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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. 9, Issue 8 | Pages 531 - 533
1 Aug 2020
Magan AA Plastow R Haddad FS


Bone & Joint Research
Vol. 8, Issue 2 | Pages 41 - 48
1 Feb 2019
Busse P Vater C Stiehler M Nowotny J Kasten P Bretschneider H Goodman SB Gelinsky M Zwingenberger S

Objectives

Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes in vitro.

Methods

Human chondrocytes and tenocytes were cultured in a medium with three different drug dilutions (1:2; 1:10; 1:100). The following drugs were used to investigate cytotoxicity: lidocaine hydrochloride 1%; bupivacaine 0.5%; triamcinolone acetonide; dexamethasone 21-palmitate; TA; iodine contrast media; HA; and distilled water. Normal saline served as a control. After an incubation period of 24 hours, cell numbers and morphology were assessed.


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.


Bone & Joint Research
Vol. 6, Issue 8 | Pages 489 - 498
1 Aug 2017
Mifuji K Ishikawa M Kamei N Tanaka R Arita K Mizuno H Asahara T Adachi N Ochi M

Objectives

The objective of this study was to investigate the therapeutic effect of peripheral blood mononuclear cells (PBMNCs) treated with quality and quantity control culture (QQ-culture) to expand and fortify angiogenic cells on the acceleration of fracture healing.

Methods

Human PBMNCs were cultured for seven days with the QQ-culture method using a serum-free medium containing five specific cytokines and growth factors. The QQ-cultured PBMNCs (QQMNCs) obtained were counted and characterised by flow cytometry and real-time polymerase chain reaction (RT-PCR). Angiogenic and osteo-inductive potentials were evaluated using tube formation assays and co-culture with mesenchymal stem cells with osteo-inductive medium in vitro. In order to evaluate the therapeutic potential of QQMNCs, cells were transplanted into an immunodeficient rat femur nonunion model. The rats were randomised into three groups: control; PBMNCs; and QQMNCs. The fracture healing was evaluated radiographically and histologically.


Bone & Joint Research
Vol. 6, Issue 6 | Pages 366 - 375
1 Jun 2017
Neves N Linhares D Costa G Ribeiro CC Barbosa MA

Objectives. This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling. Methods. A systematic search was performed in Pubmed, followed by a two-step selection process. We included in vivo original studies on Sr-containing biomaterials used for bone support or regeneration, comparing at least two groups that only differ in Sr addition in the experimental group. Results. A total of 572 references were retrieved and 27 were included. Animal models were used in 26 articles, and one article described a human study. Osteoporotic models were included in 11 papers. All articles showed similar or increased effect of Sr in bone formation and/or regeneration, in both healthy and osteoporotic models. No study found a decreased effect. Adverse effects were assessed in 17 articles, 13 on local and four on systemic adverse effects. From these, only one reported a systemic impact from Sr addition. Data on gene and/or protein expression were available from seven studies. Conclusions. This review showed the safety and effectiveness of Sr-enriched biomaterials for stimulating bone formation and remodelling in animal models. The effect seems to increase over time and is impacted by the concentration used. However, included studies present a wide range of study methods. Future work should focus on consistent models and guidelines when developing a future clinical application of this element. Cite this article: N. Neves, D. Linhares, G. Costa, C. C. Ribeiro, M. A. Barbosa. In vivo and clinical application of strontium-enriched biomaterials for bone regeneration: A systematic review. Bone Joint Res 2017;6:366–375. DOI: 10.1302/2046-3758.66.BJR-2016-0311.R1


Bone & Joint Research
Vol. 6, Issue 5 | Pages 277 - 283
1 May 2017
Yoshikawa M Nakasa T Ishikawa M Adachi N Ochi M

Objectives

Regenerative medicine is an emerging field aimed at the repair and regeneration of various tissues. To this end, cytokines (CKs), growth factors (GFs), and stem/progenitor cells have been applied in this field. However, obtaining and preparing these candidates requires invasive, costly, and time-consuming procedures. We hypothesised that skeletal muscle could be a favorable candidate tissue for the concept of a point-of-care approach. The purpose of this study was to characterize and confirm the biological potential of skeletal muscle supernatant for use in regenerative medicine.

Methods

Semitendinosus muscle was used after harvesting tendon from patients who underwent anterior cruciate ligament reconstructions. A total of 500 milligrams of stripped muscle was minced and mixed with 1 mL of saline. The collected supernatant was analysed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The biological effects of the supernatant on cell proliferation, osteogenesis, and angiogenesis in vitro were evaluated using human mesenchymal stem cells (hMSCs) and human umbilical cord vein endothelial cells (HUVECs).


Bone & Joint Research
Vol. 6, Issue 3 | Pages 162 - 171
1 Mar 2017
Walker JA Ewald TJ Lewallen E Van Wijnen A Hanssen AD Morrey BF Morrey ME Abdel MP Sanchez-Sotelo J

Objectives

Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis.

Materials and Methods

A total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis.


Bone & Joint Research
Vol. 5, Issue 10 | Pages 461 - 469
1 Oct 2016
Liu YK Deng XX Yang H

Objectives

The cytotoxicity induced by cobalt ions (Co2+) and cobalt nanoparticles (Co-NPs) which released following the insertion of a total hip prosthesis, has been reported. However, little is known about the underlying mechanisms. In this study, we investigate the toxic effect of Co2+ and Co-NPs on liver cells, and explain further the potential mechanisms.

Methods

Co-NPs were characterised for size, shape, elemental analysis, and hydrodynamic diameter, and were assessed by Transmission Electron Microscope, Scanning Electron Microscope, Energy Dispersive X-ray Spectroscopy and Dynamic Light Scattering. BRL-3A cells were used in this study. Cytotoxicity was evaluated by MTT and lactate dehydrogenase release assay. In order to clarify the potential mechanisms, reactive oxygen species, Bax/Bcl-2 mRNA expression, IL-8 mRNA expression and DNA damage were assessed on BRL-3A cells after Co2+ or Co-NPs treatment.


Bone & Joint Research
Vol. 5, Issue 7 | Pages 287 - 293
1 Jul 2016
Ismail H Phedy P Kholinne E Djaja YP Kusnadi Y Merlina M Yulisa ND

Objectives

To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone.

Methods

Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm3 (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm3 HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment.


Bone & Joint Research
Vol. 5, Issue 3 | Pages 95 - 100
1 Mar 2016
Pilge H Fröbel J Prodinger PM Mrotzek SJ Fischer JC Zilkens C Bittersohl B Krauspe R

Objectives. Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing. Methods. We measured the migration and proliferation capacity of mesenchymal stem cells (MSCs) under enoxaparin or rivaroxaban treatment for three consecutive weeks, and evaluated effects on MSC mRNA expression of markers for stress and osteogenic differentiation. Results. We demonstrate that enoxaparin, but not rivaroxaban, increases the migration potential of MSCs and increases their cell count in line with elevated mRNA expression of C-X-C chemokine receptor type 4 (CXCR4), tumor necrosis factor alpha (TNFα), and alpha-B-crystallin (CryaB). However, a decrease in early osteogenic markers (insulin-like growth factors 1 and 2 (IGF1, IGF2), bone morphogenetic protein2 (BMP2)) indicated inhibitory effects on MSC differentiation into osteoblasts caused by enoxaparin, but not by rivaroxaban. Conclusions. Our findings may explain the adverse effects of enoxaparin treatment on bone healing. Rivaroxaban has no significant impact on MSC metabolism or capacity for osteogenic differentiation in vitro. Cite this article: Dr H. Pilge. Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing. Bone Joint Res 2016;5:95–100. DOI: 10.1302/2046-3758.53.2000595


Bone & Joint Research
Vol. 5, Issue 2 | Pages 33 - 36
1 Feb 2016
Jenkins PJ Morton A Anderson G Van Der Meer RB Rymaszewski LA

Objectives

“Virtual fracture clinics” have been reported as a safe and effective alternative to the traditional fracture clinic. Robust protocols are used to identify cases that do not require further review, with the remainder triaged to the most appropriate subspecialist at the optimum time for review. The objective of this study was to perform a “top-down” analysis of the cost effectiveness of this virtual fracture clinic pathway.

Methods

National Health Service financial returns relating to our institution were examined for the time period 2009 to 2014 which spanned the service redesign.


Bone & Joint Research
Vol. 3, Issue 3 | Pages 76 - 81
1 Mar 2014
Okabe YT Kondo T Mishima K Hayase Y Kato K Mizuno M Ishiguro N Kitoh H

Objectives. In order to ensure safety of the cell-based therapy for bone regeneration, we examined in vivo biodistribution of locally or systemically transplanted osteoblast-like cells generated from bone marrow (BM) derived mononuclear cells. Methods. BM cells obtained from a total of 13 Sprague-Dawley (SD) green fluorescent protein transgenic (GFP-Tg) rats were culture-expanded in an osteogenic differentiation medium for three weeks. Osteoblast-like cells were then locally transplanted with collagen scaffolds to the rat model of segmental bone defect. Donor cells were also intravenously infused to the normal Sprague-Dawley (SD) rats for systemic biodistribution. The flow cytometric and histological analyses were performed for cellular tracking after transplantation. Results. Locally transplanted donor cells remained within the vicinity of the transplantation site without migrating to other organs. Systemically administered large amounts of osteoblast-like cells were cleared from various organ tissues within three days of transplantation and did not show any adverse effects in the transplanted rats. Conclusions. We demonstrated a precise assessment of donor cell biodistribution that further augments prospective utility of regenerative cell therapy. Cite this article: Bone Joint Res 2014;3:76–81


Bone & Joint Research
Vol. 2, Issue 10 | Pages 220 - 226
1 Oct 2013
Chang Y Tai C Hsieh P Ueng SWN

Objectives

The objective of this study is to determine an optimal antibiotic-loaded bone cement (ALBC) for infection prophylaxis in total joint arthroplasty (TJA).

Methods

We evaluated the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with vancomycin, teicoplanin, ceftazidime, imipenem, piperacillin, gentamicin, and tobramycin against methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staph. aureus (MRSA), coagulase-negative staphylococci (CoNS), Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Standardised cement specimens made from 40 g PMMA loaded with 1 g antibiotics were tested for elution characteristics, antibacterial activities, and compressive strength in vitro.


Bone & Joint Research
Vol. 1, Issue 11 | Pages 297 - 309
1 Nov 2012
McIlwraith CW Frisbie DD Kawcak CE

Osteoarthritis (OA) is an important cause of pain, disability and economic loss in humans, and is similarly important in the horse. Recent knowledge on post-traumatic OA has suggested opportunities for early intervention, but it is difficult to identify the appropriate time of these interventions. The horse provides two useful mechanisms to answer these questions: 1) extensive experience with clinical OA in horses; and 2) use of a consistently predictable model of OA that can help study early pathobiological events, define targets for therapeutic intervention and then test these putative therapies. This paper summarises the syndromes of clinical OA in horses including pathogenesis, diagnosis and treatment, and details controlled studies of various treatment options using an equine model of clinical OA.


Bone & Joint Research
Vol. 1, Issue 5 | Pages 71 - 77
1 May 2012
Keurentjes JC Van Tol FR Fiocco M Schoones JW Nelissen RG

Objectives

We aimed first to summarise minimal clinically important differences (MCIDs) after total hip (THR) or knee replacement (TKR) in health-related quality of life (HRQoL), measured using the Short-Form 36 (SF-36). Secondly, we aimed to improve the precision of MCID estimates by means of meta-analysis.

Methods

We conducted a systematic review of English and non-English articles using MEDLINE, the Cochrane Controlled Trials Register (1960–2011), EMBASE (1991–2011), Web of Science, Academic Search Premier and Science Direct. Bibliographies of included studies were searched in order to find additional studies. Search terms included MCID or minimal clinically important change, THR or TKR and Short-Form 36. We included longitudinal studies that estimated MCID of SF-36 after THR or TKR.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 558 - 565
1 Apr 2011
Xie X Wang X Zhang G Liu Z Yao D Hung L Hung VW Qin L

Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis. In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone. We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 2 | Pages 277 - 284
1 Feb 2011
Amin AK Huntley JS Patton JT Brenkel IJ Simpson AHRW Hall AC

The aim of this study was to determine whether exposure of human articular cartilage to hyperosmotic saline (0.9%, 600 mOsm) reduces in situ chondrocyte death following a standardised mechanical injury produced by a scalpel cut compared with the same assault and exposure to normal saline (0.9%, 285 mOsm). Human cartilage explants were exposed to normal (control) and hyperosmotic 0.9% saline solutions for five minutes before the mechanical injury to allow in situ chondrocytes to respond to the altered osmotic environment, and incubated for a further 2.5 hours in the same solutions following the mechanical injury.

Using confocal laser scanning microscopy, we identified a sixfold (p = 0.04) decrease in chondrocyte death following mechanical injury in the superficial zone of human articular cartilage exposed to hyperosmotic saline compared with normal saline.

These data suggest that increasing the osmolarity of joint irrigation solutions used during open and arthroscopic articular surgery may reduce chondrocyte death from surgical injury and could promote integrative cartilage repair.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 6 | Pages 889 - 893
1 Jun 2010
Kocaoglu B Agir I Nalbantoglu U Karahan M Türkmen M

We investigated the effect of mitomycin-C on the reduction of the formation of peritendinous fibrous adhesions after tendon repair. In 20 Wistar albino rats the tendo Achillis was cut and repaired using a modified Kessler technique. The rats were divided into two equal groups. In group 1, an injection of mitomycin-C was placed between the tendon and skin of the right leg. In group 2, an identical volume of sterile normal saline was injected on the left side in a similar fashion. All the rats received mitomycin-C or saline for four weeks starting from the day of operation. The animals were killed after 30 days. The formation of peritendinous fibrous tissue, the inflammatory reaction and tendon healing were evaluated. The tensile strength of the repaired tendons was measured biomechanically. Microscopic evidence of the formation of adhesions and inflammation was less in group 1. There was no significant difference in the tensile load required to rupture the repaired tendons in the two groups.

Mitomycin-C may therefore provide a simple and inexpensive means of preventing of post-operative adhesions.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 1 | Pages 159 - 163
1 Jan 2010
Aykut S Öztürk A Özkan Y Yanik K İlman AA Özdemir RM

We studied the effects of coating titanium implants with teicoplanin and clindamycin in 30 New Zealand White rabbits which were randomly assigned to three groups. The intramedullary canal of the left tibia of each rabbit was inoculated with 500 colony forming units of Staphylococcus aureus. Teicoplanin-coated implants were implanted into rabbits in group 1, clindamycin-coated implants into rabbits in group 2, and uncoated implants into those in group 3. All the rabbits were killed one week later. The implants were removed and cultured together with pieces of tibial bone and wound swabs. The rate of colonisation of the organisms in the three groups was compared.

Organisms were cultured from no rabbits in group 1, one in group 2 but from all in group 3. There was no significant difference between groups 1 and 2 (p = 1.000). There were significant differences between groups 1 and 3 and groups 2 and 3 (p < 0.001). Significant protection against bacterial colonisation and infection was found with teicoplanin- and clindamycin-coated implants in this experimental model.