The optimal treatment strategy for post-traumatic long bone non-unions is subject of an ongoing discussion. At the Maastricht University Medical Center (MUMC+) the induced membrane technique is used to treat post-traumatic long bone non-unions. This technique uses a multimodal treatment algorithm involving bone marrow aspirate concentrate (BMAC), the reamer-irrigator-aspirator (RIA) and P-15 bioactive peptide (iFactor, Cerapedics). Bioactive glass (S53P4 BAG, Bonalive) is added when infection is suspected. This study aims to objectify the effect of this treatment algorithm on the health-related quality of life (HRQoL) of patients with post-traumatic long bone non-unions. We hypothesized that HRQoL would improve after treatment. From January 2020 to March 2023, consecutive patients who were referred to a multidisciplinary (trauma, orthopaedic and plastic surgery) non-union clinic at the MUMC+, The Netherlands, were evaluated using the Non-Union Scoring System (NUSS). The EQ-5D-5L questionnaire and the Lower Extremity Functional Scale (LEFS) were employed to obtain HRQoL outcomes both prior to and subsequent to surgery, with a follow-up at 6, 18 and 35 weeks. Seventy-six patients were assessed at baseline (T0), with a mean NUSS of 40 (± 13 SD). Thirty-eight patients had their first follow-up, six weeks after surgery (T1). Thirty-one patients had a second follow-up at 18 weeks (T2), and twenty patients had the third follow-up at 35 weeks (T3). The EQ-5D index mean at baseline was 0.480, followed by an index of 0.618 at T1, 0.636 at T2, and 0.702 at T3. A significant difference was found in the HRQoL score between T0 and T1, as well as T2 and T3 (p<0.001; p=0.011). The mean LEFS significantly increased from 26 before intervention to 34, 39, and 43 after treatment (p<0.001; p=0.033; p=0.016). This study demonstrated a significant improvement in the health-related quality of life of patients with post-traumatic long bone non-unions after the standardized treatment algorithm following the induced membrane technique

Osteoarthritis is a slowly progressive disease which includes the intervention of several cytokines and macrophage metalleinoproteinases reaction, leading to the degradation of the local cartilage but also having an impact on the serum acute phase proteins (APPs). Subsequently, biomarkers seem to be essential to estimate its progression and the need for any surgical intervention such as total arthroplasty, but also can be used as therapeutic agents. Recently, among APPs, fetuin-A drew attention regarding its possible anti-inflammatory role in animal models but also as a therapeutic agent in the inflammatory joint disease in clinical trials. The purpose of this study is to investigate the possible attenuating role of the intra-articular administration of Fetuin-A in post-traumatic induced secondary osteoarthritis in rats, and also its effect on the systematic levels of IL-2,4,7, BMPs 2,4,7, CRP and Fetuin-A. 30 male Sprague Dawley rats were separated in two groups where post-traumatic osteoarthritis was induced surgically by Anterior Cruciate Ligament Transection and the transection of the Medial Collateral Ligament of the right knee. In the Control Group, only surgical intervention took place. In Fetuin Group, along with the induction of osteoarthritis, a single dose of bovine fetuin was administrated intra-articularly intra-operatively in 5 and 8 weeks of the experimental protocol. Both groups were examined for 8 weeks. The levels of interleukins, bone morphogenetic proteins, Fetuin-A and C-Reactive Protein were evaluated by ELISA of peripheral blood in three time periods: preoperatively, 5 and 8 weeks post-operatively. Knee osteoarthritic lesions were classified according to Osteoarthritis Research Society International Grading System and Modified Mankin Score, by histologic examination. IL-2 levels were significantly decreased in the Fetuin Group. No statistical difference was signed on the levels of IL-7, BMP-2,4,7 and Fetuin-A between the two groups. CRP levels were significantly increased in the Fetuin Group in 5 weeks of the experiment. Fetuin Group signed better scores according to the OARSI classification system and Modified Mankin Score, without any statistical significance. Intra-articular administration of Fetuin-A restrictively affected the progression of post-traumatic arthritis in rats, as only the levels of IL-2 were decreased as well as limited osteoarthritic lesions were observed on the Fetuin Group

To evaluate the therapeutic effect of Pulsed Electromagnetic Field (PEMF) in the treatment of meniscal tears in the avascular region. Seventy-two twelve-week-old male Sprague-Dawley rats with full-thickness longitudinal medial meniscal tears in the avascular region were divided into 3 groups: control group (G. con. ), treated with classic signal PEMF (G. classic. ), and high slew rate signal PEMF(G. HSR. ). The HSR signal has the same pulse and burst frequencies as the classic signal, but with a higher slew rate. Macroscopic observation and histological analysis of the meniscus and articular cartilage were performed to evaluate the meniscal healing and progressions of osteoarthritis. The synovium was harvested for histological and immunofluorescent analysis to assess the intra-articular inflammation. The meniscal healing, articular cartilage degeneration, and synovitis were quantitatively evaluated according to their respective scoring system. Dramatic degenerative changes of the meniscus and articular cartilage were noticed during gross observation and histological evaluation in the control group at 8 weeks. However, the menisci in the two treatment groups were restored to normal morphology with a smooth surface and shiny white color. Particularly, the HSR signal remarkably enhanced the fibrochondrogenesis and accelerated the remodeling process of the regenerated tissue. The meniscal healing scores of PEMF treatment groups were significantly higher than those in the control group at 8 weeks. Specifically, the HSR signal showed a significantly higher meniscal repair score than the classic signal at week 8 (P < .01). The degeneration score (G. con. versus G. classic. : P < .0001; Gcon versus G. HSR. : P < .0001) and synovitis score (G. con. versus Gclassic: P < .0001; G. con. versus G. HSR. : P = .0002) of the control groups were significantly higher than those in the two treatment groups. PEMF promoted the healing of meniscal tears in the avascular region and restored the injured meniscus to its structural integrity in a rat model. Compared to the classic signal, the HSR signal showed the increased capability to promote fibrocartilaginous tissue formation and modulate the inflammatory environment and therefore protected the knee joint from post-traumatic osteoarthritis development

Introduction and Objective. Evidence in literature is contradicting regarding outcomes of total knee arthroplasty (TKA) in post-traumatic osteoarthritis (PTOA) and whether they are inferior to TKA in primary osteoarthritis (OA). The aim of this review was to find out if any difference exists in the results of TKA between the two indications. Materials and Methods. The electronic databases MEDLINE, EMBASE, The Cochrane Collaboration, and PubMed were searched and screened in duplicate for relevant studies. The selected studies were further subjected to quality assessment using the modified Coleman method. The primary outcome measure was patient reported outcome, and secondary outcome measures were infection, revision, stiffness, and patella tendon rupture. Results. A total of 18 studies involved 1129 patients with a mean age of 60.6 years (range 45.7–69) and follow up of 6.3 years. The time interval from index injury to TKA was 9.1 years. Knee Society Score (KSS) in PTOA reported in 12/18 studies showed functional improvement from 42.5 to 70 post-TKA exceeding minimally clinically important difference. In TKA for primary OA vs PTOA, deep peri-prosthetic joint infection (PJI) was reported in 1.9% vs 5.4% of patients, whilst revision of prosthesis at an average of 6 years post-operatively was performed in 2.6 vs 9.7% of patients. Conclusions. TKA is a successful treatment option for PTOA. However, the risk of significant complications like PJI and implant failure requiring revision is higher than primary OA cases. Patients should be counselled about those risks. Further well-designed comparative cohort-matched studies are needed to compare outcomes between the two populations

Introduction and Objective. Traditionally, osteoarthritis (OA) has been associated mostly with degradation of cartilage only. More recently, it has been established that other joint tissues, in particular bone, are also centrally involved. However, the link between these two tissues remains unclear. This relationship is particularly evident in post-traumatic OA (PTOA), where bone marrow lesions (BMLs), as well as fluctuating levels of inflammation, are present long before cartilage degradation begins. The process of bone-cartilage crosstalk has been challenging to study due to its multi-tissue complexity. Thus, the use of explant model systems have been crucial in advancing our knowledge. Thus, we developed a novel patellar explant model, to study bone cartilage crosstalk, in particular related to subchondral bone damage, as an alternative to traditional femoral head explants or cylindrical core specimens. The commonly used osteochondral explant models are limited, for our application, since they involve bone damage during harvest. The specifics aim of this study was to validate this novel patellar explant model by using IL-1B to stimulate the inflammatory response and mechanical stimulation to determine the subsequent developments of PTOA. Materials and Methods. Lewis rats (n=48) were used to obtain patellar and femoral head explants which were harvested under an institutional ethical approval license. Explants were maintained in high glucose media (containing supplements), under sterile culture conditions. Initially, we characterised undamaged patellar explants and compared them with the commonly used femoral head. First, tissue viability was assessed using an assay of metabolic activity and cell damage. Second, we created chemical and mechanical damage in the form of IL-1B treatment, and mechanical stimulation, to replicate damage. Standard biochemical assays, histological assays and microstructural assays were used to evaluate responses. For chemical damage, explants were exposed to 10ng/ml of IL-1B for 24 hours at 0, 1, 3 and 7 days after harvesting. For mechanical damage, tissues were exposed to mechanical compression at 0.5 Hz, 10 % strain for 10 cycles, for 7 days. Contralateral patellae served as controls. In both groups, sGAG, ADAMTS4, and MMP-13 were measured as an assessment of representative cartilage responses while ALP, TRAP and CTSK were assessed as a representative of bone responses. In addition to this, histomorphometric, and immunohistochemical, evaluations of each explant system were also carried out. Results. Our results confirm that the patellar explant system is an excellent ex vivo model system to study bone-cartilage crosstalk, and one which does not induce any bone damage at the time of tissue harvest. We successfully established culture conditions to maintain viability in these explants for up to 28 days. Rat IL-1B treatment resulted in increased both proteoglycan content and bone metabolism markers after 7 days when compared with the controls. To confirm this finding, qualitative immunohistochemical staining showed chondrocytes increased expression of MMP13 after treatment with IL-1B. Furthermore, we observed that the levels of ADAMTS4 decreased in 48 hours after IL-1B exposure. Contrastingly IL-1B treatment had the opposite effect on CTSK markers when compared with the control. Mechanically compressed patellae showed a decrease in compressive moduli from day 3 to day 7, suggesting that tissue remodelling may have taken place as a compensatory mechanism in response to damage. In addition, MMP13 release decreased over 48 hours after mechanical compression, while TRAP levels were increased compared with the control. Conclusions. Thus, we successfully demonstrated that IL-1B and mechanical stimulation affects both bone and cartilage tissues independently in this system, which may have relevance in the understanding of bone-cartilage crosstalk after injury and how this is involved in PTOA development

Introduction and Objective. Osteoarthritis (OA) is the most common inflammatory and degenerative joint disease. Mesenchymal Stromal Cells (MSCs), with their chondro-protective and immune-regulatory properties, have been considered as a new approach to treat OA. Considering the risk of cell leakage outside the articular space and the poor survival rate after intra-articular (IA) injection, we hypothesized that cell encapsulation in cytoprotective hydrogels could overcome these limitations and provide cells with a suitable 3D microenvironment supporting their biological activity. We previously generated micromolded alginate particles (diameter 150 μm) and demonstrated the long-term viability of microencapsulated MSCs isolated from human adipose tissue (hASCs). Encapsulated cells maintained their in vitro ability to sense and respond to a pro-inflammatory environment (IFN-γ/TNF-α or synovial fluids from OA patients) by secreting PGE. 2. , IDO, HGF and TGF-β. In this study, we evaluated the anti-OA efficacy of these microencapsulated hASCs in a post-traumatic OA model in rabbits. Materials and Methods. OA was surgically induced by anterior cruciate ligament transection (ACLT)-mediated destabilization of the right knee in rabbits (n=24). Eight weeks after surgery, destabilized joints were injected (IA, 26G needle) with 200 μL of either PBS, blank microparticles, non-encapsulated or microencapsulated cells (5×10. 5. cells). Six weeks after injection, rabbits were euthanized and all destabilized (right) and sham-operated (left contralateral) joints were dissected and analyzed for OA severity. Tibial subchondral bone histomorphometric parameters were measured by quantitative micro-computed tomography (micro-CT). Histological sections of samples were analyzed after Safranin-O staining and quantitatively assessed according to a modified Osteoarthritis Research Society International (OARSI) scoring system. Immunohistochemical detection of NITEGE was performed to assess the extracellular matrix degradation. Results. Micro-CT analysis of destabilized joints confirmed that the rabbit ACLT significantly affected the tibial subchondral bone architecture as early as eight weeks, as revealed by significant changes of the subchondral bone parameters of operated joints compared to the sham operated joints. In particular, destabilized joints exhibited a Bone Volume/Tissue Volume ratio (BV/TV) ranging from 53.4% to 56.6%, compared to a mean BV/TV of 65.4% for sham operated joints. All destabilized joints also exhibited a significantly increased modified OARSI score, ranging from 7.4±0.4 for those injected with encapsulated cells to 8.9±0.2 for those injected with PBS, as compared to 4.8±0.4 for sham-operated joints. Of interest, we identified a slight, while not significant, reduction of the severity of OA lesions after injection of microencapsulated cells using the modified OARSI scoring. Finally, semi-quantitative analysis of NITEGE immunostaining revealed a significant increase in all destabilized joints that were injected with PBS or blank microparticles, in comparison with sham ones. On the contrary, NITEGE immunostaining in destabilized joints that were injected with non-encapsulated or encapsulated hASC revealed a significant reduced NITEGE immunostaining, indicating a decreased matrix degradation. Conclusions. Our data suggest that the microencapsulated hASCs exerted their anti-OA properties after IA injection in rabbit knees, as evidenced by the tendency toward a reduced modified OARSI score, and most importantly a significant reduction in NITEGE immunostaining associated matrix degradation. Further studies are now warranted to investigate the anti-OA efficacy of microencapsulated hASCs in the long-term

Osteoarthritis (OA) is the most common musculoskeletal disease in the EU and is characterized by cartilage degeneration, pain and restricted movement. Post-Traumatic OA (PTOA) is a specific disease subset that occurs subsequent to traumatic injury, such as ACL rupture and makes up 12% of the overall disease burden. Our current understanding PTOA is that initial injury affects multiple tissues, and many/all contribute to overall ‘joint failure.’ MRI scans show that subchondral bone marrow lesions (BMLs) are present in 80% of ACL rupture cases in the immediate aftermath of joint injury. Their presence indicates an acute consequence in subchondral bone. It has also been suggested that BMLs overlap with, or directly represent, bone microdamage. Microdamage is known to induce osteoclast-mediated remodelling in bone. Therefore, the inhibition of subchondral bone remodelling, particularly in the early phase post-injury, may be a candidate therapeutic approach for preventing PTOA. Finally, the contiguous link between subchondral bone and articular cartilage, can allow transport of small molecules across this boundary, this suggests that bone/cartilage crosstalk is likely to be a key factor in PTOA development after injury. This presentation will summarize recent advances in our understanding these phenomena in both animal and human studies

We used fresh small-fragment osteochondral allografts to reconstruct post-traumatic osteochondral defects in 126 knees of 123 patients with a mean age of 35 years. At a mean follow-up of 7.5 years (2 to 20), 108 knees were rated as successful (85%) and 18 had failed (15%). The factors related to failure included age over 50 years (p = 0.008), bipolar defects (p < 0.05), malaligned knees with overstressing of the grafts, and workers’ compensation cases (p < 0.04). Collapse of the graft by more than 3 mm and of the joint space of more than 50% were seen more frequently in radiographs of failed grafts. Our encouraging clinical results for fresh small-fragment osteochondral allografts show that they are indicated for unipolar post-traumatic osteochondral defects of the knee in young active patients

Introduction

Osteoarthritis (OA) causes pain, stiffness, and loss of function due to degenerative changes in joint cartilage and bone. In some forms of OA, exercise can alleviate symptoms by improving joint mobility and stability. However, excessive training after joint injury may have negative consequences for OA development. Sensory nerve fibers in joints release neuropeptides like alpha-calcitonin gene-related peptide (alpha-CGRP), potentially affecting OA progression. This study investigates the role of alpha-CGRP in OA pathogenesis under different exercise regimen in mice.

Summary. The ideal therapy for post-traumatic osteoarthritis (PTOA) must be mechanism-based and target multiple anabolic and catabolic pathways. Our results suggest an innovative combination of known pro-anabolic and anti-catabolic biologics to treat post-traumatic cartilage degeneration. Introduction. Untreated joint injuries can result in cartilage wear and the development of PTOA. Previous studies identified the mechanisms that may govern the progression to PTOA. Here we hypothesised that targeted biologic interventions combined based on the type/time of cellular responses may constitute an effective novel treatment algorithm to arrest PTOA. Methods. Eleven human donor normal tali, age 19–71 yo, from the Gift of Hope Organ & Tissue Donor Network were impacted using a 4mm cylindrical indenter with the impulse of 1N as discribed. 8mm cartilage explants (4mm impacted core + 4mm non-impacted adjacent ring) were removed from the joint and cultured for 14 days in 5% fetal bovine serum with or without selected biologics. Treatment groups consisted of 1) Impacted control (IC), 2) Un-impacted control (UIC); 3–5) Impaction + three combinations of BMP-7/OP-1 (100ng/ml), P188 (8 ug/ml) and tumor necrosis factor-α (TNF-α) antagonist (100ng/ml) defined as Combo1, Combo2, and Combo3. All treatments were administered according to previously reported post-injury cellular responses. Combo1: P188 administered at day 0 for 48hrs + BMP-7 administered at day 0 for 48hrs and at days 7–14 + anti-TNF-α administered at days 0–7; Combo2: All three agents administered at day 0 for 48hrs and anti-TNF-α and BMP-7 administered again at day 7 for 48hrs; Combo3: All agents administered simultaneously at day 0 for 48hrs. Tissue and media were collected on days 0, 2, 7, and 14 and analyzed for cell viability, Safranin O staining, and proteoglycan (PG) synthesis. Results. A single impact to articular cartilage resulted in cell death within the superficial layer of impacted region, which if untreated, expanded to the adjacent non-impacted area. It reduced cell viability by more than 2-fold (p<0.01) and triggered elevation of pro-inflammatory mediators within the first 24–48 hrs and again around day 10. Initial anabolic responses characterised by the synthesis of superficial zone protein, endogenous BMP-7 and PGs were initiated at days 5–7. Cell survival in the superficial layer was improved under the individual or combined treatments with the most pronounced sustained effect under Combo1 & 2 (∼1.5-fold increase vs IC, p<0.05). Combo1 and to a lesser extend Combo 2 markedly improved cell survival in the entire cartilage thickness, which increased from 59% in IC to 84% in Combo1, p=0.006. Both Combo1 & 2 had a stronger effect on Safranin O staining and preservation of matrix integrity than Combo 3. Contrary, Combo3 exhibited the highest effect on PG synthesis (1.8-fold increase vs IC or other two combinations; p<0.05). Combo1 & 2 were less effective. Discussion. Current study reports two important findings: 1) the same combination of agents, but administered at various treatment regimens, can induce different effects. Prolonged administration of anti-TNF-α and BMP-7 (Combo1) had a strong effect on cell survival and matrix preservation, but was less effective in inducing chondrocyte synthetic activity suggesting that overstimulation/overdosing can have a detrimental effect on chondrocyte anabolism; 2) a window of opportunity exists to arrest cell death and delay/prevent cartilage degeneration

Background. Post-traumatic immunosuppression (PTI) after surgery increases vulnerability to nosocomial infections, sepsis, and death. Knee arthroplasty offers a sterile clinical model to characterise PTI and explore its underlying mechanisms. Methods. This prospective non-randomised cohort study of primary total knee arthroplasty was approved by the Local Ethics Committee. Exclusion criteria included revision-arthroplasty, pre-existing infections, blood-transfusions, malignancy, and auto-immune disease. 48 recruited patients fell into two groups, the first received unwashed anti-coagulated autologous salvaged blood transfusions after surgery (ASBT cohort, n=25). The second received no salvaged blood transfusions (NSBT cohort, n=18). Venous blood was sampled pre-operatively and within 3–7 days post-operatively. Salvaged blood was sampled at one and six hours post-operatively. Biomarkers of immune status included: interleukins (IL) or cytokines (x15), chemokines (x3), Damage-Associated-Molecular-Patterns (DAMPS) (x5), anti-microbial proteins (x3), CD24, and Sialic-acid-binding-Immunoglobulin-type-Lectin-10 (Siglec-10). Results were expressed as fold-change over pre-operative values. Only significant changes are described. Results. Certain biomarkers associated with sterile trauma were common to all 43 patients, including supra-normal: IL-6, IL-1-Receptor-Antagonist, IL-8, Heat-Shock-Protein-70 (HSP70), Calprotectin, CD24 and Siglec-10. But, whereas in NSBT patients post-operative pro-inflammatory biomarkers were sub-normal consistent with PTI, they were supra-normal in ASBT patients implying its reversal. These PTI-biomarkers included: IL-1β, IL-2, IL-17A, Interferon-gamma (IFN-γ), Tumour-Necrosis-Factor-alpha (TNF-α), and Annexin-A2. Reversal of PTI by salvaged blood was further endorsed in ASBT by sub-normal levels of the anti-inflammatory biomarkers: IL-4, IL-5, IL-10, and IL-13. Salvaged blood analyses revealed sustained supra-normal levels of DAMPs, CD24 and Siglec-10; and increasingly elevated levels of cytokines and chemokines during the six hour collection period. Interestingly, plasma CD24, Siglec-10, HSP70 and Calprotectin levels were significantly correlated, implying physical association within the circulation. Conclusions. Several anti-inflammatory processes triggered by traumatised tissue induce systemic PTI, thereby increasing vulnerability to infections. Reversal of PTI by re-infusion of anti-coagulated salvaged blood suggests a novel source of immuno-stimulants

Heterotopic ossification (HO) is defined as aberrant bone formation in extraskeletal locations. In this process, local stromal cells of mesenchymal origin abnormally differentiate, resulting in pathologic cartilage and bone matrix deposition. However, the specific cell type and mechanisms beyond this process are not well understood, in part due to the heterogeneity of progenitor cells involved. Here, a combination of single cell RNA sequencing (scRNA-Seq) and lineage tracing, defined the extent to which synovial / tendon sheath progenitor cells contribute to HO. For this purpose, a Tppp3 (tubulin polymerization-promoting protein family member 3) inducible reporter model was used, in combination with either Scx (Scleraxis) or Pdgfra (Platelet derived growth factor receptor alpha) reporter animals. Both arthroplasty-induced and tendon injury-mouse experimental HO models were utilized. ScRNA-Seq of tendon-induced traumatic HO suggested that Tppp3 is a progenitor cell marker for either osteochondral or tendon or cells. After HO induction, Tppp3 reporter+ cell population expanded in number and contributed to cartilage and bone formation in tendon and joint-associated HO. Using double reporter animals, we found that both Pdgfra+Tppp3+ and Pdgfra+Tppp3- progenitor cells produced HO-associated cartilage. Finally, the examination of human samples showed a significant population of TPPP3+ cells overlapping with osteogenic markers in areas of HO. Overall, these results provide novel observations that peritenon and synovial progenitor cells undergo abnormal osteochondral differentiation and contribute to heterotopic bone formation after trauma.

Osteoarthritis (OA) is the leading cause of pain and disability worldwide and is characterized by the degenerative changes of articular cartilage. Joint loading is required for cartilage maintenance; however, hyper-physiologic loading is a risk factor for OA. Mechanosensitive ion channels Piezo1 and Piezo2 synergistically transduce hyper-physiologic compression of chondrocytes, leading to chondrocyte death and onset of OA. This injury response is inhibited by Piezo channel loss of function, however the mechanistic role of Piezo channels in vivo is unknown. We examined the hypothesis that deletion of Piezo in chondrocytes will protect mice from joint damage and pain-related behaviors following a surgical destabilization of the medial meniscus (DMM), investigating a key mechanistic and mechanobiological role of these channels in the pathogenesis of OA.

Aggrecan-Cre Piezo1 and Piezo1/2 knockout mice ((Agc)1-CRE^ERT2;Piezo1^fl/flPiezo2^fl/fl) were generated and given a 5-day Tamoxifen regimen at 12-weeks of age (n=6–12/group/sex). Cre-negative mice served as controls. At 16-weeks, mice received DMM surgery on the left knee. 12-weeks following DMM prior to sacrifice, activity and hyperalgesia were measured using spontaneous running wheels and a small animal algometer. Structural changes in bone, cartilage, and synovium were characterized using microCT, histology, and Modified Mankin Score criteria.

Knockout of Piezo1/2 channels was chondroprotective in both sexes following DMM surgery as demonstrated by reduced Modified Mankin Score compared to control animals. Piezo1 KO was chondroprotective in only female mice, indicating a sexually dimorphic response. Piezo1 and Piezo1/2 KO was protective against pain in male mice, while females displayed no differences compared to controls. No changes were observed in bone morphology.

Chondrocyte-specific Piezo1/2 knockout protects the knee joint from structural damage, hyperalgesia and functional deficits in a surgical model of PTOA in male and female mice, illustrating the importance of Piezo channels in response to injury in vivo. Future work aims to interrogate potential sexually dimorphic responses to cartilage damage and investigating Piezo2 KO mice.

Previous studies of the Ilizarov procedure have concentrated on musculoskeletal assessments rather than the opinions of patients. In a prospective trial of 25 consecutive patients, we evaluated the effect of Ilizarov reconstruction of post-traumatic deformity on general health status using the SF36 and Nottingham Health Profile (NHP). The patients had very low preoperative scores, which remained low during treatment and correction, but increased postoperatively. The mean overall SF36 score improved from 36 ± 3 to 58 ± 7 (p = 0.031) and the NHP score from 39 ± 11 to 67 ± 10 (p = 0.002). The improvements in scores were not limited to the physical components and were equal or better than the improvements reported for other orthopaedic procedures, including total joint arthroplasty. Ilizarov-type reconstruction of deformity of the lower limb not only restores bony configuration, but also produces a large improvement in the general health status of patients

Osteomyelitis is an inflammatory condition accompanied by the destruction of bone and caused by an infecting microorganism. Open contaminated fractures can lead to the development of osteomyelitis of the fractured bone in 3-25% of cases, depending on fracture type, degree of soft-tissue injury, degree of microbial contamination, and whether systemic and/or local antimicrobial therapies have been administered. Untreated, infection will ultimately lead to non-union, chronic osteomyelitis, or amputation.

We report a case series of 10 patients that presented with post-operative infected non-union of the distal femur with or without prior surgery. The cases were performed at Padmashree Dr. D. Y. Patil Hospital, Nerul, Navi Mumbai, India. All the patients’ consents were taken for the study which was carried out in accordance with the Helsinki Declaration. The methodology involved patients undergoing a two-stage procedure in case of no prior implant or a three-stage procedure in case of a previous implant. Firstly, debridement and implant removal were done. The second was a definitive procedure in form of knee arthrodesis with ring fixator and finally followed by limb lengthening surgery.

Arthrodesis was planned in view of infection, non-union, severe arthritic, subluxated knee, stiff knee, non-salvage knee joint, and financial constraints. After all the patients demonstrated wound healing in 3 months along with good radiographic osteogenesis at the knee arthrodesis site, limb lengthening surgeries by tibial osteotomy were done to overcome the limb length discrepancy. Distraction was started and followed up for 5 months. All 10 patients showed results with sound knee arthrodesis and good osteogenesis at the osteotomy site followed by achieving the limb length just 1-inch short from the normal side to achieve ground clearance while walking. Our case series is unique and distinctive as it shows that when patients with infected nonunion of distal femur come with the stiff and non-salvage knee with severe arthritic changes and financial constraints, we should consider knee arthrodesis with Ilizarov ring fixator followed by limb lengthening surgery.

Osteonecrosis is a potentially devastating condition with poorly defined pathogenesis that can affect several anatomical areas with or without a previous traumatic insult. Post traumatic osteonecrosis (PON) in the foot and ankle has been commonly described in the talus and navicular but rarely in the distal tibia. PON of the distal tibia is a rarely reported and infrequent complication of fracture dislocations of the ankle. Its scarcity can lead to misdiagnosis and inappropriate management due to a lack of clinical knowledge or suspicion with resultant severe functional compromise. We aim to highlight the clinical and radiological features of PON of the distal tibia and report the findings in a series of four patients following a fracture dislocation of the ankle. Three patients sustained a SER4 fracture dislocation and one patient sustained a PER4 fracture dislocation in keeping with standard patterns of injury seen in most trauma units. In each case, PON of the distal tibia presented with progressive anterolateral tibial plafond collapse and valgus deformity of the ankle. The radiological features previously reported in the literature are based on plain film x-ray, CT and MRI but no description of SPECT-CT findings. One of the patients in the series underwent SPECT-CT following clinical suspicion of PON and thus we describe the findings not previously reported. Our objective is to highlight this rare condition as a potential cause for ongoing pain following fracture dislocation of the ankle as well as advocating the use of SPECT/CT as a useful imaging modality to aid in the diagnosis.

Management of ankle arthritis in young patients is challenging. Although ankle arthrodesis gives consistent pain relief, it leads to loss of function and adjacent joint arthritis. Ankle joint distraction (AJD) has been shown to give good outcomes in adults with osteoarthritis or post-traumatic arthritis. The efficacy in children or young adults and those with juvenile idiopathic arthritis is less well evidenced. Clinical notes and radiographs of all patients (n=6) managed with AJD in one tertiary referral centre were retrospectively reviewed. Radiographs were taken pre-surgery, intra-operatively, 1 month following frame removal and at the last follow up, tibiotalar joint space was assessed using ImageJ software. Measurements were taken at the medial, middle and lateral talar dome using frame components as reference. Radiographic data for patients with a good clinical outcome was compared with those who did not. At time of surgery mean age was 16.1 years (12 – 25 years). Mean follow up was 3.4 years (1.5 – 5.9 years). Indications were juvenile idiopathic arthritis (4) post-traumatic (1) and post-infective arthritis (1). Three patients at last follow up had a good clinical outcome. Two patients required revision to arthrodesis (1.3 and 2.4 years following distraction). One patient had spontaneous fusion. One patient required oral antibiotics for pin site infection. Inter-observer reliability was 95%. Mean joint space was 1.17mm (SD = 0.87mm) pre-operatively which increased to 6.72mm (SD = 2.23mm) at the time of distraction and 2.09mm (SD = 1.14mm) at the time of removal. At one-year follow up, mean joint space was 1.96mm (SD = 1.97mm). Outcomes following AJD in this population are variable although significant benefits were demonstrated for 50% of the patients in this series. Radiographic joint space preoperatively did not appear to be associated with need for arthrodesis. Further research in larger groups of young patients is required

Introduction and Objective. The surgical strategy for acetabular component revision is determined by available host bone stock. Acetabular bone deficiencies vary from cavitary or segmental defects to complete discontinuity. For segmental acetabular defects with more than 50% of the graft supporting the cup it is recommended the application of reinforcement ring or ilioischial antiprotrusio devices. Acetabular reconstruction with the use of the antiprotrusion cage (APC) and allografts represents a reliable procedure to manage severe periprosthetic deficiencies with highly successful long-term outcomes in revision arthroplasty. Objective. We present our experience, results, critical issues and technical innovations aimed at improving survival rates of antiprotrusio cages. Materials and Methods. From 2004 to 2019 we performed 69 revisions of the acetabulum using defrosted morcellized bone graft and the Burch Schneider anti-protrusion cage. The approach was direct lateral in 25 cases, direct anterior in 44. Patients were re-evaluated with standard radiography and clinical examination. Results. Eight patients died from causes not related to surgery, and two patients were not available for follow up. Five patients were reviewed for, respectively, non-osseointegration of the ring, post-traumatic loosening with rupture of the screws preceded by the appearance of supero-medial radiolucency, post-traumatic rupture of the distal flange, post-traumatic rupture of the cemented polyethylene-ceramic insert, and dislocation treated with new dual-mobility insert. Among these cases, the first three did not show macroscopic signs of osseointegration of the ring, and the only areas of stability were represented by the bone-cement contact at the holes in the ring. Although radiographic studies have shown fast remodeling of the bone graft and the implant survival range from 70% to 100% in the 10-year follow up, the actual osseointegration of the ring has yet to be clarified. To improve osseointegration of the currently available APC whose metal surface in contact with the bone is sandblasted, we combined the main features of the APC design long validated by surgical experience with the 3D-Metal Technology for high porosity of the external surface already applied to and validated with the press fit cups. The new APC design is produced with the 3D-Metal technology using Titanium alloy (Ti6Al4V ELI) that Improves fatigue resistance, primary stability and favorable environment for bone graft ingrowth. We preview the results of the first cases with short-term follow up. Conclusions. Acetabular reconstruction with impacted morcellized bone graft and APC is a current and reliable surgical technique that allows the restoration of bone loss with a high survival rate of the implant in the medium to long term. The new 3D Metal Cage is designed to offer high friction for the initial stability. The high porosity of the 3D Metal structure creates a favorable environment for bone growth, thus providing valid secondary fixation reproducing the results achieved with the 3D metal press fit cup

Introduction and Objective. Virtual Surgical Planning (VSP) is becoming an increasingly important means of improving skills acquisition, optimizing clinical outcomes, and promoting patient safety in orthopedics and traumatology. Pediatric Orthopedics (PO) often deals with the surgical treatment of congenital or acquired limbs and spine deformities during infancy. The objective is to restore function, improve aesthetics, and ensure proper residual growth of limbs and spine, using osteotomies, bone grafts, age-specific or custom-made hardware and implants. Materials and Methods. Three-dimensional (3D) digital models were generated from Computed Tomography (CT) scans, using free open-source software, and the surgery was planned and simulated starting from the 3D digital model. 3D printed sterilizable models were fabricated using a low-cost 3D printer, and animations of the operation were generated with the aim to accurately explain the operation to parents. All procedures were successfully planned using our VSP method and the 3D printed models were used during the operation, improving the understanding of the severely abnormal bony anatomy. Results. The surgery was precisely reproduced according to VSP and the deformities were successfully corrected in eight cases (3 genu varum in Blount disease, 2 coxa vara in pseudo achondroplasia, 1 SCFE, 1 missed Monteggia lesion and 1 post-traumatic forearm malunion deformity). In one case, a focal fibrocartilaginous dysplasia, the intraoperative intentional undersizing of the bone osteotomy produced an incomplete correction of a congenital forearm deformity. Conclusions. Our study describes the application of a safe, effective, user-friendly, VSP process in PO surgery. We are convinced that our study will stimulate the widespread adoption of this technological innovation in routine clinical practice for the treatment of rare congenital and post-traumatic limb deformities during childhood

Infections represent a devastating complication in orthopedic and traumatological surgery, with high rates of morbidity and mortality. An early intervention is essential, and it includes a radical surgical approach supported by targeted intravenous antimicrobial therapy. The availability of parenteral antibiotics at the site of infection is usually poor, so it is crucial to maximize local antibiotic concentration using local carriers. Our work aims to describe the uses of one of these systems, Stimulan®, for the management and prevention of infections at our Institution. Analysing the reported uses of Stimulan®, we identified two major groups: bone substitute and carrier material for local antibiotic therapy. The first group includes its application as a filler of dead spaces within bone or soft tissues resulting from traumatic events or previous surgery. The second group comprehends the use of Stimulan® for the treatment of osteomyelitis, post-traumatic septic events, periprosthetic joint infections, arthroplasty revision surgery, prevention in open fractures, surgery of the diabetic foot, oncological surgery and for all those patients susceptible to a high risk of infection. We used Stimulan® in several complex clinical situations: in PJIs, in DAPRI procedure and both during the first and the second stage of a 2-stage revision surgery; furthermore, we started to exploit this antibiotic carrier also in prophylaxis of surgical site infections, as it happens in open fractures, and when a surgical site remediation is required, like in osteomyelitis following ORIF. Stimulan® is an extremely versatile and polyhedric material, available in the form of beads or paste, and can be mixed to a very broad range of antibiotics to better adapt to different bacteria and their antibiograms, and to surgeon's needs. These properties make it a very useful adjuvant for the management of complex cases of infection, and for their prevention, as well