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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 4 - 4
2 Jan 2024
Kucko N Sage K Delawi D Hoebink E Kempen D Van Susante J de Bruijn J Kruyt M
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Pseudoarthrosis after spinal fusion is an important complication leading to revision spine surgeries. Iliac Crest Bone Graft is considered the gold standard, but with limited availability and associated co-morbidities, spine surgeons often utilize alternative bone grafts.

Determine the non-inferiority of a novel submicron-sized needle-shaped surface biphasic calcium phosphate (BCP<µm) as compared to autograft in instrumented posterolateral spinal fusion.

Adult patients indicated for instrumented posterolateral spinal fusion of one to six levels from T10-S2 were enrolled at five participating centers. After instrumentation and preparation of the bone bed, the randomized allocation side of the graft type was disclosed. One side was grafted with 10cc of autograft per level containing a minimum of 50% iliac crest bone. The other side was grafted with 10cc of BCP<µm granules standalone (without autograft or bone marrow aspirate). In total, 71 levels were treated. Prospective follow-up included adverse events, Oswestry Disability Index (ODI), and a fine-cut Computerized Tomography (CT) at one year. Fusion was systematically scored as fused or not fused per level per side by two spine surgeons blinded for the procedure.

The first fifty patients enrolled are included in this analysis (mean age: 57 years; 60% female and 40% male). The diagnoses included deformity (56%), structural instability (28%), and instability from decompression (20%). The fusion rate determined by CT for BCP<μm was 76.1%, which compared favorably to the autograft fusion rate of 43.7%. Statistical analysis through binomial modeling showed that the odds of fusion of BCP<μm was 2.54 times higher than that of autograft. 14% of patients experienced a procedure or possible device-related severe adverse event and there were four reoperations. Oswestry Disability Index (ODI) score decreased from a mean of 46.0 (±15.0) to a mean of 31.7 (±16.9), and 52.4% of patients improved with at least 15-point decrease.

This data, aiming to determine non-inferiority of standalone BCP<μm as compared to autograft for posterior spinal fusions, is promising. Ongoing studies to increase the power of the statistics with more patients are forthcoming.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_14 | Pages 23 - 23
1 Dec 2022
Borciani G Montalbano G Melo P Baldini N Ciapetti G Brovarone CV
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Osteoporosis is a worldwide disease resulting in the increase of bone fragility and enhanced fracture risk in adults. In the context of osteoporotic fractures, bone tissue engineering (BTE), i.e., the use of bone substitutes combining biomaterials, cells, and bone inducers, is a potential alternative to conventional treatments. Pre-clinical testing of innovative scaffolds relies on in vitro systems where the simultaneous presence of osteoblasts (OBs) and osteoclasts (OCs) is required to mimic their crosstalk and molecular cooperation for bone remodelling. To this aim, two composite materials based on type I collagen were developed, containing either strontium-enriched mesoporous bioactive glasses or rod-like hydroxyapatite nanoparticles. Following chemical crosslinking with genipin, the nanostructured materials were tested for 2–3 weeks with an indirect co-culture of human trabecular bone-derived OBs and buffy coat-derived OC precursors. The favourable structural and biological properties of the materials proved to successfully support the viability, adhesion, and differentiation of bone cells, encouraging a further investigation of the two bioactive systems as biomaterial inks for the 3D printing of more complex scaffolds for BTE


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 71 - 71
1 Dec 2021
Giles W Komperla S Flatt E Gandhi M Eyre-Brook A Jones V Papanna M Eves T Thyagarajan D
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Abstract. Background/Objectives. The incidence of reverse total shoulder replacement (rTSR) implantation is increasing globally, but apprehension exists regarding complications and associated challenges. We retrospectively analysed the senior author's series of rTSR from a tertiary centre using the VAIOS shoulder system, a modular 4th generation implant. We hypothesised that the revision rTSR cohort would have less favourable outcomes and more complications. Methods. 114 patients underwent rTSR with the VAIOS system, over 7 years. The primary outcome was implant survival. Secondary outcomes were Oxford shoulder scores (OSS), radiographic analysis (scapular notching, tuberosity osteolysis, and periprosthetic radiolucent lines) and complications. Results. There were 55 Primary rTSR, 31 Revision rTSR and 28 Trauma rTSR. Implant survival: Primary rTSR- 0 revisions, average 3.35-year follow-up. Revision rTSR-1 revision (4.17%), average 3.52-year follow-up. Trauma rTSR- 1 revision (3.57%), average 4.56-year follow-up OSS: Average OSS improved from 15.39 to 33.8 (Primary rTSR) and from 15.11 to 29.1 (Revision rTSR). Average post-operative OSS for the Trauma rTSR was 31.4 Radiological analysis and complications: Low incidence of scapular notching One hairline fracture below the tip of stem, noted incidentally, which required no treatment. One periprosthetic fracture after alcohol related fall. Treated non-surgically One joint infection requiring two-stage revision to rTSR. One dislocation noted at 2 year follow up. This patient had undergone nerve grafting within 6 months of rTSR for axillary nerve injury sustained during the original fracture dislocation. One acromial fracture with tibial and distal humeral fracture after a fall. Conclusions. The 4th generation modular VAIOS implant is a reliable option for various indications. The revision rTSR cohort had favourable outcomes with low complication rates. In this series, early-to-medium term results suggest lower revision rates and good functional outcomes when compared to published reports. We plan to monitor long-term implant survivorship and patient reported outcomes. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 63 - 63
17 Apr 2023
MacLeod A Dal Fabbro G Grassi A Belvedere C Nervuti G Casonato A Leardini A Gil H Zaffagnini S
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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


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 140 - 140
11 Apr 2023
Gens L Marchionatti E Steiner A Stoddart M Thompson K Mys K Zeiter S Constant C
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Autologous cancellous bone graft is the gold standard in large bone defect repair. However, studies using autologous bone grafting in rats are rare and donor sites as well as harvesting techniques vary. The aim of this study was to determine the feasibility of autologous cancellous bone graft harvest from 5 different anatomical sites in rats and compare their suitability as donor sites for autologous bone graft. 13 freshly euthanised rats were used to describe the surgical approaches for autologous bone graft harvest from the humerus, iliac crest, femur, tibia and tail vertebrae (n=4), determine the cancellous bone volume and microstructure of those five donor sites using µCT (n=5), and compare their cancellous bone collected qualitatively by looking at cell outgrowth and osteogenic differentiation using an ALP assay and Alizarin Red S staining (n=4). It was feasible to harvest cancellous bone graft from all 5 anatomical sites with the humerus and tail being more surgically challenging. The microstructural analysis showed a significantly lower bone volume fraction, bone mineral density, and trabecular thickness of the humerus and iliac crest compared to the femur, tibia, and tail vertebrae. The harvested volume did not differ between the donor sites. All donor sites apart from the femur yielded primary osteogenic cells confirmed by the presence of ALP and Alizarin Red S stain. Bone samples from the iliac crest showed the most consistent outgrowth of osteoprogenitor cells. The tibia and iliac crest may be the most favourable donor sites considering the surgical approach. However, due to the differences in microstructure of the cancellous bone and the consistency of outgrowth of osteoprogenitor cells, the donor sites may have different healing properties, that need further investigation in an in vivo study


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 30 - 30
2 Jan 2024
Procter P Hulsart-Billström G Alves A Pujari-Palmer M Wenner D Insley G Engqvist H Larsson S Pippenger B Bossard D
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Surgeons treating fractures with many small osteochondral fragments have often expressed the clinical need for an adhesive to join such fragments, as an adjunct to standard implants. If an adhesive would maintain alignment of the articular surfaces and subsequently heal it could result in improved clinical outcomes. However, there are no bone adhesives available for clinical indications and few pre-clinical models to assess safety and efficacy of adhesive biomaterial candidates. A bone adhesive candidate based on water, α-TCP and an amino acid phosphoserine was evaluated in-vivo in a novel murine bone core model (preliminary results presented EORS 2019) in which excised bone cores were glued back in place and harvested @ 0, 3, 7, 14, 28 and 42days. Adhesive pull-out strength was demonstrated 0–28 days, with a dip at 14 days increasing to 11.3N maximum. Histology 0–42 days showed the adhesive progressively remodelling to bone in both cancellous and cortical compartments with no signs of either undesirable inflammation or peripheral ectopic bone formation. These favourable results suggested translation to a large animal model. A porcine dental extraction socket model was subsequently developed where dental implants were affixed only with the adhesive. Biomechanical data was collected @ 1, 14, 28 and 56 days, and histology at 1,14,28 and 56 days. Adhesive strength assessed by implant pull-out force increased out to 28 days and maintained out to 56 days (282N maximum) with failure only occurring at the adhesive bone interface. Histology confirmed the adhesive's biocompatibility and osteoconductive behavior. Additionally, remodelling was demonstrated at the adhesive-bone interface with resorption by osteoclast-like cells and followed by new bone apposition and substitution by bone. Whilst the in-vivo dental implant data is encouraging, a large animal preclinical model is needed (under development) to confirm the adhesive is capable of healing, for example, loaded osteochondral bone fragments. Acknowledgements: The murine study was supported, in part, by the Swedish Foundation for Strategic Research (#RMA15-0110)


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 95 - 95
14 Nov 2024
Machain TC Kharchenko A Hostettler R Lippl J Mouthuy PA
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Introduction. Supraspinatus tears comprise most rotator cuff injuries, the leading cause of shoulder pain and an increasing problem with ageing populations. Surgical repair of considerable or persistent damages is customary, although not invariably successful. Tissue engineering presents a promising alternative to generate functional tissue constructs with improved healing capacities. This study explores tendon tissue constructs’ culture in a platform providing physiological mechanical stimulation and reports on the effect of different loading regimes on the viability of human tendon cells. Method. Porcine decellularized tendon scaffolds were fixed into flexible, self-contained bioreactor chambers, seeded with human tenocytes, allocated in triplicates to either static control, low (15±0.8Newtons [N]), medium (26±0.5N), or high (49±2.1N)-force-regime groups, connected to a perfusion system and cultured under standard conditions. A humanoid robotic arm provided 30-minute adduction/abduction stimulation to chambers daily over a week. A metabolic activity assay served to assess cell viability at four time points. Statistical significance = p<0.05. Result. One day after beginning mechanical stimulation, chambers in the medium and high-force regimes displayed a rise in metabolic activity by 3% and 5%, respectively. By the last experimental day, all mechanical stimulation regimes had induced an augment in cell viability (15%, 57% and 39% with low, medium, and high loads, respectively) matched against the static controls. Compared to all other conditions, the medium-force regime prompted an increased relative change in metabolic activity for every time point set against day one (p<0.05). Conclusion. Human tenocytes’ viability reflected by metabolic activity in a physiologically relevant bioreactor system is enhanced by loading forces around 25N when mechanically stimulating using adduction/abduction motions. Knowing the most favourable load regime to stimulate tenocyte growth has informed the ongoing exploration of the distinctive effect of different motions on tendon regeneration towards engineering tissue grafts. This work was supported by the Engineering and Physical Sciences Research Council EP/S003509/1


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 97 - 97
17 Apr 2023
Gupta P Butt S Mahajan R Galhoum A Lakdawala A
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Prompt mobilisation after the Fracture neck of femur surgery is one of the important key performance index (‘KPI caterpillar charts’ 2021) affecting the overall functional outcome and mortality. Better control of peri-operative blood pressure and minimal alteration of renal profile as a result of surgery and anaesthesia may have an implication on early post-operative mobilisation. Aim was to evaluate perioperative blood pressure measurements (duration of fall of systolic BP below the critical level of 90mmHg) and effect on the post-operative renal profile with the newer short acting spinal anaesthetic agent (prilocaine and chlorprocaine) used alongside the commonly used regional nerve block. 20 patients were randomly selected who were given the newer short acting spinal anaesthetic agent along with a regional nerve block between May 2019 and February 2020. Anaesthetic charts were reviewed from all patients for data collection. The assessment criteria for perioperative hypotension: Duration of systolic blood pressure less than 90 mm of Hg and change of pre and post operative renal functions. Only one patient had a significant drop in systolic BP less than 90mmHg (25 minutes). 3 other patients had a momentary fall of systolic BP of less than 5 minutes. None of the above patients had mortality and had negligible change in pre and post op renal function. Only one patient in this cohort had elevation of post-operative creatinine levels but did not have any mortality. Only 1 patient died on day 3 post operatively who had multiple comorbidities and was under evaluation for GI cancer. Even in this patient the peri-operative blood pressure was well maintained (never below 90mmHg systolic) and post-operative renal function was also shown to have improved (309 pre-operatively to 150 post-operatively) in this patient. The use of short-acting spinal anaesthesia has shown to be associated with a better control of blood pressure and end organ perfusion, less adverse effects on renal function leading to early mobilisation and a more favourable patient outcome with reduced mortality, earlier mobilisation, shorter hospital stay and earlier discharge in this elderly patient cohort


Arthroscopic management of femoroacetabular impingement (FAI) has become the mainstay of treatment. However, chondral lesions are frequently encountered and have become a determinant of less favourable outcomes following arthroscopic intervention. The aim of this systematic review and meta-analysis was to assess the outcomes of hip arthroscopy (HA) in patients with FAI and concomitant chondral lesions classified as per Outerbridge. A systematic search was performed using the PRISMA guidelines on four databases including MEDLINE, EMBASE, Cochrane Library and Web of Science. Studies which included HA as the primary intervention for management of FAI and classified chondral lesions according to the Outerbridge classification were included. Patients treated with open procedures, for osteonecrosis, Legg-Calve-Perthes disease, and previous ipsilateral hip fractures were excluded. From a total of 863 articles, twenty-four were included for final analysis. Demographic data, PROMs, and radiological outcomes and rates of conversion to total hip arthroplasty (THA) were collected. Risk of bias was assessed using ROBINS-I. Improved post-operative PROMs included mHHS (mean difference:-2.42; 95%CI:-2.99 to −1.85; p<0.001), NAHS (mean difference:-1.73; 95%CI: −2.23 to −1.23; p<0.001), VAS (mean difference: 2.03; 95%CI: 0.93-3.13; p<0.001). Pooled rate of revision surgery was 10% (95%CI: 7%-14%). Most of this included conversion to THA, with a 7% pooled rate (95%CI: 4%-11%). Patients had worse PROMs if they underwent HA with labral debridement (p=0.015), had Outerbridge 3 and 4 lesions (p=0.012), concomitant lesions of the femoral head and acetabulum lesions (p=0.029). Reconstructive cartilage techniques were superior to microfracture (p=0.042). Even in concomitant lesions of the femoral head and acetabulum, employing either microfracture or cartilage repair/reconstruction provided a benefit in PROMs (p=0.027). Acceptable post-operative outcomes following HA with labral repair/reconstruction and cartilage repair in patients with FAI and concomitant moderate-to-severe chondral lesions, can be achieved. Patients suffering from Outerbridge 3 and 4 lesions, concomitant acetabular rim and femoral head chondral lesions that underwent HA with labral debridement, had worse PROMs. Reconstructive cartilage techniques were superior to microfracture. Even in concomitant acetabular and femoral head chondral lesions, employing either microfracture or cartilage repair/reconstruction was deemed to provide a benefit in PROMs


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_16 | Pages 29 - 29
17 Nov 2023
Morris T Dixon J Baldock T Eardley W
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Abstract. Objectives. The outcomes from patella fracture have remained dissatisfactory despite advances in treatment, especially from operative fixation1. Frequently, reoperation is required following open reduction and internal fixation (ORIF) of the patella due to prominent hardware since the standard technique for patella ORIF is tension band wiring (TBW) which inevitably leaves a bulky knot and irritates soft tissue given the patella's superficial position2. We performed a systematic review to determine the optimal treatment of patella fractures in the poor host. Methods. Three databases (EMBASE/Medline, ProQuest and PubMed) and one register (Cochrane CENTRAL) were searched. 476 records were identified and duplicates removed. 88 records progressed to abstract screening and 73 were excluded. Following review of complete references, 8 studies were deemed eligible. Results. Complication rates were shown to be high in our systematic review. Over one-fifth of patients require re-operation, predominantly for removal of symptomatic for failed hardware. Average infection rate was 11.95% which is higher than rates reported in the literature for better hosts. Nevertheless, reported mortality was low at 0.8% and thromboembolic events only occurred in 2% of patients. Average range of movement achieved following operative fixation was approximately 124 degrees. Upon further literature review, novel non-operative treatment options have shown acceptable results in low-demand patients, including abandoning weight-bearing restrictions altogether and non-operatively treating patients with fracture gaps greater than 1cm. Regarding operative management, suture/cable TBW has been investigated as a viable option with good results in recent years since the materials used show comparable biomechanics to stainless steel. Additionally, ORIF with locking plates have shown favourable results and have enabled aggressive post-operative rehabilitation protocols. TBW with metallic implants has shown higher complication rates, especially for anterior knee pain, reoperation and poor functional outcomes. Conclusion. There is sparse literature regarding patella fracture in the poor host. Nevertheless, it is clear that ORIF produces better outcomes than conservative treatment but the optimal technique for patella ORIF remains unclear. TBW with metallic implants should not remain the standard technique for ORIF; low-profile plates of suture TBW are more attractive solutions. Non-operative treatment may be considered for low-demand individuals however any form of patellectomy should be avoided if possible. 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


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 49 - 49
1 Dec 2021
Edwards T Prescott R Stebbins J Wright J Theologis T
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Abstract. Objectives. Single-event multilevel surgery (SEMLS) is the standard orthopaedic treatment for gait abnormalities in children with diplegic cerebral palsy (CP). The primary aim of this study was to report the long-term functional mobility of these patients after surgery. The secondary aim was to assess the relationship between functional mobility and quality of life (QoL). Methods. Patients were included if they met the following criteria: 1) diplegic CP; 2) Gross Motor Function Classification System (GMFCS) I to III; 3) SEMLS at age ≤ 18. A total of 61 patients, mean age at surgery 11 years eight months (SD 2y 5m), were included. A mean of eight years (SD 3y 10m) after SEMLS, patients were contacted and asked to complete the Functional Mobility Scale (FMS) questionnaire over the telephone and given a weblink to complete an online version of the CP QOL Teen. FMS was recorded for all patients and CP QOL Teen for 23 patients (38%). Results. Of patients graded GMFCS I and II preoperatively, at long-term follow-up the proportion walking independently at home, school/work and in the community was 71% (20/28), 57% (16/28) and 57% (16/28), respectively. Of patients graded GMFCS III preoperatively, at long-term follow-up 82% (27/33) and 76% (25/33) were walking either independently or with an assistive device at home and school/work, respectively, while over community distances 61% (20/33) required a wheelchair. The only significant association between QoL and functional mobility was better ‘feelings about function’ in patients with better home FMS scores (r=0.55; 95% confidence interval 0.15 to 0.79; p=0.01). Conclusion. The majority of children maintained their preoperative level of functional mobility at long-term follow-up after SEMLS. Despite the favourable functional mobility, there was little evidence to establish a link between functional status and quality of life


Introduction and Objective. Posterior and transforaminal lumbar interbody fusion (PLIF, TLIF) represent the most popular techniques in performing an interbody fusion amongst spine surgeons. Pseudarthrosis, cage migration, subsidence or infection can occur, with subsequent failed surgery, persistent pain and patient’ bad quality of life. The goal of revision fusion surgery is to correct any previous technical errors avoiding surgical complications. The most safe and effective way is to choose a naive approach to the disc. Therefore, the anterior approach represents a suitable technique as a salvage operation. The aim of this study is to underline the technical advantages of the anterior retroperitoneal approach as a salvage procedure in failed PLIF/TLIF analyzing a series of 32 consecutive patients. Materials and Methods. We performed a retrospective analysis of patients’ data in patients who underwent ALIF as a salvage procedure after failed PLIF/TLIF between April 2014 to December 2019. We recorded all peri-operative data. In all patients the index level was exposed with a minimally invasive anterior retroperitoneal approach. Results. Thirty-two patients (average age: 46.4 years, median age 46.5, ranging from 21 to 74 years hold- 16 male and 16 female) underwent salvage ALIF procedure after failed PLIF/TLIF were included in the study. A minimally invasive anterior retroperitoneal approach to the lumbar spine was performed in all patients. In 6 cases (18.7%) (2 infection and 4 pseudarthrosis after stand-alone IF) only anterior revision surgery was performed. A posterior approach was necessary in 26 cases (81.3%). In most of cases (26/32, 81%) the posterior instrumentation was overpowered by the anterior cage without a previous revision. Three (9%) intraoperative minor complications after anterior approach were recorded: 1 dural tear, 1 ALIF cage subsidence and 1 small peritoneal tear. None vascular injuries occurred. Most of patients (90.6%) experienced an improvement of their clinical condition and at the last follow-up no mechanical complication occurred. Conclusions. According to our results, we can suggest that a favourable clinical outcome can firstly depend from technical reasons an then from radiological results. The removal of the mobilized cage, the accurate endplate and disc space preparation and the cage implant eliminate the primary source of pain reducing significantly the axial pain, helping to realise an optimal bony surface for fusion and enhancing primary stability. The powerful disc distraction given by the anterior approach allows inserting large and lordotic cages improving the optimal segmental lordosis restoration


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 13 - 13
1 Mar 2021
Gomez-Sierra M Lackington W Alini M Thompson K
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Although 80% of fractures typically heal without any problems, there is a small proportion (<20%) that suffer complications such as delayed healing and potential progression to non-union. In patients with healing complications, the coordinated regulation between pro- and anti-inflammatory cytokines, such as interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1Ra) respectively, is often dysregulated. The aim of this study is to develop a therapeutic strategy based on the local delivery of genes to reparative mesenchymal stromal cells (MSCs) migrating into the local fracture microenvironment, thereby promoting a more favourable healing environment to enhance fracture repair. Our approach involves the local delivery of nanoparticles complexing the non-viral vector polyethyleneimine (PEI) with therapeutic plasmid DNA (pDNA) encoding for IL-1Ra. pDNA encoding green fluorescent protein and Gaussia luciferase were used as reporter genes to determine the transfection efficiency of both rat and human MSCs using flow cytometry and to assess the transgene expression profile using a luciferase expression assay. The effect of transfection with PEI on the viability of MSCs was assessed using the metabolic assay Cell Titer Blue and dsDNA quantification. Levels of IL-1Ra produced by cells following transfection with nanoparticles encoding IL-1Ra was assessed using enzyme-linked immunosorbent assays (ELISA). HEK-Blue IL-1β reporter cells, which secrete alkaline phosphatase in response to IL-1β stimulation, were used to confirm that the IL-1Ra produced by transfected cells is functionally active, i.e. the successful antagonism of IL-1β bioactivity. We have determined that using PEI-based nanoparticles we can achieve a transfection efficiency of 14.8 + 1.8% in rat MSCs. Transgene expression was found to be transient, with a peak in expression at 7 days post-transfection and a gradual decrease over time, which was maintained for up to 4 weeks. Using an optimized concentration of PEI, the impact of the nanoparticles on MSC viability was limited, with no significant difference in cellular metabolic activity compared to non-transfected cells at 10 days post-transfection. We have additionally demonstrated the capacity to successfully transfect both rat and human MSCs with pDNA encoding for IL-1Ra, resulting in enhanced levels of IL-1Ra, which is functionally active. The use of non-viral gene therapy to locally deliver immunomodulatory genes, such as IL-1Ra, to MSCs presents a promising strategy to enhance bone healing. Specifically, the transgene expression levels achieved with such an approach can remain therapeutically effective and are transient in nature, presenting an advantage over other methods such as recombinant protein delivery and viral-based gene delivery methodologies


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 334 - 334
1 Jul 2014
Kerens B Boonen B Schotanus M Lacroix H Emans P Kort N
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Summary Statement. This paper is the first to compare the results of unicompartmental to total knee arthroplasty revision surgery between cases with explained pain and cases with unexplained pain. Revision surgery for unexplained pain usually results in a less favourable outcome. Introduction. Although it is suggested in literature that results of UKA to TKA revision surgery improve when the mechanism of failure is understood, a comparative study regarding this topic is lacking. Methods. All cases of revision surgery in two hospitals in the Netherlands were listed retrospectively. Fifteen cases with unexplained pain were listed in group A and 15 cases with a cause for pain in group B. Oxford knee scores (OKS), visual analogue scores (VAS) and patient satisfaction one year after revision surgery were compared. Results. OKS improved from 19 to 25 within group A and from 23 to 38 within group B. VAS improved from 7, 7 to 5, 4 within group A and from 7, 4 to 1, 7 within group B. The difference in outcome between both groups is statistically significant, p=0,022 for OKS and p=0,002 for VAS. Subgroup analysis in group A, performed in order to define a patient factor that predicts outcome of revision surgery in case of unexplained pain, showed no preoperative differences between both subgroups. Discussion. These results are important to properly inform patients about what to expect of revision surgery, highlighting that UKA to TKA revision surgery for unexplained pain generally results in a less favourable outcome


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 63 - 63
1 Nov 2018
Kose N Köse A Bayrak C Sevencan A Akyürekli A Koparak T Korkusuz F Dogan A
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Long-term survival and favourable outcome of implant use are determined by bone-implant osseointegration and absence of infection near the implants. As with most diseases, prevention is the preferred approach. Silver ion doped calcium phosphate based ceramic coating (Silveron®) for implant coating has been shown previously to be a potent antimicrobial agent as indicated by in vitro testing. The present study reports on clinical experience using silver ion doped calcium phosphate based ceramic coated external fixator pins as surgical treatment in the management of chronic osteomyelitis and open fractures. Ten patients had external fixators: six for open fractures of ankle, three for chronic osteomyelitis of the femur, one for tibia pseudoarthrosis. The electrospray method was used for coating the external fixator pins with silver ion doped calcium phosphate-based ceramics. A radiofrequency energy source was used to sinter the coated pins. Microbiological, roentgenographic, toxic and biochemical analyzes of patients were carried out. Wound debridement, and subsequent wound care resulted in control of the infection in three chronic osteomyelitis and in healing of seven fractures after follow-up ranging from three to six months. In total 67 pins were used in 10 patients but only one pin was positive microbiologically in one patient. Collectively, these data clearly illustrate that the toxic effects of silver were not observed at the doses used. Silver ion doped calcium phosphate based ceramic coating (Silveron®) can be used to prevent infection associated with the implant


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 12 - 12
1 Nov 2018
McQuail PM McCartney BS McKenna P
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Orthopaedic surgical site infections (SSI's) prolong total hospital stays by a median of 2 weeks per patient, approximately double re-hospitalization rates, and increase healthcare costs by more than 300%. Patients with orthopaedic SSI's have significant reductions in their health-related quality of life. We performed a systematic review and meta-analysis to compare differences in outcomes between use of sutures and non-absorbable staples for closure of orthopaedic surgical wounds in adults. The primary outcomes were rates of superficial and deep SSI. Secondary outcomes included wound dehiscence, length of hospital stay, patient satisfaction and pain during removal of closure material. Data sources including PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, . clinicaltrials.gov. , National Institute for Health and Research, UK clinical trials gateway were searched for randomised controlled trials (RCT's) meeting inclusion criteria. Sixteen RCT's published between 1987 and 2017 were included. Overall, wound infection outcomes (superficial and deep infections combined) showed no statistically significant difference between closure with staples compared with sutures with arelative risk of 1.17 (95% CI 0.59–2.30, p=0.66). A subgroup was performed specific to hip wound infection outcomes. Interestingly, a sensitivity analysis demonstrated sutures to be statistically favourable (p=0.04) in terms of hip wound infection outcomes. There was no statistically significant difference among secondary outcomes between sutures and staple groups. Overall it appears the choice of sutures or staples in closure of orthopaedic wounds has no effect on wound complications. However, caution is needed in applying the findings to different population groups due to heterogeneity across studies


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_3 | Pages 18 - 18
1 Apr 2018
Caron M Janssen M Peeters L Surtel D van Rhijn L Emans P Welting T
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INTRODUCTION. The generation of cartilage from progenitor cells for the purpose of cartilage repair is often hampered by unwanted hypertrophic differentiation of the generated tissue due to endochondral ossification. Continuing on our earlier studies, our goal is to further improve the engineering of hyaline cartilage for the treatment of a cartilage defect in our in vivo model for subperiosteal generation of cartilage, by tuning the differentiation status of the generated cartilage and prevent hypertrophic differentiation. As a healthy cartilage matrix contains high amounts of aggrecan we hypothesise that aggrecan supplementation of the bio-gel used in the generation of the subperiosteal cartilage, mimics the composition of the extracellular matrix environment of cartilage with potential beneficial properties for the engineered cartilage. METHODS. A 2% (m/v) low melting agarose was injected between the bone and periosteum at the upper medial side of the tibia of both legs of New Zealand white rabbits (DEC 2012–151). The agarose was left unloaded (n=7) or supplemented (n=7) with 2% (w/v) bovine aggrecan (Sigma-Aldrich). After 14 days, rabbits were euthanised. Generated subperiosteal cartilage tissue was analysed for weight, GAG and DNA content. In addition, RT-qPCR and (immuno)histochemistry was performed for key markers of different phases of endochondral ossification. RESULTS. The nett weight of the generated subperiosteal cartilage tissue was not significantly different between groups, nor was the GAG content different. No significant differences in chondrogenic marker expression (COL2A1, SOX9, ACAN and PTHrP) were detected. Interestingly, gene expression levels of hypertrophic markers COL10A1 and ALPL were significantly decreased. COL1A1 expression was not significantly different between groups. DISCUSSION. In summary, generation of subperiosteal cartilage was successful when an agarose bio-gel was injected beneath the periosteum. The addition of aggrecan to the bio-gel did not result in differences in weight or GAG content in cartilage samples between conditions. However, lower levels of hypertrophic markers were observed, while leaving chondrogenic marker expression unaltered. These data show the potential of aggrecan to favourably influence the subperiosteal microenvironment for the in vivo generation of hyaline cartilage for the optimisation of cartilage regenerative medicine approaches


Bone & Joint Research
Vol. 6, Issue 2 | Pages 73 - 81
1 Feb 2017
Ishihara K Okazaki K Akiyama T Akasaki Y Nakashima Y

Objectives. Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts. Methods. Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays. Results. After six weeks, the area of mineralisation was significantly higher for the transplanted osteophytes than for the cancellous bone (43803 μm. 2. , . sd. 14660 versus 9421 μm. 2. , . sd. 5032, p = 0.0184, one-way analysis of variance). Compared with cancellous bone, the conditioned medium prepared using osteophytes contained a significantly higher amounts of transforming growth factor (TGF)-β1 (471 pg/ml versus 333 pg/ml, p = 0.0001, Wilcoxon rank sum test), bone morphogenetic protein (BMP)-2 (47.75 pg/ml versus 32 pg/ml, p = 0.0214, Wilcoxon rank sum test) and insulin-like growth factor (IGF)-1 (314.5 pg/ml versus 191 pg/ml, p = 0.0418, Wilcoxon rank sum test). The stronger effects of osteophytes towards osteoblasts in terms of a higher proliferation rate, upregulation of gene expression of differentiation markers such as alpha-1 type-1 collagen and alkaline phosphate, and higher migration, compared with cancellous bone, was confirmed. Conclusion. We provide evidence of favourable features of osteophytes for bone mineralisation through a direct effect on osteoblasts. The acceleration in metabolic activity of the osteophyte provides justification for future studies evaluating the clinical use of osteophytes as autologous bone grafts. Cite this article: K. Ishihara, K. Okazaki, T. Akiyama, Y. Akasaki, Y. Nakashima. Characterisation of osteophytes as an autologous bone graft source: An experimental study in vivo and in vitro. Bone Joint Res 2017;6:73–81. DOI: 10.1302/2046-3758.62.BJR-2016-0199.R1


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_4 | Pages 78 - 78
1 Apr 2018
Caron M Janssen M Peeters L Surtel D Koole L van Rhijn L Welting T Emans P
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INTRODUCTION. The generation of cartilage from progenitor cells for the purpose of cartilage repair is often hampered by unwanted ossification of the generated tissue due to endochondral ossification. Our in vitro data show that celecoxib is able to suppress the hypertrophic differentiation phase of endochondral ossification in differentiating human bone marrow stem cells via inhibition of prostaglandin signalling. Continuing on our earlier studies our goal is to further improve the engineering of hyaline cartilage for the treatment of cartilage defects, by determining if celecoxib released from poly(D,L-lactic acid)microspheres is able to prevent unwanted ossification in an in vivo model for the subperiosteal cartilage generation. METHODS. A 2% (m/v) low melting agarose was injected between the bone and periosteum at the upper medial side of the tibia of both legs of New Zealand white rabbits (DEC 2012–151). The agarose was left unloaded or (n=8) or loaded (n=7) with celecoxib-loaded PGLA microspheres (poly(D,L-lactic acid) microspheres were loaded with 20% (w/w) Celecoxib (Pfizer)). Fourteen days post-injection, rabbits were euthanised. The developed subperiosteal cartilage tissue was analysed for weight, GAG and DNA content. In addition, RT-qPCR and (immuno)histochemistry were performed for key markers of different phases of endochondral ossification. RESULTS. The Functional release of celecoxib from poly(D,L-lactic acid) microspheres was confirmed in vitro by decreased prostaglandin E2 levels in cell culture. The subperiosteal cartilage tissue from the celecoxib group was significantly higher in weight and DNA content as compared to the control condition. GAG content was not significantly different between groups. No significant differences in chondrogenic marker expression (COL2A1, SOX9, ACAN and PTHrP) were detected, but levels of hypertrophic markers COL10A1, RUNX2 and ALPL were significantly decreased. COL1A1 expression was not significantly different between groups. DISCUSSION. In summary, subperiosteal generation of cartilage was successful when an agarose bio-gel was injected subperiosteally. Supplementation of the agarose gel with celecoxib-loaded microspheres favourably changed the weight of the generated cartilage tissue, combined with significantly lower expression levels of indicators of chondrocyte hypertrophy, while leaving chondrogenic differentiation capacity unaltered. These data hold the promise that local supplementation of celecoxib during in vivo cartilage regeneration protects the tissue from adverse hypertrophic differentiation


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_4 | Pages 95 - 95
1 Apr 2018
Polak-Kraśna K MacLeod A Fletcher J Whitehouse M Preatoni E Gill H
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The screw fastening torque applied during bone fracture fixation has a decisive influence on subsequent bone healing. Insufficient screw tightness can result in device/construct instability; conversely, excessive torques risk damaging the bone causing premature fixation failure. This effect is even more prominent in osteoporotic bone, a condition associated annually with almost 9 million fractures worldwide. During fracture fixation, screw tightening torque is applied using subjective feel. This approach may not be optimal for patient”s recovery, increasing risk of fixation failure, particularly in osteoporotic bone, and potentially require revision surgical interventions. Besides bone density, various factors influence the performance of screw fixation. These factors include bone geometry, cortical thickness and time-dependant relaxation behaviour of the bone. If the influence of screw fastening torque on the bone and relationships between these factors was better understood, the surgical technique could be optimised to reduce the risk of complications. Within this study, we developed an axisymmetric finite element (FE) model of bone screw tightening incorporating viscoelastic behaviour of the cortical bone such as creep and stress relaxation. The model anticipated time-dependent behaviour of the bone for different bone thickness and density after a typical bone fixation screw had been inserted. The idealised model has been developed based on CT scans of bones with varying densities and inserted screws. The model was validated through a series of experiments involving bovine tibiae (4–5 months) to evaluate the evolution of surface strains with time (Ncorr v1.2). Stress distribution was assessed in photoelastic experiments using acrylic analogues. Relaxation tests have been performed in aqueous environment for up to 48 hours to ensure the relaxation would be complete. The creep behaviour (maximum principal strain) was compared against computational predictions. Our early simulations predicted relaxation strains on the surface of the bone to be 1.1% within 24 hours comparing favourably to 1.3% measured experimentally. Stress distribution patterns were in agreement with photoelastic results. Using experimentally derived viscoelastic properties, the model has the potential to predict creep and stress relaxation patterns after screw insertion with different fastening torques for bones with varying density and geometry. We aim to develop this into a planning tool providing guidance to surgeons for optimal tightening when using screw fixation, particularly in reduced quality bone