SaluCartilage™—ein neuer künstlicher Knorpelersatz für die arthroskopische Behandlung der fokalen Osteonekrose

The treatment of osteochondral defects still remains a therapeutic challenge for the orthopaedic surgeon. Procedures like shaving, débridement, drilling, microfracturing and abrasion arthroplasty just relieve symptoms for a certain period of time or create fibrocartilage tissue with minor mechanical properties. The common autologous osteochondral transplantation technique (OATS) shows encouraging results, nevertheless the morbidity caused by the donor defects as well as by opening a second joint in case of defects of the shoulder, elbow or ankle joint remains an unsolved problem. This report presents a new method of cartilage treatment by implantation of artificial osteochondral substitute made of polyvinyl-alcohol-hydrogel (SaluCartilage?). Advantages are the absence of a donor defect, the possibility of immediate postoperative wheightbearing without extensive rehabilitation as well as the limitation on just one joint to be operated on. First results of 12 patients are being presented with a so far short average follow-up of 2,8 months. Long-term results are expected.     

Mikrofrakturierung und spezifische Rehabilitation zur Behandlung von Arthrose des Kniegelenks

Treatment of osteoarthritis in young and middle-aged patients, in whom joint replacement is usually not appropriate, is a challenge to orthopaedic surgeons. Arthroscopic techniques can help control patients’ symptoms. In particular, the microfracture procedure combined with management of the joint volume and a specific rehabilitation protocol shows good results in patients with osteoarthritis and cartilage defects by resurfacing the defect with a combination of types I and II cartilaginous tissue. Microfracture is a single-staged arthroscopic procedure that can be combined with any other arthroscopic treatment for osteoarthritis of the knee. With an appropriate rehabilitation protocol and techniques for controlling the joint volume, these treatments are very effective for pain relief and functional improvement. The described technique is our choice for initial surgical treatment of osteoarthritis of the knee.     

Early health economic modelling of single‐stage cartilage repair. Guiding implementation of technologies in regenerative medicine

Both the complexity of clinically applied tissue engineering techniques for articular cartilage repair – such as autologous chondrocyte implantation (ACI) – plus increasing healthcare costs, and market competition, are forcing a shift in focus from two‐stage to single‐stage interventions that are more cost‐effective. Early health economic models are expected to provide essential insight in the parameters driving the cost‐effectiveness of new interventions before they are introduced into clinical practice. The present study estimated the likely incremental cost‐effectiveness ratio (ICER) of a new investigator‐driven single‐stage procedure (IMPACT) compared with both microfracture and ACI, and identified those parameters that affect the cost‐effectiveness. A decision tree with clinical health states was constructed. The ICER was calculated by dividing the incremental societal costs by the incremental Quality Adjusted Life Years (QALYs). Costs were determined from a societal perspective. A headroom analysis was performed to determine the maximum price of IMPACT compared with both ACI and microfracture, assuming a societal willingness to pay (WTP) of €30 000/QALY. One‐way sensitivity analysis was performed to identify those parameters that drive the cost‐effectiveness. The societal costs of IMPACT, ACI and microfracture were found to be €11 797, €29 741 and €6081, respectively. An 8% increase in all utilities after IMPACT changes the ICER of IMPACT vs. microfracture from €147 513/QALY to €28 588/QALY. Compared with ACI, IMPACT is less costly, which is largely attributable to the cell expansion procedure that has been rendered redundant. While microfracture can be considered the most cost‐effective treatment option for smaller defects, a single‐stage tissue engineering procedure can replace ACI to improve the cost‐effectiveness for treating larger defects, especially if clinical non‐inferiority can be achieved. Copyright © 2016 John Wiley & Sons, Ltd.     

Healing of articular cartilage defects treated with a novel drug-releasing rod-type implant after microfracture surgery

Microfracture therapy is a widely used technique for the repair of articular cartilage defects because it can be readily performed arthroscopically. However, the regenerated cartilage after microfracture surgery clearly differs from normal articular cartilage. This suggests that the clinical outcome of patients undergoing microfracture therapy could be improved. Dehydroepiandrosterone sulfate (DHEA-S) is known to protect against articular cartilage loss. Therefore, in an effort to achieve cartilage regeneration of high efficacy, we manufactured a DHEA-S-releasing rod-type implant for implantation into the holes produced by microfracture surgery. The polymeric rod-type implant was made of biodegradable poly (d, l-lactide-co-glycolide) (PLGA) and β-tricalcium phosphate to enable controlled release of DHEA-S. The implant was dip-coated with a dilute PLGA solution to prevent the burst release of DHEA-S. The rod-type implant was sufficiently stiff to permit implantation into the holes made by microfracture. DHEA-S was released from the implant for more than four weeks. Furthermore, eight weeks after implantation into rabbit knees, the implants dramatically enhanced cartilage regeneration compared to control. Moreover, the degradation of the implant over the eight weeks from implantation into the knee did not induce any adverse effects. Therefore, this polymeric rod-type implant does not only provide an improvement in microfracture surgery, but also has great potential as a new formulation for drug delivery.     

Rehabilitation following osteochondral injury to the knee

Articular cartilage injuries of the knee can be debilitating if not treated properly. Once an articular cartilage injury is sustained there are a variety of surgical interventions depending on the severity of the injury. The most common of these procedures are: osteochondral autograft transplantation (OATS), autologous chondrocyte implantation (ACI) and microfracture. The rehabilitation outlined in this article is specific to the exact surgical procedure performed and the location in the knee. The outcomes of these procedures are also discussed.     

Osteochondrale autologe Knorpel-Knochen-Transplantation (OATS) in der Behandlung der Talus-Osteonekrose

Autologous osteochondral transplantation represents today one of the most important possibilities for the treatment of talar osteonecrosis and osteochondral defects. Using this technique, cartilage-bone plugs harvested from the ipsilateral proximal femoral condyle are used for autologous transplantation into talar defects. The advantage of this method in comparison to bone marrow stimulating procedures is the restoration of the articular surface with hyaline cartilage of superior biological and biomechanical quality. The transplantation is applicable in defects up to 3 cm² and in patients up to 60 years old. The disadvantages such as the necessity of knee joint arthrotomy and of the malleolar osteotomy are, according to our mid-term data, inferior to the good clinical results. In case of a correct and early indication, autologous osteochondral transplantation today offers the alternative for active patients in the treatment of osteochondral defects of the ankle.     

Respiratory parameters as a surrogate marker for duration of intubation: potential application of automated vital sign collection

Prolonged time during endotracheal tube placement has been associated with poor outcomes, including cardiac arrest and death. For this reason, the accurate measurement of the duration of intubation time is an important metric in studies that evaluate interventions to improve airway outcomes. In the current study we correlated the gaps in routinely measured ventilatory parameters with duration of the intubation procedure to determine if these intervals could be used to accurately calculate the intubation time. Fifty-six random airway management encounters were video recorded along with a continuous video feed of the patient monitor. Intubation event times were measured and correlated with “gap” times of end-tidal carbon dioxide, airway pressure, airway flow, tidal volume, and respiratory rate defined as the disappearance of the parameter at the end of mask ventilation to the reappearance after intubation. Scatter plots were generated for intubation times versus each parameter time gap and correlation coefficients were calculated. Of the 56 recordings 50 of were suitable for analysis. The correlation of the gaps in airway pressure and airway flow correlated best with the duration of intubation (R² = 0.88) and were available on all cases. The gap in measured tidal volume of 39 ± 53 s most closely approximated the actual duration of intubation of 38 ± 28 s, (R² = 0.85, y = x ? 0.87). During intubation, the disappearance gaps in tidal volume, and the airway pressure and flow waveforms highly correlate with the duration of the intubation procedure and may be useful in the evaluation of airway management interventions. However, just as there are limitations to a labor-intensive method of recording airway management timing, there are limitations to using an automated method.     

Nichtmatrixgebundene Chondrozytentransplantation

In cartilage joint defects of adult humans, a strictly limited repair capacity can be observed. Different old methods were able to reduce the patient’s symptoms only for a short time by stimulation of a fibrous repair cartilage. In contrast to this the technique of autologous chondrocyte transplantation (ACT) introduced by Peterson seems to be able to repair cartilage tissue with a high quality of tissue. The clinical results have been stable for more then 10 years. A high revision rate because of the periosteal hypertrophy, a nonstandardized tissue quality, and fibrous tissue at the superficial zone of the repair cartilage are important disadvantages of this method. The use of different scaffolds simplifies the operation, but a lot of important questions in reference to the effectiveness and the cell-biomaterial interaction remained unanswered. Using two different clinical scores, our own study compares the clinical results of ACT with a periosteal flap and ACT with a collagen membrane (ChondroGide) followed up for 2 years.     

Arthroskopie—qualifizierte Stadieneinteilung der osteochondralen Läsion (OCL) am Knie

Chondral or osteochondral defects can be painful and disabling, have a poor capacity for repair, and may predispose patients for osteoarthritis. In the past, articular cartilage lesions have been treated by subchondral bone abrasions or drilling at the site of focal damage with procedures popularized by Pridie and Johnson. New surgical procedures that aim to reestablish hyaline cartilage have been introduced and the results seem promising. In 1992 we introduced a new classification system for osteochondral lesions of the knee, based on the technique of magnetic resonance imaging and arthroscopic view. Stage 1 shows contusion of the cartilage and minimal depressed osteochondral fracture including bone bruises, stage 2 marking of the intact cartilage, the osteochondral fragment is still attached by an osseous bridge, stage 2 A has no, stage 3 has detached non-displaced fragment, while stage 3 A shows a vital and vascularised fragment and in stage 3 B the fragment is necrotic and the cartilage is weak and degraded (crab-meat like). In stage 4 the fragment is detached, while stage 4 A shows a vital fragment. The new stage 5 includes bone cysts seen in the femoral condyle, the patella and especially in the talar dome, the final situation of a osteochondral lesions.     

关节镜下关节清理联合缺损区微骨折术治疗膝关节软骨缺损疗效观察

目的：探析关节镜下关节清理联合缺损区微骨折术治疗膝关节软骨缺损的临床疗效。方法选取宜宾市第二人民医院2011年3月至2012年6月收治的膝关节全层软骨缺损患者52例,根据美国特种外科医院（HSS）膝关节评分和Tegner评分标准综合评价术后的临床疗效,术后随访6～12个月。结果患者经治疗后, Tegner平均评分由（3．26＆#177;1．60）分升高到（6．53＆#177;1．25）分,差异有统计学意义（P＜0．05）;HSS平均评分由60．36分升高到91．28分,差异有统计学意义（ P＜0．05）。结论关节镜下关节清理联合缺损区微骨折术用于治疗膝关节软骨缺损,疗效确切,微创,安全性高,术后并发症少,可提高预后质量,值得临床推广使用。     

Scaffold‐free cartilage subjected to frictional shear stress demonstrates damage by cracking and surface peeling

Scaffold‐free engineered cartilage is being explored as a treatment for osteoarthritis. In this study, frictional shear stress was applied to determine the friction and damage behaviour of scaffold‐free engineered cartilage, and tissue composition was investigated as it related to damage. Scaffold‐free engineered cartilage frictional shear stress was found to exhibit a time‐varying response similar to that of native cartilage. However, damage occurred that was not seen in native cartilage, manifesting primarily as tearing through the central plane of the constructs. In engineered cartilage, cells occupied a significantly larger portion of the tissue in the central region where damage was most prominent (18 ± 3% of tissue was comprised of cells in the central region vs 5 ± 1% in the peripheral region; p < 0.0001). In native cartilage, cells comprised 1–4% of tissue for all regions. Average bulk cellularity of engineered cartilage was also greater (68 × 10³ ± 4 × 10³ vs 52 × 10³ ± 22 × 10³ cells/mg), although this difference was not significant. Bulk tissue comparisons showed significant differences between engineered and native cartilage in hydroxyproline content (8 ± 2 vs 45 ± 3 µg HYP/mg dry weight), solid content (12.5 ± 0.4% vs 17.9 ± 1.2%), shear modulus (0.06 ± 0.02 vs 0.15 ± 0.07 MPa) and aggregate modulus (0.12 ± 0.03 vs 0.32 ± 0.14 MPa), respectively. These data indicate that enhanced collagen content and more uniform extracellular matrix distribution are necessary to reduce damage susceptibility. Copyright © 2014 John Wiley & Sons, Ltd.     

Characterization of plasma fibronectin for migration,proliferation, and differentiation on human articular chondrocytes

Plasma fibronectin (pFN) plays a crucial role in wound healing by binding to integrins and inducing cell migration. It is known to induce the migration and proliferation of mesenchymal progenitor cells in vitro, which play a key role during microfracture in cartilage repair. Endogenous chondrocytes from the native cartilage of the defect rim might aid in cartilage repair. In this study, the effect of pFN on proliferation, migration, and differentiation was tested on human articular chondrocytes. Results showed that treatment with pFN increased the migration of chondrocytes in a range of 1–30 μg/ml as tested with no effect on proliferation. TGFβ3‐induced chondrogenesis was not affected by pFN. Especially, gene expression of matrix metalloproteinases was not increased by pFN. Plasma FN fragmentation due to storage conditions could be excluded by SDS‐PAGE. Moreover, bioactivity of pFN did not alter during storage at 4°C and 40°C for up to 14 days. Taken together, pFN induces the migration but not proliferation of human articular chondrocytes with no inhibitory effect on chondrogenic differentiation. Additionally, no loss of activity or fragmentation of pFN was observed after lyophilization and storage, making pFN an interesting bioactive factor for chondrocyte recruitment.     

Pressure overloaded right ventricles: a multicenter study on the importance of trabeculae in RV function measured by CMR

Cardiac magnetic resonance (CMR) imaging is the preferred method to measure right ventricular (RV) volumes and ejection fraction (RVEF). This study aimed to determine the impact of excluding trabeculae and papillary muscles on RV volumes and function in patients with RV pressure and/or volume overload and healthy controls and its reproducibility using semi-automatic software. Eighty patients (pulmonary hypertension, transposition of the great arteries after arterial switch operation and after atrial switch procedure and repaired Tetralogy of Fallot) and 20 controls underwent short-axis multislice cine CMR. End diastolic volume (EDV), end systolic volume (ESV), RV mass and RVEF were measured using 2 methods. First, manual contour tracing of RV endo- and epi-cardial borders was performed. Thereafter, trabeculae were excluded from the RV blood volume using semi-automatic pixel-intensity based software. Both methods were compared using a Student T test and 25 datasets were re-analyzed for reproducibility. Exclusion of trabeculae resulted in significantly decreased EDV; ranging from ?5.7 ± 1.7 ml/m² in controls to ?29.2 ± 6.6 ml/m² in patients after atrial switch procedure. RVEF significantly increased in all groups, ranging from an absolute increase of 3.4 ± 0.8 % in healthy controls to 10.1 ± 2.3 % in patients after atrial switch procedure. Interobserver agreement of method 2 was equal to method 1 for RVEDV, RVESV and RVEF and superior for RV mass. In patients with overloaded RVs exclusion of trabeculae from the blood volume results in a significant change in RV volumes, RVEF and RV mass. Exclusion of trabeculae is highly reproducible when semi-automatic pixel-intensity based software is used.     

Evaluation of apparent fracture toughness of articular cartilage and hydrogels

Recently, biomaterials‐based tissue‐engineering strategies, including the use of hydrogels, have offered great promise for repairing articular cartilage. Mechanical failure testing in outcome analyses is of crucial clinical importance to the success of engineered constructs. Interpenetrating networks (IPNs) are gaining more attention, due to their superior mechanical integrity. This study provided a combination testing method of apparent fracture toughness, which was applied to both articular cartilage and hydrogels. The apparent fracture toughnesses of two groups, hydrogels and articular cartilage, were evaluated based on the modified single‐edge notch test and ASTM standards on the single‐edge notch test and compact tension test. The results demonstrated that the toughness for articular cartilage (348 ± 43 MPa/mm^½) was much higher than that for hydrogels. With a toughness value of 10.8 ± 1.4 MPa/mm^½, IPNs of agarose and poly(ethylene glycol) diacrylate (PEG‐DA) looked promising. The IPNs were 1.4 times tougher than PEG‐DA alone, although still over an order of magnitude less tough than cartilage. A new method was developed to evaluate hydrogels and cartilage in a manner that enabled a more relevant direct comparison for fracture testing of hydrogels for cartilage tissue engineering. Moreover, a target toughness value for cartilage of using this direct comparison method has been identified (348 ± 43 MPa/mm^½), and the toughness discrepancy to be overcome between hydrogels and cartilage has been quantified. Copyright © 2014 John Wiley & Sons, Ltd.     

Knee joint preservation with autologous cartilage implantation

DAMAGE TO THE BODY'S JOINT CARTILAGE is becoming a disabling problem for Americans as they live longer and remain active.TRADITIONALLY, ARTICULAR DAMAGE has been treated with arthroscopic debridement and microfracture, abrasion arthroplasty, and osteochondral autograft. Orthopedic surgeons now can offer patients a new option: autologous cartilage implantation (ACI), in which cultured autologous cartilage cells are used to repair and promote growth in cartilage defects.USE OF ACI PRESERVES the articular surfaces of the knee in patients with early onset osteoarthritis, decreases pain, maintains patients' quality of life, and delays possible total joint replacement.     

Regenerative effects of human chondrocyte sheets in a xenogeneic transplantation model using immune‐deficient rats

Although cell transplantation has attracted much attention in regenerative medicine, animal models continue to be used in translational research to evaluate safety and efficacy because cell sources and transplantation modalities are so diverse. In the present study, we investigated the regenerative effects of human chondrocyte sheets on articular cartilage in a xenogeneic transplantation model using immune‐deficient rats. Osteochondral defects were created in the knee joints of immune‐deficient rats that were treated as Group A, untreated (without transplantation); Group B, transplantation of a layered chondrocyte sheet containing 5.0 × 10⁵ cells (layered chondrocyte sheet transplantation); Group C, transplantation of a synoviocyte sheet containing 5.0 × 10⁵ cells (synoviocyte sheet transplantation); or Group D, transplantation of both a synoviocyte sheet plus a layered chondrocyte sheet, each containing 5.0 × 10⁵ cells (synoviocyte sheet plus layered chondrocyte sheet transplantation). Histological evaluation demonstrated that Group B showed cartilage regeneration with hyaline cartilage and fibrocartilage. In Groups C and D, the defect was filled with fibrous tissue but no hyaline cartilage. Transplanted cells were detected at 4 and 12 weeks after transplantation, but the number of cells had decreased at 12 weeks. Our results indicate that layered chondrocyte sheet transplantation contributes to articular cartilage regeneration; this model proved useful for evaluating these regenerative effects.     

Stellenwert der Knochenmarkstimulation

Introduction

Bone marrow stimulation is a well-established technique for cartilage reconstruction. Over the last decades abrasion arthroplasty has been widely replaced by microfracturing. Furthermore, drilling techniques and subchondral needling are used to access deeper blood channels and have been investigated during the last years.

Results

Studies with the highest evidence levels have identified several factors which affect the clinical outcome after bone marrow stimulation for the treatment of cartilage defects of the knee; however, these influencing factors may be specific for the knee as other joints differ in biomechanics, loading and cartilage structure. In contrast, bone marrow stimulation promotes a low tissue quality in all joints which is predominantly fibrous in nature and with a variable content of hyaline-like cartilage.

Conclusion

Treatment using cartilage repair requires a careful patient selection by a specialized surgeon that considers the indication criteria, joint-specific biomechanical aspects and the reduced loading capacity of the newly formed tissue.

     

A new distraction arthroplasty device using magnetic force; a cadaveric study

Background

It is difficult for an articular cartilage injury to repair spontaneously. There are many procedures for treating cartilage injury, however there is no standard procedure for middle-aged patients who have diffuse knee osteoarthritis, especially of the lateral compartment. Therefore, Ochi developed a new distraction device that uses magnetic power to enlarge a joint space and promote cartilage regeneration with microfracture. The purpose of this study is to evaluate this new distraction arthroplasty system by using the cadaveric knee.

Methods

This study used ten knees from six cadavers that were embalmed by Thiel's methods. The medial and lateral joint space was measured by AP radiographic view before and after distraction, and after weight-bearing to evaluate the joint distraction. The contact pressure of the medial and lateral compartments at the knee extension position by using a prescale film system was measured before and after weight-bearing with a 15 or 30-kg weight-bearing load to evaluate the effectiveness of this device.

Findings

The lateral joint space significantly increased from the pre-distraction to the post-distraction; however, it did not change significantly between post-distraction and post-weight-bearing.With a 15 or 30-kg weight-bearing load, the contact pressure of the lateral compartment significantly decreased from the pre-distraction to the post-distraction.

Interpretation

The most important advantage of this device is that it maintains a continuous distraction tension and enables almost the full range of motion of the knee. We believe that joint distraction by using magnetic force can be a promising option for cartilage injury in middle-aged patients.     

SaluCartilage™—ein künstlicher Knorpelersatz für die minimal-invasive Behandlung osteochondraler Defekte

Articular cartilage defects that are symptomatic represent a clinical challenge. Symptomatic cartilage defects can lead to premature ostearthritis. Although there are different treatment options available, best therapy of osteochondral defects is still controversial. Synthetic cartilage represents a new surgical option for osteochondral resurfacing of focal osteochondral defects. In a prospective case-control-study 5 patients were enrolled. The early results concerning pain relief and joint function are promising. However, there is a need for a longer observation study including more patients from different centers to find out the indications, limits and disadvantages of this new treatment option.     

Evaluation of point-of-care analyzers’ ability to reduce bias in conductivity-based hematocrit measurement during cardiopulmonary bypass

Most point-of-care testing analyzers use the conductivity method to measure hematocrit (hct). During open-heart surgery, blood-conductivity is influenced by shifts in electrolyte and colloid concentrations caused by infusion media used, and this may lead to considerable bias in the hct measurement. We evaluated to what extent different analyzers correcting for 0, 1, 2, or 3 factors, respectively, compensated for this electrolyte/colloid interference: (1) the conductivity method with no correction (IRMA), (2) with a [Na⁺]-correction (GEM Premier 3000), (3) with a [Na⁺]/[K⁺]-correction (i-STAT), and (4) with a [Na⁺]/[K⁺]-correction in combination with an algorithm that estimates the protein dilution [i-STAT in cardiopulmonary bypass (CPB)-mode]. Bias in hct was measured during three consecutive stages of a CPB procedure: (I) before CPB, (II) start of CPB and (III) after cardioplegia. In order of high to low electrolyte/colloid interference: the analyzer with no correction, [Na⁺]-correction, [Na⁺/]/[K⁺]-correction, and [Na⁺/]/[K⁺]/estimated protein-correction showed a change of bias from stage I to stage III of ?3.9 ± 0.5, ?3.4 ± 0.4, ?2.1 ± 0.5, ?0.3 ± 0.5 %. We conclude that correcting for more parameters (Na⁺, K⁺, estimated protein) gives less bias, but residual bias remains even after [Na⁺/]/[K⁺]/estimated protein-correction. This suggests that a satisfactory algorithm should also correct for other colloidal factors than protein.