Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelschäden am Kniegelenk. / Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelschäden am Kniegelenk.

The Working Group of the German Orthopedic and Trauma Society (DGOU) on Tissue Regeneration has published recommendations on the indication of different surgical approaches for treatment of full-thickness cartilage defects in the knee joint in 2004, 2013 and 2016. Based upon new scientific knowledge and new developments, this recommendation is an update based upon the best clinical evidence available. In addition to prospective randomised controlled clinical trials, this also includes studies with a lower level of evidence. In the absence of evidence, the decision is based on a consensus process within the members of the working group.The principle of making decision dependent on defect size has not been changed in the new recommendation either. The indication for arthroscopic microfracturing has been reduced up to a defect size of 2 cm2 maximum, while autologous chondrocyte implantation is the method of choice for larger cartilage defects. Additionally, matrix-augmented bone marrow stimulation (mBMS) has been included in the recommendation for defects ranging from 1 to 4.5 cm2. For the treatment of smaller osteochondral defects, in addition to osteochondral transplantation (OCT), mBMS is also recommended. For larger defects, matrix-augmented autologous chondrocyte implantation (mACI/mACT) in combination with augmentation of the subchondral bone is recommended.

Biological Reconstruction of Localized Full-Thickness Cartilage Defects of the Knee: A Systematic Review of Level 1 Studies with a Minimum Follow-Up of 5 Years.

OBJECTIVE: The objective of this study was to evaluate the best available mid- to long-term evidence of surgical procedures for the treatment of localized full-thickness cartilage defects of the knee. DESIGN: Systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of Level 1 randomized clinical trials (RCTs), meta-analyses of RCTs and systematic reviews with a minimum follow-up of 5 years. Data extracted included patient demographics, defect characteristics, clinical and radiological outcomes, as well as treatment failures. RESULTS: Six RCTs and 3 Level 1 systematic reviews were included. Two RCTs compared microfracture (MFx) to periosteum-covered autologous chondrocyte implantation (ACI-P), 1 to matrix-associated ACI (M-ACI) and 2 to osteochondral autograft transplantation (OAT). One study compared OAT to collagen membrane covered ACI (ACI-C). The 3 Level 1 systematic reviews/meta-analyses assessed the outcome of MFx, OAT, and various ACI methods in RCTs. OAT showed significantly better outcomes compared with MFx. In the 2 RCTs comparing ACI-P and MFx, no significant differences in clinical outcomes were seen, whereas significantly better outcomes were reported for M-ACI versus MFx in 1 study including patients with larger defects (5 cm2), and for ACI-C versus OAT in terms of Cincinnati Score. Higher failure rates were reported for MFx compared with OAT and for OAT compared with ACI-C, while no significant differences in failure rates were observed for ACI-P compared to MFx. CONCLUSION: Restorative cartilage procedures (ACI-C or M-ACI and OAT) are associated with better long-term clinical outcomes including lower complication and failure rates when compared with reparative techniques (MFx). Among the restorative procedures, OAT seems to be inferior to ACI especially in larger defects after longer follow-up periods. LEVEL OF EVIDENCE: Level I: Systematic review of Level I studies.

Kinesthetic engagement in Gestalt evaluation outscores analytical 'atomic feature' evaluation in perceiving aging in crystallization images of agricultural products.

There is an increasing interest in a systemic approach to food quality. From this perspective, the copper chloride crystallization method is an interesting asset as it enables an estimation of a sample's 'resilience' in response to controlled degradation. In previous studies, we showed that an ISO-standardized visual evaluation panel could correctly rank crystallization images of diverse agricultural products according to their degree of induced degradation. In this paper we examined the role of contextual sensitivity herein, with the aim to further improve the visual evaluation. To this end, we compared subjects' performance in ranking tests, while primed according to two perceptional strategies (levels: analytical vs. kinesthetic engagement), according to a within-subject design. The ranking test consisted out of wheat and rocket lettuce crystallization images, exhibiting four levels of induced degradation. The perceptual strategy imbuing kinesthetic engagement improved the performance of the ranking test in both samples tested. To the best of our knowledge, this is the first report on the training and application of such a perceptual strategy in visual evaluation.

Degenerative Cartilage Lesions of the Medial Knee Compartment. Associated Factors, Operative Options, and Preliminary Results from the CartilageRegistry DGOU. / Degenerativ bedingte Knorpelschäden im medialen Kniekompartiment. Assoziierte Faktoren, operative Optionen und präliminäre Ergebnisse aus dem KnorpelRegister (DGOU).

PURPOSE: This study was aimed to determine the impact of bioregenerative operations in case of degenerative cartilage lesions within the media knee compartment. MATERIAL AND METHODS: The CartilageRegistry DGOU was founded in 2013. At the deadline August 2016 a total of 1847 patients were included. A total of 23.3% (n = 432) was suffering from a degenerative cartilage lesion in the medial compartment. Follow-up was performed after 6, 12, and 24 months (online evaluation). The patients were asked for their subject feeling as well as the KOOS (Knee injury and Osteoarthritis Outcome Score) was determined. RESULTS: Most of the patients (n = 358) suffered from a single femoral lesion. In 25 cases single tibial and in 49 cases combined defects ("kissing lesions") were addressed by different treatment options: 39.9% autologous chondrocyte transplantation, in 8.1% in combination with a spongiosa plasty. Other treatments were drilling, microfracturing with or without matrix. In 17.9% the surgeons had chosen combined methods. The bioregenerative treatment was combined with a concomitant operation in 39.7% in patients with medial, in 56.0% in patients with a tibial, and in 67.9% in patients with combined defects. The mostly performed additional operations were osteotomies. There were no gender differences at baseline or during follow-up. The history of patients with femoral defects was shorter than in the other groups. The patients with medial defects judged the subjective outcome significant more frequently better after 6, 12, or 24 months compared with the other groups. The KOOS raised from baseline (median 52 points) to a median of 75 after 6, to 78 points after 12, and to 80 points after 24 months. Patients with femoral defects had a better KOOS-outcome in tendency. Revision operations were required in 7.1%. CONCLUSIONS: The treatment of degenerative cartilage lesions (respective early OA) by bioregenerative procedures are well-established measures. These treatments are sufficient to produce high patients' satisfaction and acceptable short/midterm results.

Non-operative treatment of unicompartmental osteoarthritis of the knee: a prospective randomized trial with two different braces-ankle-foot orthosis versus knee unloader brace.

BACKGROUND: The use of an unloader brace is a non-surgical treatment option for patients with medial osteoarthritis (OA). However, many patients do not adhere to brace treatment, because of skin irritation due to the pads at the level of the joint space and bad fit. A new concept to unload the medial compartment of the knee is a foot ankle brace with a lever arm pressing the thigh in valgus. The aim of this prospective randomized trial was to examine the outcomes of patients with medial OA after treatment with a conventional knee unloader brace (Unloader One®) and the new foot ankle orthosis (Agilium FreeStep®). METHODS: For this multicenter trial, 160 patients (> 35 years) with medial OA were randomly allocated to treatment with a conventional knee unloader brace (Unloader One®) or treatment with the new knee OA ankle brace (Agilium FreeStep®). The primary outcome measure was pain (numerical analog scale) at baseline (T0), 8 weeks (T1), and 6 months (T2). Secondary outcome measures were knee function (Knee Injury and Osteoarthritis Outcome Score, KOOS), side effects, additional interventions, and compliance. RESULTS: In both groups, walking pain improved between T0 and T1 and also between T0 and T2 without a significant group difference. For pain at sports, both groups showed a significant improvement between T0 and T2 without a significant group difference. The KOOS subscales symptoms, pain, activity, sport, and quality of life increased significantly in both treatment groups without any significant group differences at T 0, T1, and T2. There was also no significant group difference in additional interventions and weekly or daily brace use. In the Agilium FreeStep® group (23.5%), significantly less patients reported bruises in contrast to the Unloader One® group (66.7%). DISCUSSION: The results of this clinical trial show that the foot ankle brace is as effective as a conventional knee unloader brace for the treatment of medial knee OA with regard to clinical outcome. The rate of side effects such as bruises was significantly lower in the Agilium FreeStep® group. TRIAL REGISTRATION: DRKS00009215, 13.8.2015.

[Biologic Reconstruction of Full Sized Cartilage Defects of the Hip: A Guideline from the DGOU Group "Clinical Tissue Regeneration" and the Hip Committee of the AGA]. / Biologische Rekonstruktion lokalisiert vollschichtiger Knorpelschäden des Hüftgelenks: Empfehlungen der Arbeitsgemeinschaft "Klinische Geweberegeneration" der DGOU und des Hüftkomitees der AGA.

Background Symptomatic pre-arthritic deformities such as femoroacetabular impingement (FAI) or hip dysplasia often lead to localised cartilage defects and subsequently to osteoarthritis. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) and the hip committee of the AGA (German speaking Society for Arthroscopy and Joint Surgery) provides an overview of current knowledge of the diagnosis and surgical treatment of cartilage defects, in order to infer appropriate therapy recommendations for the hip. Methods Review of FAI and resultant cartilage damage in the hip as reported in published study findings in the literature and discussion of the advantages and disadvantages of different surgical procedures to preserve the joint. Results Most published studies on the surgical treatment of cartilage damage in the hip report defects caused by cam-type FAI at the acetabulum. Development of these defects can be prevented by timely elimination of the relevant deformities. At present, current full-thickness cartilage defects are mostly treated with bone marrow-stimulating techniques such as microfracture (MFx), with or without a biomaterial, and matrix-assisted autologous chondrocyte transplantation (MACT). Osteochondral autologous transplantation (OAT) is not the treatment of choice for isolated full-thickness chondral defects at the hip, because of the unfavourable risk-benefit profile. Due to the relatively short history of cartilage repair surgery on the hip, the studies available on these procedures have low levels of evidence. However, it is already becoming obvious that the experience gained with the same procedures on the knee can be applied to the hip as well. For example, limited healing and regeneration of chondral defects after MFx can also be observed at the hip joint. Conclusions The cartilage surface of the acetabulum, where FAI-related chondral lesions appear, is considerably smaller than the weight-bearing cartilage surface of the knee joint. However, as in the knee joint, MACT is the therapy of choice for full-thickness cartilage defects of more than 1.5 - 2 cm2. Minimally invasive types of MACT (e.g. injectable chondrocyte implants) should be preferred in the hip joint. In cases where a single-stage procedure is indicated or there are other compelling reasons for not performing a MACT, a bone marrow-stimulating technique in combination with a biomaterial covering is preferable to standard MFx. For treatment of lesions smaller than 1.5 - 2 cm2 the indication for a single-stage procedure is wider. As with defects in the knee, it is not possible to determine a definite upper age limit for joint-preserving surgery or MACT in the hip, as the chronological age of patients does not necessarily correlate with their biological age or the condition of their joints. Advanced osteoarthritis of the hip is a contraindication for any kind of hip-preserving surgery. Long-term observations and prospective randomised studies like those carried out for other joints are necessary.

[Coincidence and Therapy of Dysalignments and Degenerative Knee Cartilage Lesions. Results from the German CartilageRegistry DGOU]. / Koinzidenz und Therapie von Beinachsdeviationen bei degenerativen Knorpelschäden des Kniegelenks. Ergebnisse aus dem Deutschen KnorpelRegister DGOU.

Purpose This multicenter study was aimed to evaluate the coincidence of degenerative knee cartilage lesions with a varus or valgus dysalignment. Furthermore, the frequency of the combined surgery of cartilage treatments and corrective osteotomies are determined. Material and Methods A total of 1778 patients were included in the German CartilageRegistry (deadline 01.08.2016). In 90.6% of patients, the surgeon calculated the alignment by clinical observation. Varus or valgus conditions were measured radiologically in only 56.0%. This study describes patients who underwent treatment of degenerative cartilage lesions with a complete (clinical and radiological) determination of the alignment. Results The mean mechanical tibia-femur angle (Paley) (mTFA) in clinically neutral extremities was 0.2° (SD 0.6; 0 - 5), in varus cases 5,0° (SD 3.2; 0 - 15), and - 4.7° (SD - 4.0; - 15 - 0) in valgus cases. Varus dysalignment was significantly associated with cartilage lesions in the medial compartment. Valgus dysalignment more frequently occurred in knees with lateral cartilage lesions. Independently of the surgeon's choice of the method of cartilage surgery, in 72.4% of all valgus deformities a corrective osteotomy was performed. Valgus dysalignment was corrected in 50%. Conclusions In about a quarter of all cases, cartilage lesions are associated with a varus (18.9%) or valgus (4.2%) dysalignment. In a number of cases, the treatment of cartilage lesions should include the addressing of these axial deviations. Still the efficacy of this procedure regarding prognosis and clinical outcome is unclear.

A Registry for Evaluation of Efficiency and Safety of Surgical Treatment of Cartilage Defects: The German Cartilage Registry (KnorpelRegister DGOU).

BACKGROUND: The need for documentation in cartilage defects is as obvious as in other medical specialties. Cartilage defects can cause significant pain, and lead to reduced quality of life and loss of function of the affected joint. The risk of developing osteoarthritis is high. Therefore, the socioeconomic burden of cartilage defects should not be underestimated. OBJECTIVE: The objective of our study was to implement and maintain a registry of all patients undergoing surgical treatment of cartilage defects. METHODS: We designed this multicenter registry for adults whose cartilage defects of a knee, ankle, or hip joint are treated surgically. The registry consists of two parts: one for the physician and one for the patient. Data for both parts will be gathered at baseline and at 6-, 12-, 24-, 36-, 60-, and 120-month follow-ups. RESULTS: To date, a wide range of German, Swiss, and Austrian trial sites are taking part in the German Cartilage Registry, soon to be followed by further sites. More than 2124 (as of January 31, 2016) cases are already documented and the first publications have been released. CONCLUSIONS: The German Cartilage Registry addresses fundamental issues regarding the current medical care situation of patients with cartilage defects of knee, ankle, and hip joints. In addition, the registry will help to identify various procedure-specific complications, along with putative advantages and disadvantages of different chondrocyte products. It provides an expanding large-scale, unselected, standardized database for cost and care research for further retrospective studies. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00005617; https://drks-neu.uniklinik-freiburg.de/ drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00005617 (Archived by WebCite at http://www.webcitation.org/6hbFqSws0).

Cartilage repair surgery for full-thickness defects of the knee in Germany: indications and epidemiological data from the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: Treatment of cartilage defects of the knee remains an important issue with high relevance. In October 2013 the German Cartilage Registry (KnorpelRegister DGOU) was initiated in order to study indications, epidemiology and (clinical) outcome of different cartilage repair techniques. The present evaluation of the registry baseline data was initiated to report common practices of cartilage repair surgery in Germany. MATERIALS AND METHODS: 1065 consecutive patients who underwent surgical cartilage treatment of the knee have been included (complete data sets available in 1027 cases; FU rate 96.4 %) between October 1, 2013 and June 30, 2015. Data collection was performed using a web-based RDE System. All data were provided by the attending physician at the time of arthroscopic or open surgery of the affected knee. RESULTS: In 1027 cartilage repair procedures, single defects were treated in 80 % of the cases with the majority of the defects located on the medial femoral condyle, followed by the patella. Degenerative defects grade III or IV according to ICRS were treated in 60 % of the cases and therefore were found more frequently compared to traumatic or post-traumatic lesions. Autologous chondrocyte implantation (ACI) was the most common technique followed by bone marrow stimulation (BMS) and osteochondral transplantation (OCT). While ACI was performed in defects with a mean size of 4.11 cm(2) SD SD 2.16), BMS and OCT (1.51 cm(2), SD 1.19; p < 0.01) were applied in significantly smaller defects (both p < 0.01). Independent of defect size, the ratio of ACI versus BMS applications differed between different defect locations. ACI was used preferably in defects located on the patella. CONCLUSION: The present analysis of data from the German Cartilage Registry shows that the vast majority of cartilage repair procedures were applied in degenerative, non-traumatic cartilage defects. Experts in Germany seem to follow the national and international guidelines in terms that bone marrow stimulation is applied in smaller cartilage defects while cell-based therapies are used for the treatment of larger cartilage defects. In patellar cartilage defects a trend towards the use of cell-based therapies has been observed.

Characteristics and associated factors of Klee cartilage lesions: preliminary baseline-data of more than 1000 patients from the German cartilage registry (KnorpelRegister DGOU).

INTRODUCTION: Knee cartilage lesions are very frequent in arthroscopic surgery. This multi-center-study was aimed to evaluate the distribution and possible associated factors of these pathologies in more than 1000 patients. MATERIALS AND METHODS: The German cartilage registry (KnorpelRegister DGOU) started in 2013. In this paper, we present the baseline-data (distribution of knee cartilage lesions and the demographic data) of more than 1000 cases since the registries' start-up. RESULTS: A total number of 47 centers were involved into this multicenter study. A total of 1071 patients primary were registered. Degenerative knees 629 times (61.8 %) and injured knees 302 times (29.6 %) were involved. In the remaining 89 knees (8.7 %) the genesis of cartilage lesions was unclear. Single defects were observed in 792 cases (77.6 %). Most frequently the medial femoral condyle or the patella was affected. In 78 knees (7.6 %) the main-defect was associated with a defect of the corresponding joint surface. In the remaining cases complex cartilage damages were found. CONCLUSIONS: Our results are in confirmation with other multicenter studies. But these former studies did not differentiate into traumatic and degenerative lesions. Furthermore no characteristics were given regarding to single, kissing or complex lesions. Thus this database will be a sufficient instrument for the investigation of the "natural course" of cartilage lesions, but above all about the effectiveness of different treatment options.

Practical execution of defect preparation prior to surgical cartilage intervention: results from a representative meeting survey among experts.

During a specialised orthopedic meeting held on 'the state of the art in cartilage defect repair', all previously fully-registered participants were requested to participate in an electronic survey by the use of a moderator-presented "Power Point Presentation-based" 9-item questionnaire. The aim of this survey was to assess indication, approach, and treatment execution of cartilage defect debridement prior to planned microfracture (MFX) or autologous chondrocyte implantation (ACI). All participants completed the questionnaire (n = 146) resulting in a return rate of 100 %. An uncertainty exists as to whether the removal of the calcifying layer prior to cartilage repair must be carried out or not. The same was true for the acceptability of subchondral bleeding prior to microfracturing and its handling prior to autologous chondrocyte implantation. There is a degree of unanimity among experts regarding the management of osteophytes and bone marrow edema. In a homogenous society collective of consultants that frequently deal with cartilage defective pathologies, there still remain a significant heterogeneity in selected topics of defect debridement.

Halogenated Dodecaborate Clusters as Agents to Trigger Release of Liposomal Contents.

Halogenated dodecaborates, and especially dodecaiodododecaborate(2-), are found to trigger effectively the release of the contents of phospholipid liposomes, including liposomes containing distearoylphosphatidylcholine and cholesterol, which are used clinically in cancer therapy. The basis of the release is studied through differential scanning calorimetry, cryo-transmission electron microscopy, and atomic force microscopy. Upon administration at high concentrations, drastic morphological changes are induced by the dodecaborates. Their possible use in triggered release is suggested.

Transient grating studies of femtosecond processes in ultra-thin layers of PTCDA.

Elementary processes like energy transfer, charge transport, and exciton diffusion in thin films occur on time scales of femtoseconds. Time-resolved photo-electron spectroscopy, a technique limited to ultra-high vacuum environment and the proper choice of a substrate, has been used to study ultrafast processes in sub-nanometer thin films so far. Herein we show that a transient (population) grating created by the interference of laser pulses can be used to study ultrafast processes in such films under ambient conditions. Our investigations of exciton dynamics in 1.4±0.2 nm and 0.4±0.2 nm thin films, formed by nanocrystals of 3,4,9,10-Perylenetetracarboxylic dianhydride (PTCDA) on glass and mica, show that the dynamics differ with the crystal size, possibly due to the confinement induced changes in the electronic structure. The technique is sensitive enough to investigate the dynamics in systems, where only 20 % of the surface is covered by nano-crystals. We expect such an optical technique that is sensitive enough to study dynamics in few to sub-nanometer thin layers under ambient conditions to become important in investigating ultrafast dynamics on surfaces, interfaces, functionalized materials, organic semiconductors, and quantum phenomena in ordered structures of reduced dimensions, such as quantum dots and graphene sheets.

Function and disruption of DNA methyltransferase 3a cooperative DNA binding and nucleoprotein filament formation.

The catalytic domain of Dnmt3a cooperatively multimerizes on DNA forming nucleoprotein filaments. Based on modeling, we identified the interface of Dnmt3a complexes binding next to each other on the DNA and disrupted it by charge reversal of critical residues. This prevented cooperative DNA binding and multimerization of Dnmt3a on the DNA, as shown by the loss of cooperative complex formation in electrophoretic mobility shift assay, the loss of cooperativity in DNA binding in solution, the loss of a characteristic 8- to 10-bp periodicity in DNA methylation and direct imaging of protein-DNA complexes by scanning force microscopy. Non-cooperative Dnmt3a-C variants bound DNA well and retained methylation activity, indicating that cooperative DNA binding and multimerization of Dnmt3a on the DNA are not required for activity. However, one non-cooperative variant showed reduced heterochromatic localization in mammalian cells. We propose two roles of Dnmt3a cooperative DNA binding in the cell: (i) either nucleofilament formation could be required for periodic DNA methylation or (ii) favorable interactions between Dnmt3a complexes may be needed for the tight packing of Dnmt3a at heterochromatic regions. The complex interface optimized for tight packing would then promote the cooperative binding of Dnmt3a to naked DNA in vitro.

Polyelectrolyte-coated unilamellar nanometer-sized magnetic liposomes.

Superparamagnetic nanoparticles were encapsulated in liposomes prior to the stepwise adsorption of polyelectrolytes of opposite charges commonly known as the layer-by-layer (LbL) technique. Magnetic fields allow a fast separation of coated liposomes from unbound polyelectrolytes. The coated particles were characterized by dynamic light scattering (DLS), cryo-TEM, AFM, and zeta-potential techniques. The presence of magnetic nanoparticles and the polyelectrolyte shell opens the possibility of their magnetic manipulation and targeting by applying an external magnetic or electric field.

A systematic in vitro study of nucleoprotein complexes formed by bacterial nucleoid-associated proteins revealing novel types of DNA organization.

Bacterial nucleoid is a dynamic entity that changes its three-dimensional shape and compaction depending on cellular physiology. While these changes are tightly associated with compositional alterations of abundant nucleoid-associated proteins implicated in reshaping the nucleoid, their cooperation in regular long-range DNA organization is poorly understood. In this study, we reconstitute a novel nucleoprotein structure in vitro, which is stabilized by cooperative effects of major bacterial DNA architectural proteins. While, individually, these proteins stabilize alternative DNA architectures consistent with either plectonemic or toroidal coiling of DNA, the combination of histone-like protein, histone-like nucleoid structuring protein, and integration host factor produces a conspicuous semiperiodic structure. By employing a bottom-up in vitro approach, we thus characterize a minimum set of bacterial proteins cooperating in organizing a regular DNA structure. Visualized structures suggest a mechanism for nucleation of topological transitions underlying the reshaping of DNA by bacterial nucleoid-associated proteins.

Cantilever biosensors.

This review will provide a general introduction to the field of cantilever biosensors by discussing the basic principles and the basic technical background necessary to understand and evaluate this class of sensors. Microfabricated cantilever sensors respond to changes in their environment or changes on their surface with a mechanical bending in the order of nanometers which can easily be detected. They are able to detect pH and temperature changes, the formation of self-assembled monolayers, DNA hybridization, antibody-antigen interactions, or the adsorption of bacteria. The review will focus on the surface stress mode of microfabricated cantilever arrays and their application as biosensors in molecular life science. A general background on biosensors, an overview of the different modes of operation of cantilever sensors and some details on sensor functionalization will be given. Finally, key experiments and current theoretical efforts to describe the surface stress mode of cantilever sensors will be discussed.

Articular cartilage defects in the knee--basics, therapies and results.

Full-thickness defects of the articular cartilage in the knee joint have lower regenerative properties than chondral lesions of the ankle. In order to avoid early osteoarthritis, symptomatic articular cartilage defects in younger patients should undergo biological reconstruction as soon as possible. Various surgical procedures are available to biologically resurface the articular joint line. Numerous animal experiments and clinical studies have shown that early biological reconstruction of circumscribed cartilage defects in the knee is superior to conservative or delayed surgical treatment. This superiority refers not only to defect healing but also to the elimination of changes following secondary osteoarthritis. The various surgical procedures can be differentiated by the range of indications and the final outcome. Additional malalignment, meniscus tears and/or ligament instabilities should be treated simultaneously with the cartilage resurfacing. The mid- and long-term results of the various current techniques are promising, but further modifications and improvements are needed.

Miniaturized planar lipid bilayer: increased stability, low electric noise and fast fluid perfusion.

A microfluidic device was designed allowing the formation of a planar lipid bilayer across a micron-sized aperture in a glass slide sandwiched between two polydimethylsiloxane channel systems. By flushing giant unilamellar vesicles through a 500-microm-wide channel above the hole, we were able to form a planar lipid bilayer across the hole, resulting in a giga-seal. We demonstrate incorporation of biological nanopores into the bilayer. This miniaturized system offers noise recordings comparable to open head-stage noise (under 1 pA RMS at 10 kHz), fast precision perfusion on each side of the membrane and the use of nanoliter analyte volumes. This technique shows a promising potential for automation and parallelization of electrophysiological setups.