of different protocols exist. CONCLUSIONS: This manuscript summarizes the recommendations of the members of the German clinical tissue regeneration study group on postsurgical rehabilitation and MRI assessment after ACI (level IVb/EBM).

[Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group "Tissue Regeneration" of the German Society of Orthopaedic Surgery and Traumatology (DGOU)]. / Stellenwert der autologen Chondrozytentransplantation (ACT) in der Behandlung von Knorpelschäden des Kniegelenks - Empfehlungen der AG Klinische Geweberegeneration der DGOU.

Autologous chondrocyte transplantation/implantation (ACT/ACI) is an established and recognised procedure for the treatment of localised full-thickness cartilage defects of the knee. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning potential consequences of primary cartilage lesions and the suitable indication for ACI. Based on current evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than 3-4 cm2; in the case of young and active sports patients at 2.5 cm2. Advanced degenerative joint disease is the single most important contraindication. The review gives a concise overview on important scientific background, the results of clinical studies and discusses advantages and disadvantages of ACI.

Comparison of tenocytes and mesenchymal stem cells seeded on biodegradable scaffolds in a full-size tendon defect model.

In order to investigate cell-based tendon regeneration, a tendon rupture was simulated by utilizing a critical full-size model in female rat achilles tendons. For bridging the defect, polyglycol acid (PGA) and collagen type I scaffolds were used and fixed with a frame suture to ensure postoperatively a functional continuity. Scaffolds were seeded with mesenchymal stem cells (MSC) or tenocytes derived from male animals, while control groups were left without cells. After a healing period of 16 weeks, biomechanical, PCR, histologic, and electron microscopic analyses of the regenerates were performed. Genomic PCR for male-specific gene was used to detect transplanted cells in the regenerates. After 16 weeks, central ossification and tendon-like tissue in the superficial tendon layers were observed in all study groups. Biomechanical test showed that samples loaded with tenocytes had significantly better failure strength/cross-section ratio (P < 0.01) compared to MSC and the control groups whereas maximum failure strength was similar in all groups. Thus, we concluded that the application of tenocytes improves the outcome in this model concerning the grade of ossification and the mechanical properties in comparison to the use of MSC or just scaffold materials.

[Does increased tibial slope reduce the wear rate of unicompartmental knee prostheses? An in vitro investigation]. / Reduziert ein erhöhter tibialer Slope den Abrieb bei unikondylären Schlittenprothesen? Eine In-vitro-Untersuchung.

INTRODUCTION: Unicompartmental knee arthroplasty (UKA) has become a standard procedure with good clinical outcome in patients with isolated medial osteoarthritis of the knee. However, the survival rates of UKA are still inferior compared to that of total knee arthroplasty. Aseptic loosening and wear are responsible for more than 50% of revisions. Therefore, this study evaluated the influence of the tibial slope on the wear rate in a medial UKA. MATERIALS AND METHODS: The wear rate of a medial mobile-bearing UKA (Univation® Aesculap, Tuttlingen, Deutschland) was evaluated according to the ISO 14243-1:2002(E) norm with a customized four-station servo-hydraulic knee wear simulator (EndoLab, Thansau, Germany). In the first group, the prostheses was medially implanted with 0° slope (n = 3) and in the second group the prostheses was medially implanted with 8° slope (n = 3). The lateral side was kept constant with 0° in both groups. For each implant, a total of 5.0 million cycles was performed and after every 0.5 million cycles the gravimetric wear rate was determined. RESULTS: The wear rate in the 0° slope group was 3.46 ± 0.59 mg/million cycles and therefore significantly higher than in the 8° slope group with 0.99 ± 0.42 mg/million cycles (p < 0.01). DISCUSSION: An increase in the tibial slope leads to a reduced wear rate in a mobile-bearing UKA. Therefore, at least for this mobile-bearing UKA a higher tibial slope seems favorable to reduce the wear. However, before an optimal position of the tibial slope can be recommended, further investigations are required to evaluate the influence of the tibial slope on other factors, such as the ligament tension or the strain on the lateral compartment.

Development and validation of a new method for the radiologic measurement of the tibial slope.

PURPOSE: The posterior tibial slope has a huge influence on the kinematics of the knee. In several orthopedic interventions such as high tibial osteotomy and unicondylar or bicondylar knee replacement changing, the tibial slope can result in altered knee mechanics. Therefore, an exact preoperative measurement of the posterior tibial slope is mandatory. Several methods are used on conventional radiographs and CT scans, but until now there is no standard validated method. The aim of this study was to compare several methods and imaging techniques to measure the posterior tibial slope and to establish a standard and reliable measurement method by radiography. METHODS: Fourteen knees (seven cadavers) were scanned by a 64-slice CT, a 3T-MRI, and true lateral radiographs were performed. The anatomical references (TPAA = tibial proximal anatomical axis; ATC = anterior tibial cortex; PTC = posterior tibial cortex) and the new computed reference (MPA = mean of PTA and ATC) were compared by short as well as long radiographs, CT scan and MRI. The influence of a malrotation in radiographs of the knees was also analyzed. RESULTS: CT scan and MRI are suitable for the measurement of the medial and lateral posterior tibial slopes, the results of the radiographs varied depending on the method used. The new method (MPA) showed the best correlation to the CT scan (r = 0.997), even on short radiographs (10 cm distal the joint line). CONCLUSION: The measurement of the posterior tibial slope on a short lateral radiograph using the MPA is a reliable method and should be established as a standard. LEVEL OF EVIDENCE: Diagnostic study, Level II.

Scaffold-free 3D cellulose acetate membrane-based cultures form large cartilaginous constructs.

Scaffold-free three-dimensional (3D) cultures provide clinical potential in cartilage regeneration. The purpose of this study was to characterize a scaffold-free 3D membrane-based culture system, in which human articular chondrocytes were cultivated on a cellulose acetate membrane filter, and compare it to pellet and monolayer cultures. Chondrocytes were expanded in monolayer culture for up to 5 passages, transferred to membrane-based or pellet cultures and harvested after 7 or 21 days. The chondrogenic potential was assessed by histology (toluidine blue, safranin-O), immunohistochemistry for collagen type II and quantitative analysis of collagen type II α(1) (COL2A1). Membrane-based cultures (P1) formed flexible disc-like constructs (diameter 4000 µm, thickness 150 µm) with a large smooth surface after 7 days. Positive safranin-O and collagen type II staining was found in membrane-based and pellet cultures at P1-3. Expression of COL2A1 after 7 days was increased in both culture systems compared to monolayer culture up to P3, whereas cells from monolayer > P3 did not redifferentiate. The best results for COL2A1 expression were obtained from membrane-based cultures at P1. After 21 days the membrane-based cultures did not express COL2A1. We concluded that membrane-based and pellet cultures showed the ability to promote redifferentiation of chondrocytes expanded in monolayer culture. The number of cell passages had an impact on the chondrogenic potential of cells. Membrane-based cultures provided the highest COL2A1 expression and a large, smooth and cartilage-like surface. As these are appropriate features for clinical applications, we assume that membrane-based cultures might be of use in cartilage regeneration if they displayed similar results in vivo.

Interleukin-1beta and tumor necrosis factor alpha inhibit chondrogenesis by human mesenchymal stem cells through NF-kappaB-dependent pathways.

OBJECTIVE: The differentiation of mesenchymal stem cells (MSCs) into chondrocytes provides an attractive basis for the repair and regeneration of articular cartilage. Under clinical conditions, chondrogenesis will often need to occur in the presence of mediators of inflammation produced in response to injury or disease. The purpose of this study was to examine the effects of 2 important inflammatory cytokines, interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha), on the chondrogenic behavior of human MSCs. METHODS: Aggregate cultures of MSCs recovered from the femoral intermedullary canal were used. Chondrogenesis was assessed by the expression of relevant transcripts by quantitative reverse transcription-polymerase chain reaction analysis and examination of aggregates by histologic and immunohistochemical analyses. The possible involvement of NF-kappaB in mediating the effects of IL-1beta was examined by delivering a luciferase reporter construct and a dominant-negative inhibitor of NF-kappaB (suppressor-repressor form of IkappaB [srIkappaB]) with adenovirus vectors. RESULTS: Both IL-1beta and TNFalpha inhibited chondrogenesis in a dose-dependent manner. This was associated with a marked activation of NF-kappaB. Delivery of srIkappaB abrogated the activation of NF-kappaB and rescued the chondrogenic response. Although expression of type X collagen followed this pattern, other markers of hypertrophic differentiation responded differently. Matrix metalloproteinase 13 was induced by IL-1beta in a NF-kappaB-dependent manner. Alkaline phosphatase activity, in contrast, was inhibited by IL-1beta regardless of srIkappaB delivery. CONCLUSION: Cell-based repair of lesions in articular cartilage will be compromised in inflamed joints. Strategies for enabling repair under these conditions include the use of specific antagonists of individual pyrogens, such as IL-1beta and TNFalpha, or the targeting of important intracellular mediators, such as NF-kappaB.

Free bone cement fragments after minimally invasive unicompartmental knee arthroplasty: an underappreciated problem.

The minimally invasive implantation of unicompartmental knee arthroplasty (UKA) leads to excellent functional results, but due to the reduced intraoperative visibility the removal of excessive cement may be difficult. In a retrospective study we assessed radiologically the incidence of loose and excess bone cement in 120 UKAs and correlated it to the thickness of the tibial cement layer. In 25 cases loose or attached excess cement was seen. Two of these patients with loose cement bodies required revision surgery. An additional 2 patients not operated at our institution required revision because of pain and loss of motion. The average thickness of the tibial cement layer was 3.1 (1.7-5.0) mm in all the patients. But it was significantly higher in the group with excess cement bodies [3.3 (2.3-5.0) mm] compared to the group without excess cement [3.0 (1.7-4.1) mm] (P < 0.05). Symptomatic free cement bodies need to be removed immediately, if necessary arthroscopically, in order to avoid damage to the implants. To avoid this problem in minimally invasive UKA, intraoperative fluoroscopy, a dental mirror or a nerve hook seem to be useful tools to identify and remove loose or excess cement.