One-stage focal cartilage defect treatment with bone marrow mononuclear cells and chondrocytes leads to better macroscopic cartilage regeneration compared to microfracture in goats

SummaryObjectiveThe combination of chondrocytes and mononuclear fraction (MNF) cells might solve the expansion induced dedifferentiation problem of reimplanted cells in autologous chondrocytes implantation as sufficient cells would be available for direct, one-stage, implantation. Earlier in vitro work already showed a positive stimulation of cartilage specific matrix production when chondrocytes and MNF cells were combined. Therefore, this study aimed to evaluate cartilage regeneration using a one-stage procedure combining MNF cells and primary chondrocytes for the treatment of focal cartilage lesions in goats compared to microfracture treatment.DesignFreshly created focal cartilage defects were treated with either a combination of chondrocytes and MNF cells embedded in fibrin glue or microfracture treatment. After 6 months follow-up local regeneration as well as the general joint cartilage health were evaluated using validated scores and biochemical assays.ResultsMacroscopic (P = 0.015) scores for the cartilage surface at the treated defect were, after 6 months, significantly higher for the chondrocyteMNF treatment compared to microfracture-treated defects, but microscopic scores were not (P = 0.067). The articulating cartilage showed more (P = 0.005) degeneration following microfracture treatment compared to chondrocyteMNF treatment. Biochemical glycosaminoglycans (GAG) evaluation did not reveal differences between the treatments. Both treatments had resulted in a slight to moderate cartilage degeneration at other locations in the joint.ConclusionIn conclusion, treatment of focal articular cartilage lesions in goats using a combination of MNF cells from bone marrow and unexpanded chondrocytes leads to better macroscopic regeneration compared to microfracture, however needs further fine-tuning to decrease the negative influence on other joint compartments

Cartilage collagen structure upon knee joint distraction and high tibial osteotomy as measured with T2-mapping MRI - post-hoc analyses of two RCTs

Objective High tibial osteotomy (HTO) and knee joint distraction (KJD) are joint-preserving treatments for knee osteoarthritis (OA) that have shown good clinical results and cartilage thickness increase. In this exploratory study, cartilage T2 relaxation times, as a measure of collagen structure, are evaluated after both treatments, and compared to natural OA progression. Design Ten patients indicated for total knee arthroplasty (TKA) were treated with KJD (KJDTKA). Thirty patients indicated for HTO were treated with KJD (KJDHTO; n = 10) or HTO (n = 20). 3T T2-mapping MRI scans were performed before and one (KJD groups only) and two years after treatment, from which cartilage was segmented and the volume and T2 relaxation times were calculated. Patients were matched with untreated patients from the Osteoarthritis Initiative (OAI) to compare the change in T2 values over time. Results KJDHTO (n = 8) and HTO (n = 17) patients both showed statistically significant increases in T2 values (worsening) but no volume changes. KJDTKA patients (n = 8) only showed a tendency for (first-year) T2 value increase, and a significant volume increase in the most affected compartment (MAC). There were no significant differences between the three groups. All treated patients combined showed a significantly higher increase in T2 times than untreated patients from the OAI for both femur and tibia. Conclusions KJD and HTO cause an increase in cartilage T2 relaxation times, which could indicate loss or reorganization of collagen structure integrity. In TKA-indicated KJD patients, this goes paired with volume increase, indicating it may be the result of maturation of newly formed cartilage

Metal implants in treatment of cartilage defects

Localized cartilage defects in the knee are associated with disability and symptoms such as joint pain, locking phenomena and reduced or disturbed function. Moreover, these defects predispose to severe forms of osteoarthritis. The surgical treatment of localized cartilage defects is usually aimed at stimulation of biological repair, including subchondral perforation and autologous chondrocyte transplantation. Although the biological repair treatment modalities are well established, the have limitations. Often, fibrous tissue is formed, which is frequently followed by progressive joint degeneration. A proposed alternative for the treatment of localized cartilage defects is the use of defect-sized metal implants. The central aim of this thesis was to better understand the role and limitations of using small metal (femoral condyle) implants for the treatment of cartilage defects in the knee joint as well as to investigate the surgical possibilities for replacement of a larger cartilage surface (the medial tibial plateau). This was evaluated using different materials (cobalt-chromium and oxidized zirconium) in different animal models (rabbit and goat) by applying validated outcome tools. Both rabbit and goat studies investigating a metal implant as a treatment for a femoral condyle cartilage defect showed encouraging results and raise other research questions. First, the implants of either material were firmly osseointegrated and biocompatible. It was shown that a flush positioning is essential in a rabbit knee, but this has not been investigated in a goat knee. Perhaps a larger sized implant in a goat (or human) knee should be placed different. This is still to be investigated. Furthermore, it remains unclear which bearing material is the best performer against the opposing cartilage when used as a small implant, although previous in vitro studies were favorable to OxZr. Perhaps, the femoral condyle implant model is not sensitive enough to differentiate. Other, less hard materials (with equivalent friction characteristics) should be investigated as well. All in all, caution is warranted when using small metal implants as a treatment for localized cartilage defects in a human knee joints. A major finding in these studies was the generalized cartilage degeneration irrespective of the treatment. This degeneration was not only found after treatment with a metal implant, but also after treatment with the microfracture technique, which was included as a control group. This microfracture technique is one of the frequently used treatment modalities for a localized cartilage defect. This aspect of the microfracture technique has not been given full attention in previous research. Furthermore, the current tibial plateau replacement model might be a viable tool in the evaluation of the applicability of defined hemiarthroplasty implants. Since only one bearing material (cobalt-chromium) was investigated in this study, it remains unclear whether the model is sensitive enough to discriminate between candidate materials. The implant was firmly fixed and allowed for unlimited weight bearing and movement of the knee, but considerable opposing cartilage degeneration was induced, which raises caution as to its application in the human setting

Pain following primary total knee replacement: Causes, diagnosis and treatment

De plaatsing van een totale knieprothese (TKP) is een succesvolle ingreep bij patiënten met invaliderende gonartrose. Ondanks de goede resultaten is er een grote groep patiënten die niet tevreden is na de ingreep. Mannen, jonge patiënten en patiënten met chronische pijn zijn vaker tevreden na een TKP-plaatsing, evenals patiënten met een hogere sociale status, betere mentale gesteldheid en lagere preoperatieve pijnscores.\ud De diagnostiek bij patiënten met pijn na een TKP-plaatsing is arbeidsintensief en dient op een systematische wijze te worden uitgevoerd. Behandeling van de pijn verschilt per individu en loopt uiteen van pijnstilling en fysiotherapie tot revisie van de TKP. Er zijn weinig gegevens bekend over het aantal patiënten bij wie de pijn na behandeling daadwerkelijk vermindert

Reliability, reproducibility and variability of the traditional Histologic/Histochemical Grading System vs the new OARSI Osteoarthritis Cartilage Histopathology Assessment System

SummaryObjectiveFor many years, the Histologic/Histochemical Grading System (HHGS) for osteoarthritis monitoring has been used as a histological scoring system for the quality of cartilage. There are, however, some limitations using this grading system. The goal of the investigation presented in this paper was to examine the hypothesized advantage of the recently introduced Osteoarthritis Research Society International (OARSI) Cartilage Histopathology Assessment System (OOCHAS) as compared to the most frequently used HHGS by means of reliability, reproducibility, and variability evaluation as well as the correlation analysis between the two systems in goat knee articular cartilage.MethodsNine hundred and thirty-six sections of Dutch Milk goat articular knee cartilage were scored using light microscopy. Three observers applied the HHGS for all sections and subsequently, the OOCHAS. The same scoring procedure was repeated after a minimum interval of 1 week. For each system the reliability, reproducibility and variability as well as the correlation between both systems were determined.ResultsThe reliability of the OOCHAS was higher as compared to the HHGS. Both the HHGS as well the OOCHAS have an excellent intra- and inter-observer reproducibility and variability and a good positive correlation between the scores.ConclusionsAlthough the HHGS has proven to be an excellent tool for histological scoring of cartilage quality, we recommend the OOCHAS as the premium choice while stressing the importance of further research investigating the correlation of the histological results to macroscopic and biochemical parameters

Current clinical practice of knee osteotomy in the Netherlands

Background: Realignment osteotomies is gaining popularity amongst Dutch orthopaedic surgeons. Exact numbers and used standards in clinical practice concerning osteotomies are unknown due to the absence of a national registry. The aim of this study was to inves-tigate the national statistics of performed osteotomies, utilized clinical workups, surgical techniques, and post-operative rehabilitation standards in the Netherlands. Method: Dutch orthopaedic surgeons, all members of the Dutch Knee Society, received a web-based survey between January and March 2021. This electronic survey contained 36 questions, subdivided into: general surgeon-related information, number of performed osteotomies, inclusion of patients, clinical workup, surgical techniques, and post-operative management. Results: 86 orthopaedic surgeons filled in the questionnaire, of whom 60 perform realign-ment osteotomies around the knee. All the 60 responders (100%) perform high tibial osteo-tomies and 63.3% additionally perform distal femoral osteotomies, while 30% perform double level osteotomies. Discrepancies in surgical standards were reported regarding to inclusion criteria, clinical workup, surgical techniques, and post-operative strategies. Conclusions: In conclusion, this study got more insight in knee osteotomy clinical practices as applied by Dutch orthopaedic surgeons. However, there are still important discrepancies which pleads for more standardization based on available evidence. A (inter)national knee osteotomy registry, and even more so, a (inter)national registry for joint preserving surgeries could be helpful to achieve more standardization and treatment insights. Such a registry could improve all aspects of osteotomies and its combinations with other joint-preserving interventions towards evidence for personalised treatments. (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Cartilage repair strategies in the knee according to Dutch Orthopedic Surgeons: a survey study

BackgroundThis study surveyed Dutch orthopedic surgeons on the management of cartilage defects in the knee and the adherence to the recently updated Dutch knee cartilage repair consensus statement (DCS).MethodsA web-based survey was sent to 192 Dutch knee specialists.ResultsThe response rate was 60%. Microfracture, debridement and osteochondral autografts are performed by the majority, 93%, 70% and 27% of respondents, respectively. Complex techniques are used by 80%) but also in 2-3 cm(2) (by > 40%). Concomitant procedures, e.g., malalignment corrections, are performed by 89%. Twenty-one percent of surgeons treat patients aged 40-60 years. Microfracture, debridement and autologous chondrocyte implantation are not considered to be highly affected by age > 40 years by any of the respondents (0-3%). Moreover, for the middle-aged there is a large spread in treatments considered. In case of loose bodies, the majority (84%) only performs refixation in the presence of attached bone.ConclusionSmall cartilage defects in ideal patients may be well treated by general orthopedic surgeons. The matter becomes complicated in older patients, or in case of larger defects or malalignment. The current study reveals some knowledge gaps for these more complex patients. Referral to tertiary centers might be indicated, as is stated by the DCS, and this centralization should enhance knee joint preservation. Since the data from present study are subjective, registration of all separate cartilage repair cases should fuel objective analysis of clinical practice and adherence to the DCS in the future

Cartilage degeneration in the goat knee caused by treating localized cartilage defects with metal implants

SummaryObjectiveThe purpose of the current study was to investigate the feasibility of applying defect-size femoral implants for the treatment of localized cartilage defects in a 1-year follow-up model.MethodsIn 13 goats, a medial femoral condyle defect was created in both knees. Defects were randomly treated by immediate placement of an oxidized zirconium (OxZr) (n=9) or cobalt–chromium (CoCr) implant (n=9) or left untreated (n=8). Six un-operated knee joints served as a control. Animals were sacrificed at 52 weeks. Joints were evaluated macroscopically. Cartilage quality was analyzed macroscopically and microscopically and cartilage repair of untreated defects was scored microscopically. Glycosaminoglycan (GAG) content, release and synthesis were measured in tissue and medium. Implant osseointegration was measured by automated histomorphometry.ResultsCartilage repair score of the defects was 13.3±3.0 out of 24 points (0=no repair, 24=maximal repair). Articular evaluation scores decreased (indicative of degeneration) in untreated defects and in defects treated with either implant (P<0.05). Macroscopical, microscopical and biochemical analysis showed that the presence of untreated defects and the implants caused considerable degeneration of medial tibial plateau, and to a lesser extent of the lateral compartment. Mean bone-implant contact was extensive and not different between materials (39.5±28.1% for OxZr and 42.3±31.5% for CoCr) (P=0.873).ConclusionsConsiderable cartilage degeneration was induced in the articulating cartilage of the medial tibial plateau 1 year after creating an osteochondral defect in the medial femoral condyle. Treating this defect with a small metal implant, made of either OxZr or CoCr, could not prevent this degeneration. Further optimization of defect-size implants and their placement is required to make this the therapy of choice for the treatment of local cartilage defects