Introduction: Meniscal extrusion is defined as the situation in which the meniscus is partially or totally luxated from the tibial plateau. The aim of this work is to ascertain the prevalence of meniscal extrusion in non arthritic patients and to define those factors related to it. Special attention was given to the fact of anatomic variations in the menisci attachments. Methods: The knee MRI of 100 patients that were operated on arthroscopically in our institution was prospectively studied. Seventy-two males and 28 females, average age of 36.6 years (range between 13 and 64), entered in the study. There were 43 right-knees and 57 left-knees. The average weight of the patients was 77 kg (range 44 to 135). Results: With respect to the medial meniscus 68.9% of the cases showed some degree of extrusion, averaging at 28% of the meniscal size (ranging from 10% to 60%). In the case of the lateral meniscus extrusion averaging 15% (ranging from 10% to 40%) was seen in 18.8% of the cases. In this series the posterior types of anterior medial meniscus insertion were the most frequently found (69.5%). Medial meniscal extrusion was significatively correlated to the presence of a chondral lesion (p = 0.008) and to anterior medial meniscus insertion (p = 0.001). No statistical significant relationship to the rest of parameters studied was encountered. None of the parameters studied were related to lateral meniscus extrusion. Discusion: Meniscal extrusion is frequent in our series and, the hypothesis that those patients who have an anterior variant of the anterior horn insertion of the medial meniscus tend to show greater extrusion is confirmed

We compared extrusion of the allograft after medial and lateral meniscal allograft transplantation and examined the correlation between the extent of extrusion and the clinical outcome. A total of 73 lateral and 26 medial meniscus allografts were evaluated by MRI at a mean of 32 months (24 to 59) in 99 patients (67 men, 32 women) with a mean age of 35 years (21 to 52). The absolute values and the proportional widths of extruded menisci as a percentage were measured in coronal images that showed maximum extrusion. Functional assessments were performed using Lysholm scores. The mean extrusion was 4.7 mm (1.8 to 7.7) for lateral menisci and 2.9 mm (1.2 to 6.5) for medial menisci (p < 0.001), and the mean percentage extrusions were 52.0% (23.8% to 81.8%) and 31.2% (11.6% to 63.4%), respectively (p < 0.001). Mean Lysholm scores increased significantly from 49.0 (10 to 83) pre-operatively to 86.6 (33 to 99) at final follow-up for lateral menisci (p = 0.001) and from 50.9 (15 to 88) to 88.3 (32 to 100) for medial menisci (p < 0.001). The final mean Lysholm scores were similar in the two groups (p = 0.312). Furthermore, Lysholm scores were not found to be correlated with degree of extrusion (p = 0.242). Thus, transplanted lateral menisci extrude more significantly than transplanted medial menisci. However, the clinical outcome after meniscal transplantation was not found to be adversely affected by extrusion of the allograft

Aims. Ganz’s studies made it possible to address joint deformities on both the femoral and acetabular side brought about by Perthes’ disease. Femoral head reduction osteotomy (FHRO) was developed to improve joint congruency, along with periacetabular osteotomy (PAO), which may enhance coverage and containment. The purpose of this study is to show the clinical and morphological outcomes of the technique and the use of an implemented planning approach. Methods. From September 2015 to December 2021, 13 FHROs were performed on 11 patients for Perthes’ disease in two centres. Of these, 11 hips had an associated PAO. A specific CT- and MRI-based protocol for virtual simulation of the corrections was developed. Outcomes were assessed with radiological parameters (sphericity index, extrusion index, integrity of the Shenton’s line, lateral centre-edge angle (LCEA), Tönnis angle), and clinical parameters (range of motion, visual analogue scale (VAS) for pain, Merle d'Aubigné-Postel score, modified Harris Hip Score (mHHS), and EuroQol five-dimension five-level health questionnaire (EQ-5D-5L)). Early and late complications were reported. Results. The mean follow-up was 39.7 months (standard deviation (SD) 26.4). The mean age at surgery was 11.4 years (SD 1.6). No major complications were recorded. One patient required a total hip arthroplasty. Mean femoral head sphericity increased from 46.8% (SD 9.34%) to 70.2% (SD 15.44; p < 0.001); mean LCEA from 19.2° (SD 9.03°) to 44° (SD 10.27°; p < 0.001); mean extrusion index from 37.8 (SD 8.70) to 7.5 (SD 9.28; p < 0.001); and mean Tönnis angle from 16.5° (SD 12.35°) to 4.8° (SD 4.05°; p = 0.100). The mean VAS improved from 3.55 (SD 3.05) to 1.22 (1.72; p = 0.06); mean Merle d’Aubigné-Postel score from 14.55 (SD 1.74) to 16 (SD 1.6; p = 0.01); and mean mHHS from 60.6 (SD 18.06) to 81 (SD 6.63; p = 0.021). The EQ-5D-5L also showed significant improvements. Conclusion. FHRO associated with periacetabular procedures is a safe technique that showed improved functional, clinical, and morphological outcomes in Perthes’ disease. The newly introduced simulation and planning algorithm may help to further refine the technique. Cite this article: Bone Joint J 2024;106-B(5 Supple B):40–46

Introduction: Vertebroplasty is an established minimally invasive technique, which provides consistent and sustained pain relief in patients with vertebral fractures. However cement extrusion remains a major problem and has been reported to occur in up to 70% of the cases in some reports. Cement extravasations may occur through the Basivertebral vein, the Segmental vein or through cortical defects. Cement leakage may be Epidural, Anterior, Para-vertebral, Intra-discal or distant. Most often cement leakage is asymptomatic but on occasion it may be a serious complication in the form of Cord compression, pulmonary embolism or Neuralgia. The incidence of cement leakage can be reduced by the use of high viscosity cement, use of a low pressure injection system, injecting small volumes at each level, introducing the cement under visualization and waiting for cement to set before withdrawing the needle. Patients and Methods: We describe another technique to help in reduction of cement extrusion. After satisfactory placement of the Jamshidi needle (used for injecting cement), aspiration is attempted using a 20ml Syringe. A slurry, made of very fine pieces of Gel foam mixed with Omnipaque dye and saline, is injected into the vertebral body. This embolizes the blood channels, which are communicating with the needle. Once no more blood can be aspirated, and no dye is seen extruding into the veins, toothpaste consistency cement is injected under low pressure and fluoroscopic guidance. A post-procedure CT scan was performed in all cases to confirm cement location. Results: 28 patients underwent PV, 24 of these patients had osteoporotic vertebral fractures and 4 had meta-static lesions. Vertebroplasty was done at 56 symptomatic levels. Using this method, Cement leakage was seen at 12 of the 56 levels operated on (21.4%); at 6 levels leakage was into the adjoining disc, leakage anteriorly was seen at 3 levels, there was 1 leakage into the paravertebral tissues and at 2 levels there was a streak of cement into the vertebral canal in 1 via the venous system and in the other through a cortical defect. None of the leakages were symptomatic. Epidural leakage was seen in 2 patients (3.57%). Conclusion: A slurry of gelfoam, dye and saline injected prior to cement reduces the incidence of cement extrusion, therefore increasing the safety of this effective procedure

Purpose. Injuries of the meniscal attachments can lead to meniscal extrusion. We hypothesized that the extent of lateral meniscal extrusion (LME) was associated with the severity of the lateral meniscus posterior root tear (LMPRT). This study aimed to evaluate the relationship between preoperative LME and arthroscopic findings of LMPRT in knees with anterior cruciate ligament (ACL) injury. Methods. Thirty-four knees that had LMPRTs with concomitant ACL injuries on arthroscopy were evaluated. Patients were divided into two groups, partial and complete root tears, via arthroscopic findings at the time of ACL reconstruction. We retrospectively measured preoperative LMEs using magnetic resonance imaging (MRI). Statistical analysis was performed using the Mann-Whitney U-test and Chi-square test. Results. Twenty-three knees had partial LMPRTs (type 1). Complete LMPRTs were observed in 11 knees (type 2, 2 knees; type 3, 2 knees; and type 4, 7 knees). In the partial LMPRT group, the average LME was 0.43±0.78 mm. In the complete LMPRT group, the average extrusion was 1.99±0.62 mm. A significant difference between these groups was observed in the preoperative LMEs (P<0.01). The receiver operating curve analysis identified an optimal cutoff point of 1.05 mm for the preoperative LME. This LME cutoff had a sensitivity of 100% and specificity of 85% for complete LMPRT. Conclusion. This study demonstrated that preoperative LMEs were larger in complete LMPRTs associated with ACL injuries than in partial LMPRTs. Our results suggest that preoperative MRI-detected LME may be a useful indicator for estimating LMPRT severity in knees with ACL injury

Introduction: From June 1991 to June 1995, 256 consecutive total hip arthroplasties using the Duraloc 100 TM acetabular shell, manufactured by Depuy, were performed by two surgeons. The acetabular component featured a non-locking apex hole eliminator. In January 1995 the first patient with extrusion of the apex hole eliminator was seen. Since that time 21 patients, or 8% (21/256) have been seen with partial or complete extrusion. This study reports the outcomes and discusses a possible rationale for this finding. Methods: The study group comprises 12 men, nine women, mean age was 59 years (32-86), mean weight 180 lbs. 18 (86%) femurs were cementless, three (14%) were cemented. Mean acetabular component size was 58 mm (52-64), with 18 acetabular liners manufactured with HylamerTM, and three liners EnduronTM. Sixteen (76%) liners were 10 degree hooded, and five (24%) were non-hooded. Eighteen (86%) femoral heads were ceramic, and three (14%) were chrome-cobalt. 15 (71%) femoral heads were 28 mm diameter, and six (29%) were 32 mm. Results: Radiographs were obtained at routine follow-up in 20 (95%) patients. One (5%) patient had groin pain as the indication for radiographs. Four (19%) patients had complete extrusion in to the pelvis of the apex hole eliminator, and 17 (81%) had partial backout with the apex hole eliminator still within the confines of the acetabular component. On the antero-posterior radiograph visible pelvic osteolysis was seen in the four patients with complete extrusion of the apex hole eliminator, all in zone B. Zone one femoral osteolysis was seen in one patient with incomplete extrusion of the apex hole eliminator. Sixteen patients had incomplete extrusion of the apex hole eliminator associated with no visible radiographic pelvic or femoral osteolyisis. Two (10%) patients have undergone revision with curettage and allografting of the pelvic lesion and head and liner exchange. At the time of revision surgery liner motion was grossly obvious. Discussion: The apex hole eliminator is neither watertight nor locking. Our hypothesis is that activity-related hydraulic pressure generated from excessive liner motion causes a high-pressure fluid leak into the pelvis. This fluid contains sub-micron particles generated by backside wear. The combination of particulates and fluid under pressure produces retro-acetabular osteolysis. The cyclic pressure then allows the non-locking plug to advance into the osteolytic pelvic defect

Introduction: Pressurization of PMMA can lead to cement extrusion. Although rare, the complications related to cement extrusion (‘CE’) are serious such as neurological, urological and vascular injuries. In a recent study the incidence of CE from acetabulum was found to be 42–50%, most of which was under transverse ligament. We advocate a technique of applying cancellous autograft on the medial floor and under the transverse ligament to provide cancellous surface for cement pressurisation, and to prevent CE. The aim of this study was to review our incidence of CE and radiolucent lines (‘RLL’). Methods: Study group included 380 consecutive patients undergoing primary implantation of flanged cemented cup with spacers during 2002–2003. The mean age was 68 years. Surgeons of all grades, including junior doctors under supervision, performed the procedure. Early postoperative radiographs were reviewed to identify the incidence, site and extent of CE and incidence of RLL. Results: We identified CE in 46 radiographs, 35 being inferior, 6 pelvic and 5 along retractors. The mean size of the CE was 240.5 mm. 2. Radiolucent lines (RLL) in any of the Charnley zone were present in 58 cases. Two zone RLL were seen in seven cases (1.8%) and a circumferential radiolucency in one case (0.3%). There was no significant correlation between the grade of the operating surgeon and the incidence of CE (p, 0.15). There was no significant correlation between the grade of operating surgeon and the presence of RLL (p, 0.18). Discussion: Results of this study confirm that incidence of CE with this technique is significantly less as compared with historic data (12% vs. 42%). Incidence of RLL is also less especially in zone 2 and 3. These findings support our hypothesis that use of autograft to convert acetabulum in contained hemisphere reduces incidence of CE and improves pressurization

Osteochondral fractures of the talus are uncommon. They are classified according to Berndt and Harty, as progressing in severity through four stages. This classification, however, does not address extra-articular extrusion of the osteochondral fragment. We report an osteochondral lesion of the talar dome which presented as an extruded extra-articular fragment in a closed injury of the ankle. This type of lesion may offer a continuation to the four original stages. Clinicians should be aware that this pattern of fracture can occur, and thus allow a more accurate diagnosis and the provision of some aid in the treatment of these injuries

Purpose. to evaluate the radial displacement of meniscal allograft transplants (MATs) in patients operated with an open technique vs. an arthroscopic technique at 1 year postoperatively. Radial displacement or extrusion of the graft is frequently observed after meniscus transplantation. The hypothesis is that arthroscopically inserted MATs extrude less than open MATs and therefore have a more intra-articular position than open surgery transplants. Materials and Methods. 39 patients were included in the study: the first group of open surgery transplants consisted of 16 patients (10 lateral, 6 medial). The second group of arthroscopic transplants consisted of 21 patients (14 lateral, 7 medial). MR-images were taken one year post-surgery. The displacement, evaluated on 1,5T MR coronal images, was defined as the distance between the tibial plateau and the outer edge of the meniscus. Results. The radial displacement of lateral open surgery transplants (mean = 4,04 mm; SD = 1,46) is significantly larger (p < 0,05) than the displacement of arthroscopically implanted MATs (mean = 3,38 mm; SD = 0,85). The external displacement of medial open surgery transplants (mean = 4,71 mm; SD = 0,97) is significantly larger (p < 0,05) than the displacement of arthroscopically implanted MATs (mean = 2,36 mm; SD = 0,89). Conclusion. Graft position is influenced by the surgical technique; the radial displacement of arthroscopically implanted MATs is, both lateral and medial, significantly less than meniscal transplants implanted by open surgery. The clinical relevance remains to be determined

Muller-Weiss disease is an uncommon condition with unclear etiology and no gold standard treatment. The question arises; which joints to fuse? Although no consensuses prevail, one must postulate fusion should include those affected. Consequently, to establish an algorithm for its surgical management we set out to study clinical and radiographic features with use of SPECT-CT and a literature review. 57 consecutive feet presenting with Muller-Weiss disease analysed; 15 men, 25 women, age 22–84. Condition bilateral in 17, left side 16, right in 7 patients. Specific history and examination by senior author. Radiographic series and SPECT-CT obtained with surgery performed on significantly symptomatic feet. Measurements of Meary-Tomeno angles, anteroposterior thickness of navicular at the midpoint of each naviculo-cuneiform, alongside the medial extrusion distance and percentage of compression in each case performed. Poor correlation between Meary's angle and 1) degree of compression at naviculo-cuneiform joints, 2) degree of extrusion 3) compression vs extrusion using R. 2. coefficient of determination (invalidating Maceira et al. classification). In unilateral cases, extrusion significantly greater on affected side 94.7% (P< 0.001 Fisher exact test). Degree of extrusion significantly greater in bilateral than unilateral cases (p=0.004 unpaired T test). Valgus hindfoot and Meary's negative most common pattern with no correlation between heel alignment and Meary's R. 2. = 0.003. SPECT-CT useful to determine subtalar involvement in ‘stage 2 disease.’. Following review of cases and published literature we propose the following classification for Muller-Weiss disease with treatment algorithm. 3 Stage delineation; Stage 1 (Normal hindfoot alignment); 1A. Talonavicular disease only - Isolated Talonavicular arthrodesis 1B. Talonavicular + Subtalar; double medial or triple arthrodesis. Stage 2. Talonavicular + Naviculocuneiform; 2A. Adequate bone stock - Talo-naviculo-cuneiform arthrodesis, 2B. Inadequate bone stock +- subtalar disease; Talo-naviculo-cuneiform arthrodesis with tricortical bone graft (Mayich). Stage 3; Asymmetric ankle varus. Pantalar arthrodesis Double/triple/TNC/TAR arthrodesis with hindfoot re-alignment

Background. The only existing classification of Müller-Weiss Disease (MWD), based solely on Méary's angle, serves neither as guide for prognosis nor treatment. This accounts for lack of gold standard in its management. Methods. Navicular compression, medial extrusion, Kite's angle and metatarsal lengths were measured on all radiographs of 95 feet with MWD. Joints involved, presence and location of navicular fracture were recorded. Results. We identified three distinct groups. Group 1 comprises 11 “early-onset” MWD feet, aged 9 to 29 years. These had the greatest compression and medial extrusion, and lowest Kite's angles. All except 1 were index minus and had a lateral navicular fracture. None has required surgery to date. Only 1 has moderate talonavicular joint (TNJ) degeneration. Group 2 comprises 23 “Müller-Weissoid” feet with radiologically normal navicular in their fifties and developing MWD, on average, 4.5 years later. These had the lowest compression and extrusion, and highest Kite's angles. None had complete fracture. All had TNJ arthritis, with early changes at lateral naviculocuneiform joint (NCJ) in 43%. Group 3 “late-onset” MWD, presenting in the sixth decade, is subdivided into 3 sub-groups. Only TNJ is involved in group 3A (16). Group 3B denotes affection of TNJ more than NCJ (20). In group 3C “reverse Müller-Weiss disease”, which affects NCJ more than TNJ (25), second metatarsal overlength is highest of all groups. No difference in age, compression, extrusion and Kite's angle exists among the 3 subgroups. No fracture occurred in group 3A compared to 65% and 32% in groups 3B and 3C, respectively. Conclusions. With a need to compare like-for-like pathology, the proposed classification provides a common platform for reporting outcomes of different treatment modalities, operative or nonoperative. We theorize pathogenetic pathways in the different groups and propose systematic surgical approaches for each category

Background. We have previously reported an injectable hydrogel (NPgel), which could deliver patients own stem cells, via small bore needles, decreasing damage to the annulus fibrosus. NPgel drives differentiation to NP cells and can inhibit the degenerate niche. However, clinical success of NPgel is dependent on the capacity to inject NPgel into naturally degenerate human discs, restore mechanical function to the IVD, prevent extrusion during loading and induce regeneration. This study assessed injectability of NPgel into human IVD, influence on mechanical properties, regeneration ability in an ex vivo culture system and retention under failure testing. Methodology. Cadaveric human discs were used to calculate disc height and to determine Youngs Modulus during simulated walking pre and post injection of NPgel, extrusion testing performed. Whole human IVDs were injected with NPgel +/− human BMPCs and maintained in culture under physiological loading regime for 4 weeks. Pre and post culture MRI imaging and in line biomechanical characteristics determined. Histology and immunochemistry performed for anabolic and catabolic factors. Results. NPgel injection significantly increased disc height and Youngs modulus with no extrusion observed during failure testing. T1ρ intensity was increased during culture in those injected with NPgel +/− cells compared to non-injected discs, and biomechanical restoration. Histological analysis has demonstrated excellent tissue attachment to the injected gel, and cellular migration into acellular gel systems. With increased matrix production and decreased catabolic factor expression. Conclusion. These results provide essential proof of concept data supporting the use of NPgel as an injectable therapy for disc regeneration. Conflict of interest: C Le Maitre & C Sammon are inventors on the hydrogel discussed. Funding: This work was funded by MRC and Versus Arthritis

Aims. Though the pathogenesis of Legg-Calve-Perthes disease (LCPD) is unknown, repetitive microtrauma resulting in deformity has been postulated. The purpose of this study is to trial a novel upright MRI scanner, to determine whether any deformation occurs in femoral heads affected by LCPD with weightbearing. Methods. Children affected by LCPD were recruited for analysis. Children received both standing weightbearing and supine scans in the MROpen upright MRI scanner, for coronal T1 GFE sequences, both hips in field of view. Parameters of femoral head height, width, and lateral extrusion of affected and unaffected hips were assessed by two independent raters, repeated at a one month interval. Inter- and intraclass correlation coefficients were determined. Standing and supine measurements were compared for each femoral head. Results. Following rigorous protocol development in healthy age-matched volunteers, successful scanning was performed in 11 LCPD-affected hips in nine children, with seven unaffected hips therefore available for comparison. Five hips were in early stage (1 and 2) and six were in late stage (3 and 4). The mean age was 5.3 years. All hips in early-stage LCPD demonstrated dynamic deformity on weightbearing. Femoral head height decreased (mean 1.2 mm, 12.4% decrease), width increased (mean 2.5 mm, 7.2% increase), and lateral extrusion increased (median 2.5 mm, 23% increase) on standing weightbearing MRI compared to supine scans. Negligible deformation was observed in contra-lateral unaffected hips, with less deformation observed in late-stage hips. Inter- and intraclass reliability for all measured parameters was good to excellent. Conclusion. This pilot study has described an effective novel research investigation for children with LCPD. Femoral heads in early-stage LCPD demonstrated dynamic deformity on weightbearing not previously seen, while unaffected hips did not. Expansion of this protocol will allow further translational study into the effects of loading hips with LCPD. Cite this article: Bone Joint Open 2020;1-7:364–369

Orthopaedic soft tissues, such as tendons, ligaments, and articular cartilage, rely on their unique collagen fiber architectures for proper functionality. When these structures are disrupted in disease or fail to regenerate in engineered tissues, the tissues transform into dysfunctional fibrous tissues. Unfortunately, collagen synthesis in regenerating tissues is often slow, and in some cases, collagen fibers do not regenerate naturally after injury, limiting repair options. One of the research focuses of my team is to develop functional fiber replacements that can promote in vivo repair of musculoskeletal tissues throughout the body. In this presentation, I will discuss our recent advancements in electrowriting 3D printing of natural polymers for creating functional fiber replacements. This manufacturing process utilizes electrical signals to control the flow of polymeric materials through an extrusion nozzle, enabling precise deposition of polymeric fibers with sizes that cannot be achieved using conventional extrusion printing methods. Furthermore, it allows for the formation of fiber organizations that surpass the capabilities of conventional electrospinning processes. During the presentation, I will showcase examples of electrowritten microfiber scaffolds using various naturally-derived polymers, such as gelatin (a denatured form of collagen) and silk fibroin. I will discuss the functional properties of silk-based scaffolds and highlight how they exhibit restored β-sheet and α-helix structures [1]. This restoration results in an elastic response of up to 20% deformation and the ability to withstand cyclic loading without plastic deformation. Additionally, I will present our latest results on the compatibility of this technique with patterning cell-laden fiber structures [2]. This novel biofabrication process allows for the printing of biomimetic microscale architectures with high cell viability, and offers a promising approach to understanding how shear and elongation forces influence cell development of hierarchical (collagen) fibers. Acknowledgements: The author would like to thank the Reprint project (OCENW.XS5.161) and the program “Materials Driven Regeneration” (024.003.013) by the Netherlands Organization for Scientific Research for the financial support

Ganz's studies made it possible to address joint deformities on both femoral and acetabular side brought by the Legg-Calvè-Perthes disease (LCPD). Femoral head reduction osteotomy (FHRO) was developed to improve joint congruency along with periacetabular osteotomy (PAO). The purpose of this study is to show the clinical and morphologic outcomes of the technique, and an implemented planning approach. From 2015 to 2023, 13 FHROs were performed on 11 patients for LCPD, in two centers. 11 of 13 hips had an associated PAO. A specific CT and MRI-based protocol for virtual simulation of the corrections was developed. Outcomes were assessed with radiographic parameters (sphericity index, extrusion index, integrity of the Shenton's line, LCE angle, Tonnis angle, CCD angle) and clinical parameters (ROM, VAS, Merle d'Aubigné-Postel score, modified-HHS, EQ5D-5L). Early and late complications were reported. The mean follow-up was 40 months. The mean age at surgery was 11,4 years. No major complications were recorded. One patient required a total hip arthroplasty. Femoral Head Sphericity increased from 45% to 70% (p < 0,001); LCE angle from 18° to 42,8° (p < 0,001); extrusion Index from 36,6 to 8 (p < 0,001); Tonnis Angle from 14,4° to 6,2° (p = 0.1); CCD Angle from 131,7 to 136,5° (p < 0,023). The VAS score improved from 3,25 to 0,75,(p = 0.06); Merle d'Aubigné-Postel score from 14.75 to 16 (p = 0,1); Modified-HHS from 65,6 to 89,05 (p = 0,02). The EQ 5D 5L showed significant improvements. ROM increased especially in abduction and extra-rotation. FHRO associated with periacetabular procedures is a safe technique that showed improved functional, clinical and morphologic outcomes in LCPD. The newly introduced simulation and planning algorithm may help to further refine the technique

Nanovesicle-based therapy is increasingly being pursued as a safe, cell-free strategy to combat various immunological, musculoskeletal and neurodegenerative diseases. Small secreted extracellular vesicles (sEVs) obtained from multipotent mesenchymal stromal cells (MSCs) are of particular interest for therapeutic use since they convey anti-inflammatory, anti-scarring and neuroprotective activities to the recipient cells. Cell-derived vesicles (CDVs) produced by a proprietary extrusion process are surrounded by a lipid bilayer membrane with correct membrane topology, display biological activities similar to MSC-derived EVs and may find specific application for organ-targeted drug delivery systems. Translation of nanovesicle-based therapeutics into clinical application requires quantitative and reproducible analysis of bioactivity and stability, and the potential for GMP-compliant manufacturing. Manufacturing and regulatory considerations as well as preclinical models to support clinical translation will be discussed

The aim of this scoping review is to understand the extent and type of evidence in relation to the use of guided growth for correcting rotational deformities of long bones. Guided growth is routinely used to correct angular deformities in long bones in children. It has also been proven to be a viable method to correct rotational deformities, but the concept is not yet fully examined. Databases searched include Medline, Embase, Cochrane Library, Web of Science and Google Scholar. All identified citations were uploaded into Rayyan.ai and screened by at least two reviewers. The search resulted in 3569 hits. 14 studies were included: 1 review, 3 clinical trials and 10 pre-clinical trials. Clinical trials: a total of 21 children (32 femurs and 5 tibiae) were included. Surgical methods were 2 canulated screws connected by cable, PediPlates obliquely oriented, and separated Hinge Plates connected by FiberTape. Rotation was achieved in all but 1 child. Adverse effects reported include limb length discrepancy (LLD), knee stiffness and rebound of rotation after removal of tethers. 2 pre-clinical studies were ex-vivo studies, 1 using 8-plates on Sawbones and 1 using a novel z-shaped plates on human cadaver femurs. There were 5 lapine studies (2 using femoral plates, 2 using tibial plates and 1 using an external device on tibia), 1 ovine (external device on tibia), 1 bovine (screws and cable on metacarp) and a case-report on a dog that had an external device spanning from femur to tibia. Rotation was achieved in all studies. Adverse effects reported include implant extrusions, LLD, articular deformities, joint stiffness and rebound. All included studies conclude that guided growth is a viable treatment for rotational deformities of long bones, but there is great variation in models and surgical methods used, and in reported adverse effects

As arthroplasty demand grows worldwide, the need for a novel cost-effective treatment option for articular cartilage (AC) defects tailored to individual patients has never been greater. 3D bioprinting can deposit patient cells and other biomaterials in user-defined patterns to build tissue constructs from the “bottom-up,” potentially offering a new treatment for AC defects. The aim of this research was to create bioinks that can be injected or 3D bioprinted to aid osteochondral defect repair using human cells. Novel composite bioinks were created by mixing different ratios of methacrylated alginate (AlgMA) with methacrylated gelatin (GelMA). Chondrocytes or mesenchymal stem cells (MSCs) were then encapsulated in the bioinks and 3D bioprinted using a custom-built extrusion bioprinter. UV and double-ionic (BaCl2 and CaCl2) crosslinking was deployed following bioprinting to strengthen bioink stability in culture. Chondrocyte and MSC spheroids were also produced via 3D culture and then bioprinted to accelerate cell growth and development of ECM in bioprinted constructs. Excellent viability of chondrocytes and MSCs was seen following bioprinting (>95%) and maintained in culture over 28 days, with accelerated cell growth seen with inclusion of MSC or chondrocyte spheroids in bioinks (p<0.05). Bioprinted 10mm diameter constructs maintained shape in culture over 28 days, whilst construct degradation rates and mechanical properties were improved with addition of AlgMA (p<0.05). Composite bioinks were also injected into in vitro osteochondral defects (OCDs) and crosslinked in situ, with maintained cell viability and repair of osteochondral defects seen over a 14-day period. In conclusion we developed novel composite AlgMA/GelMA bioinks that can be triple-crosslinked, facilitating dense chondrocyte and MSC growth in constructs following 3D bioprinting. The bioink can be injected or 3D bioprinted to successfully repair in vitro OCDs, offering hope for a new approach to treating AC defects

As arthroplasty demand grows worldwide, the need for a novel cost-effective treatment option for articular cartilage (AC) defects tailored to individual patients has never been greater. 3D bioprinting can deposit patient cells and other biomaterials in user-defined patterns to build tissue constructs from the “bottom-up,” potentially offering a new treatment for AC defects. The aim of this research was to create bioinks that can be injected or 3D bioprinted to aid osteochondral defect repair using human cells. Novel composite bioinks were created by mixing different ratios of methacrylated alginate (AlgMA) with methacrylated gelatin (GelMA). Chondrocytes or mesenchymal stem cells (MSCs) were then encapsulated in the bioinks and 3D bioprinted using a custom-built extrusion bioprinter. UV and double-ionic (BaCl2 and CaCl2) crosslinking was deployed following bioprinting to strengthen bioink stability in culture. Chondrocyte and MSC spheroids were also bioprinted to accelerate cell growth and development of ECM in bioprinted constructs. Excellent viability of chondrocytes and MSCs was seen following bioprinting (>95%) and maintained in culture over 28 days, with accelerated cell growth seen with inclusion of MSC or chondrocyte spheroids in bioinks (p<0.05). Bioprinted 10mm diameter constructs maintained shape in culture over 28 days, whilst construct degradation rates and mechanical properties were improved with addition of AlgMA (p<0.05). Composite bioinks were also injected into in vitro osteochondral defects (OCDs) and crosslinked in situ, with maintained cell viability and repair of osteochondral defects seen over a 14-day period. In conclusion we developed novel composite AlgMA/GelMA bioinks that can be triple-crosslinked, facilitating dense chondrocyte and MSC growth in constructs following 3D bioprinting. The bioink can be injected or 3D bioprinted to successfully repair in vitro OCDs, offering hope for a new approach to treating AC defects

Medial meniscus tear has been proposed as a potential etiology of spontaneous osteonecrosis of the knee (SONK). Disruption of collagen fibers within the meniscus causes meniscal extrusion, which results in alteration in load distribution in the knee. A recent study has demonstrated high incidence of medial meniscus extrusion in the knee with SONK. Our purpose was to determine whether the extent of medial meniscus extrusion correlates with the severity of SONK in the medial femoral condyle. Anteroposterior and lateral knee radiographs were taken with the patients standing. Limb alignment was expressed as the femorotibial angle (FTA) obtained from the anteroposterior radiograph. The stage of progression of SONK was determined according to the radiological classification system described by Koshino. After measurement of anteroposterior, mediolateral, and superoinferior dimensions of the hypointense T1 signal intensity lesion of MRI, its ellipsoid volume was calculated with the three dimensions. Meniscal pathology (degeneration, tear, and extrusion) were also evaluated by MRI. Of the 18 knees with SONK, we found 5 knees at the radiological stage 2 lesions, 9 knees at the stage 3, and 4 knees at the stage 4. Whereas the ellipsoid volume of SONK lesion significantly increased with the stage progression, the volume was significantly greater at stage 4 than stage 2 or 3. All the 18 knees with SONK in the present study showed substantial extrusion (> 3mm) and degeneration of the medial meniscus. While medial meniscal extrusion increased with the stage progression, medial meniscus was significantly extruded at stage 3 or 4 compared with stage 2. A significant increase in FTA was found with the stage progression. FTA was significantly greater at stage 4 than stage 2 or 3. Multiple linear regression analysis revealed that medial meniscus extrusion and FTA were useful predictors of the volume of SONK lesion. This study has clearly shown a significant correlation between the extent of medial meniscus extrusion and the stage and volume of SONK lesion. Degeneration and tears of the medial meniscus in combination with extrusion may result in loss of hoop stress distribution in the medial compartment, which could increase the load in the medial femoral condyle. In addition to meniscal pathology, knee alignment can influence load distribution in the medial compartment biomechanically. Multiple linear regression analysis indicates that an increase in FTA concomitant with a greater extrusion of medial meniscus could result in greater lesion and advanced radiological stage of SONK. Taken together, alteration in compressive force transmission through the medial compartment by meniscus extrusion and varus alignment could develop subchondral insufficiency fractures in the medial femoral condyle, which is considered to be one of the main contributing factors to SONK development. There was high association of medial meniscus extrusion and FTA with the radiological stage and volume of SONK lesion. Increased loading in the medial femoral condyle with greater extrusion of medial meniscus and varus alignment may contribute to expansion and secondary osteoarthritic changes of SONK lesion