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Bone & Joint 360
Vol. 12, Issue 6 | Pages 39 - 42
1 Dec 2023

The December 2023 Oncology Roundup360 looks at: A single osteotomy technique for frozen autograft; Complications, function, and survival of tumour-devitalized autografts used in patients with limb-sparing surgery; Is liquid nitrogen recycled bone and vascular fibula the biological reconstruction of choice?; Solitary pulmonary metastases at first recurrence of osteosarcoma; Is a radiological score able to predict resection-grade chondrosarcoma in primary intraosseous lesions of the long bones?; Open versus core needle biopsy in lower-limb sarcoma – current practice patterns and patient outcomes; Natural history of intraosseous low-grade chondroid lesions of the proximal humerus; Local treatment modalities and event-free survival in patients with localized Ewing’s sarcoma; Awaiting biopsy results in solitary pathological proximal femoral fractures.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 14 - 14
24 Nov 2023
Loïc F Sylvain W Kennedy M Theophile N Olivier NF Marie-Ange NY Jean B
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Aim. infected segmental bone defect (ISBD) is frequent in developing countries. The aim of this study was to assess the efficacy of the Masquelet technique in the treatment of ISBD in a low-resource setting. Patients and Method. We performed a prospective cohort study during the period from 2018 to 2022. Patients with infected bone defect of long bones were included. Management protocol consisted of two stages in all patients. The first stage consisted in debridement, tissues biopsy for microbiological culture, stabilization with external fixator and defect filling with gentamicin cement spacer. The second stage consisted of reconstruction using a cancellous bone autograft alone, or a mixture of autograft with allograft (demineralized bone matrix + tricalcium phosphate) and 1 gram of vancomycin powder. All patients were followed-up for at least one year. The results were assessed based on both objective (clinical and radiographic evaluation) and subjective (limb function and patient satisfaction) criteria. Main outcomes were bone union, reoperation and failure rates, union time, and limb function. Results. We included 31 patients in this study (80.6% men), with a median age of 35 [9 – 80] years. The tibia was affected in 12 cases and the femur in 15 cases. The median size of bone defect was 4 [1.5 – 12] cm. The most prevalent microorganisms were Klebsiella pneumoniae and Staphylococcus aureus. The mean interval between both stages was 14 (8 – 36) weeks and the median follow-up period after the second stage was 20 [12-62] months. External fixation was used in both stages in 25(80%) cases. Bone union was achieved in 26 (83.8%) patients of whom 24 without recurrence of infection, over a median time of 9 [6 – 16] months. All patients with a mixed graft (allograft and autograft) impregnated with local antibiotics achieved bone union. Two patients needed reoperation for relapse of infection between both stages, and subsequently achieved bone union without recurrence of infection. There were three cases of failure related to persistent infection or insufficient fixation stability in the second stage. Conclusions. Masquelet technique is a reliable procedure that can be safely performed in limited resources settings with satisfactory results. The mixture of autograft and allograft when available, all mixed with vancomycin seems to give promising results


Bone & Joint Research
Vol. 12, Issue 9 | Pages 546 - 558
12 Sep 2023
Shen J Wei Z Wang S Wang X Lin W Liu L Wang G

Aims

This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes.

Methods

A comprehensive search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases between 1 January 2000 and 31 October 2021. Studies with a minimum sample size of five patients with infected bone defects treated with the induced membrane technique were included. Factors associated with nonunion, infection recurrence, and additional procedures were identified using logistic regression analysis on individual patient data.


The Bone & Joint Journal
Vol. 105-B, Issue 8 | Pages 912 - 919
1 Aug 2023
Cunningham LJ Walton M Bale S Trail IA

Aims. Reverse total shoulder arthroplasty (rTSA) can be used in complex cases when the glenoid requires reconstruction. In this study, a baseplate with composite bone autograft and a central trabecular titanium peg was implanted, and its migration was assessed for two years postoperatively using radiostereometric analysis (RSA). Methods. A total of 14 patients who underwent a rTSA with an autograft consented to participate. Of these, 11 had a primary rTSA using humeral head autograft and three had a revision rTSA with autograft harvested from the iliac crest. The mean age of the patients was 66 years (39 to 81). Tantalum beads were implanted in the scapula around the glenoid. RSA imaging (stereographic radiographs) was undertaken immediately postoperatively and at three, six, 12, and 24 months. Analysis was completed using model-based RSA software. Outcomes were collected preoperatively and at two years postoperatively, including the Oxford Shoulder Score, the American Shoulder and Elbow Score, and a visual analogue score for pain. A Constant score was also obtained for the assessment of strength and range of motion. Results. RSA analysis showed a small increase in all translation and rotational values up to six months postoperatively, consistent with settling of the implant. The mean values plateaued by 12 months, with no evidence of further migration. In four patients, there was significant variation outside the mean, which corresponded to postoperative complications. There was a significant improvement in the clinical and patient-reported outcomes from the preoperative values to those at two years postoperatively (p < 0.001). Conclusion. These findings show, using RSA, that a glenoid baseplate composite of a trabecular titanium peg with autograft stabilizes within the glenoid about 12 months after surgery, and reinforce findings from a previous study of this implant/graft with CT scans at two years postoperatively, indicating that this type of structural composite results in sound early fixation. Cite this article: Bone Joint J 2023;105-B(8):912–919


Bone & Joint Open
Vol. 4, Issue 2 | Pages 110 - 119
21 Feb 2023
Macken AA Prkić A van Oost I Spekenbrink-Spooren A The B Eygendaal D

Aims

The aim of this study is to report the implant survival and factors associated with revision of total elbow arthroplasty (TEA) using data from the Dutch national registry.

Methods

All TEAs recorded in the Dutch national registry between 2014 and 2020 were included. The Kaplan-Meier method was used for survival analysis, and a logistic regression model was used to assess the factors associated with revision.


The Bone & Joint Journal
Vol. 105-B, Issue 2 | Pages 172 - 179
1 Feb 2023
Shimizu T Kato S Demura S Shinmura K Yokogawa N Kurokawa Y Yoshioka K Murakami H Kawahara N Tsuchiya H

Aims

The aim of this study was to investigate the incidence and characteristics of instrumentation failure (IF) after total en bloc spondylectomy (TES), and to analyze risk factors for IF.

Methods

The medical records from 136 patients (65 male, 71 female) with a mean age of 52.7 years (14 to 80) who underwent TES were retrospectively reviewed. The mean follow-up period was 101 months (36 to 232). Analyzed factors included incidence of IF, age, sex, BMI, history of chemotherapy or radiotherapy, tumour histology (primary or metastasis; benign or malignant), surgical approach (posterior or combined), tumour location (thoracic or lumbar; junctional or non-junctional), number of resected vertebrae (single or multilevel), anterior resection line (disc-to-disc or intravertebra), type of bone graft (autograft or frozen autograft), cage subsidence (CS), and local alignment (LA). A survival analysis of the instrumentation was performed, and relationships between IF and other factors were investigated using the Cox regression model.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 47 - 47
1 Dec 2022
Cherry A Eseonu K Ahn H
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Lumbar fusion surgery is an established procedure for the treatment of several spinal pathologies. Despite numerous techniques and existing devices, common surgical trends in lumbar fusion surgery are scarcely investigated. The purpose of this Canada-based study was to provide a descriptive portrait of current surgeons’ practice and implant preferences in lumbar fusion surgery while comparing findings to similar investigations performed in the United Kingdom. Canadian Spine Society (CSS) members were sampled using an online questionnaire which was based on previous investigations performed in the United Kingdom. Fifteen questions addressed the various aspects of surgeons’ practice: fusion techniques, implant preferences, and bone grafting procedures. Responses were analyzed by means of descriptive statistics. Of 139 eligible CSS members, 41 spinal surgeons completed the survey (29.5%). The most common fusion approach was via transforaminal lumber interbody fusion (TLIF) with 87.8% performing at least one procedure in the previous year. In keeping with this, 24 surgeons (58.5%) had performed 11 to 50 cases in that time frame. Eighty-six percent had performed no lumbar artificial disc replacements over their last year of practice. There was clear consistency on the relevance of a patient specific management (73.2%) on the preferred fusion approach. The most preferred method was pedicle screw fixation (78%). The use of stand-alone cages was not supported by any respondents. With regards to the cage material, titanium cages were the most used (41.5%). Published clinical outcome data was the most important variable in dictating implant choice (87.8%). Cage thickness was considered the most important aspect of cage geometry and hyperlordotic cages were preferred at the lower lumbar levels. Autograft bone graft was most commonly preferred (61.0%). Amongst the synthetic options, DBX/DBM graft (64.1%) in injectable paste form (47.5%) was preferred. In conclusion, findings from this study are in partial agreement with previous work from the United Kingdom, but highlight the variance of practice within Canada and the need for large-scale clinical studies aimed to set specific guidelines for certain pathologies or patient categories


The Bone & Joint Journal
Vol. 104-B, Issue 12 | Pages 1334 - 1342
1 Dec 2022
Wilcox B Campbell RJ Low A Yeoh T

Aims

Rates of reverse total shoulder arthroplasty (rTSA) continue to grow. Glenoid bone loss and deformity remains a technical challenge to the surgeon and may reduce improvements in patients’ outcomes. However, there is no consensus as to the optimal surgical technique to best reconstruct these patients’ anatomy. This review aims to compare the outcomes of glenoid bone grafting versus augmented glenoid prostheses in the management of glenoid bone loss in primary reverse total shoulder arthroplasty.

Methods

This systematic review and meta-analysis evaluated study-level data in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We performed searches of Medline (Ovid), Embase (Ovid), and PubMed from their dates of inception to January 2022. From included studies, we analyzed data for preoperative and postoperative range of motion (ROM), patient-reported functional outcomes, and complication rates.


Bone & Joint Open
Vol. 3, Issue 9 | Pages 733 - 740
21 Sep 2022
Sacchetti F Aston W Pollock R Gikas P Cuomo P Gerrand C

Aims

The proximal tibia (PT) is the anatomical site most frequently affected by primary bone tumours after the distal femur. Reconstruction of the PT remains challenging because of the poor soft-tissue cover and the need to reconstruct the extensor mechanism. Reconstructive techniques include implantation of massive endoprosthesis (megaprosthesis), osteoarticular allografts (OAs), or allograft-prosthesis composites (APCs).

Methods

This was a retrospective analysis of clinical data relating to patients who underwent proximal tibial arthroplasty in our regional bone tumour centre from 2010 to 2018.


The Bone & Joint Journal
Vol. 103-B, Issue 10 | Pages 1604 - 1610
1 Oct 2021
Takaoka Y Goto K Tamura J Okuzu Y Kawai T Kuroda Y Orita K Matsuda S

Aims

We aimed to evaluate the long-term outcome of highly cross-linked polyethylene (HXLPE) cemented acetabular components and assess whether any radiolucent lines (RLLs) which arose were progressive.

Methods

We retrospectively reviewed 170 patients who underwent 187 total hip arthroplasties at two hospitals with a minimum follow-up of ten years. All interventions were performed using the same combination of HXLPE cemented acetabular components with femoral stems made of titanium alloy. Kaplan-Meier survival analysis was performed for the primary endpoint of acetabular component revision surgery for any reason and secondary endpoint of the appearance of RLLs. RLLs that had appeared once were observed over time. We statistically assessed potential relationships between RLLs and a number of factors, including the technique of femoral head autografting and the Japanese Orthopaedic Association score.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_6 | Pages 39 - 39
1 May 2021
Ferreira N Saini A Birkholtz F Laubscher M
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Introduction. Purpose: Injuries to the long bones of the upper limb resulting in bone defects are rare but potentially devastating. Literature on the management of these injuries is limited to case reports and small case series. The aim of this study was to collate the most recent published work on the management of upper limb bone defects to assist with evidence based management when confronted with these cases. Materials and Methods. Methods: Following a preliminary search that confirmed the paucity of literature and lack of comparative trials, a scoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) was conducted. A literature search of major electronic databases was conducted to identify journal articles relating to the management of upper limb long bone defects published between 2010 and 2020. Results. Results: A total of 46 publications reporting on the management of 341 patients were reviewed. Structural autograft, bone transport, one-bone forearm and the induced membrane technique were employed in an almost equal number of cases. The implemented strategies showed similar outcomes but different indications and complication profiles were observed. Conclusions. Conclusion: Contemporary techniques for the management of post-traumatic upper limb bone defects all produce good results. Specific advantages, disadvantages and complications for each modality should be considered when deciding on which management strategy to employ for each specific patient, anatomical location, and defect size


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 12 - 12
1 Mar 2021
Glazebrook M Baumhauer J Younger A Fitch D Quiton J Daniels T DiGiovanni C
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Autologous bone has been the gold standard for grafting material in foot and ankle arthrodesis. While autograft use has been effective, the harvest procedure does present risks to the patient including readmission, infection, and persistent graft harvest site pain. Previous studies have examined graft harvest site pain, but most have focused on the iliac crest and none have long term follow-up. The purpose of this study was to examine long-term (7–10 year) harvest site pain in subjects undergoing autograft harvest from multiple sites for hindfoot and/or ankle arthrodesis. Sixty (60) subjects underwent hindfoot or ankle arthrodesis supplemented with autograft as part of the control arm of a prospective, randomized trial. The mean subject age was 59.4 years (range, 24.7–76.8) and mean body mass index was 30.6 kg/m2 (range, 22.0–44.0). There were 29 males and 31 female subjects. Subjects had the tibiotalar (37.9%), subtalar (24.1%), talonavicular (10.3%), subtalar/talonavicular (5.1%), or subtalar/calcaneocuboid/talonavicular (22.4%) joints arthrodesed. Autograft was harvested from either the proximal tibia (51.7%), iliac crest (17.2%), calcaneous (15.5%), distal tibia (6.8%), or other location (8.6%). Graft harvest site pain was evaluated using a 100-point visual analog score (VAS), with clinically significant pain being any score greater than 20. Subjects were followed a mean of 9.0 years (range, 7.8–10.5). The percentage of subjects who reported clinically significant pain was 35.7%, 21.4%, 18.2%, 10.5%, 8.9%, and 5.2% at 2, 6, 12, 24, 52 weeks, and final follow-up (7.8–10.5 years), respectively. The mean VAS autograft harvest site pain at final follow-up was 4.4 (range, 0.0–97.0), with 37.9% of subjects reporting at least some pain. For three subjects (5%) with clinically significant pain (VAS >20) at final follow-up, two had proximal tibial harvest sites and one had an iliac crest harvest site. There was no correlation between graft volume and harvest site pain. This study is the first to examine long-term pain following autologous bone graft harvest for hindfoot and/or ankle arthrodesis. Over a third of patients reported having some pain at an average follow-up of nine years, with 5% experiencing clinically significant pain. The results of this study suggest that harvesting autograft bone carries a risk of persistent, long-term pain regardless of the volume of graft that is harvested. This potential for persistent pain should be considered when informing patients of procedure risks and when deciding to use autograft or a bone graft substitute material


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 75 - 75
1 Mar 2021
Mendes L Bosmans K Maréchal M Luyten F
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Joint surface restoration of deep osteochondral defects represents a significant unmet clinical need. Moreover, untreated lesions lead to a high rate of osteoarthritis. The current strategies to repair deep osteochondral defects such as osteochondral grafting or sandwich strategies combining bone autografts with ACI/MACI fail to generate long-lasting osteochondral interfaces. Herein, we investigated the capacity of juvenile Osteochondral Grafts (OCGs) to repair osteochondral defects in skeletally mature animals. With this regenerative model in view, we set up a new biological, bilayered, and scaffold-free Tissue Engineered (TE) construct for the repair of the osteochondral unit of the knee. Skeletally immature (5 weeks old) and mature (11 weeks old) Lewis rats were used. Cylindrical OCGs were excised from the intercondylar groove of the knee of skeletally immature rats and transplanted into osteochondral defects created in skeletally mature rats. To create bilayered TE constructs, micromasses of human periosteum-derived progenitor cells (hPDCs) and human articular chondrocytes (hACs) were produced in vitro using chemically defined medium formulations. These constructs were subsequently implanted orthotopically in vivo in nude rats. At 4 and 16 weeks after surgery, the knees were collected and processed for subsequent 3D imaging analysis and histological evaluation. Micro-computed tomography (µCT), H&E and Safranin O staining were used to evaluate the degree of tissue repair. Our results showed that the osteochondral unit of the knee in 5 weeks old rats exhibit an immature phenotype, displaying active subchondral bone formation through endochondral ossification, the absence of a tidemark, and articular chondrocytes oriented parallel to the articular surface. When transplanted into skeletally mature animals, the immature OCGs resumed their maturation process, i.e., formed new subchondral bone, partially established the tidemark, and maintained their Safranin O-positive hyaline cartilage at 16 weeks after transplantation. The bilayered TE constructs (hPDCs + hACs) could partially recapitulate the cascade of events as seen with the immature OCGs, i.e., the regeneration of the subchondral bone and the formation of the typical joint surface architecture, ranging from non-mineralized hyaline cartilage in the superficial layers to a progressively mineralized matrix at the interface with a new subchondral bone plate. Cell-based TE constructs displaying a hierarchically organized structure comprising of different tissue forming units seem an attractive new strategy to treat osteochondral defects of the knee


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_7 | Pages 1 - 1
1 Jul 2020
Paul R Maldonado-Rodriguez N Docter S Leroux T Khan M Veillette C Romeo A
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Reverse total shoulder arthroplasty (RSA) with glenoid bone grafting has become a common option for the management of significant glenoid bone loss and deformity associated with glenohumeral osteoarthritis. Despite the increasing utilization of this technique, our understanding of the rates of bone graft union, complications and outcomes are limited. The objectives of this systematic review are to determine 1) the overall rate of bone graft union, 2) the rate of union stratified by graft type and technique, 3) the reoperation and complication rates, and 4) functional outcomes, including range of motion (ROM) and functional outcome scores following RSA with glenoid bone grafting. A comprehensive search of MEDLINE, Embase, and CINAHL databases was completed for studies reporting outcomes following RSA with glenoid bone grafting. Inclusion criteria included clinical studies with greater than 10 patients, and minimum follow up of one year. Studies were screened independently by two reviewers and quality assessment was performed using the MINORs criteria. Pooled and frequency-weighted means and standard deviations were calculated where applicable. Overall, 15 studies were included, including nine retrospective case series (level IV), four retrospective cohort studies (level III), one prospective cohort study (level II) and one randomized control trial (level I). The entire cohort consisted of 555 patients with a mean age of 71.9±2.1 years and 70 percent female. The mean follow-up was 33.8±9.4 months. Across all procedures, 84.9% (N=471) were primary arthroplasties, and 15.1% (N=84) were revisions. The overall graft union rate was 89.2%, but was higher at 96.1% among studies that used autograft bone (9 studies, N=308). When stratified by technique, bone graft for the purposes of lateralization resulted in a 100% union rate (4 studies, N=139), while eccentric bone grafts used in asymmetric bone loss resulted in a lower union rate of 84.9% (10 studies, N=345). The overall revision rate was 6.5%, and was lowest following primary cases at 1.8% (11 studies, N=393). The pooled mean scapular notching rate was 20.1% (12 studies, N=497). Excluding notching, the pooled mean complication rate was 21.5% for all cases and 13% for primary cases (11 studies, N=393). When reported, there was significant improvement in post-operative ROM in all planes. There was also improvement in functional outcome scores, whereby the frequency-weighted mean Constant score increased from 25.9 to 67.2 (8 studies, N=319), ASES score increased from 34.7 to 75.2 (4 studies, N=142), and SST score increased from 2.1 to 7.6 (5 studies, N=196) at final follow up. This review demonstrates that glenoid bone grafting with RSA results in good mid-term clinical and radiographic outcomes. Union rate appears to depend highly on graft type and technique, whereby the highest union rates were seen following the use of autograft bone for the purposes of lateralization. Interestingly, the union rate of autograft bone for the purposes of augmentation in eccentric bone loss is considerably lower and its impact on the long-term survivorship of the implant remains unknown


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1238 - 1247
1 Oct 2019
Soreide E Denbeigh JM Lewallen EA Thaler R Xu W Berglund L Yao JJ Martinez A Nordsletten L van Wijnen AJ Kakar S

Aims

Options for the treatment of intra-articular ligament injuries are limited, and insufficient ligament reconstruction can cause painful joint instability, loss of function, and progressive development of degenerative arthritis. This study aimed to assess the capability of a biologically enhanced matrix material for ligament reconstruction to withstand tensile forces within the joint and enhance ligament regeneration needed to regain joint function.

Materials and Methods

A total of 18 New Zealand rabbits underwent bilateral anterior cruciate ligament reconstruction by autograft, FiberTape, or FiberTape-augmented autograft. Primary outcomes were biomechanical assessment (n = 17), microCT (µCT) assessment (n = 12), histological evaluation (n = 12), and quantitative polymerase chain reaction (qPCR) analysis (n = 6).


Bone & Joint 360
Vol. 8, Issue 3 | Pages 18 - 19
1 Jun 2019


The Bone & Joint Journal
Vol. 101-B, Issue 1 | Pages 96 - 103
1 Jan 2019
Colo E Leenders LAM Rijnen WHC Schreurs BW Hannink G

Aims

The aim of this study was to analyze the effect of a lateral rim mesh on the survival of primary total hip arthroplasty (THA) in young patients, aged 50 years or younger.

Patients and Methods

We compared a study group of 235 patients (257 hips) who received a primary THA with the use of impaction bone grafting (IBG) with an additional lateral rim mesh with a group of 306 patients (343 hips) who received IBG in the absence of a lateral rim mesh during the same period from 1988 to 2015. In the mesh group, there were 74 male and 183 female patients, with a mean age of 35 years (13 to 50). In the no-mesh group, there were 173 male and 170 female patients, with a mean age of 38 years (12.6 to 50). Cox regression analyses were performed to study the effect of a lateral rim mesh on acetabular component survival. Kaplan–Meier analyses with 95% confidence intervals (CIs) were performed to estimate the survival of the acetabular implant.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_15 | Pages 49 - 49
1 Nov 2018
Stuckensen K Lamo-Espinosa J Muiños-López E Ripalda-Cemboráin P López-Martínez T Andreu I Elizalde R Prósper F Groll J Granero-Moltó F
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In the treatment of bone non-unions an alternative to bone autografts is the use of bone morphogenetic proteins (BMP-2, BMP-7) with powerful osteoinductive and osteogenic properties. In clinical settings, BMPs are applied using absorbable collagen sponges. Supraphysiological doses are needed and major side effects may occur as induce ectopic bone formation, chronic inflammation and excessive bone resorption. In order to increase the efficiency of the delivered for BMPs we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic, ANI) or trabecular bone (random distributed porosity, isotropic, ISO). We hypothesize that anisotropic structure would enhance osteoconductive properties of the scaffolds increasing rhBMP-2 regenerative properties. In vitro, both scaffolds presented similar mechanical properties, rhBMP-2 retention and delivery capacity. For in vivo testing, a rat femoral critical size defect model was created. Four groups were assessed depending on the implant applied to the bone defect: ISO, unloaded isotropic sponge; ISO-BMP, isotropic sponge loaded with 5 μg of hrBMP-2; ANI, unloaded anisotropic sponge; and ANI-BMP, anisotropic sponge loaded with 5 μg of hrBMP-2. Regeneration was allowed for 10 weeks. X-ray, μCT, biomechanical testing and histology were used to evaluate repair. Independently of their structure, sponges loaded with rhBMP-2 demonstrate increased bone volume, and biomechanical properties than their controls (p<0.01 and p<0.05 respectively). Globally, ANI-BMP group demonstrated better bone regeneration outputs with increased defect bridging (p<0.05 when compared ANI-BMP vs ISO-BMP groups). In conclusion, anisotropic cryostructured collagen scaffolds improve the efficiency of rhBMP-2 in bone regeneration


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_4 | Pages 65 - 65
1 Apr 2018
González-Gil AB Lamo-Espinosa JM Muiños-López E Ripalda-Cemboráin P Stuckensen K Abizanda G Juan-Pardo EM Groll J Hutmacher DW Prosper F Granero-Moltó F
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INTRODUCTION. In the treatment of nonunions, and other complications of bone repair, an attractive alternative to bone autografts would be the use of a combination of autologous mesenchymal progenitors cells (MSCs), biomaterials and growth factors. Our goal was to determine the therapeutic potential and contribution to the repair process of different sources of mesenchymal stem cells for the treatment of nonunions. METHODS. The right femur of Sprague-Dawley (SD) rats was stabilized with an aluminum plate (20 mm long, 4 mm wide, 2 mm thick) and four screws (1.5 mm diameter, 8 mm long). A diaphyseal critical size defect was performed (5 mm). Six groups (n=6–8 animals each) were created. A nonunion group (Control group, empty defect); LBA group, live bone allograft; BMP2 group, rhBMP-2 (2 μg) in collagen sponge; PCL group, polycaprolactone scaffold; PMSCs group, PCL scaffold loaded with 5×10. 6. periosteum-derived MSCs; and BMSCs group, PCL scaffold loaded with 5×10. 6. bone marrow-derived MSCs. For cell tracking purposes, LBA and MSCs were derived from SD-GFP transgenic rats. The repair process was followed up by x-rays up to sacrifice, week 10. After sacrifice, femurs were analyzed by micro computed tomography (μCT), histology and immunohistochemistry. For multiple comparisons one-way ANOVA followed by Dunnett”s test for single comparisons was used. Statistical significance was established for p<0.05. RESULTS. Control group did not show healing during follow up or by μCT and histological analysis. Treatment groups BLA and BMP2 showed full healing by week 10 (LBA, 6 out of 6 animals; BMP2, 4 out of 6 animals). The repair callus was quantified by mCT, Control group showed limited formation of bone (11.47±2.01 mm. 3. ) while both LBA and BMP2 groups showed increased bone formation by week 10 when compared with control group (LBA, 35.36±2.24 mm. 3. , p=0.0022; BMP2, 33.32±1.84 mm. 3. , p=0.0022). Histological and μCT analysis confirmed the experimental nonunion model. In PCL treated groups a low number of animals showed radiographic healing: PCL group 1 out of 8 animals; PMSCs group, 2 out of 6 animals; BMSCs group, 0 out of 6 animals. Interestingly, quantification of the repaired callus showed that only PMSCs group produced a significant volume of bone when compared with the Control group (PMSCs, 24.97±6.03 mm. 3. , p=0.0411). PCL and BMSCs groups do not produced significant amount of bone in the repair callus (PCL, 19.00±4.25 mm. 3. , p=0.3095; BMSCs, 12.88±2.38 mm. 3. , p=0.9372). Healing was confirmed by histology and μCT analysis. Finally, the engraftment of transplanted cells was analysed by immunohistochemistry (anti-GFP antibody). Of the three groups receiving cells only the LBA group showed positive signal for GFP at week 10-post surgery. CONCLUSIONS. In conclusion, periosteum-derived progenitor cells are suitable for mimetic autograft design although integration is not yet achieved


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_3 | Pages 23 - 23
1 Apr 2018
Geurts J Müller M Pagenstert G Netzer C Schären S
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Introduction. Elevated remodelling of subchondral bone and marrow tissues has been firmly established as diagnostic and prognostic radiological imaging marker for human osteoarthritis. While these tissues are considered as promising targets for disease-modifying OA drugs, the development of novel treatment approaches is complicated by the lack of knowledge whether similar tissue changes occur in rodent OA models and poor understanding of joint-specific molecular and cellular pathomechanisms in human OA. Here, we describe the establishment of a human OA explant model to address this crucial niche in translational preclinical OA research. Methods. Osteochondral (knee, spine) and bone (iliac crest) clinical specimens were acquired from patients undergoing total knee arthroplasty (n=4) or lumbar spine fusion using bone autografts (n=6). Fresh specimens were immediately cut in equal-sized samples (50–500 mg wet weight) and cultured in 8 mL osteogenic medium for one week. Samples were either left untreated (control) or stimulated with lipopolysaccharide (LPS, 100 ng/mL) in the absence and presence of transforming growth factor-beta inhibitor (SB-505124, 10 μm). Pro-collagen-I (Col-I), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) secretion was determined in conditioned medium by ELISA. Tissue viability was assessed using MTT and alkaline phosphatase (ALP) activity staining. Results. Explanted tissues remained viable after one week culture in control and treatment conditions. Osteocytes, subchondral marrow spaces and calcified cartilage stained positive for ALP activity without gross morphological differences between groups. Median basal secretion levels were Col-I (2.3 ng/mg), IL-6 (90 pg/mg) and MCP-1 (25 pg/mg). LPS treatment led to a significant increase of IL-6 (330 pg/mg) and MCP-1 (70 pg/mg), but not Col-I secretion. Interestingly, inhibition of TGF-beta signalling in osteochondral tissues specifically reduced Col-I levels (0.4 ng/mg) compared to controls and LPS-treated samples. LPS-induced IL-6 and MCP-1 levels were slightly reduced (−120 pg/mg, p=0.03) and increased (+50 pg/mg) by SB-505124 treatment, respectively. IL-6 and MCP-1 levels were strongly correlated under basal (r=0.80) and treatment conditions (r=0.62). Conclusion. In this study, we provided proof of concept for the first ex vivo explant model of human osteoarthritis. Osteochondral tissue specimens can readily be cultured without loss of tissue viability and mount a robust inflammatory response upon LPS challenge. Treatment with a potential disease-modifying agent (TGF-beta signalling inhibitor) reduced collagen metabolism in bone and marrow and modified cytokine and chemokine expression. The osteochondral explant model might be highly valuable to evaluate disease-modifying OA drugs