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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 59 - 59
1 Dec 2021
Vemulapalli KV Kumar KHS Khanduja V
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Abstract. Purpose. Clinical registries are an important aspect of orthopaedic research in assessing the outcomes of surgical intervention and track medical devices. This study aimed to explore the research methodology available to account for patients lost to follow-up (LTFU) specifically in studies related to arthroscopic intervention and whether the rates of patient LTFU are within the acceptable margins for survey studies. Methods. A scoping review, where a literature search for studies from nine arthroscopy registries, was performed on EMBASE, MEDLINE, and the annual reports of each registry. Inclusion criteria included studies with information on patient-reported outcome measures and being based on nine national registries identified. Exclusion criteria included review articles, conference abstracts, studies not based on registry data, and studies from regional, claims-based, or multi-centre registries. Studies were then divided into categories based on method of LTFU analysis used. Results. Thirty-six articles were identified for the final analysis. Categories for LTFU analysis included dropout analyses (n=10), referencing validation studies (n=12), contacting non-responders (n=4), and sensitivity analyses (n=1). Referencing validation studies was the most common method (n=12). Majority (n=35) of the studies exceeded the recommended maximum rates for LTFU. Conclusions. Most arthroscopy studies have rates of LTFU higher than traditionally acceptable. Therefore, any conclusions drawn from these research papers may not be sufficiently valid or free from non-response bias


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 134 - 134
2 Jan 2024
Ghezzi D Sartori M Boi M Montesissa M Sassoni E Fini M Baldini N Cappelletti M Graziani G
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Prosthetic joint infections represent complications connected to the implantation of biomedical devices, they have high incidence, interfere with osseointegration, and lead to a high societal burden. The microbial biofilm, which is a complex structure of microbial cells firmly attached to a surface, is one of the main issues causing infections. Biofilm- forming bacteria are acquiring more and more resistances to common clinical treatments due to the abuse of antibiotics administration. Therefore, there is increasing need to develop alternative methods exerting antibacterial activities against multidrug-resistant biofilm-forming bacteria. In this context, metal-based coatings with antimicrobial activities have been investigated and are currently used in the clinical practice. However, traditional coatings exhibit some drawbacks related to the insufficient adhesion to the substrate, scarce uniformity and scarce control over the toxic metal release reducing their efficacy. Here, we propose the use of antimicrobial silver-based nanostructured thin films to discourage bacterial infections. Coatings are obtained by Ionized Jet Deposition, a plasma-assisted technique that permits to manufacture films of submicrometric thickness having a nanostructured surface texture, allow tuning silver release, and avoid delamination. To mitigate interference with osseointegration, here silver composites with bone apatite and hydroxyapatite were explored. The antibacterial efficacy of silver films was tested in vitro against gram- positive and gram-negative species to determine the optimal coatings characteristics by assessing reduction of bacterial viability, adhesion to substrate, and biofilm formation. Efficacy was tested in an in vivo rabbit model, using a multidrug-resistant strain of Staphylococcus aureus showing significant reduction of the bacterial load on the silver prosthesis both when coated with the metal only (>99% reduction) and when in combination with bone apatite (>86% reduction). These studies indicate that IJD films are highly tunable and can be a promising route to overcome the main challenges in orthopedic prostheses.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 86 - 86
1 Nov 2021
Cicione C Papalia R Giacomo GD Tilotta V Ambrosio L Russo F Vasta S Vadalà G Denaro V
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Introduction and Objective. Osteoarthritis (OA) represents one of the leading cause of disability all over the world. Cell therapies, mainly based on mesenchymal stem cells (MSCs), have shown to modulate the pathogenesis of OA in basic, preclinical and clinical studies. Adipose tissue (AT) have emerged as a rich and promising source of MSCs called adipose derived stem cells (ASCs). Different systems are available for processing lipoaspirate to purify the samples from oily and haemorrhagic fractions, minimizing the risk of complications and maximizing the biological yield for subsequent grafting. However, few studies compared the efficacy of the different processing devices already used in clinical practice. This study aims to characterize the products obtained by the use of two different systems such as micro-fragmentation or nano-fragmentation comparing them with the starting material (AT) and the collagenase isolated ASCs. Materials and Methods. AT from 12 donors arrived without selection to the laboratories: 4 lipoaspirated (LA), 4 micro-fragmented (mF) and 4 nano-fragmented (nF). The samples were divided into three aliquots for paraffin embedding, RNA extraction and digestion with collagenase for ASCs isolation. Paraffin embedded tissue sections were stained with hematoxylin-eosin to analyze morphology. RNA was extracted, retro-transcribed and analyzed with real-time PCR to analyze the expression of pluripotency genes (SOX2, NANOG and POU5F1) and inflammatory genes (IL-1beta and iNOS). Data were analyzed using Graphpad Prism 8.0 and expressed as mean ± SD. One-way ANOVA followed by Tukey test was used to compare the different groups. Results. The LA comprised small lobules, with intact cell membranes and structurally integer adipocytes. mF samples showed the presence of integer adipocytes, small lobules and higher amount of cell clusters. nF samples showed the almost completely absence of adipocytes, a high amount of cells without lipid content and a high amount of stromal matrix. Real-time PCR results showed the lowest expression levels of pluripotency genes in LA samples that were assumed equal to 1.0 and used to calculate the expression levels of the other samples. mF showed expression levels of pluripotency genes similar to AT. nF showed expression levels of pluripotency genes higher than AT and mF, but without statistically significant differences. ASCs showed statistically significant higher expression levels of these genes compared to LA and mF (p ≤ 0.001). Likewise, the expression of inflammatory genes resulted to be lowest in LA samples (assumed equal to 1.0), higher in mF samples and in nF samples without statistical significance. As expected, the highest values were found in ASCs isolated cells compared to all the other samples (p ≤ 0.0001). Conclusions. These results confirmed that micro-fragmentation (mF) and nano-fragmentation (nF) permitted to separate a cell mixture enriched in ASCs from a lipoaspirate sample without activating the inflammatory pathways. Both processing methods gave a minimally manipulated product suitable for OA cell therapy application. Further studies are needed to elucidate possible different activities of the ASCs enriched AT-derivatives


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 25 - 25
1 Dec 2021
Solis J Edwards JH Fermor H Brockett C Herbert A
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Abstract

Decellularised porcine superflexor tendon (pSFT) provides an off-the-shelf, cost-efficient option for ACL reconstruction (ACLR). During decellularisation, phosphate buffered saline (PBS) is used for washing out cytotoxic solutes and reagents, maintaining tissue hydration. It has been shown to increase water content in tendon, swelling the tissue reducing mechanical properties. End stage PBS washes in the standard protocol were substituted with alternative solutions to study tissue swelling and its impact on the mechanical behaviour and matrix composition of pSFTs. 25%, 100% Ringers and physiological saline test groups were used (n=6 for all groups). pSFTs were subject to tensile and confined compression testing. Relative hydroxyproline (HYP), glycosaminoglycan (GAG) and denatured collagen content (DNC) were quantified. Modified decellularised tendon groups were compared to tendons decellularised using the standard protocol and native tendons. Specimen dimensions reduced (p=0.004) post-decellularisation only in 25% Ringers group. In all other modified groups, less swelling was apparent but not statistically different from standard group. Only 25% Ringers group had higher linear modulus (p=0.0035) and UTS (p=0.013) compared to standard group. All decellularised groups properties were reduced compared to native pSFTs. Stress relaxation properties showed a significant reduction in decellularised groups compared to native. Compression testing showed no significant differences in peak stress for modified decellularised groups compared to native. A reduction (p=0.036) was observed in standard group. Quantification of GAGs and DNC showed no significant differences between groups. HYP content was higher (p<0.0001) for saline group. A significant reduction in tissue swelling could be related to improved mechanical properties of decellularised pSFTs. Alternative solutions in end stage washes had no significant effect on quantities of matrix components, but altered structure/function could explain the differences in tensile and compressive behaviour, and should be further studied. In all decellularised groups, pSFTs retained suitable mechanical properties for ACLR.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 64 - 64
1 Dec 2020
Misir A Kaya V Basar H
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The ideal treatment method regarding various defect sizes after local aggressive tumor resection is unknown. We investigated the biomechanical properties of metaphyseal defect filling regarding different defect sizes and fixation methods.

Ninety-one sheep tibias were divided into five groups as 21 tibias per four study groups and 7 tibias in the control group. Study groups were further divided into three subgroups according to 25%, 50% and 75% metaphyseal defect size. Control group tibias were left intact. In study group 1, a metaphyseal defect was created and no further process was applied. Metaphyseal defects were filled with cement without fixation in group 2. Cement filling and fixation with 2 screws were performed in group 3. In addition to cement filling, plate-screw fixation was performed in group 4. Axial loading test was applied to all tibias and the results were compared between study subgroups and control group.

Plate-screw fixation was found to have the best biomechanical properties in all defect sizes. Load to failure for screw fixation was found to be significantly decreased between 25% and 50% defect size (P<0.05). However, load to failure for isolated cement filling was not affected from defect size (p>0.05).

In conclusion, size of the defect predicts the fixation method in addition to filling with cement. Filling with cement in metaphyseal defects was found to be biomechanically insufficient. In addition to filling with cement, additional screw fixation in less than 25% defects and plate-screw fixation in more than 25% defects may decrease tibial plateau fracture or metaphyseal fracture risk after local aggressive tumor resection.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_2 | Pages 45 - 45
1 Jan 2019
Thavayogan R Ashraf W Askar M Morassi G Bayston R
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Metal instrumentation (rods and screws) is used to stabilise the spine after trauma, malignancy or deformity. Approx 3% become infected often necessitating removal of metal. At surgery tissue samples and metal are removed for culture, but many clinical laboratories are not equipped to process metal or use simple culture methods. The causative bacteria exist as biofilms on the metal and they are often anaerobic and slow-growing, so conventional culture methods often fail to detect them. Also, they are common contaminants leading to diagnostic uncertainty. We have established a laboratory protocol to overcome these problems.

Removed metalwork was sonicated and the sonicate centrifuged and the supernatant discarded. Quantitative aerobic and anaerobic culture of the resuspended pellet for 14 days and microscopy were carried out.

Metalwork from 11 suspected infected cases was culture-positive (median 2857, 60–5000cfu/mL). Microscopy revealed an infection due to Candida albicans that would not have been detected otherwise. Bacteria were isolated from 8 of 10 non-infected cases (median 15, 0–35 cfu/mL). Conventionally processed samples failed to grow in 4 infected cases. (cfu/mL infected vs noninfected cases p=0.0093)

Micro-organisms on spinal metalwork grow as biofilms and they require sonication to dislodge them. The causative bacteria are slow-growing and P acnes is anaerobic and requires prolonged incubation. S epidermidis and P acnes are common contaminants and quantitative culture helps to distinguish pathogens from contaminants, removing the diagnostic uncertainty that conventional methods give. Microscopy of the sonicate can reveal micro-organisms that fail to grow on culture. We recommend that sonication of metalwork, prolonged anaerobic incubation and quantitative culture be adopted to improve diagnostic clarity for spinal instrumentation infections.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 32 - 32
1 Nov 2018
Hoang-Kim A
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We need to shift our focus to integrating sex and gender into research proposals, so we can answer some of the most basic unanswered questions in the field of fracture management. Current evidence in guidelines indicate a near-to-linear increase from the 1990s for inclusion of sex and gender. However, these recommendations remain expressed in absolute terms, with little explanatory power, affecting uptake and implementation in clinical practice. This co-branded session, with members of the Orthopaedic Research Society – International section of fracture repair (ORS-ISFR), will provide participants with guiding principles and tools to assist researchers and grant reviewers understand what it means to include sex and gender in meaningful ways: from formulating research questions, recruitment strategies, to conducting sex-stratified analyses. In this presentation, we will consider diverse approaches, methods and, analyses to elevate sex and gender within trauma. A strong emphasis on the ways and means of including marginalized and vulnerable populations in research will be addressed.


To describe clinical situations for use of modified VAC in POC based on: diagnosis, comorbidities, BMI, wound size in cm, days following trauma when VAC was first applied, total duration of uninterrupted use, frequency of change, settings, bacterial growth, outcomes

To report the outcomes of mVAC use in POC within 6 months to help improve and standardize its application in the institution

This study involves data gathering from inpatients handled by orthopedic surgeons in training and subspecialty rotations in POC. The data collected are highly dependent on the doctors-in-charge's complete charting, thorough reporting and accurate documentation. Modified Vacuum Assisted Closure (mVAC) is used frequently in this study and is defined as a form of revised, adapted and reformed use of VAC based on available materials in the involved institution. The materials that are included are, but not limited to the following: sterile Uratex™ blue foam, nasogastric or suction tubing, phlegm suction machine, Bactigras™ and Opsite™ or Ioban™.

A total of 58 patients were included in the study. The average age of the population was 35 and are predominantly male. The most common mechanism of injury was motorcycle accident and 37 of the patients were diagnosed with an open fracture of the lower extremity with open tibia fractures (22) being the most common. Average wound area measured was 24.12 cm3. All patients yield a bacteria growth with e. coli being the most frequent. Average during of uninterrupted use was 39 days. Of the 58 included in the study, 8 patients underwent STSG, 2 had a flap coverage surgery, 4 patients eventually underwent amputation and 33 with complete resolution of soft tissue defect after conversion to biologic dressing post-mVAC. The rest of the population were still ongoing mVAC at the end of the study.

mVAC is an alternative temporary medium for soft tissue coverage for cases with or without concomitant fractures. mVAC promotes removal of exudate from the wound, supports wound apposition and granulation bed proliferation. Usage mVAC helps prepare for skin coverage procedure and on some cases leads to full resolution of defect.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 10 - 10
1 Nov 2018
Kelly A McEvoy F Tiernan S Morris S
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Balloon kyphoplasty (BKP) is a minimally invasive surgical technique used to correct kyphosis and vertebral compression fractures. BKP uses cement to fill a void created by the inflation of a balloon in a vertebra, it can be used as an alternative to vertebroplasty to reduce cement extravasation. Issues such as poor inter digitisation of the cement and the trabecular bone can arise with the BKP method. This can be due to a compacted layer created during the procedure which can cause complications post-surgery. The primary aim of this study was to investigate alternative cement application methods which could improve the mechanical strength of the bone-cement interface. Three alternative methods were investigated, and cylindrical bone-cement specimens were created for all methods (BKP and three alternatives). An important part of this study was to replicate the compacted layer created by the inflation of the balloon tamp in BKP. Synthetic trabecular bone specimens (Sawbones®, Pacific Research Laboratories, Vashon Island, Washington, USA) were pre-loaded in compression and the resultant compacted layers were found to replicate the compacted layers found in surgery. Mechanical testing was carried out with an MTS Model 858 Bionix® Servohydraulic load frame using static tensile and torsion loads. Static tests revealed that two of the three alternative methods were an improvement on BKP, with a high statistical significance in relation to the mechanical performance of the bone-cement interface (P < 0.001). This data illustrates the potential to improve the standard BKP technique, in terms of bone-cement interface performance.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_4 | Pages 24 - 24
1 Apr 2018
Magill H Shaath M Hajibandeh S Hajibandeh S Chandrappa MH
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Objectives. Our objective was to perform a systematic review of the literature and conduct a meta-analysis to investigate the outcomes of open versus arthroscopic methods of ankle fusion. Methods. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards, we performed a systematic review. Electronic databases MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify randomised and non-randomised studies comparing outcomes of arthroscopic and open ankle arthrodesis. The Newcastle-Ottawa scale was used to assess the methodological quality and risk of bias of the selected studies. Fixed-effect or random-effects models were applied to calculate pooled outcome data. Results. We identified one prospective cohort study and 5 retrospective cohort studies, enrolling a total of 286 patients with ankle arthritis. Our analysis showed that open ankle fusion was associated with a lower fusion rate (OR 0.26, 95% CI 0.13–0.52, P = 0.0002), longer tourniquet time (MD 16.49, 95% CI 9.46–23.41, P<0.00001), and longer length of stay (MD 1.60,95% CI 1.10–2.10, P<0.00001) compared to arthroscopic ankle fusion; however, there was no significant difference between two groups in terms of infection rate (OR 2.41, 95% CI 0.76–7.64, P = 0.14), overall complication rate (OR: 1.54, 95% CI 0.80–2.96, P = 0.20), and operation time (MD 4.09, 95% CI −2.49–10.66, P = 0.22). The between-study heterogeneity was high for tourniquet time but low or moderate for other outcomes. The direction of the effect sizes remains unchanged throughout sensitivity analyses. Conclusions. The best available evidence demonstrates that arthroscopic ankle fusion may be associated with a higher fusion rate, shorter tourniquet time, and shorter length of stay compared to open ankle fusion. We found no significant difference between two groups in terms of infection rate, overall complication rate, and operation time. The best available evidence is not adequately robust to make definitive conclusions. Long-term results of the comparative efficacy of arthroscopic ankle fusion over open ankle fusion are not currently available. Further high quality randomised controlled trials that are adequately powered are required


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_2 | Pages 9 - 9
1 Jan 2019
Askar M Ashraf W Scammell B Bayston R
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Protocols for processing of tissue from arthroplasty infections vary and might affect the recovery of bacteria. We compared homogenization, bead beating and enzymatic disruption for recovery of live bacteria from tissue samples.

Suspensions of Staphylococcus aureus and Escherichia coli were prepared as controls. Three samples were taken from each and the first was bead beaten, the second homogenized, and Proteinase K was added for 10 and 30 minutes to the third sample before culturing. In addition, artificially inoculated pork tissue and known infected human tissue samples were processed by either homogenization or bead beating prior to cultures and results were compared.

Number of cycles of bead beating and homogenization and duration of Proteinase K treatment had significant effects. Bead beating for 2 and 4 cycles reduced the yield of S.aureus to 52% and 20% of control, and E.coli to 33% and 8%. Homogenization for 2 and 4 cycles reduced S.aureus to 86% and 65% of control, and E.coli to 90% and 87%. Proteinase K for 10 minutes and 30 minutes reduced the yield of S.aureus to 75% and 33% of control, and E.coli to 91% and 49% respectively. Inoculated Pork tissue showed a reduction in S.aureus recovery of 90% for bead beating compared to homogenization, and 80% in the case of E.coli. Bead beating of infected human tissue samples reduced the yield by 58% compared to homogenization.

Bead-beating is a common recommended method of processing tissue from arthroplasty cases. However, even though it produces a homogeneous sample, it does so at the cost of significant loss of viable bacteria. Homogenization and 10 minutes of Proteinase K incubation are almost equivalent, but the homogenizer is preferred being more controllable and cheaper. This should help to define guidelines for diagnosing infections using tissue samples.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 107 - 107
1 Mar 2021
Çiftçi-Dede E Korkusuz F Korkusuz P
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Mesenchymal stem cell (MSC) exosomes are intracellular vesicles, which can regulate transcription and control gene expression through the molecules they carry, easily enter into the target cell, contain no regenerative effect, and do not produce an immune response. There are different methods in the literature to obtain these vesicles. However, studies on the isolation of MSC-derived exosomes and their comparative characterization using magnetically active cell sorting (MACS) and ultracentrifugation methods are lacking. The most appropriate isolation method for MSC-derived exosomes can be determined by comparing the isolation and characterization parameters of mesenchymal stem cells using magnetically active cell sorting and ultracentrifugation methods. The aim of this study was to define the advantages and disadvantages of the methods used for determining the purpose-oriented method. Human bone marrow-derived mesenchymal stem cells were cultured in standard MSC culture conditions (37ºC and 5% CO 2). Exosomal contamination was prevented by removal of exosomes from the serum that used in the standard growth medium. For exosome isolation of the cells reaching sufficient density, the media were replaced with new ones every two days, the old media were collected in liquid refrigerated with liquid nitrogen and stored at −80ºC. Part of the accumulated exosomes were isolated by using the MACS method, while the other was isolated by using the ultracentrifugation method, which included serial centrifugation steps. The amount of protein contained in the phosphate buffer solution in which the exosomes were reconstituted was determined by microplate reader using the BCA kit. Based on the protein concentration obtained, exosomes were read by means of a dye flow cytometer with fluorescent antibodies attached to surface markers specific to CD9, CD63, and CD81 specific for exosomes by latex beads. Finally, the exosomes were stained with uranyl acetate and phosphotungstic acid and then placed on 200 mesh and formvar-carbon film coated grids. Exosomes were isolated using both ultracentrifugation and MACS methods. While ultra-large amounts of exosomes can be isolated by ultracentrifugation method, MACS method provides a lower amount of isolation. Exosomes with magnetically active cell sorting are selected with specific surface markers, therefore, exosomal purity is thought to be higher. Exosomes which were isolated by both ultracentrifugation and MACS methods were monitored by using transmission electron microscopy and they were not found to be morphologically different. In conclusion, MACS and ultracentrifugation are effective methods for the isolation of human bone marrow-derived MSC exosomes. Both methods have advantages and disadvantages. Exosomes can be isolated together with magnetic beads using the MACS method. In the ultracentrifuge method, cleaner exosomes can be isolated. While the exosomes are isolated by MACS, they can also be characterized by beads.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_4 | Pages 50 - 50
1 Apr 2018
Hafez M Cameron R Rice R
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Background. Surgical wound closure is not the surgeon”s favorite part of the total knee arthroplasty (TKA) surgery however it has vital rule in the success of surgery. Knee arthoplasty wounds are known to be more prone to infection, breakdown or delayed healing compared to hip arthroplasty wounds, and this might be explained by the increased tensile force applied on the wound with knee movement. This effect is magnified by the enhanced recovery protocols which aim to obtain high early range of movement. Most of the literature concluded that there is no difference between different closure methods. Objectives. We conducted an independent study comparing the complication rate associated with using barbed suture (Quill-Ethicon), Vicryl Rapide (polyglactins910-Ethicon) and skin staples for wound closure following TKA. Study Design & Methods. Retrospective study where the study group included all the patients admitted to our unit for elective primary knee arthroplasty in 2015, we excluded patients admitted for partial knee arthroplasty, revision knee arthroplasty or arthroplasty for treatment of acute trauma due to the relatively higher complication rates. All the patients notes were reviewed to identify wound related problems such as wound dehiscence, wound infection and delayed healing (defined as delayed wound healing more than 6 weeks). Results. 327 patients were included in this study; 151 in Quill group, 99 in staples group and 77 in the last group where the wound closed with Rapide. We identified 9 (5.9%) cases of wound dehiscence in the Quill group, 3 cases of wound dehiscence in each of other two groups (3.8%) with Rapide and (3%) with staples. On the other hand superficial wound infection was higher with staples with 6 (6%) cases of wound infection compared to the other groups, wound infection occurred in 2 patients (2.5%) with Rapide and 5 patients (3.3%) in the Quill”s group. Most of the delayed wound healing happened after using Quill where it is reported in 5 patients (3.3%) and the lowest was in staples group with 1 patient (1%) and slightly higher percentage in Rapide group 2 patients (2.5%). The total figure of wound related problems was the highest in Quill”s group with 19 reported cases (12.5%), lower in staples” group with 10 cases (1.1%) and the lowest in Rapide”s group with 7 cases (9%). Conclusions. Our study showed different results to the reported literature suggesting that each closure method has its own advantages and disadvantages. Quill is quick, knotless and absorbable but on the other side it is significantly more expensive than other alternatives and it is associated with the highest complication rates. On the other hand Rapide is cheap absorbable alternative with the lowest percentage of wound problems but on the negative side it is time consuming. Finally staples method is the quickest, relatively cheap and rarely associated with wound dehiscence but it is not absorbable which might cause inconvenience to patients


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 65 - 65
1 Nov 2018
Havıtçıoğlu H
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Scaffold-based bone tissue engineering holds great promise for the future of osseous defects therapies. Prepare the suitable scaffold properties are physiochemical modifications in terms of porosity, mechanical strength, cell adhesion, biocompatibility, cell proliferation, mineralization and osteogenic differentiation are required. We produce various bone tissue scaffolds with different techniques such as lyophilization, 3D printing and electrospinning. We wish to overview all the different novel scaffold methods and materials. To improve scaffolds poor mechanical properties, while preserving the porous structure, it is possible to coat the scaffold with synthetic or natural polymers. An increasing interest in developing materials in bone tissue engineering is directed to the organic/inorganic composites that mimic natural bone. Specifically, bone tissue is a composite of an organic and inorganic matrix. Using PLLA, loofah, chitin and cellulose biomaterials we produced bone tissue scaffold with lyophilization technique. Also, using fish scale powder and wet electrospun Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) a sponge structure had created. Using MRI image data and 3D printer method, a bone tissue scaffold is created by PLA filament. Their mechanical properties had analysed with compression tests and their biocompatibilities had investigated. In order to provide novel strategies for future treatment of bone tumours, the properties of the scaffold, including its in vitro extended-release properties, the inhibition effects of chemotherapeutic agent on the bone tumours and its bone repair capacities were investigated in vitro by using MG63 cells. To develop chemotherapeutic agent-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles in a porous nano-hydroxyapatite scaffold we aimed to use double emulsion method.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 131 - 131
1 Jul 2014
van der Veen A Bisschop A Mullender M van Dieen J
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Summary Statement. Creep behaviour can only be quantified accurately when the testing time exceeds the estimated time constant of the creep process. The new parameters obtained in this paper can be used to describe normal behaviour up to 24 hrs. Background. Diurnal loading on the human spine consists of 16hrs loading and 8hrs rest. After an initial load increase, due to rising in the morning, an axial loading is maintained throughout the day. As a consequence subsidence of the intervertebral disc (IVD) occurs during the day while disc height recovers during the night. This behaviour is time dependent (non-linear). In literature different constitutive equations have been used to describe creep. A stretched exponential (Kolraush-Wilson-Watts, KWW) and a double Voight (DV) model have both been used to quantify the creep behaviour. Using these models, time constants and the deformation at equilibrium are estimated. It is unsure whether these different approaches yield to valid predictions. In this study we compared the validity of different equations for the prediction of creep behavior. Materials and Methods. IVDs (T9-T12) were obtained from 5 human spines. IVD's with osteophytes and/or disc narrowing were excluded from the test. The transverse area of each disc was measured and used to calculate the required compression load. IVDs were preloaded at 0.1MPa for 12hrs, compressed (0.8MPa, 24hrs) and finally unloaded (0.1MPa, 24hrs). Tests were performed in a saline bath. A KWW model and a DV model were fitted to the measured creep data (least squares method). Model parameters, e.g. the time constant and maximum deformation, were calculated for a test duration of 4, 8, 12, 16, 20 and 24hrs. Results. 4hours loading: KWW model: Time constant = 70hrs. Deformation = 3.0 mm. DV model: Time constant = 5hrs, Deformation = 1.7 mm. 24hours loading: KWW model: Time constant = 17hrs. Deformation = 3.2 mm. DV model: Time constant =12.5hrs, Deformation = 2.1 mm. Discussion. Both models described the measured data well but the model parameters were highly sensitive to test duration. For both models the estimated time constant varied with test duration. When extrapolating the measured data beyond test duration, the DV model under-estimated and the KWW model over-estimated creep behaviour. The 24hrs experiment was still too short for an accurate determination of the parameters. The upper and lower limits of the parameters can be estimated using a KWW and Voight model. Conclusions. Creep behaviour can only be quantified accurately when test duration exceeds the estimated time constant of the creep process. All reported time constants in current literature are based upon experiments that lack sufficient test duration. The new parameters obtained in this paper can be used to describe normal behaviour up to 24 hrs., but are not suitable for extrapolation beyond the test duration


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_15 | Pages 107 - 107
1 Nov 2018
Sheridan G Kelly R McDonnell S Kenny P
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This was a retrospective study of registry data from a National Orthopaedic Hospital for all THRs with 10-year follow-up data. Inclusion criteria were all THRs with a minimum of 10-year follow-up data. All metal-on-metal (MoM) THRs and MoM resurfacings were excluded from the analysis due to the high rate of revision associated with these bearings. Univariate and multivariate analyses controlling for confounding variables were performed to compare outcomes. A total of 1,697 THRs were performed in 1,553 patients. The four significant predictors for revision were fixation type (p<0.01), surface bearing type (p<0.01), age (P<0.05) and head size (p<0.05). Gender, BMI and approach had no effect on revision rates. The lowest 10-year all-cause revision rates were seen in cemented THRs at 1.7%. Ceramic-on-poly bearings had the lowest revision rate at only 1.2%. Metal-on-poly bearings had a 1.7% revision rate. Ceramic on ceramic bearings had a 7.1% revision rate with 1 revision for squeak and 1 revision for ceramic head fracture. The causes for revision in order of decreasing frequency were as follows: Infection (n=13, 0.7%), dislocation (n=7, 0.4%), periprosthetic fracture (n=3, 0.2%) and aseptic loosening (n=2, 0.1%). There were 2 re-revisions at 10 years in total. The smaller 22.225mm head sizes had a significantly lower revision rate than other head sizes (p<0.05). Ceramic-on-poly bearings, cemented fixation and smaller head sizes perform better in the experience of this registry. However, with multivariate analysis, these differences were shown to be insignificant.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_2 | Pages 14 - 14
1 Jan 2019
Warren JP Coe R Sikora S Miles DE Beales P Wilcox RK
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The purpose of this study was to develop a novel, minimally invasive therapy for nucleus pulposus augmentation without the need for major surgical incision.

Two optimum patented self-assembling peptides based on natural amino acids were mixed with glycosaminoglycans (GAGs) to form reversible, tunable hydrogels that mimic the vital biological osmotic pumping action and aid in swelling pressure of the intervertebral disc (IVD). Separate peptide and GAG solutions can be switched from fluid to gel upon mixing inside the body. The gels were analysed using a series of complementary techniques (FTIR, TEM & rheometry) to determine their cross-length scale structure and properties. Approaches to developing a clinical product were then developed including the incorporation of a fluorescent probe and a CT contrast agents to aid visualization of the gels, and a semi-automatic syringe driver rig, incorporating a pressure sensor, for the delivery of the solutions into the intervertebral discs. The efficacy of the procedure in restoring disc height and biomechanics was examined using chemically degenerated bovine caudal samples.

It was found the presence of the GAGs stabilized the peptides forming stiffer gels, even upon injection through a long (∼10cm) small gauge needle. The injected gels were easily visualized post injection by microCT and by eye during dissection under visible and UV light. It was also noted that following injection, the disc height of the degenerated samples was restored to a similar level of that observed for native discs.

A hydrogel has been developed that is injected through a narrow bore needle using a semi-automatic delivery rig and forms a self-assembled gel in situ which has shown to restore the disc height. Further tests are now underway to examine their biomechanical performance across more physiological time periods.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 75 - 75
1 May 2012
Li J Evans S Blain E Piccinelli S Holt C Dini D Accardi M
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Patient specific knee modelling has the potential to help understand the development of the mechanically induced degenerative disease, Osteoarthritis. A full joint contact model of the knee involves modelling the bones, ligaments, articular cartilage (AC) and meniscus, as well as, the kinematics and geometry of real joints. These finite element models will inevitably require great computational resource to run and it is desirable to find resource effective material model formulations which can accurately describe the mechanical behaviour of the soft tissues. Biphasic models (BIMs) have long been established as an effective formulation for modelling AC. However, the swelling behaviour caused by changes in the ionic phase is a major recovery mechanism and is neglected in the BIMs. It is therefore believed that BIMs alone are insufficient to fully describe the mechanical behaviour of AC. Instead, a thermal analogy method which is generically a BIM that includes the swelling behaviour has been thought to be suitable and has been validated against literature data using material parameters optimized to match the numerical and experimental results. To ensure the model is suitable for patient specific modelling where it will have the ability to reflect the individual AC material properties of the patients in the mechanical behaviour it predicts, two experiments have been planned and are currently being carried out using bovine AC. The first experiment is to investigate the diffusivity of the tissue in solutions of different molarity by measuring the change in tissue weight over time. Eleven explants are taken from the same bovine articular joint using a 6mm biopsy punch and are left in 10mM of PBS overnight to ensure ionic equilibrium has been reached before experiments are carried out. The explants are then placed in PBS solutions of molarities ranging from 0mM to 10mM and weighed at regular time intervals. In the final stage, the explants are then lyophilized and weighed for determining the volume of water in the tissues. Using Archimedes principle, the change in porosity of the tissue is found. A preliminary study has shown that explants submerged in a solution of 5mM has an approximately 4% change in weight after the first 24h and a further 1.73% change in the following 24h. Control specimens left in a solution of 10mM had a 0% change in weight. The second experiment is to carry out mechanical loading on the AC specimens while submerged in a solution of different ion concentrations. Experiments with various loading conditions are being investigated to explore their efficacy for validation. Preliminary compression tests have been carried out where steps of 1% strain was applied, giving a total of 10% strain. Between each step, strain was held constant until full relaxation has been achieved. The reaction force measured from the second experiment in conjunction with data collected from the first experiment will be compared to results predicted in the numerical model. This will allow the determination of whether thermal analogy is adequate or whether more complex triphasic models need to be considered. Furthermore, the development of these experimental methods will contribute to the validation of other AC material models in the future.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 85 - 85
1 Jul 2014
Russell N Oliver R Walsh W
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Summary Statement. Supercritical fluid (SCF) sterilization produces clean and osteoconductive allograft bone capable of healing a critical-sised bony defect. SCF treated graft induces an increased anabolic response and decreased catabolic reponse compared to gamma irradiated graft. Introduction. Clinically, allogeneic bone graft is used extensively because it avoids the donor site morbidity associated with autograft. However, there are concerns over the optimal sterilization method to eliminate immunological risks whilst maintaining the biological efficacy of the graft. This study compared the effect of Supercritical fluid (SCF) sterilization and gamma irradiation on the osteoconductivity of allograft bone in a bilateral critical-sised defect rabbit model. Methods. Cortical-cancellous allograft bone was milled, defatted and terminally sterilised with either gamma irradiation at 25kGy or SCF treatment. The graft was then implanted bilaterally into a critical-sised metaphyseal defect in 10 New Zealand White rabbits (n=5 sites per time point per group). Osteoconductivity was evaluated at 2 and 4 weeks to measure the early inflammatory response and early new bone formation respectively, using X-ray, CT, and both qualitative and quantitative histology and immunohistochemistry (Alkaline Phosphatase and Cathepsin-K). Results. Both grafts were well tolerated and osteoconductive. At 2 weeks, there were significant reductions in bone volume and density in the gamma irradiated graft compared to the SCF treated graft as measured by CT. Inside the defect this corresponded with a greater inflammatory response in the gamma irradiated graft, with a less organised fibrous tissue infiltration and mild granuloma reaction. Conversely, the SCF group had a highly organised and densely packed fibrous tissue infiltration around the allograft chips. Immunohistochemistry results supported these findings with an up-regulation in the expression and distribution of Cathepsin-K in the gamma irradiation group; while Alkaline Phosphatase expression was higher in the SCF group. At 4 weeks, resorptive behavior predominated in both groups. Radiographic and CT results detected no significant difference between groups. Histology at 4 weeks showed larger bone chips were undergoing substantial remodeling with areas of simultaneous osteoclastic resorption and osteoblastic new bone formation. Smaller allograft chips and areas of new bone formation were infiltrated by fibrous tissue and undergoing osteoclastic resorption. Quantitative immunohistochemistry showed an up-regulation of Cathepsin-K expression in both groups from 2 to 4 weeks. At both time points Cathepsin-K expression was higher in the gamma irradiated graft compared to the SCF group. This was greatest at 2 weeks where there was a substantial 82% increase in expression which was reduced to a 38% discrepancy at 4 weeks. Alkaline Phosphatase expression was greater in the SCF group at both time-points. Discussion/Conclusion. Allograft bone sterilised with either gamma irradiation or SCF treatment was osteoconductive and capable of healing a critical-sised defect in a rabbit. Gamma irradiated allografts elicited an acute inflammatory reaction when implanted which increased the amount graft resorption compared to the SCF treated bone. Increased osteoclastic resorption may be a concern for structural graft applications leaving the graft more susceptible to premature failure. SCF sterilization produced a clean, highly biocompatible graft with increased anabolic activity compared to gamma irradiation which may facilitate earlier healing clinically. These results suggest that SCF sterilization has considerable expediency for allograft processing and may facilitate more optimal extraction of the inherent properties of the graft compared to current practices


Aims. This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. Methods. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results. Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Conclusion. Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing. Cite this article: Bone Joint Res 2024;13(9):427–440