Stem cells are known to have low levels of intracellular reactive oxygen species (ROS) and high levels of glutathione. ROS are thought to interact with several pathways that affect the transcription machinery required for stem cell differentiation, and are critical for maintaining stem cell function. In this study, we are developing a new fluorescent probe that rapidly and reversibly reacts with glutathione (GSH), the most abundant non-protein thiol in living cells that acts as an antioxidant and redox regulator. Multipotent perivascular progenitor cells derived from human ESCs (hESC-PVPCs): Differentiated ESCs as embryoid bodies in the presence of BMP4 to induce mesoderm differentiation followed by a simple cell selection strategy using attachment of single cells onto collagen-coated dishes. Differential gene expression profiling was performed among H9 hESCs, EBs induced by BMP4 and naturally selected CD140B+CD44+ population at Day 7 (PVPCs). Colony-forming assay: GSHhigh and GSHlow PVPCs were plated on 10-cm tissue culture-treated polystyrene dishes in triplicate in growth medium and cultured for 14 days. Transwell migration assay: GSHhigh and GSHlow PVPCs at passage 4 were resuspended at 1 × 10. 6. /mL in the migration medium and seeded in the upper chamber. The following human recombinant SDF-1 and PDGF-AA proteins were used as chemoattractants in the lower compartment. Probe-GSH conjugate shows shifts in fluorescence excitation and emission spectra that enables ratiometric measurement of GSH levels. Using these properties, stem cells can be purified by FACS-based technology according to intracellular GSH level. We are developing a protocol both for comparing GSH level in stem cell from different culture conditions and for preparing stem cells with high-GSH level . Our results reveal that GSHhigh PVPC purified by FACS show increased colony forming ability compared with that GSHlow PVPC, indicating that intracellular GSH contributes to the maintenance of stemness. Moreover, transplantation of GSHlow PVPC is more effective than that of GSHlow PVPC for cartilage regeneration in osteochondral defect. This technique enable FACS-based sorting of stem cells according to intracellular GSH levels and thus investigation of functional role of GSH (high antioxidant capacity) in the stem cell maintenance and chondrogenic differentiation

More and more evidences showed that cartilage harbored local progenitor cells that could differentiate toward osteoblast, chondrocyte, and adipocyte. However, our previous results showed that osteoarthritis derived chondroprogenitor cells (OA-CPC) exhibited strong osteogenic potential even in chondrogenic condition. How to promote their chondrogenic potential is the key for cartilage repair and regeneration in osteoarthritis. Recently, lipid availability was proved to determine skeletal progenitor fate. Therefore, we aim to determine whether lipid inhibition under 3D culture condition could enhance OA-CPC chondrogenesis. Moreover, glucose concentration was also evaluated for chondrogenic capacity. Although there are many researches showed that lower glucose promotes chondrogenesis, in our results, we found that OA-CPC in high concentration of glucose (4.5g/L) with lipid inhibitor (GW1100) showed strongest chondrogenic potential, which could form largest cell pellet with strong proteoglycan staining, COL II expression and no COL I expression. Besides, COL2A1 was increased and COL10A1 was decreased significantly by GW1100 under high glucose condition in 2D culture. Interestingly, although the expression level of MMP13 was not changed by GW1100 at RNA and protein level, less MMP13 protein secreted out of cell nuclear. In summary, we estimated that higher glucose and lower lipid supplies benefit OA-CPC chondrogenesis and cartilage repair

Unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are well-established operative interventions in the treatment of knee osteoarthritis (KOA). However, which of these interventions is more beneficial, to patients with KOA, is not known and remains a topic of much debate. Aims: (i) To determine whether UKA or HTO is more beneficial in the treatment of isolated medial compartment KOA, via an assessment of patient-reported outcome measures (PROMs). (ii) To investigate the relationship between PROMs and radiographic parameters of knee joint orientation/alignment. This longitudinal observational study assessed a total of 42 patients that had undergone UKA (n=23) or HTO (n=19) to treat isolated medial compartment KOA. The PROMs assessed, pre-operatively and 1-year post-operatively, consisted of the: self-administered comorbidity questionnaire; short form-12; oxford knee score; knee injury and osteoarthritis outcome score; and the EQ-5D-5L. The radiographic parameters of knee joint alignment/orientation assessed, pre-operatively and 8-weeks post-operatively, included the: hip-knee-ankle angle; mechanical axis deviation; and the angle of the Mikulicz line. Statistical analysis demonstrated an overall significant (p<0.001), pre-operative to post-operative, improvement in the PROM scores of both groups. There were no significant differences in the post-operative PROM scores of the UKA and HTO group. Correlation analyses revealed that pre-operatively, a more distolaterally angled Mikulicz line was associated with worse knee function (p<0.05) and overall health (p<0.05); a relationship that, until now, has not been investigated nor commented upon within the literature. UKAs and HTOs are both efficacious operations that provide a comparable degree of clinical benefit to patients with isolated medial compartment KOA. To further the scientific/medical community's understanding of the factors that impact upon health-outcomes in KOA, future research should seek to investigate the mechanism underlying the relationship, between Mikulicz line and PROMs, observed within the current study

Medial opening wedge high tibial osteotomy (MOWHTO) is the workhorse procedure for correcting varus malalignment of the knee. There have been recent developments in the synthetic options to fill the osteotomy gap. The current gold standard for filling this osteotomy gap is autologous bone graft which is associated with donor site morbidity. We would like to introduce and describe the process of utilizing the novel Osteopore® 3D printed, honeycomb structured, Polycaprolactone and β-Tricalcium Phosphate wedge for filling the gap in MOWHTO. In the advent of additive manufacturing and the quest for more biocompatible materials, the usage of the Osteopore® bone wedge in MOWHTO is a promising technique that may improve the biomechanical stability as well the healing of the osteotomy gap

This study aimed to characterise the microarchitecture of bone in different species of animal leading to the development of a physiologically relevant 3D printed cellular model of trabecular (Tb) and cortical bone (CB). Using high resolution micro-computed tomography (μ-CT) bone samples from multiple species were scanned and analysed before creating in silico models for 3D printing. Biologically relevant printing materials with physical characteristics similar to that of in vivo bone will be selected and tested for printability. Porcine and murine bone samples were scanned using μ-CT, with a resolution of 4.60 μM for murine and 11 μM for porcine and reconstructed to determine the architectural properties of both Tb and CB independently. A region of interest, 1 mm in height, will be used to generate an in-silico 3D model with dimensions (10 mm. 3. ) and suitable resolution before being translated into printable G code using CAD assisted software. A 1 mm section of each bone was analysed, to determine the differences in the microarchitecture with the intent of setting a benchmark for the developmental 3D in vitro model to be comparable against. In contrast, porcine caudal vertebrae (PCV) have an increased volume due to the size of the bone sample. Interestingly, BV/TR for Tb is similar between species in all samples except murine femur. Murine tibia and PCV have a similar Tb. number and thickness, however different SMI shape and separation. μ-CT scanning and analysis permits tessellation of the 3D output which will lead to the generation of an in silico printable model. Biomaterials are currently under optimisation to allow printability and shape integrity to reflect the morphological and physiological properties of bone

It is still difficult to determine an appropriate hinge position to prevent fracture in the lateral cortex of tibia in the process of making an open wedge during biplane open wedge high tibial osteotomy. The objective of this study was to present a biomechanical basis for determining the hinge position as varus deformity. T Three-dimensional lower extremity models were constructed using Mimics. The tibial wedge started at 40 mm distal to the medial tibial plateau, and osteotomy for three hinge positions was performed toward the head of the fibula, 5 mm proximal from the head of the fibula, and 5 mm distal from the head of the fibula. The three tibial models were made with varus deformity of 5, 10, 15 degrees with heterogeneous material properties. These properties were set to heterogeneous material properties which converted from Hounsfield's unit to Young's modulus by applying empirical equation in existing studies. For a loading condition, displacement at the posterior cut plane was applied referring to Hernigou's table considering varus deformity angle. All computational analyses were performed to calculate von-mises stresses on the tibial wedges. The maximum stress increased to an average of 213±9% when the varus angle was 10 degrees compared to 5 degrees and increased to an average of 154±8.9% when the varus angle was 15 degrees compared to 10 degrees. In addition, the maximum stress of the distal position was 19 times higher than that of the mid position and 5 times higher than that of the proximal position on average. Conclusion:. For varus deformity angles, the maximum stress of the tibial wedge tended to increase as the varus deformity angle increased. For hinge position of tibial wedge, maximum stress was the lowest in the mid position, while the highest in the distal position. *This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2022R1A2C1009995)

Femoroacetabular impingement (FAI) results from a morphological deformity of the hip and is associated with osteoarthritis (OA). Increased bone mineral density (BMD) is observed in the antero-superior acetabulum rim where impingement occurs. It is hypothesized that the repeated abnormal contact leads to damage of the cartilage layer, but could also cause a bone remodelling response according to Wolff's Law. Thus the goal of this study was to assess the relationship between bone metabolic activity measured by PET and BMD measured in CT scans. Five participants with asymptomatic cam deformity, three patients with uni-lateral symptomatic cam FAI and three healthy controls were scanned in a 3T PET-MRI scanner following injection with [18F]NaF. Bone remodelling activity was quantified with Standard Uptake Values (SUVs). SUVmax was analyzed in the antero-superior acetabular rim, femoral head and head-neck junction. In these same regions, BMD was calculated from CT scans using the calibration phantom included in the scan. The relationship between SUVmax and BMD from corresponding regions was assessed using the coefficient of determination (R. 2. ) from linear regression. High bone activity was seen in the cam deformity and acetabular rim. SUVmax was negatively correlated with BMD in the antero-superior region of the acetabulum (R. 2. =0.30, p=0.08). SUVmax was positively correlated with BMD in the antero-superior head-neck junction of the femur (R. 2. =0.359, p=0.067). Correlations were weak in other regions. Elevated bone turnover was seen in patients with a cam deformity but the relationship to BMD was moderate. This study demonstrates a pathomechanism of hip degeneration associated with FAI deformities, consistent with Wolff's law and the proposed mechanical cause of hip degeneration in FAI. [18F]-NaF PET SUV may be a biomarker of degeneration, especially in early stages of degeneration, when joint preservation surgery is likely to be the most successful

Recently, a new suture was designed to minimize laxity in order to preserve consistent tissue approximation while improving footprint compression after tendon repair. The aims of this study were: (1) to compare the biomechanical competence of two different high strength sutures in terms of slippage and failure load, (2) to investigate the influence of both knots number and different media (air, saline and fat) on the holding capacity of the knots. Alternating surgical knots of two different high-strength sutures (group1: FibreWire; group2: DynaCord; n = 105) were tied on two roller bearings with 50N tightening force. Biomechanical testing was performed in each medium applying ramped monotonic tension to failure defined in terms of either knot slippage or suture rupture. For each group and medium, seven specimens with either 3, 4, 5, 6, or 7 knots each were tested, evaluating their knot slippage and ultimate load to failure. The minimum number of knots preventing slippage failure and thus resulting in suture rupture was determined in each group and medium, and taken as a criterium for better performance when comparing the groups. In each group and medium failure occurred via suture rupture in all specimens for the following minimum knot numbers: group1: air – 7, saline – 7, fat – 7; group2: air – 6; saline – 4; fat – 5. The direct comparison between the groups when using 7 knots demonstrated significantly larger slippage in group1 (6.5 ± 2.2 mm) versus group2 (3.5 ± 0.4 mm) in saline (p < 0.01) but not in the other media (p ≥0.52). Ultimate load was comparable between the two groups for all three media (p ≥ 0.06). The lower number of required knots providing sufficient repair stability, smaller slippage levels and identical suture strength, combined with the known laxity alleviation effect demonstrate advantages of DynaCord versus FibreWire

Critical-sized bone defects remain challenging in the clinical setting. Autologous bone grafting remains preferred by clinicians. However, the use of autologous tissue is associated with donor-site morbidity and limited accessibility to the graft tissue. Advances in the development of synthetic bone substitutes focus on improving their osteoinductive properties. Whereas osteoinductivity has been demonstrated with ceramics, it is still a challenge in case of polymeric composites. One of the approaches to improve the regenerative properties of biomaterials, without changing their synthetic character, is the addition of inorganic ions with known osteogenic and angiogenic properties. We have previously reported that the use of a bioactive composite with high ceramic content composed of poly(ethyleneoxide terephthalate)/poly(butylene terephthalate) (1000PEOT70PBT30, PolyActive, PA) and 50% beta-tricalcium phosphate (β-TCP) with the addition of zinc in a form of a coating of the TCP particles can enhance the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) (3). To further support the regenerative properties of these scaffolds, inorganic ions with known angiogenic properties, copper or cobalt, were added to the coating solution. β-TCP particles were immersed in a zinc and copper or zinc and cobalt solution with a concentration of 15 or 45 mM. 3D porous scaffolds composed of 1000PEOT70PBT30 and pure or coated β-TCP were additively manufactured by 3D fibre deposition. The osteogenic and angiogenic properties of the fabricated scaffolds were tested in vitro through culture with hMSCs and human umbilical vein endothelial cells, respectively. The materials were further evaluated through ectopic implantation in an in vivo mini-pig model. The early expression of relevant osteogenic gene markers (collagen-1, osteocalcin) of hMSCs was upregulated in the presence of lower concentration of inorganic ions. Further analysis will focus on the evaluation of ectopic bone formation and vascularisation of these scaffolds after implantation in a mini-pig ectopic intramuscular model

High tibial osteotomy (HTO) is a joint preserving alternative to knee replacement for medial tibiofemoral osteoarthritis in younger, more active patients. The procedure is technically challenging and limited also by ‘one size fits all’ plates which can result in patient discomfort necessitating plate removal. This clinical trial evaluated A novel custom-made HTO system – TOKA (3D Metal Printing LTD, Bath, UK) for accuracy of osteotomy correction and improvements in clinical outcome scores. The investigation was a single-arm single-centre prospective clinical trial (IRCCS Istituto Ortopedico Rizzoli; ClinicalTrials.gov NCT04574570), with recruitment of 25 patients (19M/6F; average age: 54.4 years; average BMI: 26.8), all of whom received the TOKA HTO 3D planning and surgery. All patients were predominantly diagnosed with isolated medial knee osteoarthritis and with a varus deformity under 20°. Patients were CT scanned pre- and post-operatively for 3D virtual planning and correctional assessment. All surgeries were performed by the lead clinical investigator – a consultant knee surgeon with a specialist interest in and clinical experience of HTO. On average, Knee Society Scores (KSS) improved significantly (p<0.001) by 27.6, 31.2 and 37.2 percentage points respectively by 3-, 6- and 12-months post-surgery respectively. Other measures assessed during the study (KOOS, EQ5D) produced similar increases. Our early experience using custom implants is extremely promising. We believe the reduced profile of the plate, as well as the reduced invasiveness and ease of surgery contributed to faster patient recovery, and improved outcome scores compared to conventional techniques. These clinical outcome results compare very favourably other case-series with published KOOS scores using different devices

Objective. To analyze the short-term outcome after medial open-wedge high tibial osteotomy with a 3D-printing technology in early medial keen osteoarthritis and varus malalignment. Design and Method. 32 knees(28 cases) of mOWHTO (fixation with an angular-stable TomoFix implant(Synthes)) with a 3D-printing technology combined with arhtroscopy were prospectively surveyed with regard to functional outcome(Hospital for special knee score [HSS] score). Pre- and postoperative tibial bone varus angle (TBVA), mechanical medial proximal tibial angle (MPTA), and alignment were analyzed with regard to the result. Results. 32 knees were included (28 patients; mean age 46.5±9.3 years). The follow-up rate was 100% at 1.7±0.6 years (range, 1.2–3.2 years). Pre- and postoperative mechanical tibiofemoral axis were 6.8°±2°of varus and 1.2°± 3.4° of valgus, respectively. HSS score significantly improved from 46.0±18.3 preoperatively to 84±12 at one, 80±7 at two years (P<0.01). Conclusions. Medial open-wedge high tibial osteotomy with a 3D-printing technology combined with arthroscopy in medial keen osteoarthritis and varus malalignment is an accurate and good treatment option. High preoperative TBVA and appropriate corrected angle(0–3° of valgus)) was associated with better functional outcome at final follow-up

High tibial osteotomy (HTO) is an effective surgical treatment for isolated medial compartment knee osteoarthritis; however, widespread adoption is limited due to difficulty in achieving the planned correction, and patient dissatisfaction due to soft tissue irritation. A new HTO system – Tailored Osteotomy Knee Alignment (TOKA®, 3D Metal Printing Ltd, Bath, UK) could potentially address these barriers having a custom titanium plate and titanium surgical guides featuring a unique mechanism for precise osteotomy opening as well as saw cutting and drilling guides. The aim of this study was to assess the accuracy of this novel HTO system using cadaveric specimens; a preclinical testing stage ahead of first-in-human surgery according to the ‘IDEAL-D’ framework for device innovation. Local ethics committee approval was obtained. The novel opening wedge HTO procedure was performed on eight cadaver leg specimens. Whole lower limb CT scans pre- and post-operatively provided geometrical assessment quantifying the discrepancy between pre-planned and post-operative measurements for key variables: the gap opening angle and the patient specific surgical instrumentation positioning and rotation - assessed using the implanted plate. The average discrepancy between the pre-operative plan and the post-operative osteotomy correction angle was: 0.0 ± 0.2°. The R2 value for the regression correlation was 0.95. The average error in implant positioning was −0.4 ± 4.3 mm, −2.6 ± 3.4 mm and 3.1 ± 1.7° vertically, horizontally, and rotationally respectively. This novel HTO surgery has greater accuracy and smaller variability in correction angle achieved compared to that reported for conventional or other patient specific methods with published data available. This system could potentially improve the accuracy and reliability of osteotomy correction angles achieved surgically

Varus malalignment increases the susceptibility of cartilage to mechanical overloading, which stimulates catabolic metabolism to break down the extracellular matrix and lead to osteoarthritis (OA). The altered mechanical axis from the hip, knee to ankle leads to knee joint pain and ensuing cartilage wear and deterioration, which impact millions of the aged population. Stabilization of the remaining damaged cartilage, and prevention of further deterioration, could provide immense clinical utility and prolong joint function. Our previous work showed that high tibial osteotomy (HTO) could shift the mechanical stress from an imbalanced status to a neutral alignment. However, the underlying mechanisms of endogenous cartilage stabilization after HTO remain unclear. We hypothesize that cartilage-resident mesenchymal stem cells (MSCs) dampen damaged cartilage injury and promote endogenous repair in a varus malaligned knee. The goal of this study is to further examine whether HTO-mediated off-loading would affect human cartilage-resident MSCs' anabolic and catabolic metabolism. This study was approved by IACUC at Xi'an Jiaotong University. Patients with medial compartment OA (52.75±6.85 yrs, left knee 18, right knee 20) underwent open-wedge HTO by the same surgeons at one single academic sports medicine center. Clinical data was documented by the Epic HIS between the dates of April 2019 and April 2022 and radiographic images were collected with a minimum of 12 months of follow-up. Medial compartment OA with/without medial meniscus injury patients with unilateral Kellgren /Lawrence grade 3–4 was confirmed by X-ray. All incisions of the lower extremity healed well after the HTO operation without incision infection. Joint space width (JSW) was measured by uploading to ImageJ software. The Knee injury and Osteoarthritis Outcome Score (KOOS) toolkit was applied to assess the pain level. Outerbridge scores were obtained from a second-look arthroscopic examination. RNA was extracted to quantify catabolic targets and pro-inflammatory genes (QiaGen). Student's t test for two group comparisons and ANOVA analysis for differences between more than 2 groups were utilized. To understand the role of mechanical loading-induced cartilage repair, we measured the serial changes of joint space width (JSW) after HTO for assessing the state of the cartilage stabilization. Our data showed that HTO increased the JSW, decreased the VAS score and improved the KOOS score significantly. We further scored cartilage lesion severity using the Outerbridge classification under a second-look arthroscopic examination while removing the HTO plate. It showed the cartilage lesion area decreased significantly, the full thickness of cartilage increased and mechanical strength was better compared to the pre-HTO baseline. HTO dampened medial tibiofemoral cartilage degeneration and accelerate cartilage repair from Outerbridge grade 2 to 3 to Outerbridge 0 to 1 compared to untreated varus OA. It suggested that physical loading was involved in HTO-induced cartilage regeneration. Given that HTO surgery increases joint space width and creates a physical loading environment, we hypothesize that HTO could increase cartilage composition and collagen accumulation. Consistent with our observation, a group of cartilage-resident MSCs was identified. Our data further showed decreased expression of RUNX2, COL10 and increased SOX9 in MSCs at the RNA level, indicating that catabolic activities were halted during mechanical off-loading. To understand the role of cartilage-resident MSCs in cartilage repair in a biophysical environment, we investigated the differentiation potential of MSCs under 3-dimensional mechanical loading conditions. The physical loading inhibited catabolic markers (IL-1 and IL-6) and increased anabolic markers (SOX9, COL2). Knee-preserved HTO intervention alleviates varus malalignment-related knee joint pain, improves daily and recreation function, and repairs degenerated cartilage of medial compartment OA. The off-loading effect of HTO may allow the mechanoregulation of cartilage repair through the differentiation of endogenous cartilage-derived MSCs

Background. Medial open wedge high tibial osteotomy (MOWHTO) has been accepted as a highly effective option for the treatment of medial unicompartmental osteoarthritis of the knee. Although pain in the medial joint line is significantly relieved after MOWHTO, some patients complain of pain over pes anserinus after the osteotomy, necessitating implant removal for pain relief. Purpose. The purpose of this study is to define the implant removal rate after MOWHTO due to patient complaints. Methods. 103 knees of 72 patients who underwent MOWHTO for medial unicompartmental osteoarthritis between 2010 and 2018 with a follow-up of at least 24 months were enrolled in the study. Patients were evaluated with the Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS) and Visual Analogue Score (VAS) for pain in the medial knee joint (VAS-MJ). All tests were performed before the surgery, at 12 months after surgery. VAS value for pain over pes anserinus (VAS-PA) was recorded at 12 months after MOWHTO and at 3 months after implant removal. Results. Mean follow-up was 31±5.4 months. TomoFix® medial high tibia plate (DePuy Synthes, Raynham, MA, USA) was used for the fixation of osteotomy in all cases. Significant improvement in KOOS, OKS and VAS-MJ were observed 12 months after MOWHTO. Average values of VAS-MJ and VAS-PA were 21.7±7.1 and 34±8.4, respectively. Implant removal was needed for 65 (63.1%) knees. There were no significant differences in regard of postoperative KOOS (p=0.134), OKS (p=0.287) and VAS-MJ (p=0.416) scores between patients for which implant removal was needed or not. VAS-PA value decreased significantly at 3 months after implant removal (p<0.001). Conclusion. A large portion of patients needed implant removal after MOWHTO to relieve pain over pes anserinus even if knee function was significantly improved. Lower profile plates may be preferred to avoid secondary implant removal surgery after MOWHTO

Introduction. Simultaneous correction of knee varus malalignment with medial open wedge high tibial osteotomy (MOWHTO) combined with anterior cruciate ligament (ACL) surgery aims to address symptomatic unicompartmental osteoarthritis in addition to restore knee stability in order to improve outcomes. The aim of this study is to present at least 5 years results of 32 patients who underwent simultaneous knee realignment osteotomy with ACL surgery. Methods. Patients with symptomatic instability due to chronic ACL deficiency or failed previous ACL surgery together with a varus malalignment of ≥6°, previous medial meniscectomy and symptomatic medial compartment pain who were treated with MOWHTO combined with ACL surgery were enrolled. ACL surgery was performed with the anatomical single bundle all-inside technique using TightRope. ®. RT (Arthrex, Naples, FL, USA) and MOWHTO using TomoFix. ®. medial high tibia plate (DePuy Synthes, Raynham, MA, USA) in all cases. Patients were evaluated preoperatively and at 6 months, 12 months and annually postoperatively using the Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS) and Euroqol's Visual Analogue Score (VAS) for pain. Results. 32 patients (22 men and 10 women) with a mean age of 41.2 years and mean BMI of 28.6 kg/m. 2. , underwent the combined procedures. Tibiofemoral neutral re-alignment was achieved in all patients with HTO. Complete subjective and objective scores have been obtained in 84.4% of patients with at least 5 years of follow-up (mean 8.7 years). An improvement in total KOOS of 27.1 points (p<0.003), OKS of 15.1 (p<0.003) and VAS for pain of 24.7 points (p<0.001) were detected. No ACL reconstruction failure was noted. Complications consisted of one superficial wound infection and one delayed union. Plate removal was needed in 20 (62.5%) patients due to pes anserinus pain. Conclusions. Simultaneous restoration of coronal knee axis by applying HTO and stability by ACL reconstruction/revision were reported to offer excellent improvement in early outcomes in patients with ACL rupture and symptomatic unicompartmental osteoarthritis. The combined procedure requires careful pre-operative planning and is therefore technically challenging. However, by restoring the neutral axis and providing stability, it represents a good joint preserving alternative to arthroplasty for active middle-aged patients

The medial opening-wedge high tibial osteotomy (OW-HTO) is an accepted option to treat the isolated medial compartment osteoarthritis (OA) in varus knee. Despite satisfactory outcomes were described in literature, consistent complication rate has been reported and the provided accuracy of coronal alignment correction using conventional HTO techniques falls short. Patient specific instrumentations has been introduced with the aim to reduce complications and to improve the intra-operative accuracy according to the pre-operative plan, which is responsible for the clinical result of the surgery. In this talk, an overview of the clinical results of HTO patient specific instrumentation available in literature will be performed. Moreover, preliminary intra-operative and clinical results of a new customised 3-D printed cutting guide and fixation plate for OW-HTO will be presented

Abstract. OBJECTIVES. Valgus high tibial osteotomy (HTO) represents an effective treatment for patients with medial compartment osteoarthritis (OA) in a varus knee. However, the mechanisms which cause this clinical improvement are unclear. Previous studies suggest a wider stance gait can reduce medial compartment loading via reduction in the external knee adduction moment (KAM); a measure implicated in progression of medial compartment OA. This study aimed to measure whether valgus HTO is associated with a postoperative increase in static stance width. METHODS. 32 patients, recruited in the Biomechanics and Bioengineering Centre Versus Arthritis HTO study, underwent valgus (medial opening wedge) HTO. Weightbearing pre- and post- operative radiographs were taken showing both lower limbs. The horizontal distance, measured from a fixed point on the right talus to the corresponding point on the left, was divided by the talus width to give a standardised “stance width” for each radiograph. The difference between pre- and post- operative stance width was compared for each patient using a paired sample t-test. RESULTS. Preoperatively, mean stance was 4.00 talar-widths but postoperatively this increased to 5.41. This mean increase of 1.42 talar-widths was statistically significant (p=0.001) and represents a mean proportional increase in stance width of 35.5% following HTO. Of the 32 patients, 23 showed increased stance width and 9 decreased (range −4.64 to 6.00 talar-widths). CONCLUSIONS. These findings indicate an association of frontal plane surgical realignment at the proximal tibia via a medial opening wedge HTO with an increased stance width on postoperative radiographs. Considering both wider stance gait and HTO have been shown to affect the progression of medial compartment OA, these results may explain one mechanism contributing to the efficacy of HTO surgery. However, the range of changes in stance width suggests significant variability in how patients adapt at a whole-limb and whole-body level following HTO. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Introduction and Objective. After anterior cruciate ligament reconstruction one of the risk factors for graft (re-)rupture is an increased posterior tibial slope (PTS). The current treatment for PTS is a high tibial osteotomy (HTO). This is a free-hand method, with 1 degree of tibial slope correction considered to be equal to 1 or even 1.67 mm of the anterior wedge resection. Error rates in the frontal plane reported in literature vary from 1 – 8.6 degrees, and in the sagittal plane outcomes in a range of 2 – 8 degrees are reported when planned on PTSs of 3 – 5 degrees. Therefore, the free-hand method is considered to have limited accuracy. It is expected that HTO becomes more accurate with patient specific saw guides (PSGs), with an accuracy margin reported in literature of 2 degrees. This proof of concept porcine cadaver case study aimed to investigate whether the use of PSGs improves the accuracy of HTO to less than 2 degrees. Secondly, the reproducibility of tibial slope measurement was evaluated. Materials and Methods. Preoperative MRI images of porcine cadaver knees (n = 3) were used to create 3D anatomical bone models (Mimics, Materialise, Belgium). These 3D models were subsequently used to develop PSGs (3-Matic, Materialise, Belgium) to correct all tibias for 3 degrees PTS and 4 degrees varus. The PSG mediated HTOs were performed by an experienced orthopaedic surgeon, after which postoperative MRI images were obtained. 3D anatomical models of postoperative tibias were created, and tibial slopes were assessed on both pre- and postoperative tibias. The tibial slope was defined as the angle between the mechanical axis and 3D tibial reference plane in the frontal and sagittal plane. The accuracy of the PSG mediated HTO (median and range) was defined as the difference in all possible combinations of the preoperatively planned and postoperatively obtained tibial slopes. To ensure reproducibility, the pre- and postoperative tibial slopes were measured thrice by one observer. The intra-class correlation coefficients (ICCs) were subsequently calculated to assess the intra-rater reliability (SPSS, IBM Corp., Armonk, N.Y., USA). Results. An accuracy within 2 degrees was achieved in all three cases. The median and range in accuracy for each specimen were +0.46 (−0.57 – 1.45), +0.60 (−1.07 – 1.00), and +0.45 (−0.16 – 0.71) degrees in the frontal plane, and −0.45 (−1.97 – 1.22), −0.80 (−2.42 – 1.77), and 0.00 (−2.19 – 1.93) degrees in the sagittal plane. The pre- and postoperatively planned tibial slopes in the frontal and sagittal plane were measured with a good up to excellent reproducibility. The ICCs of the preoperative planned tibial slopes were 0.82 (95% CI, 0.11 – 1.0), and 0.77 (95% CI, 0.17 – 1.0) for the frontal and sagittal plane, respectively. Postoperative, the ICC for the frontal plane was 0.92 (95% CI, 0.43 – 1.0), and 0.67 (95% CI, −0.06 – 0.99) for the sagittal plane. Conclusions. This proof of concept porcine case study showed an accuracy for the PSG mediated HTO within 2 degrees for each specimen. Moreover, the tibial slopes were measured with a good up to excellent reproducibility. Therefore, the PSG mediated HTO seems to be accurate and might be better than the current used free-hand HTO method. These results offer perspective for implementation of PSG mediated HTO to correct PTS and metaphyseal varus

Higher uric acid levels or hyperuricemia is a product of more uric acid production, dysfunctional renal excretion, or a combination of both leading to deposition of urate crystals in the joints and kidneys and has been strongly linked with the development of gout, that is, acute inflammatory arthritis. Uric acid levels have been suggested to depend on multiple factors including lifestyle, diet, alcohol consumption, etc. As these are risk parameters for hyperuricemia and since lifestyle choices vary amongst different Indian communities, we sought to study the prevalence of hyperuricemia in these communities. Also, large-scale data (in terms of gender, age, lifestyle, community) on the prevalence of hyperuricemia in subjects amongst different community populations, Hindu, Muslim, Sikh, and Christian was generated.

In a retrospective study conducted at Dr. D. Y. Patil School of Medicine & Research Centre, Navi Mumbai from April 2018 to May 2021, information was gathered from four major communities on a range of indicators including serum uric acid levels followed by a thorough multilevel logistic analysis. We evaluated uric acid levels in 10,378 patients of four different communities. Outcomes were assessed biochemically as well as clinically based on the levels of serum uric acid.

The mean serum uric acid levels were highest in Sikhs (7.6 mg%, n=732) followed by Christians (7.3 mg%, n=892) and then by Hindus (5.9 mg%, n=6846) and Muslims (5.6 mg%, n=1908). About 83.7% of Christians consumed meat in a non-vegetarian diet followed by 45.7% Muslims. Percentage of Christians who binge drink were highest whereas percentage of Sikh people in the heavy drinkers’ category were 5.2%. Further, 9.5% Hindus were current smokers followed by 7.8% Sikhs who smoked at present.

Overall, our study of 10,378 patients demonstrated that the serum uric acid levels varied from one Indian community to another due to varying external factors like diet, age, lifestyle, and addictions. Thus, lifestyle modification in communities with higher serum uric acid levels is highly advocated and this may reduce the healthcare burden of gouty arthritis in these communities.

Objectives. The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy. Methods. Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined. Results. In tenocyte cultures grown under high glucose conditions, gene expressions of NOX1, MMP-2, TIMP-1 and -2 after 48 and 72 hours, NOX4 after 48 hours and IL-6, type III collagen and TIMP-2 after 72 hours were significantly higher than those in control cultures grown under control glucose conditions. Type I collagen expression was significantly lower after 72 hours. ROS accumulation was significantly higher after 48 hours, and cell proliferation after 48 and 72 hours was significantly lower in high glucose than in control glucose conditions. In the diabetic rat model, NOX1 expression within the Achilles tendon was also significantly increased. Conclusion. This study suggests that high glucose conditions upregulate the expression of mRNA for NOX1 and IL-6 and the production of ROS. Moreover, high glucose conditions induce an abnormal tendon matrix expression pattern of type I collagen and a decrease in the proliferation of rat tenocytes. Cite this article: Y. Ueda, A. Inui, Y. Mifune, R. Sakata, T. Muto, Y. Harada, F. Takase, T. Kataoka, T. Kokubu, R. Kuroda. The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo. Bone Joint Res 2018;7:362–372. DOI: 10.1302/2046-3758.75.BJR-2017-0126.R2