Common tendon injuries impair healing, leading to debilitation and an increased re-rupture risk. The impact of oxygen-sensing pathways on repair mechanisms, vital in regulating inflammation and fibrosis, remains unclear despite their relevance in tendon pathologies. Recent studies show that pulsed electromagnetic field (PEMF) reduce inflammation in human tendon cells (hTDCs) and in hypoxia-induced inflammation. We investigated the hypoxia's impact (1% and 2% oxygen tension) using magnetic cell sheet constructs (IL-1β-magCSs) primed with IL-1β. IL-1β-magCSs were exposed to low OT (1h, 4h,6h) in a hypoxic chamber. To confirm the role of PEMF (5Hz, 4mT, 50% duty cycle) on hypoxia modulation, IL-1β-magCSs, previously exposed to OT, were 1h-stimulated with PEMF. Our results show a significant increase in HIF- 1a and HIF-2a expression on IL-1β-magCSs after exposure to 2%-OT at all time points, compared to 1%- OT and normoxia. TNFa, IL-6, and IL-8 expression increased after 6 hours of 1%-OT exposure. PEMF stimulation of hypoxic IL-1β-magCSs led to decreased pro-inflammatory genes and increased anti-inflammatory (IL-4,IL-10) expression compared to unstimulated magCSs. IFN-g, TNF-α, and IL-6 release increased after 6 hours, regardless of %-OT, while IL-10 levels tended to rise after PEMF stimulation at 2%-OT. Also, NFkB expression was increased on IL-1β-magCSs exposed to 4 h and 6 h of 2%-OT, suggesting a link between NFkB and the production of pro-inflammatory factors. Moreover, PEMF stimulation showed a significantly decreased NFkB level in IL-1β-magCSs.

Overall, low OT enhances expression of hypoxia-associated genes and inflammatory markers in IL-1β-magCSs with the involvement of NFkB. PEMF modulates the response of magCSs, previously conditioned to hypoxia and to inflammatory triggers, favouring expression of anti-inflammatory genes and proteins, supporting PEMF impact in pro-regenerative tendon strategies.

Acknowledgements: ERC CoG MagTendon(No.772817), FCT under the Scientific Employment Stimulus-2020.01157.CEECIND. Thanks to Hospital da Prelada for providing tendon tissue samples (Portugal), and TERM

RES Hub (Norte-01-0145-FEDER-022190).

Early identification of patients at risk for impaired tendon healing and corresponding novel therapeutic approaches are urgent medical needs. This study aimed to clarify the role of CD3+ T-cells during acute Achilles tendon (AT) healing. Blood and hematoma aspirate were taken from 26 patients during AT reconstruction, and additional blood samples were obtained during clinical follow-up at 6, 26 and 52 weeks after surgery. T-cell subsets were analyzed by flow cytometry using CD3, CD4, CD8, CD11a, CD57 and CD28 antibodies. Clinical follow-up included functional tests, MRI assessments, and subjective questionnaires. In vitro, the functional behavior of patient-derived tenocytes was investigated in co-cultures with autologous unpolarized CD4+ or CD8+ T-cells, or IFNy-polarized CD8+ or IL17-polarized CD4+ Tcells (n=5-6). This included alterations in gene expression (qPCR), MMP secretion (ELISA), migration rate (scratch wound healing assay) or contractility (collagen gels). Analysis revealed that elevated CD4+ T-cell levels and reduced CD8+ T-cell levels (increased CD4/CD8 ratio) in hematoma aspirate and pre-operative blood were associated with inferior clinical outcomes regarding pain and function at 26 and 52 weeks. Increased levels of CD8+ -memory T-cell subpopulations in blood 6 weeks after surgery were associated with less tendon elongation. In vitro, tenocytes showed increased MMP1/2/3 levels and collagen III/I ratio in co-culture with unpolarized and/or IL17-polarized CD4+ T-cells compared to unpolarized CD8+ T-cells. This coincided with increased IL17 receptor expression in tenocytes co-cultured with CD4+ T-cells. Exposure of tenocytes to IL17-polarized CD4+ T-cells decreased their migration rate and increased their matrix contractility, especially compared to IFNy-polarized CD8+ T-cells. The CD4+ /CD8+ T-cell ratio could serve as prognostic marker for early identification of patients with impaired AT healing potential. Local reduction of CD4+ T-cell levels or their IL17 secretion represent a potential therapeutic approach to improve AT healing and to prevent weakening of the tendon ECM.

A spine compression fracture is a very common form of fracture in elderly with osteoporosis. Injection of polymethyl methacrylate (PMMA) to fracture sites is a minimally invasive surgical treatment, but PMMA has considerable clinical risks. We develop a novel type thermoplastic injectable bone substitute contains the proprietary composites of synthetic ceramic bone substitute and absorbable thermoplastic polymer.

We used thermoplastic biocompatible polymers Polycaproactone (PCL) to encapsulate calcium-based bone substitutes hydroxyapatite (Ca10(PO4)6(OH)2, HA) and tricalcium phosphate (TCP) to form a biodegradable injectable bone composite material. The space occupation ration PCL:HA/TCP is 1:9. After heating process, it can be injected to fracture site by specific instrument and then self-setting to immediate reinforce the vertebral body.

The thermoplastic injection bone substitute can obtain good injection properties after being heated by a heater at 90˚C for three minutes, and has good anti-washout property when injected into normal saline at 37˚C. After three minutes, solidification is achieved. Mechanical properties were assessed using the material compression test system and the mechanical support close to the vertebral spongy bone.

In vitro cytotoxicity MTT assay (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was performed and no cell cytotoxicity was observed.

In vivo study with three New Zealand rabbits was performed, well bone growth into bone substitute was observed and can maintain good mechanical support after three months implantation.

The novel type thermoplastic injection bone substitute can achieve (a) adequate injectability and viscosity without the risk of cement leakage; (b) adequate mechanical strength for immediate reinforcement and prevent adjacent fracture; (c) adequate porosity for new bone ingrowth; (e) biodegradability. It could be developed as a new option for treating vertebral compression fractures.

Articular cartilage (AC) and subchondral bone (SB) are intimately intertwined, forming a complex unit called the AC-SB interface. Our recent studies have shown that cartilage and bone marrow are connected by a three-dimensional network of microchannels (i.e. cartilage-bone marrow microchannel connector; CMMC), which differ microarchitecturally in number, size and morphology depending on the maturation stage of the bone and the region of the joint. However, the pathological significance of CMMC is largely unknown. Here, we quantitatively assessed how CMMC microarchitecture relates to cartilage condition and regional differences in early idiopathic osteoarthritis (OA).

Two groups of cadaveric female human femoral heads (intact cartilage vs early cartilage lesions) were identified and biopsy-based high-resolution micro-CT imaging was used. Subchondral bone (SB) thickness, CMMC number, maximum and minimum CMMC size, and CMMC morphology were quantified and compared between the two groups. The effect of joint region and cartilage condition on each dependent variable was examined.

The number and morphology of CMMCs were influenced by the region of the joint, but not by the cartilage condition. On the other hand, the minimum and maximum CMMC size was modified by both joint location and cartilage condition. The smallest CMMCs were consistently found in the load bearing region (LBR) of the joint. Compared to healthy subjects, the size of the microchannels was increased in early OA, most notably in the non-load bearing region (NLBR) and the peripheral rim (PR) of the femoral head. In addition, subchondral bone thinning was observed in early OA as a localized event associated with areas of partial chondral defect.

Our data suggest an enlargement of the SB microchannel network and a collective structural deterioration of the SB in early idiopathic OA.

The influence of patient age on functional outcomes after periacetabular osteotomy (PAO) for acetabular dysplasia remains unclear, with previous studies utilising scores developed for older, arthritic patients. The purpose of this study is to assess the influence of patient age on International Hip Outcome Tool (iHOT-12) scores, two years after PAO.

Eighty-six patients (72 female, 14 male; mean age 26.9 years) who underwent PAO by a single surgeon and had completed a minimum of two years follow up were identified. Patients were categorised into three groups according to age at the time of surgery: adolescent (11-20 years; n=29), young adult (21–30 years; n=29), and mature (≥31 years; n=28). The three groups were compared with respect to baseline variables and functional outcomes (iHOT-12, EQ-5D quality of life score, University of California Los Angeles (UCLA) activity score, pain visual analogue score (VAS)). Multivariate regression was undertaken to assess for independent predictors of two-year iHOT-12 score.

The adolescent group demonstrated a lower BMI (p=0.004) while the mature group had a greater American Society of Anaesthesiology (ASA) score (p=0.049). There were otherwise no significant differences in baseline variables between the three groups (all p>0.05).

The three groups demonstrated significant post-operative improvements across all functional outcome measures. There were no significant differences in two-year iHOT-12, EQ-5D, UCLA score or pain VAS between the three groups (all p>0.05). Regression modelling found that patient age at the time of surgery did not have an independent effect on two-year iHOT-12 score (p=0.878).

We found that patient age at the time of surgery did not influence functional outcomes two years after PAO. Our results suggest that patient age should not be considered in isolation as an indication or contraindication for PAO.

Autologous tendon cell injection (ATI) is a promising non-surgical treatment for tendinopathies and tendon tear that address its underlying pathology. The procedure involves harvesting autologous tendon tissue, the isolation of the tendon cells, expansion under quality assured GMP cell laboratory and the injection of the tendon cells via U/S into the degenerative tendon tissue. In clinical practice, the patella (PT) and palmaris longus (PL) tendons are common sites used for tendon tissue biopsy. The objective of this study is to compare the tendon cell quality, identity, purity, doubling time and yield of cells between PT and PL tendons for ATI.

Tendon tissue biopsies were harvested from PT via U/S using a 14-gauge needle or resected surgically from the PL tendon. The biopsies were transported to a GMP cell laboratory, where tendon cells were isolated, cultured and expanded for 4 to 6 weeks, and analysed for viability, cell doubling time, cellular characteristics including cell purity, potency and identity (PPI).

Tendon samples from 149 patients were analysed (63 PT). Average biopsy weight was 62mg for PT and 119mg for PI (p<0.001). Average cell doubling time (83.9 vs 82.7 hours), cellular yield (16.2 vs 15.2×106), viability (98.7 vs 99.0%) and passage number (3 vs 3) were not significantly different between tendons. Additionally, ddPCR analyses showed no differences of PPI including tendon cell markers of collagen type I, scleraxis and tenomodulin. No post-biopsy complications or contamination were reported for either group. Assessing tendon tissue from palmaris tendon is relatively easier.

Tendon tissue biopsy tissue for autologous tendon cell therapy can be obtained from either the PT or PL tendons. Tendon cells isolated from PT and PL were equal in growth characteristics and PPI. There are no differences in the quality of tendon cells isolated from the PT or PL.

A painful “dreaded black line” (DBL) has been associated with progression to complete fractures in atypical femur fractures (AFF). Adjacent sclerosis, an unrecognized radiological finding, has been observed in relation to the DBL. We document its incidence, associated features, demographics and clinical progression.

We reviewed plain radiographs of 109 incomplete AFFs between November 2006 and June 2021 for the presence of sclerosis adjacent to a DBL. Radiographs were reviewed for location of lesions, and presence of focal endosteal or periosteal thickening. We collected demographical data, type and duration of bisphosphonate therapy, and progression to fracture or need for prophylactic stabilization, with a 100% follow up of 72 months (8 – 184 months).

109 femurs in 86 patients were reviewed. Seventeen sclerotic DBLs were observed in 14 patients (3 bilateral), involving 15.6% of all femora and 29.8% of femora with DBLs. Location was mainly subtrochanteric (41.2%), proximal diaphyseal (35.3%) and mid-diaphyseal (23.5%), and were associated with endosteal or periosteal thickening. All patients were female, mostly Chinese (92.9%), with a mean age of 69 years. 12 patients (85.7%) had a history of alendronate therapy, and the remaining 2 patients had zoledronate and denosumab therapy respectively. Mean duration of bisphosphonate therapy was 62 months. 4 femora (23.5%) progressed to complete fractures that were surgically managed, whilst 6 femora (35.3%) required prophylactic fixation.

Peri-lesional sclerosis in DBL is a new radiological finding in AFFs, predominantly found in the proximal half of the femur, at times bilateral, and are always associated with endosteal or periosteal thickening. As a high proportion of patients required surgical intervention, these lesions could suggest non-union of AFFs, similar to the sclerotic margins commonly seen in fractures with non-union. The recognition of and further research into this new feature could shed more light on the pathophysiological progression of AFFs.

µCT images are commonly analysed to assess changes in bone density and architecture in preclinical murine models. Several platforms provide automated analysis of bone architecture parameters from volumetric regions of interest (ROI). However, segmentation of the regions of subchondral bone to create the volumetric ROIs remains a manual and time-consuming task. This study aimed to develop and evaluate automated pipelines for trabecular bone architecture analysis of mouse proximal tibia subchondral bone.

A segmented dataset involving 62 knees (healthy and arthritic) from 10-week male C57BL/6 mice were used to train a U-Net type architecture, with µCT scans (downsampled) input that output segmentation and bone volume density (BV/TV) of the subchondral trabecular bone. Segmentations were upsampled and used in tandem with the original scans (10µ) as input for architecture analysis along with the thresholded trabecular bone. The analysis considered the manually and U-Net segmented ROIs using two available pipelines: the ITKBoneMorphometry library and CTan (SKYSCAN). The analyses included: bone volume (BV), total volume (TV), BV/TV, trabecular number (TbN), trabecular thickness (TbTh), trabecular separation (TbSp), and bone surface density (BSBV).

There was good agreement for bone measures between the manual and U-Net pipelines utilizing ITK (R=0.88-0.98) and CTan (R=0.91-0.98). ITK and CTan showed good agreement for BV, TV, BV/TV, TbTh and BSBV (R=0.9-0.98). However, a limited agreement was seen between TbN (R=0.73) and TbSb (R=0.59) due to methodological differences in how spacing is evaluated.

This U-Net/ITK pipeline seamlessly automated both segmentation and quantification of the proximal tibia subchondral bone. This automated pipeline allows the analysis of large volumes of data, and its open-source nature may enable the standardization of stereologic analysis of trabecular bone across different research groups.

There is still no consensus on which concentration of mesenchymal stem cells (MSCs) to use for promoting fracture healing in a rat model of long bone fracture.

To assess the optimal concentration of MSCs for promoting fracture healing in a rat model.

Wistar rats were divided into four groups according to MSC concentrations: Normal saline (C), 2.5 × 106 (L), 5.0 × 106 (M), and 10.0 × 106 (H) groups. The MSCs were injected directly into the fracture site. The rats were sacrificed at 2 and 6 자 post-fracture. New bone formation [bone volume (BV) and percentage BV (PBV)] was evaluated using micro-computed tomography (CT). Histological analysis was performed to evaluate fracture healing score. The protein expression of factors related to MSC migration [stromal cell-derived factor 1 (SDF-1), transforming growth factor-beta 1 (TGF-β1)] and angiogenesis [vascular endothelial growth factor (VEGF)] was evaluated using western blot analysis. The expression of cytokines associated with osteogenesis [bone morphogenetic protein-2 (BMP-2), TGF-β1 and VEGF] was evaluated using real-time polymerase chain reaction.

Micro-CT showed that BV and PBV was significantly increased in groups M and H compared to that in group C at 6 wk post-fracture (P = 0.040, P = 0.009; P = 0.004, P = 0.001, respectively). Significantly more cartilaginous tissue and immature bone were formed in groups M and H than in group C at 2 and 6 wk post-fracture (P = 0.018, P = 0.010; P = 0.032, P = 0.050, respectively). At 2 wk post fracture, SDF-1, TGF-β1 and VEGF expression were significantly higher in groups M and H than in group L (P = 0.031, P = 0.014; P < 0.001, P < 0.001; P = 0.025, P < 0.001, respectively). BMP-2 and VEGF expression were significantly higher in groups M and H than in group C at 6 wk postfracture (P = 0.037, P = 0.038; P = 0.021, P = 0.010). Compared to group L, TGF-β1 expression was significantly higher in groups H (P = 0.016). There were no significant differences in expression levels of chemokines related to MSC migration, angiogenesis and cytokines associated with osteogenesis between M and H groups at 2 and 6 wk post-fracture.

The administration of at least 5.0 × 106 MSCs was optimal to promote fracture healing in a rat model of long bone fractures.

The objective of this study was to investigate how a new customizable light-curable osteosynthesis method (AdFix) compared to traditional metal hardware when loaded in torsion in an ovine phalanx model.

Twenty-one ovine proximal phalanges were given a 3mm transverse osteotomy and four 1.5mm cortex screws were inserted bicortically on either side of the gap. The light-curable polymer composite was then applied using the method developed by Hutchinson [1] to create osteosyntheses in two groups, having either a narrow (6mm, N=9) or a wide (10mm, N=9) fixation patch. A final group (N=3) was fixated with conventional metal plates. The constructs were loaded in torsion at a rate of 6°/second until failure or 45° of rotation was reached. Torque and angular displacement were measured, torsional stiffness was calculated as the slope of the Torque-Displacement curve, and maximum torque was queried for each specimen.

The torsional stiffnesses of the narrow, wide, and metal plate constructs were 39.1 ± 6.2, 54.4 ± 6.3, and 16.2 ± 3.0 Nmm/° respectively. All groups were statistically different from each other (p<0.001). The maximum torques of the narrow, wide, and metal plate constructs were 424 ± 72, 600 ± 120, and 579 ± 20 Nmm respectively. The narrow constructs were statistically different from the other two (p<0.05), while the wide and metal constructs were not statistically different from each other (p=0.76).

This work demonstrated that the torsional performance of the novel solution is comparable to metal fixators. As a measure of the functional range, the torsional stiffness in the AdhFix exceeded that of the metal plate. Furthermore, the wide patches were able to sustain a similar maximum toque as the metal plates. These results suggest AdhFix to be a viable, customizable alternative to metal implants for fracture fixation in the hand.

Due to their immunomodulatory and regenerative capacity, human bone marrow-derived mesenchymal stromal cells (hBMSCs) are promising in the treatment of polytrauma patients. However, few studies evaluated the effects of sera from polytraumatized patients on hBMSCs. The aim of this study was to explore changes in hBMSCs exposed to serum from polytrauma patients from different time points after trauma.

Sera from 84 patients on day 1 (D1), 5 (D5) and 10 (D10) after polytrauma (ISS ≥ 16) were pooled respectively to test the differential influence on hBMSC. As a control, sera from three healthy age- and gender-matched donors (HS) were collected. The pooled sera were analyzed by Multicytokine Array for pro-/anti-inflammatory cytokines. For the cell culture experiments, hBMSCs from four healthy donors were used. The influence of the different sera on hBMSC regarding cell proliferation, colony forming unit-fibroblast (CFU-F) assay, cell viability and toxicity, cell migration, as well as osteogenic and chondrogenic differentiation was analyzed. One-Way-ANOVA and LSD-test were used for the parametric, Kruskal-Wallis-test for non-parametric data. p≤0.05 was considered as statistically significant.

The results showed that D5 serum reduced hBMSCs cell proliferation capacity by 41.26% (p=0.000) compared with HS and increased the proportion of dead cells by 3.19% (p=0.008) and 2.25% (p=0.020) compared with D1 and D10. The frequency of CFU-F was reduced by 49.08% (p=0.041) in D5 and 53.99% (p=0.027) in D10 compared with HS, whereas the other parameters were not influenced.

The serological effect of polytrauma on hBMSCs was related to the time after trauma. It is disadvantageous to use BMSCs in polytraumatized patients five days after the incidence as obvious cytological changes could be found at that time point. However, it is promising to use hBMSCs to treat polytrauma after 10 days, combined with the concept of “Damage Control Orthopaedics” (DCO).

Following anterior cruciate ligament reconstruction (ACLR) using a semitendinosus (ST) autograft measures such as length, cross-sectional area, and volume may not fully describe the effects of tendon harvest on muscle morphology as these discrete measures cannot characterize three-dimensional muscle shape. This study aimed to determine between-limb ST shape similarity and regional morphology in individuals with a unilateral history of ACLR using a ST graft, and healthy controls.

A secondary analysis of magnetic resonance imaging was undertaken from 18 individuals with unilateral history of ST ACLR and 18 healthy controls. ST muscles were manually segmented, and shape similarity were assessed between limbs and groups using Jaccard index (0-1) and Hausdorff distance (mm). ST length (cm), peak cross-sectional area (CSA) (cm²), and volume (cm³) was compared between surgically reconstructed and uninjured contralateral limbs, and between the left and right limbs of control participants with no history of injury. Cohen's d was reported as a measure of effect size.

Compared to healthy controls, the ACLR group had significantly (p<0.001, d= −2.33) lower bilateral ST shape similarity. Furthermore, the deviation in muscle shape was significantly (p<0.001, d= 2.12) greater in the ACLR group. Within the ACLR group, maximum Hausdorff distance indicated ST from the ACLR limb deviated (23.1±8.68 mm) from the shape of the healthy contralateral ST, this was observed particularly within the distal region of the muscle. Compared to the uninjured contralateral limb and healthy controls, deficits in peak cross-sectional area and volume in ACLR group were largest in proximal (p<0.001, d= −2.52 to −1.28) and middle (p<0.001, d= −1.81 to −1.04) regions.

Findings highlight morphological features in distal ST not identified by traditional discrete morphology measures. ST shape was most different in the distal region of the muscle, despite deficits in CSA and volume being most pronounced in proximal and middle regions. ST shape following ACLR may affect force transmission and distribution within the hamstrings and contribute to persistent deficits in knee flexor and internal rotator strength.

Dislocation is one of the most common complications in total hip arthroplasty (THA) and is primarily driven by bony or prosthetic impingement. The aim of this study was two-fold. First, to develop a simulation that incorporates the functional position of the femur and pelvis and instantaneously determines range of motion (ROM) limits. Second, to assess the number of patients for whom their functional bony alignment escalates impingement risk.

468 patients underwent a preoperative THA planning protocol that included functional x-rays and a lower limb CT scan. The CT scan was segmented and landmarked, and the x-rays were measured for pelvic tilt, femoral rotation, and preoperative leg length discrepancy (LLD). All patients received 3D templating with the same implant combination (Depuy; Corail/Pinnacle). Implants were positioned according to standardised criteria.

Each patient was simulated in a novel ROM simulation that instantaneously calculates bony and prosthetic impingement limits in functional movements. Simulated motions included flexion and standing-external rotation (ER). Each patient's ROM was simulated with their bones oriented in both functional and neutral positions.

13% patients suffered a ROM impingement for functional but not neutral extension-ER. As a result, 48% patients who failed the functional-ER simulation would not be detected without consideration of the functional bony alignment. 16% patients suffered a ROM impingement for functional but not neutral flexion. As a result, 65% patients who failed the flexion simulation would not be detected without consideration of the functional bony alignment.

We have developed a ROM simulation for use with preoperative planning for THA surgery that can solve bony and prosthetic impingement limits instantaneously. The advantage of our ROM simulation over previous simulations is instantaneous impingement detection, not requiring implant geometries to be analysed prior to use, and addressing the functional position of both the femur and pelvis.

Knee swelling is common after injury or surgery, resulting in pain, restricted range of movement and limited mobility. Accurately measuring knee swelling is critical to assess recovery. However, current measurement methods are either unreliable or expensive [1,2]. Therefore, a new measurement method is developed. This wearable (the ‘smart brace’) has shown the ability to distinguish a swollen knee from a not swollen knee using multi-frequency-bio impedance analysis (MF-BIA) [3].

This study aimed to determine the accuracy of this smart brace. The study involved 25 usable measurements on patients treated for unilateral knee osteoartritis with a 5mL injection of Lidocaïne + DepoMedrol (1:4). MF-BIA measurements were taken before and after the injection, both on the treated and untreated knee. The smart brace accurately measured the effect of the injection by a decrease in resistance of up to 2.6% at 100kHz (p<0.01), where commonly used gel electrodes were unable to measure the relative difference. Remarkably, both the smart brace and gel electrodes showed a time component in the MF-BIA measurements.

To further investigate this time component, 10 participants were asked to lie down for 30 minutes, with measurements taken every 3 minutes using both gel electrodes and the smart brace on both legs. The relative change between each time step was calculated to determine changes over time. The results showed presence of a physiological aspect (settling of knee fluids), and for the brace also a mechanical aspect (skin-electrode interface) [4]. The mechanical aspect mainly interfered with reactance values.

Overall, the smart brace is a feasible method for quantitatively measuring knee swelling as a relative change over time. However, the skin-electrode interface should be improved for reliable measurements at different moments in time. The findings suggest that the smart brace could be a promising tool for monitoring knee swelling during rehabilitation.

Our previous rat study demonstrated an ex vivo-created “Biomimetic Hematoma” (BH) that mimics the intrinsic structural properties of normal fracture hematoma, consistently and efficiently enhanced the healing of large bone defects at extremely low doses of rhBMP-2 (0.33 μg). The aim of this study was to determine if an extremely low dose of rhBMP-2 delivered within BH can efficiently heal large bone defects in goats.

Goat 2.5 cm tibial defects were stabilized with circular fixators, and divided into groups (n=2-3): 2.1 mg rhBMP-2 delivered on an absorbable collagen sponge (ACS); 52.5 μg rhBMP-2 delivered within BH; and an empty group. BH was created using autologous blood with a mixture of calcium and thrombin at specific concentrations. Healing was monitored with X-rays. After 8 weeks, femurs were assessed using microCT.

Using 2.1 mg on ACS was sufficient to heal 2.5 cm bone defects. Empty defects resulted in a nonunion after 8 weeks. Radiographic evaluation showed earlier and more robust callus formation with 97.5 % (52.5 μg) less of rhBMP-2 delivered within the BH, and all tibias were fully bridged at 3 weeks. The bone mineral density was significantly higher in defects treated with BH than with ACS. Defects in the BH group had smaller amounts of intramedullary and cortical trabeculation compared to the ACS group, indicating advanced remodeling.

The results confirm that the delivery of rhBMP-2 within the BH was much more efficient than on an ACS. Not only did the large bone defects heal consistently with a 40x lower dose of rhBMP-2, but the quality of the defect regeneration was also superior in the BH group. These findings should significantly influence how rhBMP-2 is delivered clinically to maximize the regenerative capacity of bone healing while minimizing the dose required, thereby reducing the risk of adverse effects.

Iliopsoas tendonitis occurs in up to 30% of patients after hip resurfacing arthroplasty (HRA) and is a common reason for revision. The primary purpose of this study was to validate our novel computational model for quantifying iliopsoas impingement in HRA patients using a case-controlled investigation. Secondary purpose was to compare these results with previously measured THA patients.

We conducted a retrospective search in an experienced surgeon's database for HRA patients with iliopsoas tendonitis, confirmed via the active hip flexion test in supine, and control patients without iliopsoas tendonitis, resulting in two cohorts of 12 patients. The CT scans were segmented, landmarked, and used to simulate the iliopsoas impingement in supine and standing pelvic positions. Three discrete impingement values were output for each pelvic position, and the mean and maximum of these values were reported. Cup prominence was measured using a novel, nearest-neighbour algorithm.

The mean cup prominence for the symptomatic cohort was 10.7mm and 5.1mm for the asymptomatic cohort (p << 0.01). The average standing mean impingement for the symptomatic cohort was 0.1mm and 0.0mm for the asymptomatic cohort (p << 0.01). The average standing maximum impingement for the symptomatic cohort was 0.2mm and 0.0mm for the asymptomatic cohort (p << 0.01). Impingement significantly predicted the probability of pain in logistic regression models and the simulation had a sensitivity of 92%, specificity of 91%, and an AUC ROC curve of 0.95.

Using a case-controlled investigation, we demonstrated that our novel simulation could detect iliopsoas impingement and differentiate between the symptomatic and asymptomatic cohorts. Interestingly, the HRA patients demonstrated less impingement than the THA patients, despite greater cup prominence. In conclusion, this tool has the potential to be used preoperatively, to guide decisions about optimal cup placement, and postoperatively, to assist in the diagnosis of iliopsoas tendonitis.

In the unstable patellofemoral joint (PFJ), the patella will articulate in an abnormal manner, producing an uneven distribution of forces. It is hypothesised that incongruency of the PFJ, even without clinical instability, may lead to degenerative changes. The aim of this study was to record the change in joint contact area of the PFJ after stabilisation surgery using an established and validated MRI mapping technique.

A prospective MRI imaging study of patients with a history of PFJ instability was performed. The patellofemoral joints were imaged with the use of an MRI scan during active movement from 0° through to 40° of flexion. The congruency through measurement of the contact surface area was mapped in 5-mm intervals on axial slices. Post-stabilisation surgery contact area was compared to the pre-surgery contact area.

In all, 26 patients were studied. The cohort included 12 male and 14 female patients with a mean age of 26 (15-43). The greatest mean differences in congruency between pre- and post-stabilised PFJs were observed at 0-10 degrees of flexion (0.54 cm² versus 1.18 cm², p = 0.04) and between 11° and 20° flexion (1.80 cm² versus 3.45 cm²; p = 0.01).

PFJ stabilisation procedures increase joint congruency. If a single axial series is to be obtained on MRI scan to compare the pre- and post-surgery joint congruity, the authors recommend 11° to 20° of tibiofemoral flexion as this was shown to have the greatest difference in contact surface area between pre- and post-operative congruency.

Macrophages play a critical role in innate immunity by promoting or inhibiting tissue inflammation and repair. Classically, macrophages can differentiate into either pro-inflammatory (M1) or pro-reparative (M2) phenotypes in response to various stimuli. Therefore, this study aimed to address how extracellular vesicles (EVs) derived from polarized macrophages can affect the inflammatory response of tendon cells.

For that purpose, human THP-1 cells were stimulated with lipopolysaccharide (LPS), and interleukins -4 and -13 (IL- 4, IL-13), to induce macrophages polarization into M1, M2, and hybrid M1/M2 phenotypes. Subsequently, the EVs were isolated from the culture medium by ultracentrifugation. The impact of these nanovesicles on the inflammation and injury scenarios of human tendon-derived cells (hTDCs), which had previously been stimulated with interleukin- 1 beta (IL-1ß) to mimic an inflammatory scenario, was assessed.

We were able to isolate three different nanovesicles populations, showing the typical shape, size and surface markers of EVs. By extensively analyzing the proteomic expression profiles of M1, M2, and M1/M2, distinct proteins that were upregulated in each type of macrophage-derived EVs were identified. Notably, most of the detected pro- inflammatory cytokines and chemokines had higher expression levels in M1-derived EVs and were mostly absent in M2-derived EVs. Hence, by acting as a biological cue, we observed that M2 macrophage-derived EVs increased the expression of the tendon-related marker tenomodulin (TNMD) and tended to reduce the presence of pro-inflammatory markers in hTDCs. Overall, these preliminary results show that EVs derived from polarized macrophages might be a potential tool to modulate the immune system responses becoming a valuable asset in the tendon repair and regeneration fields worthy to be further explored.

Iliopsoas impingement occurs in between 5-30% of patients after hip arthroplasty and has been thought to only be caused by an oversized cup, cup malpositioning, or the depth of the psoas valley. However, no study has associated the relationship between preoperative measurements with the risk of impingement. This study sought to assess impingement between the iliopsoas and acetabular cup using a novel validated model to determine the risk factors for iliopsoas impingement.

413 patients received lower limb CT scans and lateral x-rays that were segmented, landmarked, and measured using a validated preoperative planning protocol. Implants were positioned according to the preference of ten experienced surgeons. The segmented bones were transformed to the standing reference frame and simulated with a novel computational model that detects impingement between the iliopsoas and acetabular cup. Definitions of patients at-risk and not at-risk of impingement were defined from a previous validation study of the simulation. At-risk patients were propensity score matched to not at-risk patients.

21% of patients were assessed as being at-risk of iliopsoas impingement. Significant differences between at-risk patients and not at-risk patients were observed in standing pelvic tilt (p << 0.01), standing femoral internal rotation (p << 0.01), medio-lateral centre-of-rotation (COR) change (p << 0.01), supine cup anteversion (p << 0.01), pre- to postoperative cup offset change (p << 0.001), postoperative gross offset (p = 0.009), and supero-inferior COR change (p = 0.02).

Impingement between the iliopsoas and acetabular cup is under-studied and may be more common than is published in the literature. Previously it has been thought to only be related to cup size or positioning. However, we have observed significant differences between at-risk and not at-risk patients in additional measurements. This indicates that its occurrence is more complex than simply being related to cup position.

A Morel-Lavallee lesion (MLL) is a benign cystic lesion that occurs due to injury to the soft-tissue envelope's perforating vascular and lymphatic systems, resulting in a distinctive hemolymphatic fluid accumulation between the tissue layers. The MLL has the potential to make a significant impact on the treatment of orthopaedic injuries.

A 79-year-old male patient community ambulatory with assisting aid (cane) known case of Diabetes mellitus, hypertension, bronchial asthma and ischemic heart disease. He was brought to the Emergency, complaining of right hip discomfort and burning sensation for the last 5 days with no history of recent trauma at all. Patient had history of right trochanteric femur fracture 3 years ago, treated with DHS in a privet service. Clinical and Radiological assessment showed that the patient mostly has acute MLL due to lag screw cut out. We offered the patient the surgical intervention, but he refused despite explaining the risks of complications if not treated and preferred to receive the conservative treatment. Compression therapy management explained to him including biker's shorts (instructed to be worn full-time a day) and regular follow up in clinic. Symptom's improvement was reported by the patient in the subsequent visits.

In the polytrauma patient, a delayed diagnosis of these lesions is conceivable due to the presence of more visible injuries. It's located over the greater trochanter more commonly, but sometimes in other areas such as the lower lumbar region, the thigh, or the calf. Incorrect or delayed diagnosis and care can have unfavorable outcomes such as infection, pseudocyst development, and cosmetologically deformity. Magnetic resonance imaging (MRI) and ultrasound will aid in MLL diagnosis. However, the effectiveness of MLL therapy remains debatable.

We strongly believe that the MLL caused due to tangential shear forces applied to the soft tissue leads to accumulation of the blood and/or lymph between the subcutaneous and overlying fascia and it often misdiagnosed due to other distracting injuries. Nontheless, in our case we reported MLL occur due to internal pressure on the fascia caused by cut out of DHS lag screw.