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Bone & Joint Research
Vol. 7, Issue 10 | Pages 570 - 579
1 Oct 2018
Kallala R Harris WE Ibrahim M Dipane M McPherson E

Aims. Calcium sulphate has traditionally been used as a filler of dead space arising during surgery. Various complications have been described following the use of Stimulan bio-absorbable calcium sulphate beads. This study is a prospective observational study to assess the safety profile of these beads when used in revision arthroplasty, comparing the complication rates with those reported in the literature. Methods. A total of 755 patients who underwent 456 revision total knee arthroplasties (TKA) and 299 revision total hip arthroplasties (THA), with a mean follow-up of 35 months (0 to 78) were included in the study. Results. A total of 32 patients (4.2%) had wound drainage, and this was higher with higher bead volumes and in McPherson grade C patients. There was also a significantly higher bead volume in the 41 patients who developed hypercalcaemia, two of which were symptomatic (p < 0.0001). A total of 13 patients (1.7%) had heterotopic ossification (HO). There was no statistically significant relationship between the development of HO and bead volume (p > 0.05). Conclusion. The strength of this study lies in the large number of patients and the detailed data collection, making it the most comprehensive report available in the literature on the use of calcium sulphate-based bone substitutes. Cite this article: R. Kallala, W. Edwin Harris, M. Ibrahim, M. Dipane, E. McPherson. Use of Stimulan absorbable calcium sulphate beads in revision lower limb arthroplasty: Safety profile and complication rates. Bone Joint Res 2018;7:570–579. DOI: 10.1302/2046-3758.710.BJR-2017-0319.R1


Objectives. Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair in vivo. Methods. ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% β-tricalcium phosphate (β-TCP) underwent EB treatment. In vitro degradation over 36 weeks was investigated by recording mass loss, pH change, and Ca release. Implant performance was investigated in vivo over 36 weeks using a lapine femoral condyle model. Bone growth and osteoclast activity were assessed by histology and enzyme histochemistry. Results. Calcium release doubled in the EB-treated group before returning to a level seen in untreated samples at 28 weeks. Extensive bone growth was observed around the perimeter of all implant types, along with limited osteoclastic activity. No statistically significant differences between comparative groups was identified. Conclusion. The higher than normal dose of EB used for surface modification did not adversely affect tissue response around implants in vivo. Surprisingly, incorporation of β-TCP and the subsequent accelerated release of Ca had no significant effect on in vivo implant performance, calling into question the clinical evidence base for these commercially available devices. Cite this article: I. Palmer, S. A. Clarke, F. J Buchanan. Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study. Bone Joint Res 2019;8:266–274. DOI: 10.1302/2046-3758.86.BJR-2018-0224.R2


Bone & Joint Research
Vol. 12, Issue 7 | Pages 412 - 422
4 Jul 2023
Ferguson J Bourget-Murray J Hotchen AJ Stubbs D McNally M

Aims. Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up. Methods. A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery. Results. The median follow-up was 4.6 years (interquartile range (IQR) 3.2 to 5.4; range 1.3 to 10.5) in Group OT compared to 4.9 years (IQR 2.1 to 6.0; range 1.0 to 8.3) in Group CG. The groups had similar defect sizes following excision (both mean 10.9 cm. 3. (1 to 30)). Infection recurrence was higher in Group OT (20/179 (11.2%) vs 8/180 (4.4%), p = 0.019) than Group CG, as was early wound leakage (33/179 (18.4%) vs 18/180 (10.0%), p = 0.024) and subsequent fracture (11/179 (6.1%) vs 1.7% (3/180), p = 0.032). Group OT cases had an odds ratio 2.9-times higher of developing any one of these complications, compared to Group CG (95% confidence interval 1.74 to 4.81, p < 0.001). The mean bone-void healing in Group CG was better than in Group OT, in those with ≥ six-month radiological follow-up (73.9% vs 40.0%, p < 0.001). Conclusion. Local antibiotic carrier choice affects outcome in chronic osteomyelitis surgery. A biphasic injectable carrier with a slower dissolution time was associated with better radiological and clinical outcomes compared to a preformed calcium sulphate pellet carrier. Cite this article: Bone Joint Res 2023;12(7):412–422


Bone & Joint Research
Vol. 11, Issue 11 | Pages 787 - 802
1 Nov 2022
Sebastian S Tandberg F Liu Y Raina DB Tägil M Collin M Lidgren L

Aims. There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). Methods. The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. Results. Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. Conclusion. Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802


Bone & Joint Research
Vol. 9, Issue 8 | Pages 477 - 483
1 Aug 2020
Holweg P Herber V Ornig M Hohenberger G Donohue N Puchwein P Leithner A Seibert F

Aims. This study is a prospective, non-randomized trial for the treatment of fractures of the medial malleolus using lean, bioabsorbable, rare-earth element (REE)-free, magnesium (Mg)-based biodegradable screws in the adult skeleton. Methods. A total of 20 patients with isolated, bimalleolar, or trimalleolar ankle fractures were recruited between July 2018 and October 2019. Fracture reduction was achieved through bioabsorbable Mg-based screws composed of pure Mg alloyed with zinc (Zn) and calcium (Ca) ( Mg-Zn0.45-Ca0.45, in wt.%; ZX00). Visual analogue scale (VAS) and the presence of complications (adverse events) during follow-up (12 weeks) were used to evaluate the clinical outcomes. The functional outcomes were analyzed through the range of motion (ROM) of the ankle joint and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Fracture reduction and gas formation were assessed using several plane radiographs. Results. The follow-up was performed after at least 12 weeks. The mean difference in ROM of the talocrural joint between the treated and the non-treated sites decreased from 39° (SD 12°) after two weeks to 8° (SD 11°) after 12 weeks (p ≤ 0.05). After 12 weeks, the mean AOFAS score was 92.5 points (SD 4.1). Blood analysis revealed that Mg and Ca were within a physiologically normal range. All ankle fractures were reduced and stabilized sufficiently by two Mg screws. A complete consolidation of all fractures was achieved. No loosening or breakage of screws was observed. Conclusion. This first prospective clinical investigation of fracture reduction and fixation using lean, bioabsorbable, REE-free ZX00 screws showed excellent clinical and functional outcomes. Cite this article: Bone Joint Res 2020;9(8):477–483


Bone & Joint Research
Vol. 12, Issue 12 | Pages 722 - 733
6 Dec 2023
Fu T Chen W Wang Y Chang C Lin T Wong C

Aims

Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration.

Methods

A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses.


Bone & Joint Research
Vol. 11, Issue 6 | Pages 349 - 361
9 Jun 2022
Jun Z Yuping W Yanran H Ziming L Yuwan L Xizhong Z Zhilin W Xiaoji L

Aims

The purpose of this study was to explore a simple and effective method of preparing human acellular amniotic membrane (HAAM) scaffolds, and explore the effect of HAAM scaffolds with juvenile cartilage fragments (JCFs) on osteochondral defects.

Methods

HAAM scaffolds were constructed via trypsinization from fresh human amniotic membrane (HAM). The characteristics of the HAAM scaffolds were evaluated by haematoxylin and eosin (H&E) staining, picrosirius red staining, type II collagen immunostaining, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Human amniotic mesenchymal stem cells (hAMSCs) were isolated, and stemness was verified by multilineage differentiation. Then, third-generation (P3) hAMSCs were seeded on the HAAM scaffolds, and phalloidin staining and SEM were used to detect the growth of hAMSCs on the HAAM scaffolds. Osteochondral defects (diameter: 3.5 mm; depth: 3 mm) were created in the right patellar grooves of 20 New Zealand White rabbits. The rabbits were randomly divided into four groups: the control group (n = 5), the HAAM scaffolds group (n = 5), the JCFs group (n = 5), and the HAAM + JCFs group (n = 5). Macroscopic and histological assessments of the regenerated tissue were evaluated to validate the treatment results at 12 weeks.


Bone & Joint Research
Vol. 10, Issue 6 | Pages 340 - 347
1 Jun 2021
Jenkinson MRJ Meek RMD Tate R MacMillan S Grant MH Currie S

Elevated levels of circulating cobalt ions have been linked with a wide range of systemic complications including neurological, endocrine, and cardiovascular symptoms. Case reports of patients with elevated blood cobalt ions have described significant cardiovascular complications including cardiomyopathy. However, correlation between the actual level of circulating cobalt and extent of cardiovascular injury has not previously been performed. This review examines evidence from the literature for a link between elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties and cardiomyopathy. Correlation between low, moderate, and high blood cobalt with cardiovascular complications has been considered. Elevated blood cobalt at levels over 250 µg/l have been shown to be a risk factor for developing systemic complications and published case reports document cardiomyopathy, cardiac transplantation, and death in patients with severely elevated blood cobalt ions. However, it is not clear that there is a hard cut-off value and cardiac dysfunction may occur at lower levels. Clinical and laboratory research has found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Further work needs to be done to clarify the link between severely elevated blood cobalt ions and cardiomyopathy.

Cite this article: Bone Joint Res 2021;10(6):340–347.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 411 - 424
14 Jul 2021
Zhao D Ren B Wang H Zhang X Yu M Cheng L Sang Y Cao S Thieringer FM Zhang D Wan Y Liu C

Aims

The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration.

Methods

IL4 at concentrations of 0, 30, and 100 ng/ml was used at day 3 to create a biomimetic environment for bone marrow mesenchymal stromal cell (BMMSC) osteogenesis and macrophage polarization on the DT. The osteogenic and immune responses of BMMSCs and macrophages were evaluated respectively.


Bone & Joint Research
Vol. 8, Issue 7 | Pages 333 - 341
1 Jul 2019
Grossner TL Haberkorn U Gotterbarm T

Objectives

Bone tissue engineering is one of the fastest growing branches in modern bioscience. New methods are being developed to achieve higher grades of mineral deposition by osteogenically inducted mesenchymal stem cells. In addition to well established monolayer cell culture models, 3D cell cultures for stem cell-based osteogenic differentiation have become increasingly attractive to promote in vivo bone formation. One of the main problems of scaffold-based osteogenic cell cultures is the difficulty in quantifying the amount of newly produced extracellular mineral deposition, as a marker for new bone formation, without destroying the scaffold. In recent studies, we were able to show that 99mTc-methylene diphosphonate (99mTc-MDP), a gamma radiation-emitting radionuclide, can successfully be applied as a reliable quantitative marker for mineral deposition as this tracer binds with high affinity to newly produced hydroxyapatite (HA).

Methods

Within the present study, we evaluated whether this promising new method, using 99mTc-hydroxydiphosphonate (99mTc-HDP), can be used to quantify the amount of newly formed extracellular HA in a 3D cell culture model. Highly porous collagen type II scaffolds were seeded with 1 × 106 human mesenchymal stem cells (hMSCs; n = 6) and cultured for 21 days in osteogenic media (group A – osteogenic (OSM) group) and in parallel in standard media (group B – negative control (CNTRL) group). After incubation with 99mTc-HDP, the tracer uptake, reflected by the amount of emitted gamma counts, was measured.


Bone & Joint Research
Vol. 9, Issue 7 | Pages 402 - 411
1 Aug 2020
Sanghani-Kerai A Coathup M Brown R Lodge G Osagie-Clouard L Graney I Skinner J Gikas P Blunn G

Aims

For cementless implants, stability is initially attained by an interference fit into the bone and osteo-integration may be encouraged by coating the implant with bioactive substances. Blood based autologous glue provides an easy, cost-effective way of obtaining high concentrations of growth factors for tissue healing and regeneration with the intention of spraying it onto the implant surface during surgery. The aim of this study was to incorporate nucleated cells from autologous bone marrow (BM) aspirate into gels made from the patient’s own blood, and to investigate the effects of incorporating three different concentrations of platelet rich plasma (PRP) on the proliferation and viability of the cells in the gel.

Methods

The autologous blood glue (ABG) that constituted 1.25, 2.5, and 5 times concentration PRP were made with and without equal volumes of BM nucleated cells. Proliferation, morphology, and viability of the cells in the glue was measured at days 7 and 14 and compared to cells seeded in fibrin glue.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 601 - 612
1 Sep 2020
Rajagopal K Ramesh S Walter NM Arora A Katti DS Madhuri V

Aims

Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold.

Methods

Rabbit bone marrow mesenchymal stem cells (MSCs) were differentiated into the chondrogenic lineage on scaffolds. Quality of in vitro regenerated cartilage was assessed by cell viability, growth, matrix synthesis, and differentiation. Bilateral osteochondral defects were created in 15 four-month-old male New Zealand white rabbits and segregated into three treatment groups with five in each. The groups were: 1) untreated and allogeneic chondrocytes; 2) multi-layered scaffold with and without cells; and 3) randomly aligned scaffold with and without cells. After four months of follow-up, the outcome was assessed using histology and immunostaining.


Bone & Joint Research
Vol. 8, Issue 2 | Pages 81 - 89
1 Feb 2019
Funk GA Menuey EM Cole KA Schuman TP Kilway KV McIff TE

Objectives

The objective of this study was to characterize the effect of rifampin incorporation into poly(methyl methacrylate) (PMMA) bone cement. While incompatibilities between the two materials have been previously noted, we sought to identify and quantify the cause of rifampin’s effects, including alterations in curing properties, mechanical strength, and residual monomer content.

Methods

Four cement groups were prepared using commercial PMMA bone cement: a control; one with 1 g of rifampin; and one each with equimolar amounts of ascorbic acid or hydroquinone relative to the amount of rifampin added. The handling properties, setting time, exothermic output, and monomer loss were measured throughout curing. The mechanical strength of each group was tested over 14 days. A radical scavenging assay was used to assess the scavenging abilities of rifampin and its individual moieties.


Bone & Joint Research
Vol. 7, Issue 6 | Pages 430 - 439
1 Jun 2018
Eggermont F Derikx LC Verdonschot N van der Geest ICM de Jong MAA Snyers A van der Linden YM Tanck E

Objectives

In this prospective cohort study, we investigated whether patient-specific finite element (FE) models can identify patients at risk of a pathological femoral fracture resulting from metastatic bone disease, and compared these FE predictions with clinical assessments by experienced clinicians.

Methods

A total of 39 patients with non-fractured femoral metastatic lesions who were irradiated for pain were included from three radiotherapy institutes. During follow-up, nine pathological fractures occurred in seven patients. Quantitative CT-based FE models were generated for all patients. Femoral failure load was calculated and compared between the fractured and non-fractured femurs. Due to inter-scanner differences, patients were analyzed separately for the three institutes. In addition, the FE-based predictions were compared with fracture risk assessments by experienced clinicians.