Factors Influencing Long-term Outcomes After Matrix-Induced Autologous Chondrocyte Implantation: Long-term Results at 10 Years.

BACKGROUND: Matrix-induced autologous chondrocyte implantation (MACI), the third-generation of the technique, is an established procedure for the treatment of focal cartilage defects in the knee. However, the literature lacks long-term results of MACI with good statistical power. PURPOSE: To determine long-term survival and patient-reported outcomes (PROs) in a representative cohort and to identify patient- and surgery-related parameters that may influence long-term clinical outcomes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 103 patients were clinically evaluated at the current follow-up of 8.1 years (range, 5-11.9 years). PRO measures (PROMs) included the Knee injury and Osteoarthritis Outcome Score (KOOS), EQ-5D, visual analog scale for pain, and Tegner Activity Scale. Magnetic resonance imaging results were evaluated by using the AMADEUS (area measurement and depth and underlying structures) and MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 knee score classification systems. Potential factors influencing PROs were first identified univariately and investigated in a multivariate regression model. RESULTS: The defects had a mean size of 4.8 cm2 (range, 1.2-12 cm2) and were predominantly femorotibial (66%). The mean Kaplan-Meier survival rate of revision for any reason was 97.2% 6 1.6% at 10 years. In comparison to preoperative values, all PROMs were significantly improved at the current follow-up (P < .05). The MOCART 2.0 score peaked at 12 months (mean, 80.2 6 15.3 months) and showed no significant change at 96 months (mean, 76.1 ± 19.5 months; P = .142). The linear multivariate regression model identified an association of body mass index (BMI), MOCART 2.0 score, and number of previous knee surgeries with KOOS (R2 = 0.41; f2 = 0.69). Further analysis of the individual determinants revealed an optimal BMI range of 20 to 29 for favorable PROs at 96 months. Significant correlations of MOCART subscores with the overall KOOS were found for graft surface and structure, bony reaction, and subchondral detectable changes. Only 30% of patients with 2 previous surgeries and 20% of patients with 3 previous surgeries achieved a Patient Acceptable Symptom State (χ2 = 10.93; P = .012). CONCLUSION: The present study shows consistently good long-term clinical outcomes after MACI with a low revision rate and high patient satisfaction. BMI and number of previous knee surgeries may influence clinical outcomes and should be considered in patient selection and education. There is a correlation between graft structure, subchondral bone changes on magnetic resonance imaging, and long-term PROMs.

Differences in Success Rate of Two-Stage Revision for Periprosthetic Joint Infection of the Knee Depending on the Applied Definition.

BACKGROUND: Success rates of two-stage exchange arthroplasty are subject to substantial variance in the literature. An explanation is the lack of a universally accepted definition of what constitutes treatment success for periprosthetic joint infection (PJI). Therefore, the main objective of this study was to assess success rates, applying four definitions to identify the one definition that best captures "true" success from both a clinical and patient-centered perspective. METHODS: This was a retrospective study investigating the outcome of a consecutive series of 78 chronic knee PJIs that were treated with a two-stage revision at a single center between 2017 and 2020. Kaplan-Meier survival analyses were conducted to estimate success rates. RESULTS: After a mean follow-up of 36 months (range, 25 to 60), 64 patients (82%) were reimplanted after a mean interim period of 90 days (range, 22 to 201). There was one patient (1%) lost to follow-up, and the overall mortality was 15% (n = 12). Kaplan-Meier survival analyses were used to estimate treatment success at 2- and 3-years: implant survival was 93% (95% CI [confidence interval]: 82 to 97) and 87% (95% CI: 73 to 94), infection control was 90% (95% CI: 79 to 95) and 87% (95% CI: 73 to 93), success according to Delphi criteria was 88% (95% CI: 78 to 94), and success according to Musculoskeletal Infection Society (MSIS) criteria was 65% (95% CI: 53 to 74) at both timepoints. CONCLUSION: Success rates were ranging between 65 and 93% depending on the applied definition, highlighting the need for universal success criteria. This variability mainly results from the differing approaches to patients who did not undergo reimplantation or passed away within a year of surgery. These patients exemplify cases of fatal treatment failures. Consequently, the MSIS criteria should be routinely employed to accurately report the "true" success rate.

Secondary matrix-associated autologous chondrocyte implantation after failed cartilage repair shows superior results when combined with autologous bone grafting: Findings from the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: The aim of this study was to evaluate whether additive autologous bone grafting (ABG) improves clinical outcome and survival in revision matrix-associated autologous chondrocyte implantation (M-ACI) after failed cartilage repair (CR). METHODS: A retrospective, registry-based, matched-pair analysis was performed to compare patient-reported outcomes and survival in secondary M-ACI with or without additional bone grafting for focal full-thickness cartilage defects of the knee and to compare it with those in primary M-ACI. Patients were matched for age, sex, body mass index, defect size and localization, and number of previous CRs. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was assessed over a follow-up period of 36 months. The patient acceptable symptomatic state, the clinical response rate and the survival of the subgroups were determined. RESULTS: A total of 818 patients were matched. Revision M-ACI (n = 238) with concomitant bone grafting was associated with significantly higher PRO as measured by KOOS (80.8 ± 16.8 vs. 72.0 ± 17.5, p = 0.032) and higher CRR (81.4% vs. 52.0%, p = 0.018) at 36 months compared to patients with revision M-ACI alone. KOOS and KOOS improvement in these patients did not differ from those who underwent primary M-ACI (p = n.s.). The combination of M-ACI and ABG resulted in a significantly higher KOOS at 36 months than M-ACI alone, regardless of whether bone marrow stimulation (89.6 ± 12.5 vs. 68.1 ± 17.9, p = 0.003) or ACI (82.6 ± 17.0 vs. 72.8 ± 16.0, p = 0.021) was performed before. Additional bone grafting results in equivalent survival rates at 7 years in secondary compared to primary M-ACI (83% vs. 84%, p = n.s.). CONCLUSIONS: Regardless of the type of previous CR, additional bone grafting in secondary M-ACI improves the clinical outcome, response rate and survival at 36 months compared to M-ACI alone. Secondary M-ACI with ABG had comparable clinical response and survival rates to primary M-ACI. Therefore, subchondral bone should be treated even in cases of mild bone involvement in revision M-ACI. LEVEL OF EVIDENCE: Level III.

Differences in gait analysis and clinical outcome after dynamic fixation or screw fixation in acute syndesmosis tear: a prospective randomized pilot study.

INTRODUCTION: Acute syndesmosis tears can be treated by static screw or dynamic fixation. Various studies have compared these techniques regarding postoperative outcome. However, to our knowledge, no study has used 3D-instrumented gait analysis (IGA). We hypothesized that a dynamic fixation would perform non-inferior to screw fixation in terms of biomechanical and clinical outcomes. MATERIALS AND METHODS: Patients were prospectively randomized to both groups. All patients received the same follow-up rehabilitation and consultations (6 and 12 weeks; 6 and 12 months) postoperatively. Standardized questionnaires were used to objectify pain and ankle function. At 6 months follow-up, IGA was conducted additionally to objectify the biomechanical outcome. RESULTS: Twenty-five patients in the dynamic fixation (DF) group using TightRope® and twenty-five in the screw fixation group (SF) completed gait analysis. The DF group showed significantly higher mean values for maximum moment in the affected ankle joint (DF: 1.40 ± 0.21 Nm, SF: 1.23 ± 0.30 Nm; p = 0.023) and the unaffected ankle joint (DF: 1.52 ± 0.20 Nm, SF: 1.37 ± 0.27 Nm; p = 0.035). The difference between the affected and unaffected ankle joint was significantly higher in the SF group for active plantarflexion (DF: 1.52 ± 0.20°, SF: 1.37 ± 0.27°; p = 0.035). Both dynamic and screw fixation groups exhibited significantly reduced plantarflexion during the push-off and early swing phase, with moments and powers in the ankle joint also significantly impaired. CONCLUSIONS: Our study demonstrated that dynamic fixation has better or similar biomechanical and clinical outcomes compared to screw fixation. Future research should focus on biomechanical differences during gait as well as clinical outcomes in case of earlier weight-bearing after dynamic fixation. TRIAL REGISTRATION NUMBER (TRN): DRKS00013562 Date of Registration: 07/12/2017.

Mechanoinduction of PTHrP/cAMP-signaling governs proteoglycan production in mesenchymal stromal cell-derived neocartilage.

Abnormal mechanical loading is one of the major risk factors for articular cartilage degeneration. Engineered mesenchymal stromal cell (MSC)-derived cartilage holds great promise for cell-based cartilage repair. However, physiological loading protocols were shown to reduce matrix synthesis of MSC-derived neocartilage in vitro and the regulators of this undesired mechanoresponse remain poorly understood. Parathyroid hormone-related protein (PTHrP) is involved in cartilage development and can affect extracellular matrix (ECM) production during MSC chondrogenesis opposingly, depending on a continuous or transient exposure. PTHrP is induced by various mechanical cues in multiple tissues and species; but whether PTHrP is regulated in response to loading of human engineered neocartilage and may affect matrix synthesis in a positive or negative manner is unknown. The aim of this study was to investigate whether dynamic loading adjusts PTHrP-signaling in human MSC-derived neocartilage and whether it regulates matrix synthesis and other factors involved in the MSC mechanoresponse. Interestingly, MSC-derived chondrocytes significantly upregulated PTHrP mRNA (PTHLH) expression along with its second messenger cAMP in response to loading in our custom-built bioreactor. Exogenous PTHrP(1-34) induced the expression of known mechanoresponse genes (FOS, FOSB, BMP6) and significantly decreased glycosaminoglycan (GAG) and collagen synthesis similar to loading. The adenylate-cyclase inhibitor MDL-12,330A rescued the load-mediated decrease in GAG synthesis, indicating a direct involvement of cAMP-signaling in the reduction of ECM production. According to COL2A1-corrected hypertrophy-associated marker expression, load and PTHrP treatment shared the ability to reduce expression of MEF2C and PTH1R. In conclusion, the data demonstrate a significant mechanoinduction of PTHLH and a negative contribution of the PTHrP-cAMP signaling axis to GAG synthesis in MSC-derived chondrocytes after loading. To improve ECM synthesis and the mechanocompetence of load-exposed neocartilage, inhibition of PTHrP activity should be considered for MSC-based cartilage regeneration strategies.

Assessment Accuracy of 2D vs. 3D Imaging for Custom-Made Acetabular Implants in Revision Hip Arthroplasty.

Revision total hip arthroplasty (rTHA) presents significant challenges, particularly in patients with severe acetabular bone defects. Traditional treatment options often fall short, leading to the emergence of custom-made 3D-printed acetabular implants. Accurate assessment of implant positioning is crucial for ensuring optimal postoperative outcomes and for providing feedback to the surgical team. This single-center, retrospective cohort study evaluates the accuracy of standard 2D radiographs versus 3D CT scans in assessing the positioning of these implants, aiming to determine if 2D imaging could serve as a viable alternative for the postoperative evaluation. We analyzed the implant positions of seven rTHA patients with severe acetabular defects (Paprosky ≥ Type IIIA) using an alignment technique that integrates postoperative 2D radiographs with preoperative CT plans. Two independent investigators, one inexperienced and one experienced, measured the positioning accuracy with both imaging modalities. Measurements included translational shifts from the preoperatively templated implant position in the craniocaudal (CC), lateromedial (LM), and ventrodorsal (VD) directions, as well as rotational differences in anteversion (AV) and inclination (INCL). The study demonstrated that 2D radiographs, when aligned with preoperative CT data, could accurately assess implant positions with precision nearly comparable to that of 3D CT scans. Observed deviations were 1.4 mm and 2.7 mm in CC and LM directions, respectively, and 3.6° in AV and 0.7° in INCL using 2D imaging, all within clinically acceptable ranges. For 3D CT assessments, mean interobserver variability was up to 0.9 mm for translational shifts and 1.4° for rotation, while for 2D alignment, observer differences were 1.4 mm and 3.2° for translation and rotation, respectively. Comparative analysis of mean results from both investigators, across all dimensions (CC, LM, AV, and INCL) for 2D and 3D matching, showed no significant differences. In conclusion, conventional anteroposterior 2D radiographs of the pelvis can sufficiently determine the positioning of custom-made acetabular implants in rTHA. This suggests that 2D radiography is a viable alternative to 3D CT scans, potentially enhancing the implementation and quality control of advanced implant technologies.

Fe-doped 45S5 bioactive glass compositions impair the metabolic activity and proliferation of metastatic human breast cancer cellsin vitro.

Many kinds of human tumors, including breast carcinomas, frequently metastasize to the bone, making it prone to pathologic fractures. Surgical management of bone metastases ranges from the resection of metastases to bone repair. Current surgical methods for the repair of bone defects include the use of polymethyl methacrylate (PMMA)-based bone cements. A promising alternative material are bioactive glass (BG) particles that in addition to providing physical stability can also induce bone regeneration. Moreover, BGs doped with Fe2O3may also have a negative impact on tumor cells. Here, we tested the hypothesis that BGs can affect metastatic human breast cancer cells. To this end, we assessed the effects of different BG compositions with and without Fe2O3on metastatic human MDA-MB-231 breast cancer cellsin vitro. We found that all BGs tested impaired the viability and proliferation of breast cancer cells in a concentration-dependent manner. The anti-proliferative effects inversely correlated with BG particle size, and were in general less pronounced in mesenchymal stromal cells (MSCs) that served as a control. Moreover, Fe2O3-doped BGs were more potent inhibitors of tumor cell proliferation and metabolic activity than Fe2O3-free BG. Our data therefore indicate that BGs can affect human breast cancer cells more strongly than MSCs, and suggest that the presence of Fe2O3can potentiate anti-proliferative and anti-metabolic effects of BGs. Fe2O3-doped BGs thus have the potential to be used for the surgical management of metastatic bone lesions, and may in addition to their regenerative properties also allow the local control of bone metastases.

High comorbidity burden and low incidence of adverse events in primary shoulder arthroplasty in tertiary care at a university hospital.

Background: Reducing perioperative risk is in the focus of primary arthroplasty caregivers. Primary shoulder arthroplasty patients are considered among those with the lowest perioperative risk. Nonetheless, in tertiary care centres and university settings patients with significant comorbidities are being treated. It remains unclear whether the overall comorbidity burden is truly higher and if this results in an increased frequency of adverse events (AE). As a result, we conducted a study to assess the comorbidity burden and the frequency of major perioperative adverse events and predictive factors following primary shoulder arthroplasty in the university setting. Methods: A retrospective cohort analysis was conducted on patients undergoing primary shoulder arthroplasty for a non-trauma, non-tumour indication from January 1st, 2014 through December 31st, 2018. Administrative data were recorded to assess comorbidity burden and revision surgery within the first postoperative year. Major adverse events were routinely recorded on a weekly basis by the treating physicians. Descriptive and comparative statistical analyses were performed. The cohort was compared against a large North American sample. Results: Of 386 patients who underwent 400 primary shoulder arthroplasties 14 (3.5 %) experienced adverse events. While AE were distributed equally among anatomical and reverse shoulder arthroplasties, no adverse event was recorded in the 34 hemiarthroplasty patients. The cohort showed an increased comorbidity burden in international comparison. Peptic ulcer disease was significantly associated with AE, while mild liver disease experienced a trend towards AE. Conclusion: We found an increased comorbidity burden and a low rate of AE for primary shoulder arthroplasty in a tertiary care and university setting. The distinct role of peptic ulcer disease in this cohort and the trend in mild liver disease merit further investigation in larger samples. The findings underscore the importance of perioperative risk assessment and management. Level of evidence: III, retrospective cohort study.

From Benign Lipoma to G3 Liposarcoma: Contrast-Enhanced Ultrasound Reveals Tumor Microperfusion and Indicates Malignancy.

OBJECTIVE: Lipomatous soft tissue tumors (STT), ranging from benign lipomas to malignant liposarcomas, require accurate differentiation for timely treatment. Complementary to MRI, Contrast-enhanced ultrasound (CEUS) is emerging as a promising tool, providing insight into tumor microperfusion in real-time. This study aims to explore the potential of preoperative CEUS in differentiating benign lipomatous tumors from malignant liposarcoma subtypes. METHODS: Eighty-seven patients with lipomatous STT scheduled for surgery were enrolled. Clinical and MRI assessments were conducted to obtain general tumor characteristics. CEUS was used for a standardized tumor perfusion evaluation. Perfusion analysis included peak enhancement, rise time, wash-in perfusion index, and wash-out rate, reflecting the perfusion kinetics. Histopathological results were obtained for every STT and compared to perfusion characteristics. RESULTS: In total, 48 lipoma, 23 ALT and 11 liposarcoma were identified. Significant differences in tumor microperfusion were demonstrated, with higher perfusion levels indicating higher malignancy (Peak enhancement [a.u.] of Lipoma: 145 ± 238; ALT: 268 ± 368; Liposarcoma: 3256 ± 4333; p (ALT vs. Liposarcoma) < 0.001). A perfusion-based identification of a benign lipoma or ALT versus sarcoma resulted in a positive predictive value of 93%. Patient-related factors (age, gender, BMI, ASA score, smoking status) had no significant impact on the CEUS-based perfusion parameters. CONCLUSION: Our study suggests CEUS as a capable non-invasive tool for improving preoperative assessment of lipomatous STT. It can assist in the distinction between benign and malignant STT, accelerating treatment decisions and enhancing patient outcomes. Significant correlations between CEUS-derived parameters and malignancy highlight its risk assessment potential.

Favourable clinical outcomes and low revision rate after M-ACI in adolescents with immature cartilage compared to adult controls: Results at 10 years.

PURPOSE: The purpose of this study was to evaluate long-term survival, patient-reported outcomes (PROs) and radiographic results of matrix-associated autologous chondrocyte implantation (M-ACI) in adolescents with immature cartilage and compare them to adult controls. METHODS: A retrospective matched-pair analysis was performed comparing the PRO after M-ACI for focal cartilage defect of the knee in cartilaginous immature adolescents to mature adults. Groups were matched for sex, body mass index, defect site and size, symptom duration and the number of previous knee surgeries. Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART 2.0) scores were assessed at least 60 months postoperatively. Patient acceptable symptomatic state (PASS) and clinical response rate in KOOS and KOOS subscores were calculated. RESULTS: A total of 54 patients were matched. At a mean of 96 months (65-144 months), no surgical complications, graft hypertrophy or reoperations were noted in the cohorts studied. Adolescents showed superior PROs at the final follow-up (76.9 ± 14.1 vs. 66.4 ± 15.0, p = 0.03) and were significantly more likely to achieve PASS (74.1% vs. 55.6%; p = 0.02) compared to the adult cohort. The KOOS subscale analysis showed long-term benefits for adolescents in terms of symptom improvement, pain reduction, activities of daily living, sports and quality of life (p < 0.05). None of the patients in the adolescent group showed graft hypertrophy on magnet resonance imaging or signs of osteoarthritis on radiographs at long-term follow-ups. CONCLUSIONS: M-ACI is an effective treatment for chondral defects of the knee in patients with immature cartilage with low revision rates and high patient satisfaction over the long term. Adolescents showed comparable clinical and radiographic results in the short and medium term, with slightly more favourable, clinically relevant functional results in adolescents in the long term. M-ACI can be safely used in adolescents, and consideration should be given to expanding the indication to include these patients. LEVEL OF EVIDENCE: Level III.

Elevated Blood Tantalum Concentrations in Patients Following Reconstruction of Severe Acetabular Defects in Total Hip Arthroplasty Using Modular Tantalum Augments in Combination With Uncemented Tantalum Cups.

INTRODUCTION: The reconstruction of acetabular defects in total hip arthroplasty (THA) can be challenging. An option to treat uncontained acetabular defects is to use modular tantalum augments in combination with cementless press-fit cups. However, modularity is associated with an increased risk of debonding and mechanical failure. In addition, metal wear particles can be released due to micromotions at the implant interface. Clinical data on the long-term results of this treatment strategy is limited. The purposes of this study were: (1) to evaluate the clinical and radiological outcome of complex THA using modular trabecular metal augments and uncemented revision cups; (2) to investigate the blood tantalum concentrations in these patients at mid-term (mean 4.5 year) follow-up; and (3) to report complications and mechanisms of failure related to this procedure. MATERIALS AND METHODS: In this single-center study, we retrospectively reviewed data from a consecutive cohort of 27 patients who underwent complex acetabular defect reconstruction using a modular tantalum acetabular augment in combination with an uncemented tantalum cup. We evaluated the implant survival, and the radiological and clinical outcomes after a mean follow-up of 4.5 years (SD 2.1; range 2.5 to 10.6 years) using patient-reported outcome scores (PROMs). Blood samples were analyzed regarding tantalum concentration and compared with a control group. RESULTS: The cumulative survival rate at 4.5 years with the endpoint "revision of the acetabular component for aseptic loosening" was 94.4% (95% confidence interval (CI) 71.6 to 99.2) and 82.9% (95 % CI 60.5 to 93.3) for the endpoint "revision for any reason." The PROMs improved significantly up to the latest follow-up, and radiographic data showed no signs of loosening or implant migration. Median blood tantalum concentrations were significantly higher in the study group (0.15 µg/L) compared to the control group (0.002 µg/L) (P < 0.001). CONCLUSIONS: This study demonstrated acceptable clinical and radiological results of cementless revision THA using modular trabecular metal implants for the reconstruction of large acetabular defects. Tantalum concentrations were significantly higher in patients who had tantalum implants compared to the control group, however, the systemic and local effects of an increased tantalum exposure are not yet fully understood and have to be further investigated.

Neutral to slightly undercorrected mechanical leg alignment provides superior long-term results in patients undergoing matrix-associated autologous chondrocyte implantation.

PURPOSE: The aim of this study was to evaluate the role of leg alignment on long-term clinical outcome after matrix-associated autologous chondrocyte implantation (M-ACI) and to define an individualized target range to optimize clinical outcome. METHODS: The present study examined patients who underwent M-ACI of the femoral condyle. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) were used to assess the results. Clinical outcomes were related to Patient Acceptable Symptomatic State (PASS). For intra- and interobserver reliability of mechanical tibiofemoral angle, mechanical medial proximal tibial angle and mechanical lateral distal femoral angle, we calculated intraclass correlation coefficients using a two-way mixed model with absolute agreement. A regression model and receiver-operating characteristics curve were used to identify an individual range of alignment where a favourable clinical outcome could be expected in the long term. RESULTS: Additional osteotomy was performed in 50% of patients with similar clinical outcomes as physiologically aligned patients (p > 0.05). The curve-fitting regression model identified a target range of -2.5° valgus to 4.5° varus for ideal postoperative alignment (R2 = 0.12, p = 0.01). Patients within this range were more likely to achieve PASS (70% vs. 27%, p = 0.001). In medially treated defects, a refined range of -2.5° valgus to 4° varus alignment was found (R2 = 0.15, p = 0.01). These patients were more likely to achieve PASS (67% vs. 30%, p = 0.01) and showed favourable postoperative KOOS and MOCART scores (p = 0.02). Patients with lateral defects were more likely to achieve PASS within a range of -2° valgus and 0.5° varus (90% vs. 45%, p = 0.03) and showed favourable postoperative KOOS and MOCART scores (p = not significant). CONCLUSIONS: An individual range of leg alignment-whether achieved by osteotomy or physiologic alignment-should be respected in M-ACI treatment. A neutral to slightly undercorrected alignment favours the postoperative outcome after M-ACI. When planning surgery for patients with focal cartilage defects of the femoral condyle, these ranges should be recognized as critical factors. LEVEL OF EVIDENCE: Level III.

Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis.

Mesenchymal stromal cells (MSCs) that are promising for cartilage tissue engineering secrete high amounts of prostaglandin E2 (PGE2), an immunoactive mediator involved in endochondral bone development. This study aimed to identify drivers of PGE2 and its role in the inadvertent MSC misdifferentiation into hypertrophic chondrocytes. PGE2 release, which rose in the first three weeks of MSC chondrogenesis, was jointly stimulated by endogenous BMP, WNT, and hedgehog activity that supported the exogenous stimulation by TGF-ß1 and insulin to overcome the PGE2 inhibition by dexamethasone. Experiments with PGE2 treatment or the inhibitor celecoxib or specific receptor antagonists demonstrated that PGE2, although driven by prohypertrophic signals, exerted broad autocrine antihypertrophic effects. This chondroprotective effect makes PGE2 not only a promising option for future combinatorial approaches to direct MSC tissue engineering approaches into chondral instead of endochondral development but could potentially have implications for the use of COX-2-selective inhibitors in osteoarthritis pain management.

A comparative in vitro and in vivo analysis of the impact of copper substitution on the cytocompatibility, osteogenic, and angiogenic properties of a borosilicate bioactive glass.

The 0106-B1-bioactive glass (BG) composition (in wt %: 37.5 SiO2, 22.6 CaO, 5.9 Na2O, 4.0 P2O5, 12.0 K2O, 5.5 MgO, and 12.5 B2O3) has demonstrated favorable processing properties and promising bone regeneration potential. The present study aimed to evaluate the biological effects of the incorporation of highly pro-angiogenic copper (Cu) in 0106-B1-BG in vitro using human bone marrow-derived mesenchymal stromal cells (BMSCs) as well as its in vivo potential for bone regeneration. CuO was added to 0106-B1-BG in exchange for CaO, resulting in Cu-doped BG compositions containing 1.0, 2.5 and 5.0 wt % CuO (composition in wt %: 37.5 SiO2, 21.6/ 20.1/17.6 CaO, 5.9 Na2O, 4.0 P2O5, 12.0 K2O, 5.5 MgO, 12.5 B2O3, and 1.0/ 2.5/ 5.0 CuO). In vitro, the BGs' impact on the viability, proliferation, and growth patterns of BMSCs was evaluated. Analyses of protein secretion, matrix formation, and gene expression were used for the assessment of the BGs' influence on BMSCs regarding osteogenic differentiation and angiogenic stimulation. The presence of Cu improved cytocompatibility, osteogenic differentiation, and angiogenic response when compared with unmodified 0106-B1-BG in vitro. In vivo, a critical-size femoral defect in rats was filled with scaffolds made from BGs. Bone regeneration was evaluated by micro-computed tomography. Histological analysis was performed to assess bone maturation and angiogenesis. In vivo effects regarding defect closure, presence of osteoclastic cells or vascular structures in the defect were not significantly changed by the addition of Cu compared with undoped 0106-B1-BG scaffolds. Hence, while the in vitro properties of the 0106-B1-BG were significantly improved by the incorporation of Cu, further evaluation of the BG composition is necessary to transfer these effects to an in vivo setting.

Static spacers play a crucial role in the treatment of complex periprosthetic joint infections of the knee.

PURPOSE: To determine the superior spacer design, a growing number of studies are comparing treatment results between patients having been treated with articulating and static knee spacers in the setting of two-stage revision for periprosthetic joint infection (PJI). In contrast, the primary objective of this study was to compare preoperative characteristics between patients from both spacer groups and examine whether significant differences were present prior to spacer implantation. METHODS: This retrospective, single-centre, cohort study examined the preoperative situation of 80 consecutive knee PJIs between 2017 and 2020. All patients underwent two-stage revision, with 35 (44%) receiving an articulating and 45 (56%) a static spacer. RESULTS: No significant differences were observed in terms of patient gender (p = 0.083), age (p = 0.666), comorbidity (p = 0.1) and preoperative clinical function (p = 0.246). Static spacers were significantly more often used in the presence of a periarticular fistula (p = 0.033), infection of a revision implant (p < 0.001), higher degree of bone loss (p < 0.001) and infection caused by a difficult-to-treat pathogen (p = 0.038). Complication and revision rates were similar for both spacer types during the interim period, while patients with articulating spacers demonstrated a superior clinical function (p < 0.001) during the interim period and after reimplantation. CONCLUSION: Static spacers are being utilised in significantly more complex and unfavourable preoperative scenarios. Therefore, a preoperative selection bias may be at least partially accountable for any disparities observed in postoperative outcomes. To achieve the best possible results, surgeons should know and respect the distinct indications of static and articulating spacers and consequently understand and use them as complementary surgical options. LEVEL OF EVIDENCE: Level III.

The role of autologous bone grafting in matrix-associated autologous chondrocyte implantation at the knee: Results from the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: To investigate whether concomitant autologous bone grafting adversely affects clinical outcome and graft survival after matrix-associated autologous chondrocyte implantation (M-ACI). METHODS: The present study examines registry data of patients who underwent M-ACI with or without autologous bone grafting for large-sized chondral or osteochondral defects. Propensity score matching was performed to exclude potential confounders. A total of 215 patients with similar baseline characteristics were identified. Clinical outcome was assessed at the time of surgery and at 6, 12, 24, 36 and 60 months using the Knee Injury and Osteoarthritis Outcome Score (KOOS). KOOS change, clinical response rate, KOOS subcomponents and failure rate were determined. RESULTS: Patients treated with M-ACI and autologous bone grafting achieved comparable clinical outcomes compared with M-ACI alone. At 24 months postoperatively, the patient-reported outcome (PRO) of patients treated with M-ACI and autologous bone grafting was even significantly better as measured by KOOS (74.9 ± 18.8 vs. 79.2 ± 15.4; p = 0.043). However, the difference did not exceed the minimal clinically important difference (MCID). In patients with M-ACI and autologous bone grafting, a greater change in KOOS relative to baseline was observed at 6 (9.3 ± 14.7 vs. 15.0 ± 14.7; p = 0.004) and 12 months (12.6 ± 17.2 vs. 17.7 ± 14.6; p = 0.035). Overall, a high clinical response rate was observed in both groups at 24 months (75.8% vs. 82.0%; p = n.s.). The estimated survival at the endpoint of reoperation for any reason was 82.1% (SD 2.8) at 8.4 years for isolated M-ACI and 88.7% (SD 2.4) at 8.2 years for M-ACI with autologous bone grafting (p = 0.039). CONCLUSIONS: Even in the challenging cohort of large osteochondral defects, the additional treatment with autologous bone grafting leads to remarkably good clinical outcomes in patients treated with M-ACI. In fact, they tend to benefit more from surgery, have lower revision rates and achieve clinical response rates earlier. Subchondral bone management is critical to the success of M-ACI and should be addressed in the treatment of borderline defects. LEVEL OF EVIDENCE: Level III.

How Do Spinopelvic Characteristics Change Post-Total Hip Arthroplasty? A Longitudinal Assessment Raising Awareness of the Postoperative Period.

BACKGROUND: Spinopelvic characteristics, including sacral slope (SS), are commonly evaluated in different positions pre-total hip arthroplasty (THA). This study aimed to: 1) investigate the change in spinopelvic parameters at 7 days (early) and 1-year post-THA; and 2) identify patient characteristics associated with a change in SS of more than 7° post-THA. METHODS: We prospectively studied 250 patients who underwent unilateral THA [132 women, age 66 years (range, 32 to 88)] and underwent biplanar images preoperatively and at 7 days and 1-year post-THA. Parameters measured included pelvic incidence, standing lumbar lordosis, SS, and proximal femoral angle (PFA). A SS change ≥ 7° was considered the threshold as it would result in more than a 5° change in cup orientation. RESULTS: Early post-THA SSstanding remained within ± 6º from preoperative measurements in 75% of patients, reduced by ≥ 7° in 9%, and increased by ≥ 7° in 16%. Those that showed a reduction in SS had the lowest PFA and the highest SS pre-THA (P = .028, .107, and < 0.001, respectively). From 7 days until the 1-year mark, pelvic tilt increased, SS reduced (mean: -4º, range: -29 to 17º, P < .001), and patients stood with greater hip extension ΔPFAstanding (mean 7°, range: -34 to 37°, P < .001). At 1 year, SSseated had remained within ± 6º, relative to the pre-THA value, in 49% of patients. CONCLUSIONS: Standing spinopelvic characteristics, especially SSstanding, remain within ±6° in three-quarters of patients both early- and at 1-year post-THA. In the remaining cases, pelvic tilt changes significantly. In 9% of cases, SS reduces ≥ 7° early THA, probably due to the alleviation of fixed-flexion contractures. The SSseated changes by ≥ ± 7° in almost 50% of cases in this study, and its clinical value as a preoperative planning tool should be questioned. LEVEL OF EVIDENCE: Level II, diagnostic study.

Capsule elongation occurs after first time shoulder dislocation A biomechanical in-vitro investigation on human cadaveric specimen.

Purpose: As capsule elongation is assumed to weaken the static stability of the shoulder joint, the purpose of this biomechanical study was to demonstrate that capsule elongation occurs immediately after a first-time shoulder dislocation and not just after recurrent dislocation events. We hypothesize an increment in joint clearance due to joint capsule elongation after a first-time dislocation. Methods: An experimental in-vitro study was conducted on 6 paired fresh frozen human shoulders (4 females; 2 males; 12 specimen) with a mean age of 80 (Range 67-89) years. The shoulder joint with the articular capsule was exposed and an inferior static tension force of 2.5 N was applied to the humerus prior to dislocation. Next, the humeral head was dislocated and was then immediately reduced back into the start position. The joint gap as well as joint capsule deformation was assessed using optical techniques. Results: The radiographic joint gap increased from 13.7 ± 6.9 mm (prior to dislocation) to 18.1 ± 6.5 mm (post dislocation) (p < .001). The increase in joint clearance was 4.4 mm. The joint capsule elongated from 5.9 ± 0.005 % (prior to dislocation) to 9.4 ± 0.007 % (post dislocation) (p < .001). The mean increase in joint capsule elongation was 3.5 %. Conclusions: Capsule elongation was observed immediately after a simulated first-time shoulder dislocation in an in-vitro model of elderly human cadavers. It might therefore not only be a phenomenon of recurrent dislocation events.

A comparative analysis of the cytocompatibility, protein adsorption, osteogenic and angiogenic properties of the 45S5- and S53P4-bioactive glass compositions.

Despite their long history of application in orthopedics, the osteogenic and angiogenic properties as well as the cytocompatibility and protein adsorption of the 45S5- (in wt%: 45.0 SiO2, 24.5 Na2O, 24.5 CaO, 6.0 P2O5) and S53P4- (in wt%: 53.0 SiO2, 23.0 Na2O, 20.0 CaO, 4.0 P2O5) bioactive glass (BG) compositions have not yet been directly compared in one and the same experimental setting. In this study, the influence of morphologically equal granules of both BGs on proliferation, viability, osteogenic differentiation and angiogenic response of human bone-marrow-derived mesenchymal stromal cells (BMSCs) was assessed. Furthermore, their impact on vascular tube formation and adsorption of relevant proteins was evaluated. Both BGs showed excellent cytocompatibility and stimulated osteogenic differentiation of BMSCs. The 45S5-BG showed enhanced stimulation of bone morphogenic protein 2 (BMP2) gene expression and protein production compared to S53P4-BG. While gene expression and protein production of vascular endothelial growth factor (VEGF) were stimulated, both BGs had only limited influence on tubular network formation. 45S5-BG adsorbed a higher portion of proteins, namely BMP2 and VEGF, on its surface. In conclusion, both BGs show favorable properties with slight advantages for 45S5-BG. Since protein adsorption on BG surfaces is important for their biological performance, the composition of the proteome formed by osteogenic cells cultured on BGs should be analyzed in order to gain a deeper understanding of the mechanisms that are responsible for BG-mediated stimulation of osteogenic differentiation.

The Addition of Zinc to the ICIE16-Bioactive Glass Composition Enhances Osteogenic Differentiation and Matrix Formation of Human Bone Marrow-Derived Mesenchymal Stromal Cells.

An ICIE16-bioactive glass (BG) composition (in mol%: 49.5 SiO2, 6.6 Na2O, 36.3 CaO, 1.1 P2O5, and 6.6 K2O) has demonstrated excellent in vitro cytocompatibility when cultured with human bone marrow-derived mesenchymal stromal cells (BMSCs). However, its impact on the development of an osseous extracellular matrix (ECM) is limited. Since zinc (Zn) is known to enhance ECM formation and maturation, two ICIE16-BG-based Zn-supplemented BG compositions, namely 1.5 Zn-BG and 3Zn-BG (in mol%: 49.5 SiO2, 6.6 Na2O, 34.8/33.3 CaO, 1.1 P2O5, 6.6 K2O, and 1.5/3.0 ZnO) were developed, and their influence on BMSC viability, osteogenic differentiation, and ECM formation was assessed. Compared to ICIE16-BG, the Zn-doped BGs showed improved cytocompatibility and significantly enhanced osteogenic differentiation. The expression level of the osteopontin gene was significantly higher in the presence of Zn-doped BGs. A larger increase in collagen production was observed when the BMSCs were exposed to the Zn-doped BGs compared to that of the ICIE16-BG. The calcification of the ECM was increased by all the BG compositions; however, calcification was significantly enhanced by the Zn-doped BGs in the early stages of cultivation. Zn constitutes an attractive addition to ICIE16-BG, since it improves its ability to build and calcify an ECM. Future studies should assess whether these positive properties remain in an in vivo environment.