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Bone & Joint Research
Vol. 12, Issue 5 | Pages 311 - 312
5 May 2023
Xu C Liu Y

Cite this article: Bone Joint Res 2023;12(5):311–312.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 66 - 66
11 Apr 2023
Sebastian S Collin M Liu Y Raina D Tägil M Lidgren L
Full Access

There is a lack of carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotic for Staphylococcus aureus deep bone infections (DBIs). RIF is also associated with systemic side effects, and known for causing rapid development of antibiotic resistance when given as monotherapy. We evaluated a clinically usedbi-phasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). It was hypothesized that this combined approach could provide improved biofilm eradication and prevent the development of RIF resistance.

Methods: 1) Biofilm eradication: Using a modified crystal violet staining biofilm quantification method, the antibiotics released at different time points (Day 1, 3, 7, 14, 21, 28 and 35) from the hemispherical pellets of CaS/HA(500 mg)-VAN (24.57 mg) / GEN (10.35 mg) composites with or without RIF (8.11 mg) were tested for their ability to disrupt the preformed 48-h old biofilms of S. aureus ATCC 25923, and S. aureus clinical strain P-3 in 96-well microtitre plate. For each tested group of antibiotic fractions, five separate wells were used (n=5). 2) Testing for resistance development: Similar to the method mentioned above the 48-h biofilm embeded bacteria exposed to antibiotic fractions from different time points continuously for 7 days. The biofilms remained were then tested for RIF resistant strains of bacteria.

Overall, there was clear antibiofilm biofilm activity observed with CaS/HA-VAN/GEN+RIF combinations compared with CaS/HA-VAN/GEN alone. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with combinations of CaS/HA-VAN/GEN+RIF

Enhanced antibiofilm effects without development of RIF resistance indicates that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for additional local delivery in clinically demanding DBIs.

Acknowledgement: We deeply acknowledge the Royal Fysiographic Society of Lund, Landshövding Per Westlings Minnesfond and the Stina and Gunnar Wiberg fond for financial support.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 55 - 55
11 Apr 2023
Raina D Markeviciute V Arvidsson L Törnquist E Stravinskas M Kok J Jacobson I Liu Y Tengattini A Sezgin E Vater C Zwingenberger S Isaksson H Tägil M Tarasevicius S Lidgren L
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Majority of osteoporosis related fractures are treated surgically using metallic fixation devices. Anchorage of fixation devices is sometimes challenging due to poor osteoporotic bone quality that can lead to failure of the fracture fixation.

Using a rat osteoporosis model, we employed neutron tomography and histology to study the biological effects of implant augmentation using an isothermally setting calcium sulphate/hydroxyapatite (CaS/HA) biomaterial with synthetic HA particles as recruiting moiety for systemically administered bisphosphonates. Using an osteoporotic sawbones model, we then provide a standardized method for the delivery of the CaS/HA biomaterial at the bone-implant interface for improved mechanical anchorage of a lag-screw commonly used for hip fracture fixation. As a proof-of-concept, the method was then verified in donated femoral heads and in patients with osteoporosis undergoing hip fracture fixation.

We show that placing HA particles around a stainless-steel screw in-vivo, systemically administered bisphosphonates could be targeted towards the implant, yielding significantly higher peri-implant bone formation compared to un-augmented controls. In the sawbones model, CaS/HA based lag-screw augmentation led to significant increase (up to 4 times) in peak extraction force with CaS/HA performing at par with PMMA. Micro-CT imaging of the CaS/HA augmented lag-screws in cadaver femoral heads verified that the entire length of the lag-screw threads and the surrounding bone was covered with the CaS/HA material. X-ray images from fracture fixation surgery indicated that the CaS/HA material could be applied at the lag-screw-bone interface without exerting any additional pressure or risk of venous vascular leakage.: We present a new method for augmentation of lag-screws in fragile bone. It is envisaged that this methodcould potentially reduce the risk of fracture fixation failure especially when HA seeking “bone active” drugs are used systemically.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 128 - 128
4 Apr 2023
Li M Wu G Liu Y
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Miniscrew implants (MSIs) are widely used to provide absolute anchorage for the orthodontic treatment. However, the application of MSIs is limited by the relatively high failure rate (22.86%). In this study, we wished to investigate the effects of amorphous and crystalline biomimetic calcium phosphate coating on the surfaces of MSIs with or without the incorporated BSA for the osteointegration process with an aim to facilitate the early loading of MSIs.

Amorphous and crystalline coatings were prepared on titanium mini-pin implants. Characterizations of coatings were examined by Scanning electron microscopy (SEM), Confocal laser-scanning dual-channel-fluorescence microscopy (CLSM) and Fourier-transform infrared spectroscopy (FTIR). The loading and release kinetics of bovine serum albumin (BSA) were evaluated by Enzyme linked immunosorbent assay (ELISA). Activity of alkaline phosphate (ALP) was measured by using the primary osteoblasts. In vivo, a model of metaphyseal tibial implantation in rats was used (n=6 rats per group). We had 6 different groups: no coating no BSA, no coating but with surface adsorption of BSA and incorporation of BSA in the biomimetic coating in the amorphous and crystalline coatings. Time points were 3 days, 1, 2 and 4 weeks. Histological and histomorphometric analysis were performed and the bone to implant contact (BIC) of each group was compared.

In vitro, the incorporation of BSA changed the crystalline coating from sharp plates into curly plates, and the crystalline coating showed slow-release profile. The incorporation of BSA in crystalline coating significantly decreased the activity of ALP in vitro. In vivo study, the earliest significant increase of BIC appeared in crystalline coating group at one week.

The crystalline coating can serve as a carrier and slow release system for the bioactive agent and accelerate osteoconductivity at early stage in vivo. The presence of BSA is not favorable for the early establishment of osteointegration.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 219 - 230
10 Mar 2023
Wang L Li S Xiao H Zhang T Liu Y Hu J Xu D Lu H

Aims

It has been established that mechanical stimulation benefits tendon-bone (T-B) healing, and macrophage phenotype can be regulated by mechanical cues; moreover, the interaction between macrophages and mesenchymal stem cells (MSCs) plays a fundamental role in tissue repair. This study aimed to investigate the role of macrophage-mediated MSC chondrogenesis in load-induced T-B healing in depth.

Methods

C57BL/6 mice rotator cuff (RC) repair model was established to explore the effects of mechanical stimulation on macrophage polarization, transforming growth factor (TGF)-β1 generation, and MSC chondrogenesis within T-B enthesis by immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Macrophage depletion was performed by clodronate liposomes, and T-B healing quality was evaluated by histology and biomechanics. In vitro, bone marrow-derived macrophages (BMDMs) were stretched with CELLOAD-300 load system and macrophage polarization was identified by flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). MSC chondrogenic differentiation was measured by histochemical analysis and qRT-PCR. ELISA and qRT-PCR were performed to screen the candidate molecules that mediated the pro-chondrogenic function of mechanical stimulated BMDMs.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 80 - 90
20 Jan 2023
Xu J Si H Zeng Y Wu Y Zhang S Liu Y Li M Shen B

Aims

Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.

Methods

Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis.


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.


Bone & Joint Research
Vol. 11, Issue 1 | Pages 29 - 31
20 Jan 2022
Ma M Tan Z Li W Zhang H Liu Y Yue C


Bone & Joint Research
Vol. 11, Issue 1 | Pages 26 - 28
20 Jan 2022
Ma M Tan Z Li W Zhang H Liu Y Yue C


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_11 | Pages 29 - 29
1 Sep 2021
Lee C Lee MG Lim WJ Liu Y Pakdeenit B Kim JS
Full Access

Although interlaminar endoscopic lumbar discectomy (IELD) is considered to be less invasive than microscopic lumbar discectomy (MLD) in treatment of lumbar herniated nucleus pulposus, the radiologic change of multifidus muscles by each surgery has rarely been reported. The aim of the present study was to compare the quantitative and qualitative changes of multifidus muscles between two surgical approaches and to analyze the correlation between various parameters of multifidus muscles and long term surgical outcome.

21 patients who received MLD and 18 patients who received IELD in a single tertiary hospital were enrolled and their preoperative, postoperative (≤15 days), and follow-up (≥6 months) MRIs were analyzed. The cross-sectional area (CSA) and fatty degeneration rate (FD) were quantitatively estimated at the level of surgery. The correlations among CSA, FD, body mass index, follow-up visual analogue scale(VAS) and Oswestry Disability Index(ODI) were assessed.

Mean intervals of postoperative MRI and follow-up MRI from surgery were 3.0±3.7 days and 14.5±10.7 months, respectively. During the follow-up period, VAS was improved from 7.1±1.3 to 2.1±1.8 in MLD and from 8.2±1.4 to 2.2±1.8 in IELD. In cases of MLD, comparing with preoperative MRI, ipsilateral CSA was significantly increased in postoperative MRI (795.6mm2 vs. 906.5mm2, p<0.01), but it was not significantly different in follow-up MRI (795.6mm2 vs. 814.4mm2, p=1.00). However, in case of IELD, the ipsilateral CSAs in preoperative, postoperative, and follow-up periods were 892.0 mm2, 909.3 mm2, and 900.3 mm2, respectively. These changes were not significant over time (p=0.691). The ipsilateral FDs were not significantly changed between preoperative and follow-up periods in both MLD (21.4% vs. 20.9%, p=0.81) and IELD groups (23.5% vs. 21.8%, p=0.19). The increment of ipsilateral CSA had significant correlations with follow-up ODI (r=−0.368, p=0.02).

Comparing with IELD, MLD induced more surgical trauma on multifidus muscle in postoperative period, but the muscular damage was recovered in follow-up period. IELD can minimize surgical trauma on multifidus muscle showing similar pain relief as MLD. Favorable surgical outcome in follow-up period may be related to increment of multifidus muscle volume.

Figure 1

(A-C) The multifidus muscles in preoperative, postoperative, and follow-up periods, respectively, in patient with MLD. Comparing with preoperative period, the CSA of right multifidus muscle (ipsilateral side) was increased in postoperative period, but recovered in follow-up period. (D-F) The multifidus muscle in preoperative, postoperative, and follow-up periods, respectively, in patient with IELD. The CSA of left multifidus muscles (ipsilateral side) was not significantly changed over time. Comparing preoperative MRIs with follow-up MRIs, the FDs of multifidus muscles were not significantly changed regardless of surgical technique.

Figure 2

The CSA was measured by marking region of interest (ROI) and FD was measured by calculating the rate of pixels beyond the threshold in ROI. All measurements were performed using ImageJ software (version 1.52a, National Institutes of Health, Bethesda, Maryland, USA).

For any figures or tables, please contact the authors directly.


Bone & Joint Research
Vol. 10, Issue 8 | Pages 474 - 487
2 Aug 2021
Duan M Wang Q Liu Y Xie J

Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases.


The Bone & Joint Journal
Vol. 103-B, Issue 7 Supple B | Pages 9 - 16
1 Jul 2021
Hadden WJ Ibrahim M Taha M Ure K Liu Y Paish ADM Holdsworth DW Abdelbary H

Aims

The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time.

Methods

Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces.


The Bone & Joint Journal
Vol. 103-B, Issue 6 | Pages 1021 - 1030
1 Jun 2021
Liu X Dai T Li B Li C Zheng Z Liu Y

Aims

The aim of this meta-analysis was to assess the prognosis after early functional rehabilitation or traditional immobilization in patients who underwent operative or nonoperative treatment for rupture of the Achilles tendon.

Methods

PubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials (RCTs) from their inception to 3 June 2020, using keywords related to rupture of the Achilles tendon and rehabilitation. Data extraction was undertaken by independent reviewers and subgroup analyses were performed based on the form of treatment. Risk ratios (RRs) and weighted mean differences (WMDs) (with 95% confidence intervals (CIs)) were used as summary association measures.


The Bone & Joint Journal
Vol. 103-B, Issue 5 | Pages 931 - 938
1 May 2021
Liu Y Lu H Xu H Xie W Chen X Fu Z Zhang D Jiang B

Aims

The morphology of medial malleolar fracture is highly variable and difficult to characterize without 3D reconstruction. There is also no universally accepeted classification system. Thus, we aimed to characterize fracture patterns of the medial malleolus and propose a classification scheme based on 3D CT reconstruction.

Methods

We retrospectively reviewed 537 consecutive cases of ankle fractures involving the medial malleolus treated in our institution. 3D fracture maps were produced by superimposing all the fracture lines onto a standard template. We sliced fracture fragments and the standard template based on selected sagittal and coronal planes to create 2D fracture maps, where angles α and β were measured. Angles α and β were defined as the acute angles formed by the fracture line and the horizontal line on the selected planes.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 100 - 100
1 Mar 2021
Raina D Liu Y Isaksson H Tägil M Lidgren L
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Targeted delivery of drugs is a major challenge in diseases such as infections and tumors. The aim of this study was to demonstrate that hydroxyapatite (HA) particles can act as a recruiting moiety for various bioactive molecules and as a proof-of-concept demonstrate that the affinity of drugs to hydroxyapatite can exert a biological effect. A bisphosphonate, zoledronic acid (ZA), was used as a model drug. Experiment 1 (ZA seeks HA): Calcium sulphate (CaS)/hydroxyapatite (HA) biomaterial pellets (diameter¸=5 mm, height=2 mm) were implanted in the abdominal muscle pouch of rats. After 2-weeks of implantation, a sub-cutaneous injection of 14C-ZA (0.1 mg/kg) was given. 24 h later, the animals were sacrificed and the uptake of ZA determined in the pellets using scintillation counting. Experiment 2 (Systemically administered ZA seeks HA and exerts a biological effect): A fenestrated implant was filled with the CaS/HA biomaterial and inserted in the proximal tibia of rats. 2-weeks post-op, a subcutaneous injection of ZA (0.1 mg/kg) was given. Animals were sacrificed at 6-weeks post-op. Empty implant was used as a control. Peri-implant bone formation was evaluated using different techniques such as micro-CT, mechanical testing and histology. Welch's t-test was used for mechanical testing and Mann-Whitney U test for micro-CT data analysis. Experiment 1: Uptake of radioactive ZA in the CaS/HA biomaterial was confirmed. Almost no ZA was present in the surrounding muscle. These results show high specific binding between systemically administered ZA and synthetic particulate HA. Experiment 2: Significantly higher peri-implant bone was measured using micro-CT in the group wherein the implant contained the CaS/HA biomaterial and ZA was administered systemically (This study presents a method for biomodulating HA in situ by different bioactive molecules. The approach of implanting a biomaterial capable of recruiting systemically given drugs and thereby activate the material is novel and may present a possibility to treat bone infections or tumors.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 100 - 100
1 Dec 2020
Sebastian S Liu Y Sezgin EA Tarasevičius Š Raina DB
Full Access

Background

With promising antibiofilm properties, rifampicin is considered as a cornerstone in the complementary treatment of bone and joint infections. But, achieving an adequate concentration of rifampicin long-term in bone tissue is a challenge. Long-term systemic administration also comes with concomitant side effects. Thus, local delivery of rifampicin in a carrier to ensure the high local concentration of antibiotic in surgical site after intervention due to infection could be a valuable alternative. However, an ideal platform for local delivery of rifampicin is still lacking. A calcium sulphate/hydroxyapatite (CaS/HA) (Cerament, Bonesupport AB, Sweden) biomaterial was used as a local delivery platform. Here we aimed 1) to evaluate the injectability of CaS/HA hand-mixed with rifampicin at various concentrations up to maximum one daily dose used systemically in clinical practice 2) to test a clinically used and commercially available mixing device containing the biphasic ceramic with rifampicin.

Materials & Methods

Three different concentrations (100 mg, 300 mg and 600 mg) of rifampicin powder (Rifampicin Ebb, Sanofi S.P.A, Italy) diluted in 5 mL of mixing solution (C-TRU, Bonesupport AB, Sweden) were used. Rifampicin solution was mixed to the CaS/HA powder and the injectability of the CaS/HA plus rifampicin composite was evaluated by extruding 250 µL of paste manually through a graduated 1 mL syringe connected to an 18G needle (Ø=1.2 mm, L=4 cm). Mixing was done with a spatula for 30 s at 22°C ±1°C. Total weight of the paste before and after extrusion were measured. To normalize the amount of composite that remained in the needle and syringe tip after injection, the mean of the paste extruded from the syringe at 3 min was calculated for the tested concentrations (normalized value). Injectability (%) was calculated by dividing the weight of the paste extruded from the syringe with normalized value. Each test was repeated for three times at various time points (3, 5, 7 and 9 min). Additionally, 300 mg rifampicin was chosen to mix with the CaS/HA in a commercially available mixing system, which is used clinically.


Bone & Joint Research
Vol. 9, Issue 11 | Pages 751 - 760
1 Nov 2020
Li Y Lin X Zhu M Xun F Li J Yuan Z Liu Y Xu H

Aims

This study aimed to investigate the effect of solute carrier family 20 member 2 (SLC20A2) gene mutation (identified from a hereditary multiple exostoses family) on chondrocyte proliferation and differentiation.

Methods

ATDC5 chondrocytes were cultured in insulin-transferrin-selenium medium to induce differentiation. Cells were transfected with pcDNA3.0 plasmids with either a wild-type (WT) or mutated (MUT) SLC20A2 gene. The inorganic phosphate (Pi) concentration in the medium of cells was determined. The expression of markers of chondrocyte proliferation and differentiation, the Indian hedgehog (Ihh), and parathyroid hormone-related protein (PTHrP) pathway were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 709 - 718
1 Oct 2020
Raina DB Liu Y Jacobson OLP Tanner KE Tägil M Lidgren L

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health.

Cite this article: Bone Joint Res 2020;9(10):709–718.


The Bone & Joint Journal
Vol. 102-B, Issue 9 | Pages 1210 - 1218
14 Sep 2020
Zhang H Guan L Hai Y Liu Y Ding H Chen X

Aims

The aim of this study was to use diffusion tensor imaging (DTI) to investigate changes in diffusion metrics in patients with cervical spondylotic myelopathy (CSM) up to five years after decompressive surgery. We correlated these changes with clinical outcomes as scored by the Modified Japanese Orthopedic Association (mJOA) method, Neck Disability Index (NDI), and Visual Analogue Scale (VAS).

Methods

We used multi-shot, high-resolution, diffusion tensor imaging (ms-DTI) in patients with cervical spondylotic myelopathy (CSM) to investigate the change in diffusion metrics and clinical outcomes up to five years after anterior cervical interbody discectomy and fusion (ACDF). High signal intensity was identified on T2-weighted imaging, along with DTI metrics such as fractional anisotropy (FA). MJOA, NDI, and VAS scores were also collected and compared at each follow-up point. Spearman correlations identified correspondence between FA and clinical outcome scores.


Bone & Joint Research
Vol. 9, Issue 2 | Pages 60 - 70
1 Feb 2020
Li Z Arioka M Liu Y Aghvami M Tulu S Brunski JB Helms JA

Aims

Surgeons and most engineers believe that bone compaction improves implant primary stability without causing undue damage to the bone itself. In this study, we developed a murine distal femoral implant model and tested this dogma.

Methods

Each mouse received two femoral implants, one placed into a site prepared by drilling and the other into the contralateral site prepared by drilling followed by stepwise condensation.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 179 - 186
1 Feb 2018
Wu T Zhang J Wang B Sun Y Liu Y Li G

Objectives

As one of the heat-stable enterotoxins, Staphylococcal enterotoxin C2 (SEC2) is synthesized by Staphylococcus aureus, which has been proved to inhibit the growth of tumour cells, and is used as an antitumour agent in cancer immunotherapy. Although SEC2 has been reported to promote osteogenic differentiation of human mesenchymal stem cells (MSCs), the in vivo function of SCE2 in animal model remains elusive. The aim of this study was to further elucidate the in vivo effect of SCE2 on fracture healing.

Materials and Methods

Rat MSCs were used to test the effects of SEC2 on their proliferation and osteogenic differentiation potentials. A rat femoral fracture model was used to examine the effect of local administration of SEC2 on fracture healing using radiographic analyses, micro-CT analyses, biomechanical testing, and histological analyses.


Bone & Joint Research
Vol. 6, Issue 12 | Pages 649 - 655
1 Dec 2017
Liu Y Zhu H Hong H Wang W Liu F

Objectives

Recently, high failure rates of metal-on-metal (MOM) hip implants have raised concerns of cobalt toxicity. Adverse reactions occur to cobalt nanoparticles (CoNPs) and cobalt ions (Co2+) during wear of MOM hip implants, but the toxic mechanism is not clear.

Methods

To evaluate the protective effect of zinc ions (Zn2+), Balb/3T3 mouse fibroblast cells were pretreated with 50 μM Zn2+ for four hours. The cells were then exposed to different concentrations of CoNPs and Co2+ for four hours, 24 hours and 48 hours. The cell viabilities, reactive oxygen species (ROS) levels, and inflammatory cytokines were measured.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_20 | Pages 8 - 8
1 Dec 2017
Tian W Fan M Liu Y
Full Access

To introduce a new robot-assisted surgical system for spinal posterior fixation which called TiRobot, based on intraoperative three-dimensional images. TiRobot has three components: the planning and navigation system, optical tracking system and robotic arm system. By combining navigation and robot techniques, TiRobot can guide the screw trajectories for orthopedic surgeries.

In this randomised controlled study approved by the Ethics Committee, 40 patients were involved and all has been fully informed and sign the informed consent. 17 patients were treated by free-hand fluoroscopy-guided surgery, and 23 patients were treated by robot-assisted spinal surgery.

A total of 190 pedicle screws were implanted. The overall operation times were not different for both groups. None of the screws necessitated re-surgery for revised placement. In the robot-assisted group, assessment of pedicle screw accuracy showed that 102 of 102 screws (100%) were safely placed (<2 mm, category A+B). And mean deviation in entry point was 1.70 +/− 0.83mm, mean deviation in end point was 1.84 +/− 1.04mm. In the conventional freehand group, assessment of pedicle screw accuracy showed that 87 of 88 (98.9%) were safely placed (<2 mm, category A+B), 1 screw fall in category C, mean deviation in entry point was 3.73 +/− 2.28mm, mean deviation in end point was 4.11 +/− 2.31mm.

This randomised controlled study verified that robot-assisted pedicle screw placement with real-time navigation is a more accuracy and safer method, and also revealed great clinical potential of robot-assisted surgery in the future.


Bone & Joint Research
Vol. 6, Issue 10 | Pages 572 - 576
1 Oct 2017
Wang W Huang S Hou W Liu Y Fan Q He A Wen Y Hao J Guo X Zhang F

Objectives

Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data

Method

We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients’ BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_5 | Pages 53 - 53
1 Feb 2016
Tian W Zeng C An Y Liu Y
Full Access

Background

Accurate insertion of pedicle screws in scoliosis patients is a great challenge for surgeons due to the severe deformity of thoracic and lumbar spine. Meanwhile, mal-position of pedicle screw in scoliosis patients could lead to severe complications. Computer-assisted navigation technique may help improving the accuracy of screw placement and reducing complications. Thus, this meta-analysis of the published researches was conducted concentrating on accuracy of pedicle screw placement and postoperative assessment in scoliosis patients using computer-assisted navigation technique.

Methods

PubMed, Cochrane and Web of Science databases search was executed. In vivo comparative studies that assessed accuracy and postoperative evaluation of pedicle screw placement in scoliosis patients with or without navigation techniques were involved and analysed.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_5 | Pages 14 - 14
1 Feb 2016
Lang Z Tian W Liu Y Liu B Yuan Q
Full Access

Minimally invasive (MIS) screw fixation for Hangman's fracture can decrease iatrogenic soft-tissue injury compared with conventional open approach, but increase the risk of instrumentation-related complications due to lack of anatomical landmarks. With the advantages, the intra-operative three-dimensional fluoroscopy-based navigation (ITFN) system seems to be an inherent partner for MIS techniques. The purpose of this study was to evaluate the accuracy and feasibility of MIS techniques incorporating with ITFN for treating Hangman's fracture. 20 patients with Hangman's fracture underwent C2-C3 pedicle screw fixation using ITFN. 6 patients used MIS technique, with the other 14 patients using conventional open technique. Preoperative visual analogue score (VAS) was 5.7±1.4 in CAOS-MIS group and 5.5±0.9 in CAOS-open group. Operative time, blood loss and postoperative neurovascular complications were recorded. The accuracy of screw positions was studied by postoperative CT scan. All patients were followed up for at least 6 months and the fusion status was ascertained by dynamic radiographs. The average operative time was 134.2±8.0 min in CAOS-MIS group and 139.3±25.8 min in CAOS-open group, and there was no significant difference between the two (p&gt;0.01). The blood loss was 66.7±25.8 ml in CAOS-MIS group and 250.0±141.4 ml in CAOS-open group. Statistical difference existed with CAOS-MIS group significant less than CAOS-open group (p&lt;0.01). A total of 80 screws were inserted. No screw-related neurovascular injury was observed. Post-operative CT scan revealed 83.3% (20/24) screws of grade 1 and 16.7% screws of grade 2 (4/24) in CAOS-MIS group, meanwhile 89.3% screws of grade 1 (50/56) and 10.7% screws of grade 2 (6/56) in CAOS-open group. There was no grade 3 screw detected. Fisher's exact test showed there was no statistical difference between these two groups (p&gt;0.01). There was no statistical difference in pre-operative VAS between these two groups (p&gt;0.01). Compared with the CAOS-open group (1.7±0.6), neck pain VAS at 6-month follow-up in CAOS-MIS group (0.3±0.5) was significantly lower (p&lt;0.01). Solid fusion was demonstrated in all the cases by dynamic radiographs. So it is feasible and safe for percutaneous minimally invasive C2-C3 pedicle screw fixation for Hangman's fracture using intra-operative three-dimensional fluoroscopy-based navigation, which can also decrease the incidence of post-operative neck pain.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_5 | Pages 10 - 10
1 Feb 2016
Tian W Liu Y Fan M Han X
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Background

The Robotic Spinal Surgery System (RSSS) is a robot system designed for pedicle screw insertion containing image based navigation system, trajectory planning system and force state recognition system. The special force state recognition system can guarantee the safety during the operation. The RSSS is helpful in pedicle screw insertion surgery and it will be applied in clinic in the near future. In this study, we evaluated the accuracy and safety of RSSS in an animal experiment.

Methods

Computer tomography (CT) scan data for two anesthetised experimental sheep was acquired using the C-arm and transferred to RSSS for pre-surgery screw trajectory planning. With the assist of RSSS, we inserted 8 and 4 screws into two sheep respectively. Operation time and blood loss during the surgery were recorded, and CT scan was repeated after surgery. Real screw position and trajectory acquired by the post-surgery CT scan and ideal trajectory planned by RSSS were compared to evaluate the accuracy and safety of RSSS. The result is shown as mean±SD.


The Bone & Joint Journal
Vol. 95-B, Issue 4 | Pages 543 - 547
1 Apr 2013
Qi M Chen H Liu Y Zhang Y Liang L Yuan W

In a retrospective cohort study we compared the clinical outcome and complications, including dysphagia, following anterior cervical fusion for the treatment of cervical spondylosis using either a zero-profile (Zero-P; Synthes) implant or an anterior cervical plate and cage. A total of 83 patients underwent fusion using a Zero-P and 107 patients underwent fusion using a plate and cage. The mean follow-up was 18.6 months (sd 4.2) in the Zero-P group and 19.3 months (sd 4.1) in the plate and cage group. All patients in both groups had significant symptomatic and neurological improvement. There were no significant differences between the groups in the Neck Disability Index (NDI) and visual analogue scores at final follow-up. The cervical alignment improved in both groups. There was a higher incidence of dysphagia in the plate and cage group on the day after surgery and at two months post-operatively. All patients achieved fusion and no graft migration or nonunion was observed.

When compared with the traditional anterior cervical plate and cage, the Zero-P implant is a safe and convenient procedure giving good results in patients with symptomatic cervical spondylosis with a reduced incidence of dysphagia post-operatively.

Cite this article: Bone Joint J 2013;95-B:543–7.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 278 - 278
1 May 2010
Klenke F Wernike E Liu Y Sebald H Hunziker E Siebenrock K Hofstetter W
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The reconstruction of bone defects with biomaterials represents a potential alternative to the transplantation of autologous and allogenic bone. Ceramic materials can be combined with growth factors (i.e. BMPs) to render them osteoinductive. Coating of biomaterials with growth factors has mostly been attempted by adsorption onto the material’s surface. The superficial deposition usually results in an immediate passive release of the proteins, thus restricting their temporal availability during bone healing. It was hypothesized that a co-precipitation of proteins onto calcium phosphate ceramics may provide the possibility to achieve a prolonged release of proteins from the material without impairing the biologic activity of growth factors.

Tritium labelled bovine serum albumin ([3H]BSA) and recombinant human BMP2 (rhBMP2) were coated onto biphasic calcium phosphate (BCP) ceramics using a coprecipitation technique of proteins together with calcium phosphate (Liu Y et al. 2001). The co-precipitation was compared to conventional adsorption of proteins to ceramic materials. The passive and cell-mediated release of [3H]BSA was investigated during 19 days. To analyze the cell-mediated protein release, murine bone marrow cells were seeded onto ceramics and differentiated to osteoclasts or to monocytes/macrophages. To assess whether rhBMP2 co-precipitated to BCP ceramics retained its biologic activity the growth factor’s ability to induce the differentiation of primary murine osteoblasts was studied.

After 19 days 71.7±5.3% of the adsorbed [3H]BSA was passively released (63.0±6.0% within 4 days). The passive liberation of [3H]BSA was effectively reduced using the coprecipitation technique (12.5±2.0% within 19 days, 10.1±2.3% within 4 days, p< 0.001). Further analysis demonstrated a sustained, osteoclast-mediated release of coprecipitated [3H]BSA from calcium phosphate ceramics which was blocked by the addition of calcitonin. Passive release of adsorbed and co-precipitated BMP2 led to a temporally restricted stimulation of murine osteoblasts. Cell-mediated liberation of co-precipitated BMP2 induced a sustained stimulation of the differentiation of osteoblasts.

The successful application of exogenously added growth factors depends critically on the mode of delivery. It has been shown that a sustained availability of BMP2 is beneficial for bone healing. Application of the co-precipitation technique resulted in a long-term release of proteins from BCP ceramics mediated by active resorbing osteoclasts without impairing the biologic activity of rhBMP2. Co-precipitating growth factors onto BCP ceramics provides a potential to shift the initial extensive liberation to a sustained release of bioactive proteins. This method of protein delivery may represent a possibility to achieve a more physiological availability of growth factors during bone regeneration.