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Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Methods

In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.


Bone & Joint Research
Vol. 13, Issue 6 | Pages 279 - 293
7 Jun 2024
Morris JL Letson HL McEwen PC Dobson GP

Aims

Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Methods

Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.


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. Results. At 12 weeks, the VBPC group significantly increased new bone formation volume compared with the other groups. Biomechanical testing demonstrated higher torque strength in the VBPC group. Notably, the haematoxylin and eosin, Masson’s trichrome, and immunohistochemistry-stained histological results revealed that VBPC promoted neovascularization and new bone formation in the spine fusion areas. Conclusion. The tissue-engineered VBPC showed great capability in promoting angiogenesis and osteogenesis in vivo. It may provide a novel approach to create a superior blood supply and nutritional environment to overcome the deficits of current artificial bone graft substitutes. Cite this article: Bone Joint Res 2023;12(12):722–733


Bone & Joint Research
Vol. 12, Issue 5 | Pages 339 - 351
23 May 2023
Tan J Liu X Zhou M Wang F Ma L Tang H He G Kang X Bian X Tang K

Aims

Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing.

Methods

A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 58 - 71
17 Jan 2023
Dagneaux L Limberg AK Owen AR Bettencourt JW Dudakovic A Bayram B Gades NM Sanchez-Sotelo J Berry DJ van Wijnen A Morrey ME Abdel MP

Aims

As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).

Methods

Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections.


Aims

This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night.

Methods

In this study, a titanium rod was implanted in the medullary cavity of one femoral metaphysis in OVX rats, and then the rats were randomly divided into four groups: Sham group (Sham, n = 10), OVX rat group (OVX, n = 10), melatonin day treatment group (OVX + MD, n = 10), and melatonin night treatment group (OVX + MN, n = 10). The OVX + MD and OVX + MN rats were treated with 30 mg/kg/day melatonin at 9 am and 9 pm, respectively, for 12 weeks. At the end of the research, the rats were killed to obtain bilateral femora and blood samples for evaluation.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 585 - 593
1 Aug 2022
Graham SM Jalal MMK Lalloo DG Hamish R. W. Simpson A

Aims

A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process.

Methods

A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 503 - 512
25 Jul 2022
Wu Y Shao Y Xie D Pan J Chen H Yao J Liang J Ke H Cai D Zeng C

Aims. To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction. Methods. In vitro: the mobility of the rat bone mesenchymal stem cells (BMSCs) treated with SLPI was evaluated by scratch assay. Then the expression levels of osteogenic differentiation-related genes were analyzed by real-time quantitative PCR (qPCR) to determine the osteogenic effect of SLPI on BMSCs. In vivo: a rat model of ACL reconstruction was used to verify the effect of SLPI on tendon-to-bone healing. All the animals of the SLPI group and the negative control (NC) group were euthanized for histological evaluation, micro-CT scanning, and biomechanical testing. Results. SLPI improved the migration ability of BMSCs and upregulated the expression of genes related to osteogenic differentiation of BMSCs in vitro. In vivo, the SLPI group had higher histological scores at the tendon-bone interface by histological evaluation. Micro-CT showed more new bone formation and bone ingrowth around the grafted tendon in the SLPI group. Evaluation of the healing strength of the tendon-bone connection showed that the SLPI group had a higher maximum failure force and stiffness. Conclusion. SLPI can effectively promote early tendon-to-bone healing after ACL reconstruction via enhancing the migration and osteogenic differentiation of BMSCs. Cite this article: Bone Joint Res 2022;11(7):503–512


Bone & Joint Research
Vol. 11, Issue 5 | Pages 270 - 277
6 May 2022
Takegami Y Seki T Osawa Y Imagama S

Aims. Periprosthetic hip fractures (PPFs) after total hip arthroplasty are difficult to treat. Therefore, it is important to identify modifiable risk factors such as stem selection to reduce the occurrence of PPFs. This study aimed to clarify differences in fracture torque, surface strain, and fracture type analysis between three different types of cemented stems. Methods. We conducted biomechanical testing of bone analogues using six cemented stems of three different types: collarless polished tapered (CPT) stem, Versys Advocate (Versys) stem, and Charnley-Marcel-Kerboull (CMK) stem. Experienced surgeons implanted each of these types of stems into six bone analogues, and the analogues were compressed and internally rotated until failure. Torque to fracture and fracture type were recorded. We also measured surface strain distribution using triaxial rosettes. Results. There was a significant difference in fracture torque between the three stem types (p = 0.036). Particularly, the median fracture torque for the CPT stem was significantly lower than that for the CMK stem (CPT vs CMK: 164.5 Nm vs 200.5 Nm; p = 0.046). The strain values for the CPT stem were higher than those for the other two stems at the most proximal site. The fracture pattern of the CPT and Versys stems was Vancouver type B, whereas that of the CMK stem was type C. Conclusion. Our study suggested that the cobalt-chromium alloy material, polished surface finish, acute-square proximal form, and the absence of a collar may be associated with lower fracture torque, which may be related to PPF. Cite this article: Bone Joint Res 2022;11(5):270–277


Bone & Joint Research
Vol. 11, Issue 5 | Pages 260 - 269
3 May 2022
Staats K Sosa BR Kuyl E Niu Y Suhardi V Turajane K Windhager R Greenblatt MB Ivashkiv L Bostrom MPG Yang X

Aims. To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants. Methods. 3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH). Radiological analysis, micro-CT (µCT), and biomechanical pull-out testing were performed to assess implant loosening, bone formation, and osseointegration. Peri-implant tissue formation and cellular composition were evaluated by histology. Results. iPTH reduced radiological signs of loosening and led to an increase in peri-implant bone formation over the course of four weeks (timepoints: one week, two weeks, and four weeks). Observational histological analysis shows that iPTH prohibits the progression of fibrosis. Delaying iPTH treatment until after onset of peri-implant fibrosis still resulted in enhanced osseointegration and implant stability. Despite initial instability, iPTH increased the mean pull-out strength of the implant from 8.41 N (SD 8.15) in the PBS-control group to 21.49 N (SD 10.45) and 23.68 N (SD 8.99) in the immediate and delayed iPTH groups, respectively. Immediate and delayed iPTH increased mean peri-implant bone volume fraction (BV/TV) to 0.46 (SD 0.07) and 0.34 (SD 0.10), respectively, compared to PBS-control mean BV/TV of 0.23 (SD 0.03) (PBS-control vs immediate iPTH, p < 0.001; PBS-control vs delayed iPTH, p = 0.048; immediate iPTH vs delayed iPTH, p = 0.111). Conclusion. iPTH treatment mediated successful osseointegration and increased bone mechanical strength, despite initial implant instability. Clinically, this suggests that initially unstable implants may be osseointegrated with iPTH treatment. Cite this article: Bone Joint Res 2022;11(5):260–269


Bone & Joint Research
Vol. 10, Issue 12 | Pages 767 - 779
8 Dec 2021
Li Y Yang Y Wang M Zhang X Bai S Lu X Li Y Waldorff EI Zhang N Lee WY Li G

Aims. Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation. Methods. The effects of a HSR PEMF signal with three daily treatment durations (0.5, one, and three hours/day) were investigated in an established rat DO model with comparison of an FDA-approved classic signal (three hrs/day). PEMF treatments were applied to the rats daily for 35 days, starting from the distraction phase until termination. Radiography, micro-CT (μCT), biomechanical tests, and histological examinations were employed to evaluate the quality of bone formation. Results. All rats tolerated the treatment well and no obvious adverse effects were found. By comparison, the HSR signal (three hrs/day) treatment group achieved the best healing outcome, in that endochondral ossification and bone consolidation were enhanced. In addition, HSR signal treatment (one one hr/day) had similar effects to treatment using the classic signal (three three hrs/day), indicating that treatment duration could be significantly shortened with the HSR signal. Conclusion. HSR signal may significantly enhance bone formation and shorten daily treatment duration in DO, making it a potential candidate for a new clinical protocol for patients undergoing DO treatments. Cite this article: Bone Joint Res 2021;10(12):767–779


Bone & Joint Research
Vol. 10, Issue 5 | Pages 298 - 306
1 May 2021
Dolkart O Kazum E Rosenthal Y Sher O Morag G Yakobson E Chechik O Maman E

Aims

Rotator cuff (RC) tears are common musculoskeletal injuries which often require surgical intervention. Noninvasive pulsed electromagnetic field (PEMF) devices have been approved for treatment of long-bone fracture nonunions and as an adjunct to lumbar and cervical spine fusion surgery. This study aimed to assess the effect of continuous PEMF on postoperative RC healing in a rat RC repair model.

Methods

A total of 30 Wistar rats underwent acute bilateral supraspinatus tear and repair. A miniaturized electromagnetic device (MED) was implanted at the right shoulder and generated focused PEMF therapy. The animals’ left shoulders served as controls. Biomechanical, histological, and bone properties were assessed at three and six weeks.


Bone & Joint Research
Vol. 10, Issue 2 | Pages 105 - 112
1 Feb 2021
Feng X Qi W Fang CX Lu WW Leung FKL Chen B

Aims

To draw a comparison of the pullout strengths of buttress thread, barb thread, and reverse buttress thread bone screws.

Methods

Buttress thread, barb thread, and reverse buttress thread bone screws were inserted into synthetic cancellous bone blocks. Five screw-block constructs per group were tested to failure in an axial pullout test. The pullout strengths were calculated and compared. A finite element analysis (FEA) was performed to explore the underlying failure mechanisms. FEA models of the three different screw-bone constructs were developed. A pullout force of 250 N was applied to the screw head with a fixed bone model. The compressive and tensile strain contours of the midsagittal plane of the three bone models were plotted and compared.


Bone & Joint Research
Vol. 9, Issue 12 | Pages 840 - 847
1 Dec 2020
Nie S Li M Ji H Li Z Li W Zhang H Licheng Z Tang P

Aims

Restoration of proximal medial femoral support is the keystone in the treatment of intertrochanteric fractures. None of the available implants are effective in constructing the medial femoral support. Medial sustainable nail (MSN-II) is a novel cephalomedullary nail designed for this. In this study, biomechanical difference between MSN-II and proximal femoral nail anti-rotation (PFNA-II) was compared to determine whether or not MSN-II can effectively reconstruct the medial femoral support.

Methods

A total of 36 synthetic femur models with simulated intertrochanteric fractures without medial support (AO/OTA 31-A2.3) were assigned to two groups with 18 specimens each for stabilization with MSN-II or PFNA-II. Each group was further divided into three subgroups of six specimens according to different experimental conditions respectively as follows: axial loading test; static torsional test; and cyclic loading test.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 534 - 542
1 Sep 2020
Varga P Inzana JA Fletcher JWA Hofmann-Fliri L Runer A Südkamp NP Windolf M

Aims

Fixation of osteoporotic proximal humerus fractures remains challenging even with state-of-the-art locking plates. Despite the demonstrated biomechanical benefit of screw tip augmentation with bone cement, the clinical findings have remained unclear, potentially as the optimal augmentation combinations are unknown. The aim of this study was to systematically evaluate the biomechanical benefits of the augmentation options in a humeral locking plate using finite element analysis (FEA).

Methods

A total of 64 cement augmentation configurations were analyzed using six screws of a locking plate to virtually fix unstable three-part fractures in 24 low-density proximal humerus models under three physiological loading cases (4,608 simulations). The biomechanical benefit of augmentation was evaluated through an established FEA methodology using the average peri-screw bone strain as a validated predictor of cyclic cut-out failure.


Bone & Joint Research
Vol. 9, Issue 8 | Pages 493 - 500
1 Aug 2020
Fletcher JWA Zderic I Gueorguiev B Richards RG Gill HS Whitehouse MR Preatoni E

Aims

To devise a method to quantify and optimize tightness when inserting cortical screws, based on bone characterization and screw geometry.

Methods

Cortical human cadaveric diaphyseal tibiae screw holes (n = 20) underwent destructive testing to firstly establish the relationship between cortical thickness and experimental stripping torque (Tstr), and secondly to calibrate an equation to predict Tstr. Using the equation’s predictions, 3.5 mm screws were inserted (n = 66) to targeted torques representing 40% to 100% of Tstr, with recording of compression generated during tightening. Once the target torque had been achieved, immediate pullout testing was performed.


Bone & Joint Research
Vol. 9, Issue 6 | Pages 302 - 310
1 Jun 2020
Tibbo ME Limberg AK Salib CG Turner TW McLaury AR Jay AG Bettencourt JW Carter JM Bolon B Berry DJ Morrey ME Sanchez-Sotelo J van Wijnen AJ Abdel MP

Aims

Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits.

Methods

A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein).


Bone & Joint Research
Vol. 9, Issue 6 | Pages 314 - 321
1 Jun 2020
Bliven E Sandriesser S Augat P von Rüden C Hackl S

Aims

Evaluate if treating an unstable femoral neck fracture with a locking plate and spring-loaded telescoping screw system would improve construct stability compared to gold standard treatment methods.

Methods

A 31B2 Pauwels’ type III osteotomy with additional posterior wedge was cut into 30 fresh-frozen femur cadavers implanted with either: three cannulated screws in an inverted triangle configuration (CS), a sliding hip screw and anti-rotation screw (SHS), or a locking plate system with spring-loaded telescoping screws (LP). Dynamic cyclic compressive testing representative of walking with increasing weight-bearing was applied until failure was observed. Loss of fracture reduction was recorded using a high-resolution optical motion tracking system.


Bone & Joint Research
Vol. 9, Issue 6 | Pages 285 - 292
1 Jun 2020
Wang Z Li H Long Z Lin S Thoreson AR Moran SL Gingery A Amadio PC Steinmann SP Zhao C

Aims

Many biomechanical studies have shown that the weakest biomechanical point of a rotator cuff repair is the suture-tendon interface at the medial row. We developed a novel double rip-stop (DRS) technique to enhance the strength at the medial row for rotator cuff repair. The objective of this study was to evaluate the biomechanical properties of the DRS technique with the conventional suture-bridge (SB) technique and to evaluate the biomechanical performance of the DRS technique with medial row knots.

Methods

A total of 24 fresh-frozen porcine shoulders were used. The infraspinatus tendons were sharply dissected and randomly repaired by one of three techniques: SB repair (SB group), DRS repair (DRS group), and DRS with medial row knots repair (DRSK group). Specimens were tested to failure. In addition, 3 mm gap formation was measured and ultimate failure load, stiffness, and failure modes were recorded.


Objectives. MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture. Methods. Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined. Results. MicroRNA-186 was predicted to regulate SMAD6. Furthermore, SMAD6 was verified as a target gene of miR-186. Overexpressed miR-186 and SMAD6 silencing resulted in increased callus formation, BMD and BV/TV, as well as maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. In addition, the mRNA and protein levels of SMAD6 were decreased, while BMP-2 and BMP-7 levels were elevated in response to upregulated miR-186 and SMAD6 silencing. Conclusion. In conclusion, the study indicated that miR-186 could activate the BMP signalling pathway to promote fracture healing by inhibiting SMAD6 in a mouse model of femoral fracture. Cite this article: Bone Joint Res 2019;8:550–562