In vitro chondrogenically differentiated mesenchymal stem cells (MSCs) have a tendency to undergo hypertrophy, mirroring the fate of transient "chondrocytes" in the growth plate. As hypertrophy would ...result in ossification, this fact limits their use in cartilage tissue engineering applications. During limb development, retinoic acid receptor (RAR) signaling exerts an important influence on cell fate of mesenchymal progenitors. While retinoids foster hypertrophy, suppression of RAR signaling seems to be required for chondrogenic differentiation. Therefore, we hypothesized that treatment of chondrogenically differentiating hMSCs with the RAR inverse agonist, BMS204,493 (further named BMS), would attenuate hypertrophy. We induced hypertrophy in chondrogenic precultured MSC pellets by the addition of bone morphogenetic protein 4. Direct activation of the RAR pathway by application of the physiological RAR agonist retinoic acid (RA) further enhanced the hypertrophic phenotype. However, BMS treatment reduced hypertrophic conversion in hMSCs, shown by decreased cell size, number of hypertrophic cells, and collagen type X deposition in histological analyses. BMS effects were dependent on the time point of application and strongest after early treatment during chondrogenic precultivation. The possibility of modifing hypertrophic cartilage via attenuation of RAR signaling by BMS could be helpful in producing stable engineered tissue for cartilage regeneration.
Background:
A 3-dimensional, scaffold-free, and completely autologous form of chondrocyte transplantation (ACT3D) has been developed and applied in clinical practice in the past decade to overcome ...disadvantages of previous-generation procedures.
Purpose:
To document and analyze the available literature on the results of ACT3D in the treatment of articular chondral lesions in the knee and hip joints.
Study Design:
Systematic review; Level of evidence, 4.
Methods:
All studies published in English addressing ACT3D were identified and included those that fulfilled the following criteria: (1) level 1 through 4 evidence, (2) measures of radiological or functional/clinical outcome, and (3) outcome related to cartilage lesions of the knee and hip joints.
Results:
A total of 10 studies were selected: 2 randomized controlled trials, 1 cohort study, and 7 case series. The studies revealed significant increases in patients’ subjective quality of life, satisfaction, pain reduction, and improvement in joint function at short- to medium-term follow-up. Magnetic resonance imaging-assisted examination and second-look arthroscopy showed a hyaline-like repair tissue with a high degree of defect filling and integration.
Conclusion:
ACT3D shows promising results in the therapy of articular cartilage defects in the knee as well as in the hip, but well-designed, long-term studies are lacking. ACT3D might have relevant advantages over common matrix-associated autologous chondrocyte transplantation products, but systematic evaluation and randomized controlled studies are crucial to verify the potential of this tissue-engineered approach.
Background: The management of pelvic fractures is a significant challenge. Surgical site infection can result in the need for revision surgery, cause functional impairment, and lead to a prolonged ...length of stay and increased treatment costs. Although reports on fracture-related infection (FRI) after pelvic fracture fixation are sparsely reported in the literature, it is a serious complication. This study analysed patients with FRIs after pelvic fracture regarding patient characteristics, treatment strategies, and an evaluation of risk factors for FRI. Methods: In this retrospective single-centre study, FRI was diagnosed based on clinical symptoms of infection and a positive culture of a bacterial infection. Depending on the severity and acuteness of the infection, osseous stabilization was restored either via implant retention (stable implant, no osteolysis), exchange (loose implant or bony defect), or external fixation (recurrence of infection after prior implant retaining revision). Healing of infection was defined as no sign of recurring infection upon clinical, radiological, and laboratory examination in the last follow-up visit. Results: The FRI rate in our patient population was 7.5% (24/316). In 8/24 patients, the FRI occurred within the first three weeks after initial surgery (early) and 16/24 presented with a late onset of symptoms of FRI. A strategy of debridement, antibiotics, and implant retention (DAIR) was successful in 9/24 patients with FRI after pelvic fracture. A total of 10 patients required an exchange of osteo-synthetic implants, whereof three were exchanged to an external fixator. In five patients, we removed the implant because the fracture had already consolidated at the time of revision for infection. A total of 17/24 patients had a poly-microbial infection after a pelvic fracture and 3/24 patients died from post-traumatic multi-organ failure within the first 6 months after trauma. There were no cases of persistent infection within the remaining 21 patients. Conclusions: Although poly-microbial infection is common in FRI after pelvic fracture, the recurrence rate of infection is relatively low. A complex pelvic trauma with significant soft tissue injury is a risk factor for recurrent infection and multiple revisions. A strategy of DAIR can be successful in patients with a stable implant. In cases with recurrent infection or an unstable fracture site, the exchange of implants should be considered.
: Pathologies of the long head of the biceps (LHB) tendon are a common cause of anterior shoulder pain. While the influence of the anatomical morphology of the intertubercular groove (ITG) on the ...development of LHB tendon instability has been investigated with ambiguous results, the relationship of the LHB to ITG anatomy has not yet been considered in this context. The objective of this study was to reliably extract the tendon-to-groove ratio from MRI scans of symptomatic patients and examine its potential influence on the occurrence of certain causes for LHB-associated symptoms.
: In this retrospective study, preoperative MRI scans of 35 patients (mean age of 46 ± 14 years) presenting with anterior shoulder pain and clinical indications of LHB tendinopathy were analyzed in transversal planes. Long and short diameters of the LHB tendon and ITG were measured, cross-sectional areas of the LHB tendon and ITG were calculated from these measurements, and the ratio of cross-sectional areas (LHB/ITG) was introduced. All measurements were repeated independently by three investigators and inter-rater reliability was assessed using intraclass correlation coefficient (ICC). Thereafter, tendon-to-groove ratios were compared in patients with and without intraoperative signs of LHB tendon instability.
: All patients exhibited intraoperative signs of LHB tendinitis, with additional findings including pulley lesions and SLAP lesions. Analysis revealed variations in the dimensions of the LHB tendon and ITG cross sections, with the tendon-to-groove ratio decreasing from 37% at the pulley to 31% at the deepest point of the sulcus. Very good inter-rater reliability was observed for all measurements. The tendon-to-groove ratio did not significantly differ (
> 0.05) in patients with or without pulley lesions or SLAP lesions.
: Our study introduced the novel parameter of the tendon-to-groove ratio of cross-sectional areas as a reproducible parameter for the description of local anatomy in the field of targeted diagnosis of LHB tendon disorders. While our findings do not yet support the predictive value of the tendon-to-groove ratio, they underscore the importance of further research with larger cohorts and control groups to validate these observations.
Vertebral osteomyelitis (VO) often necessitates surgical intervention due to bone loss-induced spinal instability. Anterior column reconstruction, utilizing expandable vertebral body replacement ...(VBR) implants, is a recognized approach to restore stability and prevent neurological compromise. Despite various techniques, clinical evidence regarding the safety and efficacy of these implants in VO remains limited.
A retrospective cohort analysis, spanning 2000 to 2020, was conducted on 24 destructive VO cases at a Level 1 orthopedic trauma center. Diagnosis relied on clinical, radiological, and microbiological criteria. Patient demographics, clinical presentation, surgical interventions, and radiological outcomes were assessed.
The study included 24 patients (62.5% male; mean age 65.6 ± 35.0 years), with 58% having healthcare-associated infections (HAVO). The mean radiological follow-up was 137.2 ± 161.7 weeks. Surgical intervention significantly improved the bi-segmental kyphotic endplate angle (BKA) postoperatively (mean -1.4° ± 13.6°). However, a noticeable loss of correction was observed over time. The study reported a mortality rate of 1/24.
Anterior column reconstruction using expandable VBR effectively improved local spinal alignment in destructive VO. However, the study underscores the necessity for prolonged follow-up and continuous research to refine surgical techniques and postoperative care. Addressing long-term complications and refining surgical approaches will be pivotal as the field progresses.
Background and Objectives: Abdominal trauma among severely injured patients with an injury severity score (ISS) of 16 and above can lead to potentially life-threatening injuries that might need ...immediate surgical intervention. Traumatic injuries to the diaphragm (TID) are a challenging condition often accompanied by other injuries in the thoracoabdominal region. Materials and Methods: We retrospectively analyzed the occurrence and clinical course of TID among severely injured patients treated at our center between 2008 and 2019 and compared them to other groups of severely injured patients without TID. Results: Thirty-five patients with TID and a median ISS of 41 were treated in the period mentioned above. They were predominantly middle-aged men and mostly victims of blunt trauma as a consequence of motor vehicle accidents. A total of 70.6% had left-sided TID, and in 69.6%, the size of defect was larger than 10 cm. The diagnosis was made with computed tomography (CT) in 68.6% of the cases, while in 25.8%, it was made intraoperatively or delayed by a false-negative initial CT scan, and in 5.7%, an intraoperative diagnosis was made without preoperative CT imaging. Surgical repair was mostly conducted via laparotomy, performing a direct closure with continuous suture. A comparison to 191 patients that required laparotomy for abdominal injuries other than TID revealed significantly higher rates of concomitant injuries to several abdominal organs among patients suffering from TID. Compared to all other severely injured patients treated in the same period (n = 1377), patients suffering from TID had a significantly higher median ISS and a longer mean duration of hospital stay. Conclusions: Our findings show that TID can be seen as an indicator of particularly severe thoracoabdominal trauma that requires increased attention from the treatment team so as not to miss relevant concomitant injuries that require immediate intervention.
: Translational large animal models are inevitable to transfer cartilage repair methods into clinical practice. Guidelines for these trials have been published by guiding agencies (FDA, ASTM, EMEA) ...including recommendations for study descriptors and study outcomes. However, practical adherence to these recommendations is not achieved in all aspects. This study includes an assessment of the recommended aspects regarding practical relevance in large animal models for cartilage repair by professionals in the field.
: In an online based survey, 11 aspects regarding study design and 13 aspects regarding study outcome from previously published guidelines were evaluated (0-10 points, with 10 being most important) by study participants. Additionally, the survey contained questions related to professional experience (years), professional focus (preclinical, clinical, veterinarian, industry) and the preferred translational large animal model for cartilage repair.
: The total number of survey participants was 37. Rated as most important for study design parameters was lesion size (9.54 pts., SD 0.80) followed by study duration (9.43 pts., SD 1.21); and method of scaffold fixation (9.08 pts., SD 1.30) as well as depth of the lesion (9.03 pts., SD 1.77). The most important aspects of study outcome were considered histology (9.41 pts., SD 0.86) and defect filling (8.97 pts., SD 1.21), while gene expression was judged as the least important (6.11 pts., SD 2.46) outcome. A total of 62.2% of all participants were researchers, 18.9% clinicians, 13.5% veterinarians and 5.4% industry employees.
: In translational research, recommendations published by guiding agencies receive broad theoretical consensus within the community, including both clinically and preclinically orientated scientists. However, implementation into practical research lacks in major aspects. Ongoing re-evaluation of the guidelines under involvement of all stakeholders and approaches to overcome financial and infrastructural limitations could support the acceptance of the guidance documents and contribute to standardization in the field.
The present study analysed current rehabilitation protocols to investigate whether there is a standard for early rehabilitation after microfracturing (MFX), matrix-assisted cartilage transplantation ...(MACT), and osteochondral autograft transfer (OATS) of the knee joint in clinical routine, and if rehabilitation protocols differ in the repair technique used or the localization of the cartilage defect. The evaluation included rehabilitation criteria such as weight-bearing, range of motion, use of an orthosis, motion therapy, and rehabilitation training during the early rehabilitation phase after MFX, MACT, and OATS of the femorotibial and retropatellar joint space. We analysed 153 rehabilitation protocols after cartilage repair of the knee joint, including 137 protocols for after repair of the main weight-bearing (femorotibial) area and 16 for after retropatellar cartilage repair. Most of the protocols differed significantly according to the location of the repair and the procedure performed. Our findings indicate that full weight-bearing can be achieved significantly faster after MFX (5.6 weeks) and OATS (5.3 weeks) than after MACT of the main weight-bearing zone (6.6 weeks, p < 0.001). In addition, after retropatellar cartilage repair, patients are allowed full weight-bearing after 2.1 weeks compared to the main weight-bearing zone (5.3–6.6 weeks; p < 0.001). No standardized rehabilitation recommendations have been established. The present study shows that rehabilitation needs to be adjusted to the surgical technique and the location of the defect zone, and further investigation is warranted to establish standardized rehabilitation protocols after cartilage repair of the knee joint.
Purpose: Articular cartilage defects are a prevalent consequence of femoroacetabular impingement (FAI) in young active patients. In accordance with current guidelines, large chondral lesions of the ...hip joint over 2 cm2 are recommended to be treated with matrix-associated, autologous chondrocyte transplantation (MACT); however, the conditions in the hip joint are challenging for membrane-based MACT options. Injectable MACT products can solve this problem. The purpose of the trial was to assess clinical and radiological outcomes 24 months after injectable MACT of focal chondral lesions caused by FAI. Methods: We present data of 21 patients with focal cartilage defects of the hip 3.0 ± 1.4 cm2 (mean ± SD), ICRS Grade III and IV caused by CAM-type impingement, who underwent arthroscopic MACT (NOVOCART® Inject) and FAI correction. The outcome was evaluated with the patient-reported outcome instruments iHOT33 and EQ-5D-5L (index value and VAS), whilst graft morphology was assessed based on the MOCART score over a follow-up period of 24 months. Results: The iHOT33 score increased significantly from 52.9 ± 21.1 (mean ± SD) preoperatively to 85.8 ± 14.8 (mean ± SD; p < 0.0001) 24 months postoperatively. The EQ-5D-5L index value (p = 0.0004) and EQ-5D VAS (p = 0.0006) showed a statistically significant improvement as well. MRI evaluation after 24 months showed successful integration of the implant in all patients with a complete defect filling in 11 of 14 patients. Conclusions: Injectable MACT for the treatment of full-thickness chondral lesions of the hip joint due to FAI in combination with FAI correction improved symptoms, function, and quality of life in the treated cohort. Alongside the treatment of the underlying pathology by the FAI correction, the developed cartilage defect can be successfully repaired by MACT, which is of considerable clinical relevance.
Objective: According to current recommendations, large cartilage defects of the hip over 2 cm2 are suggested to undergo autologous chondrocyte transplantation (ACT), while small defects should be ...treated with microfracture. We investigated if patients with small chondral defects of the hip joint (≤100 mm2) actually benefit from microfracture. Design: In this retrospective multicenter cohort study 40 patients with focal acetabular cartilage defects smaller than 100 mm2 and of ICRS grade ≥2 caused by femoroacetabular impingement were included. Twenty-six unrandomized patients underwent microfracture besides treatment of the underlying pathology; in 14 patients cartilage lesions were left untreated during arthroscopy. Over a mean follow-up of 28.8 months patient-reported outcome was determined using the iHOT33 (international hip outcome tool) and the VAS (visual analog scale) for pain. Results: The untreated group showed a statistically significant improvement of the iHOT33 after 12 (p = 0.005), 24 (p = 0.019), and 36 months (p = 0.002) compared to the preoperative score, whereas iHOT33 in the microfracture group did not reveal statistically significant changes over time. There was no significant difference between both groups on any time point. Regarding pain both groups did not show a significant improvement over time in the VAS. Conclusion: The subjective outcome of patients with small cartilage defects of the hip (≤100 mm2) improves 12 months after arthroscopic FAIS surgery without any cartilage treatment. However, no improvement could be seen after microfracture. Therefore, a reserved surgical treatment for small cartilage defects of the hip under preservation of the subchondral bone is recommended especially if a simultaneous impingement correction is performed.
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