Highly cross-linked polyethylene (HXLPE) greatly reduces wear in total hip arthroplasty, compared to conventional polyethylene (CPE). Cross-linking is commonly achieved by irradiation. This study aimed to compare the degree of cross-linking and in vitro wear rates across a cohort of retrieved and unused polyethylene cups/liners from various brands. Polyethylene acetabular cups/liners were collected at one centre from 1 April 2021 to 30 April 2022. The trans-vinylene index (TVI) and oxidation index (OI) were determined by Fourier-transform infrared spectrometry. Wear was measured using a pin-on-disk test.Aims
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Aim. Treatment of prosthetic joint infection (PJI) by systemic administration of high doses of long-term antibiotics often proves ineffective, causing severe side effects. Thus, we presented the phage Sb-1, which coding extracellular
Introduction. When designing a new osteosynthesis device, the biomechanical competence must be evaluated with respect to the acting loads. In a previous study, the loads on the proximal phalanx during rehabilitation exercises were calculated. This study aimed to assess the safety of a novel customizable osteosynthesis device compared to those loads to determine when failure would occur. Method. Forty proximal phalanges were dissected from skeletally mature female sheep and divided into four testing groups. A custom 3D printed cutting and drilling guide was used to create a reduced osteotomy and pilot holes to insert four 1.5 mm cortical screws. A novel light-curable
Introduction. The incidences of fragility fractures, often because of osteoporosis, are increasing. Research has moved towards bioresorbable scaffolds that provide temporary mechanical stability and promote osteogenesis. This research aims to fabricate a 3D printed composite Poly (l-lactic-co-glycolic acid)-strontium doped tricalcium phosphate (PLGA-SrTCP) scaffold and evaluate in an in vitro co culture study containing osteoporotic donor cells. Method. PLGA, PLGA TCP, and PLGA SrTCP scaffolds were produced using Fused Filament Fabrication (FFF). A four-group 35-day cell culture study was carried out using human bone marrow derived mesenchymal stem cells (hMSCs) from osteoporotic and control donors (monoculture) and hMSCs & human monocytes (hMCs) (Co culture). Outcome measures were biochemical assays, PCR, and cell imaging. Cells were cultured on scaffolds that had been pre-degraded for six weeks at 47°C prior to drying and gamma sterilisation. Result. 3D printed scaffolds were successfully produced by FFF. All groups in the study supported cell attachment onto the scaffolds, producing extracellular matrices as well as evidence of osteoclast cell structures. Osteoporotic cells increased CTSK activity and CAII activity and decreased ALP activity compared to controls. In control cultures, the addition of bTCP and bTCP/Sr to the PLGA reduced TRAP5b, CAII and ALP activity compared to PLGA alone. The addition of Sr did not show any differences between donors. Conclusion. This study details suitability of 3D printed
Introduction. Piezo1 is a mechanosensitive Ca. 2+. ion channel that has been shown to transduce hyper-physiologic mechanical loads in chondrocytes. In osteoarthritic cartilage, Piezo1 expression was shown to be upregulated by interleukin-1 alpha (IL-1α) and resulted in altered calcium dynamics and actin cytoskeleton rarefication. Together these studies highlight the importance of Piezo1 channels during joint injury. However, the mechanism by which Piezo1 regulates chondrocyte physiology and mechanotransduction during homeostasis is still largely unknown. In this study, we investigate the impact of Piezo1 activation on nuclear mechanics and chromatin methylation state. Methods. Porcine chondrocytes (n=3-5 pigs) were treated with Yoda1, a Piezo1-specific agonist, for either 2, 5, 15 or 180 minutes. To characterize chromatin state, we monitored the abundance of a chromatin methylation marker (H3K9Me3) using immunofluorescence (IF). Atomic force microscopy (AFM, 25 nm cantilever) was employed to quantify the nuclear elastic modulus (NEM) of individual cell nuclei. To explore the interplay between cytoskeletal dynamics and nuclear mechanics, chondrocytes were treated with Latrunculin A (LatA), an actin
Introduction. The ACTIVE(Advanced Cartilage Treatment with Injectable-hydrogel Validation of the Effect) study investigates safety and performance of a novel dextran-tyramine hydrogel implant for treatment of small cartilage defects in the knee (0.5-2.0cm2). The hydrogel is composed of a mixture of natural
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. Air pouches created in female BalBc mice by subcutaneous injection of air. In the first of two independent studies, pouches were implanted with titanium cylinders (400, 700, and 100 µm pore sizes) and inoculated with Aims
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This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs). A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant Aims
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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). A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR.Aims
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In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.Aims
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Large bone defects resulting from osteolysis, fractures, osteomyelitis, or metastases pose significant challenges in acetabular reconstruction for total hip arthroplasty. This study aimed to evaluate the survival and radiological outcomes of an acetabular reconstruction technique in patients at high risk of reconstruction failure (i.e. periprosthetic joint infection (PJI), poor bone stock, immunosuppressed patients), referred to as Hip Reconstruction In Situ with Screws and Cement (HiRISC). This involves a polyethylene liner embedded in cement-filled bone defects reinforced with screws and/or plates for enhanced fixation. A retrospective chart review of 59 consecutive acetabular reconstructions was performed by four surgeons in a single institution from 18 October 2018 to 5 January 2023. Cases were classified based on the Paprosky classification, excluding type 1 cases (n = 26) and including types 2 or 3 for analysis (n = 33). Radiological loosening was evaluated by an orthopaedic surgeon who was not the operating surgeon, by comparing the immediate postoperative radiographs with the ones at latest follow-up. Mean follow-up was 557 days (SD 441; 31 to 1,707).Aims
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Refobacin Bone Cement R and Palacos Overall, 75 patients were included in the study and 71 were available at two years postoperatively. Prior to surgery, they were randomized to one of the three combinations studied: Palacos cement with use of the Optivac mixing system, Refobacin with use of the Optivac system, and Refobacin with use of the Optipac system. Cemented MS30 stems and cemented Exceed acetabular components were used in all hips. Postoperative radiographs were used to assess the quality of the cement mantle according to Barrack et al, and the position and migration of the femoral stem. Harris Hip Score, Oxford Hip Score, Forgotten Joint Score, and University of California, Los Angeles Activity Scale were collected.Aims
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Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against
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In cartilage tissue engineering (TE),new solutions are needed to effectively drive chondrogenic differentiation of mesenchymal stromal cells in both normal and inflammatory milieu. Ultrasound waves represent an interesting tool to facilitate chondrogenesis. In particular, low intensity pulsed ultrasound (LIPUS)has been shown to regulate the differentiation of adipose mesenchymal stromal cells. Hydrogels are promising biomaterials capable of encapsulating MSCs by providing an instructive biomimetic environment, graphene oxide (GO) has emerged as a promising nanomaterial for cartilage TE due to its chondroinductive properties when embedded in
MicroRNA (miR) delivery to regulate chronic inflammation hold extraordinary promise, with new therapeutic possibilities emanating from their ability to fine-tune multiple target gene regulation pathways which is an important factor in controlling aberrant inflammatory reactions in complex multifactorial disease. However, several hurdles have prevented advancements in miR-based therapies. These include off-target effects of miRs, limited trafficking, and inefficient delivery. We propose a magnetically guided nanocarrier to transport therapeutically relevant miRs to assist self- resolving inflammation processes at injury sites and reduce the impact of chronic inflammation- related diseases such as tendinopathies. The high prevalence, significant socio-economic burden and increasing recognition of dysregulated immune mediated pathways in tendon disease provide a compelling rationale for exploring inflammation-targeting strategies as novel treatments in this condition. By combining cationic
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
After knee replacement, therapy resistant, chronic synovitis is common and leads to effusion and pain. A cohort of 55 patients with 57 knee replacements and chronic synovitis underwent radiosynoviorthesis. In summary, 101 joints were treated using 182±9 MBq of 90Y-citrate. The number of radiosynoviorthesis ranged from 1 to 4 (53%, 21%, 23%, and 4%). Every patient received a 99mTc-MDP scintigraphy before and three months after every radiosynoviorthesis. Follow-up ranged from 5.7 to 86.7 months. For qualitative analysis, an four steps scoring was used (0 = no response or worsening, 1 = slight, 2 = good, 3 = excellent response). For quantification, the uptake was determined within the 99mTc-MDP scintigraphy soft tissue phase before and after therapy. At the end of long-term follow-up 27% of patients have an excellent, 24% good, 30% slight and 20% no response. The duration of response was 7.5±8.3 months (maximum 27 months). In repeated treatment, the effect after the first therapy was lesser than in patients who received a single treatment in total. However, three months after the last radiosynoviorthesis, patients with repeated treatment showed a similar effectiveness than single treated patients. At the end of long-term follow-up, patients with repeated radiosynoviorthesis had a higher effectiveness at similar duration response. In the 99mTc-MDP scan 65% of patients showed a reduction of uptake. When comparing subjective and objective response 78% of patients showed a concordance in both, symptoms and scintigraphy. Pilot histological analysis revealed that the synovitis is triggered by small plastic particles. Radiosynoviorthesis is effective in patients with knee replacement and chronic synovitis. It shows good subjective and objective response rates and long response duration. Repeated treatment leads to a stronger long-time response. The chronic synovitis is caused by plastic particles, which result from the abrasion of the
Chronic inflammatory events have been associated to almost every chronic disease, including cardiovascular-, neurodegenerative- and autoimmune- diseases, cancer, and host-implant rejection. Given the toll of chronic inflammation in healthcare and socioeconomical costs developing strategies to resolve and control chronic states of inflammation remain a priority for the significant benefit of patients. Macrophages (Mφ) hold a central role both in the initiation and resolution of inflammatory events, assuming different functional profiles. The outstanding features of Mφ counting with the easy access to tissues, and the extended networking make Mφ excellent candidates for precision therapy. Moreover, sophisticated macrophage-oriented systems could offer innovative immune-regulatory alternatives to effectively regulate chronic environments that traditional pharmacological agents cannot provide. We propose magnetically assisted systems for balancing Mφ functions at the injury site. This platform combines
The aim of this study is to print 3D polycaprolactone (PCL) scaffolds at high and low temperature (HT/LT) combined with salt leaching to induced porosity/larger pore size and improve material degradation without compromising cellular activity of printed scaffolds. PCL solutions with sodium chloride (NaCl) particles either directly printed in LT or were casted, dried, and printed in HT followed by washing in deionized water (DI) to leach out the salt. Micro-Computed tomography (Micro-CT) and scanning electron microscope (SEM) were performed for morphological analysis. The effect of the porosity on the mechanical properties and degradation was evaluated by a tensile test and etching with NaOH, respectively. To evaluate cellular responses, human bone marrow-derived mesenchymal stem/stromal cells (hBMSCs) were cultured on the scaffolds and their viability, attachment, morphology, proliferation, and osteogenic differentiation were assessed. Micro-CT and SEM analysis showed that porosity induced by the salt leaching increased with increasing the salt content in HT, however no change was observed in LT. Structure thickness reduced with elevating NaCl content. Mass loss of scaffolds dramatically increased with elevated porosity in HT. Dog bone-shaped specimens with induced porosity exhibited higher ductility and toughness but less strength and stiffness under the tension in HT whereas they showed decrease in all mechanical properties in LT. All scaffolds showed excellent cytocompatibility. Cells were able to attach on the surface of the scaffolds and grow up to 14 days. Microscopy images of the seeded scaffolds showed substantial increase in the formation of extracellular matrix (ECM) network and elongation of the cells. The study demonstrated the ability of combining 3D printing and particulate leaching together to fabricate porous PCL scaffolds. The scaffolds were successfully printed with various salt content without negatively affecting cell responses. Printing porous thermoplastic
Orthopaedic soft tissues, such as tendons, ligaments, and articular cartilage, rely on their unique collagen fiber architectures for proper functionality. When these structures are disrupted in disease or fail to regenerate in engineered tissues, the tissues transform into dysfunctional fibrous tissues. Unfortunately, collagen synthesis in regenerating tissues is often slow, and in some cases, collagen fibers do not regenerate naturally after injury, limiting repair options. One of the research focuses of my team is to develop functional fiber replacements that can promote in vivo repair of musculoskeletal tissues throughout the body. In this presentation, I will discuss our recent advancements in electrowriting 3D printing of natural