Aims

Autologous bone graft (ABG) is considered the ‘gold standard’ among graft materials for bone regeneration. However, complications including limited availability, donor site morbidity, and deterioration of regenerative capacity over time have been reported. P-15 is a synthetic peptide that mimics the cell binding domain of Type-I collagen. This peptide stimulates new bone formation by enhancing osteogenic cell attachment, proliferation, and differentiation. The objective of this study was to conduct a systematic literature review to determine the clinical efficacy and safety of P-15 peptide in bone regeneration throughout the skeletal system.

Cite this article: Bone Joint Res 2024;13(12):790–792.

Periprosthetic joint infection (PJI) represents a complex challenge in orthopaedic surgery associated with substantial morbidity and healthcare expenditures. The debridement, antibiotics, and implant retention (DAIR) protocol is a viable treatment, offering several advantages over exchange arthroplasty. With the evolution of treatment strategies, considerable efforts have been directed towards enhancing the efficacy of DAIR, including the development of a phased debridement protocol for acute PJI management. This article provides an in-depth analysis of DAIR, presenting the outcomes of single-stage, two-stage, and repeated DAIR procedures. It delves into the challenges faced, including patient heterogeneity, pathogen identification, variability in surgical techniques, and antibiotics selection. Moreover, critical factors that influence the decision-making process between single- and two-stage DAIR protocols are addressed, including team composition, timing of the intervention, antibiotic regimens, and both anatomical and implant-related considerations. By providing a comprehensive overview of DAIR protocols and their clinical implications, this annotation aims to elucidate the advancements, challenges, and potential future directions in the application of DAIR for PJI management. It is intended to equip clinicians with the insights required to effectively navigate the complexities of implementing DAIR strategies, thereby facilitating informed decision-making for optimizing patient outcomes.

Cite this article: Bone Joint J 2024;106-B(12):1377–1384.

Introduction. Osteoarthritis (OA) occurs due to a multi-scale degradation of articular cartilage (AC) surface which aggravates the disease condition. Investigating the micro-scale structural alterations and mechano-tribological properties facilitates comprehension of disease-mechanisms to improve future injectable-therapies. This study aims to analyze these properties using various experimental and analytical methods to establish correlations between their morpho-physiological features. Method. In this study, Raman-spectroscopy was used to investigate microscale changes in AC constituents and categorize OA damage regions in knee-joint samples from joint replacement patients (Samples = 5 and Regions = 40). Following, microscale indentation and sliding tests were performed on these regions to evaluate variations in aggregate-modulus (AM) and elastic-modulus (EM), with coefficient of friction (COF). Finally, scanning electron microscopy (SEM) was employed to analyze these morphological variations. Result. Raman spectroscopy revealed degree of collagen-damage (Amide-3 α-helix to random-coil ratio I-1250/I-1280), proteoglycan-damage (Sulphated bonds SO. 3-. to CH. 2. twist ratio I-1065/I-1206), amount of bone exposure (Phosphated-hydroxyapatite PO. 4. 3-. to Amide-1 ratio I-959/I-1669) and increased crystallinity (Carbonated hydroxyapatite CO. 3. 2-. to Amide-1 ratio I-1075/I-959) in ECM. Subsequently, these regions were categorized into different groups (G) based on these damages; G1 (Proteoglycan); G2 (Collagen + Proteoglycan); G3 (Collagen + Proteoglycan + Carbonated crystallinity) G4 (Collagen or Proteoglycan + bone exposure); and G5 (Collagen + Proteoglycan + Bone exposure). Further experimentation revealed the differences in mechano-tribological properties (AM, EM, and COF) between the different groups. G5 displayed the highest values of AM (1.5 ± 0.2MPa), EM (0.3 ± 0.01MPa) and COF (0.39 ± 0.08), compared to other groups. These altered properties were confirmed via SEM that revealed micro-asperity junctions, superficial fronding, fibrillations and bone exposure at these damaged regions. Conclusion. This study demonstrated micro-scale changes in AC among OA patients commensurate to the degree of tissue damage, which correlates with disease progression altering joint structure and function particularly in regions with high COF

Aims

The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.

Aims

To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration.

Aims

Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI).

Introduction. Tibial Pilon fractures are potentially limb threatening, yet standards of care are lacking from BOFAS and the BOA. The mantra of “span, scan, plan” describes staged management with external fixation to allow soft tissue resuscitation, followed by a planning CT-scan. Our aim was to evaluate how Tibial Pilon fractures are acutely managed. Methods. ENFORCE was a multi-centre retrospective observational study of the acute management of partial and complete articular Tibial Pilon fractures over a three-year period. Mechanism, imaging, fracture classification, time to fracture reduction and cast, and soft tissue damage control details were determined. Results. 656 patients (670 fractures) across 27 centres were reported. AO fracture classifications were: partial articular (n=294) and complete articular (n=376). Initial diagnostic imaging mobilities were: plain radiographs (n=602) and CT-scan (n=54), with all but 38 cases having a planning CT-scan. 526 fractures had a cast applied in the Emergency Department (91 before radiological diagnosis), with the times taken to obtain post cast imaging being: mean 2.7 hours, median 2.3 hours, range 28 mins – 14 hours). 35% (102/294) of partial articular and 57% (216/376) of complete articular (length unstable) fractures had an external fixator applied, all of which underwent a planning CT-scan. Definitive management consisted of: open reduction internal fixation (n=495), fine wire frame (n=86), spanning external fixator (n=25), intramedullary nail (n=25), other (n=18). Conclusion. The management of Tibial Pilon fractures is variable, with prolonged delays in obtaining post cast reduction radiographs, and just over half of length unstable complete articular fractures being managed with the gold standard “span, scan, plan” staged soft tissue resuscitation. A BOFAS endorsed BOAST (British Orthopaedic Association Standard for Trauma) for Tibial Pilon fractures is suggested for standardisation of the acute management of these potentially limb threatening injuries, together with setting them apart from more straightforward ankle fractures

Aims

This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection.

Aims

The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies.

Aims

Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium.

Aims

This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Abstract. Objectives. A promising therapy for early osteoarthritis (OA) is the transplantation of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs). The synovial fluid (SF) from a pre-clinical ovine model treated with hUC-MSCs has been profiled using proteomics and bioinformatics to elucidate potential mechanisms of therapeutic effect. Methods. Four weeks after a medial meniscus transection surgery, sheep were injected with 10. 7. hUC-MSCs in Phosphate Buffered Saline (PBS) or PBS only (n=7) and sacrificed at 12 weeks. SF was normalised for protein abundance (ProteoMiner. TM. ) and analysed using label-free quantitation proteomics. Bioinformatics analyses (Ingenuity Pathway Analysis (IPA) and STRING) were used to assess differentially regulated functions from the proteomic data. Human orthologues were identified for the ovine proteins using UniProt and DAVID resources and proteins that were ≥±1.3 fold differentially abundant between treatment groups, were included in the bioinformatics analyses. Results. hUC-MSC treated animals demonstrated significantly less joint space narrowing. Nineteen SF proteins were differentially abundant in treated cf. control sheep (FC±2.0; p<0.05). Biglycan (a small leucine-rich proteoglycan of the cartilage extracellular matrix) abundance was increased by 2.1 fold in treated compared to untreated sheep (p=0.024). IPA indicated that lipid synthesis (z-score=1.772; p=0.00267) and immune cell migration pathways (cell movement of mononuclear leukocytes: z-score=1.761; p=0.00259), amongst others, were likely to be activated in the treated sheep. Conversely, tissue damage (z-score=−2; p=0.00019), senescence (z-score=−1.981; p=0.00007) and necrosis (z-score=−1.728; p=0.00829) associated pathways as well as inflammation (z-score=−1.718; p=0.00057) and vascular permeability (z-score=−1.698; p=0.00002) were likely to be inhibited in treated cf. untreated sheep. Conclusions. hUC-MSC treatment prevented/delayed OA progression, demonstrated via a reduction in joint space narrowing. SF proteome bioinformatics revealed potential mechanisms of therapeutic action related to immunomodulation and the inhibition of multiple cell death, and tissue damage associated pathways. Further, a potential predicted upregulation in lipid synthesis in treated sheep represents a novel mechanism warranting further investigation. Additional work is required to validate these discovery phase proteomic findings in studies which specifically target and manipulate the proposed mechanisms highlighted. 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

Abstract. Background. Ultrasonic cutting of bone boasts many advantages over alternatively powered surgical instruments, including but not limited to: elimination of swarf, reduced reaction forces, increased precision in cutting and reduced adjacent soft tissue damage, reduced post-operative complications such as bleeding and bone fracture, reduced healing time, reduced intra-operative noise and ease of handling. Despite ultrasonic cutting devices being well established in oral and maxillofacial surgery, applications in orthopaedic surgery are more niche and are not as well understood. The aim of this study was to investigate the cutting speed (mm/s) and cutting forces (N) of orthopaedic surgeons using a custom-designed state of the art ultrasonic cutting tool to cut fresh human bone samples. Methods. A setup based on the Robot Operating System (ROS) and AprilTag was designed to track and to record the real time position of the ultrasonic cutting tool in space. Synchronised load cell axial force readings of three separate orthopaedic surgeons during ultrasonic cutting were recorded. Each surgeon was asked to find a comfortable position that reflects as close as possible their clinical handling of a cutting instrument used in surgery, and to perform two cuts in each of three samples of human cortical bone. Bone samples were obtained following ethical approval from an institutional review board (ethics approval number: SR1342) and prior informed consent was obtained from all patients. Bone samples were extracted from the femoral neck region of three hip osteoarthritis patients. During cutting, surgeons were allowed a total cutting time of one minute and cutting was conducted using an ultrasonic tool with frequency of a 35kHz (35.7 µm peak to peak displacement amplitude) under constant irrigation using a MINIPULS® 3 Peristaltic pump (38 revolutions per minute) using Phosphate-Buffered Saline (PBS) at 25°C. From the recorded data, the average instantaneous cutting velocity was calculated and the maximum cutting force was identified. Results. All surgeons assumed a back-and-forth cutting motion, variation in the applied cutting force was observed. The average vertical cutting speed, axial cutting force and cutting depth across all surgeons and all samples was 1.64 mm/s, 1.91 N and 0.73 mm, respectively. While increasing the axial cutting force resulted in a deeper cut, overloading of the ultrasound transducer occurred when the tool advanced too quickly into the bone tissue during cutting. The exact force threshold, or the optimal speed at which the surgeon can maintain a constant force during cutting, requires further investigation. Conclusions. In this study, all surgeons cut using a back-and-forth cutting motion, with variation in the applied cutting force which may ultimately inform which clinical applications in orthopaedic engineering are most suitable for this technology. Applying too much force caused overloading of the ultrasound transducer, which is a limitation with the current cutting tool. The results from this study may facilitate the eventual uptake of ultrasonic cutting tools for application in orthopaedic surgery. 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

In 2020 almost 90% of femoral heads for total hip implants in Germany were made of ceramic. Nevertheless, the cellular interactions and abrasion mechanisms in vivo have not been fully understood until now. Metal transfer from the head-neck taper connection, occurring as smear or large-area deposit, negatively influences the surface quality of the articulating bearing. In order to prevent metal transfer, damage patterns of 40 Biolox delta ceramic retrievals with CoC and CoPE bearings were analysed. A classification of damage type and severity for each component (n=40) was done according to an established scoring system. To investigate the physical properties, the surface quality was measured using confocal microscopy, quantitative analysis of phase composition were performed by Raman spectroscopy and qualitative analysis of metal traces was done by scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDX). The periprosthetic tissue was analysed for abrasion particles with SEM and EDX. Both bearing types show different damage patterns. Dotted/ drizzled metal smears were identified in 82 % of CoC (n=16) and 96 % of CoPE (n=24) bearings. Most traces on the ceramic heads were identified in the proximal area while they were observed predominantly in the distal area for the ceramic inlays. The identified marks are similar to those of metallic bearings. Metallic smears lead to an increase of up to 30 % in the monoclinic crystalline phase of the ceramic. The roughness increases by up to six times to Ra=48 nm. Ceramic and metallic wear particles from the articulating surfaces or head neck taper junctions were found in the periprosthetic tissue. Damage patterns on CoC hip implants seem to be similar to those of metallic implants. More detailed analysis of CoC implants are needed to understand the described damage patterns and provide advice for prevention

Mesenchymal stem cells (MSCs) have the potential to repair and regenerate damaged tissues in response to injury, such as fracture or other tissue injury. Bone marrow and adipose tissue are the major sources of MSCs. Previous studies suggested that the regenerative activity of stem cells can be enhanced by exposure to tissue microenvironments. The aim of our project was to investigate whether extracellular matrix (ECM) engineered from human induced pluripotent stem cells-derived mesenchymal-like progenitors (hiPSCs-MPs) can enhance the regenerative potential of human bone marrow mesenchymal stromal cells (hBMSCs). ECM was engineered from hiPSC-MPs. ECM structure and composition were characterized before and after decellularization using immunofluorescence and biochemical assays. hBMSCs were cultured on the engineered ECM, and differentiated into osteogenic, chondrogenic and adipogenic lineages. Growth and differentiation responses were compared to tissue culture plastic controls. Decellularization of ECM resulted in efficient cell elimination, as observed in our previous studies. Cultivation hBMSCs on the ECM in osteogenic medium significantly increased hBMSC growth, collagen deposition and alkaline phosphatase activity. Furthermore, expression of osteogenic genes and matrix mineralization were significantly higher compared to plastic controls. Chondrogenic micromass culture on the ECM significantly increased cell growth and expression of chondrogenic markers, including glycosaminoglycans and collagen type II. Adipogenic differentiation of hBMSCs on the ECM resulted in significantly increased hBMSC growth, but significantly reduced lipid vacuole deposition compared to plastic controls. Together, our studies suggest that BMSCs differentiation into osteogenic and chondrogenic lineages can be enhanced, whereas adipogenic activity is decreased by the culture on engineered ECM. Contribution of specific matrix components and underlying mechanisms need to be further elucidated. Our studies suggest that the three-lineage differentiation of aged BMSCs can be modulated by culture on hiPSC-engineered ECM. Further studies are aimed at scaling-up to three-dimensional ECM constructs for osteochondral tissue regeneration

Irrigation with antiseptic agents, antibiotics, and surfactants are used for treatment and prevention of infections. Despite desirable microbicidal actions, studies have demonstrated cytotoxic effects on host tissue that may impair healing. This study investigated the extent of tissue damage caused by commonly used irrigation solutions in the presence or absence of infection. Air pouches created in 60 balb/c mice were divided into two groups (n=30): infected with Staphylococcus aureus and control. One week later the infected group was subdivided into 5 subgroups (n=6) based on irrigation solutions and by day 0 (immediately) and day7 after irrigation (n=3). Solutions included Saline, Bacitracin, Clorpactin, Irrisept and Bactisure. In infected group wash fluid was collected for quantitative analysis of bacterial growth. At the specified times mice were sacrificed, pouch tissue sent for histology, and sections analyzed for inflammation, necrosis, and edema. Inflammation decreased in infected vs sterile pouches for all solutions except Bacitracin day 0 and for all solutions day 7 with significance in all except Bacitracin (p<0.05). On day 0, necrosis increased in infected vs sterile pouches in Bacitracin (p=0.006), Irrisept (p=0.18), or Bactisure (p=0.07); however, on day 7, necrosis significantly decreased in infected pouches for all solutions (p<0.05) except for Clorpactin (p=0.18). Edema decreased in infected vs sterile pouches on day 0 for all solutions with significance in saline, Irrisept, and Bacitracin (p<0.05). On day 7, infected pouches had decreased edema in saline, Bacitracin, and Bactisure (p<0.05) and increased in Irrisept (p<0.05) and Clorpactin (p=0.069) compared to sterile pouches. Bacterial culture of washouts demonstrated that Clorpactin, Irrisept and Bactisure controlled the infection, whereas saline and Bacitracin showed bacterial multiplication 3.9 × 10^7 CFU/ml and 6.7 × 10^7 CFU/ml respectively. Bacitracin wash showed significantly more bacteria growth compared to Clorpactin (p=0.024), Irrisept (p=0.025) and Bactisure (p=0.025). Tissue damage varied with irrigation solutions and the presence or absence of infection. Presence of bacteria appeared to lead to less tissue inflammation and edema. Tissue necrosis varied over time with different solutions. Surgeons must weigh risks and benefits when selecting solutions and determining when to irrigate