Aims. Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. Methods. Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67. phox. was involved in suramin-enhanced chondrocyte phenotype maintenance. Results. Suramin enhanced the COL2A1 and ACAN expression and lowered COL1A1 synthesis. Also, in 3D pellet culture GAG and COL2A1 production was significantly higher in pellets consisting of chondrocytes expanded with suramin compared to controls. Surprisingly, suramin also increased ROS generation, which is largely caused by enhanced NOX (p67. phox. ) activity and membrane translocation. Overexpression of p67. phox. but not p67. phox. AD (deleting amino acid (a.a) 199 to 212) mutant, which does not support ROS production in chondrocytes, significantly enhanced chondrocyte phenotype maintenance, SOX9 expression, and AKT (S473) phosphorylation. Knockdown of p67. phox. with its specific short hairpin (sh) RNA (shRNA) abolished the suramin-induced effects. Moreover, when these cells were treated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor LY294002 or shRNA of AKT1, p67. phox. -induced COL2A1 and ACAN expression was significantly inhibited. Conclusion. Suramin could redifferentiate dedifferentiated chondrocytes dependent on p67. phox. activation, which is mediated by the PI3K/AKT/SOX9 signalling pathway. Cite this article: Bone Joint Res 2022;11(10):723–738

Aims. Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism. Methods. Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks. Results. The AOPP levels were increased in aged mice and correlated with degeneration of osteocyte network, loss of bone mass, and decreased Cx43 expression. AOPP intervention induced NADPH oxidase activation and mitochondrial dysfunction, triggered ROS generation, reduced Cx43 expression, and ultimately impaired osteocytes’ GJIC, which were ameliorated by NADPH oxidase inhibitor apocynin, mitochondria-targeted superoxide dismutase mimetic (mito-TEMPO), and ROS scavenger N-acetyl cysteine. Chronic AOPP loading accelerated the degradation of osteocyte networks and decreased Cx43 expression, resulting in deterioration of bone mass and mechanical properties in vivo. Conclusion. Our study suggests that AOPP accumulation contributes to age-related impairment of GJIC in osteocytes of male mice, which may be part of the pathogenic mechanism responsible for bone loss during ageing. Cite this article: Bone Joint Res 2022;11(7):413–425

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

Medial open-wedge high tibial osteotomy has been gaining popularity in recent years, but adequate supporting material is required in the osteotomy gap for early weight-bearing and rapid union. The purpose of this study was to investigate whether the implantation of a polycaprolactone-tricalcium phosphate composite scaffold wedge would enhance healing of the osteotomy in a micro pig model. We carried out open-wedge high tibial osteotomies in 12 micro pigs aged from 12 to 16 months. A scaffold wedge was inserted into six of the osteotomies while the other six were left open. Bone healing was evaluated after three and six months using plain radiographs, CT scans, measurement of the bone mineral density and histological examination. Complete bone union was obtained at six months in both groups. There was no collapse at the osteotomy site, loss of correction or failure of fixation in either group. Staining with haematoxylin and eosin demonstrated that there was infiltration of new bone tissue into the macropores and along the periphery of the implanted scaffold in the scaffold group. The CT scans and measurement of the bone mineral density showed that at six months specimens in the scaffold group had a higher bone mineral density than in the control group, although the implantation of the polycaprolactone-tricalcium phosphate composite scaffold wedge did not enhance healing of the osteotomy

Bone scanning with radioactive isotopes has been used to study a wide variety of disorders. Recently certain phosphate compounds, labelled with technetium, have been used as bone scanning agents. The comparative merits of three technetium-labelled phosphate compounds currently available for bone scanning–pyrophosphate, tripolyphosphate and ethylhydroxydiphosphonate (EHDP) have been compared in rabbits. Each substance was injected into ten rabbits and blood was withdrawn at regular intervals. The animals were killed at four hours and the blood and tissue samples were assayed for radioactivity. The results show that EHDP has a more rapid blood clearance than the other two agents, with a resultant improvement in the bone to soft-tissue ratio. Of the three substances investigated technetium-labelled EHDP was the best and might allow the technique of scanning to be used on a wide scale for the general study of bone and its pathology

1. A method is described of demonstrating in vivo the utilisation of radioactive sulphur. 35. and of radioactive phosphorus. 32. during bone growth and repair. 2. The relationship between labelled chondroitin sulphuric acid and labelled phosphate complexes has been studied, the importance and significance of vascularity and the localisation of the enzyme alkaline phosphatase being noted. 3. It was found that bone growth by external accretion, both epiphysial and periosteal, was accompanied by an increased utilisation of radioactive chondroitin sulphuric acid and calcium phosphate complexes. 4. During repair in a fracture site, although there was deposition of radioactive phosphate, no preferential localisation of radioactive sulphur was observed and the possible explanations of this are discussed

Bone growth into cementless prosthetic components is compromised by osteoporosis, by any gap between the implant and the bone, by micromotion, and after the revision of failed prostheses. Recombinant human transforming growth factor-β1 (rhTGF-β1) has recently been shown to be a potent stimulator of bone healing and bone formation in various models in vivo. We have investigated the potential of rhTGF-β1, adsorbed on to weight-loaded tricalcium phosphate (TCP) coated implants, to enhance bone ongrowth and mechanical fixation. We inserted cylindrical grit-blasted titanium alloy implants bilaterally into the weight-bearing part of the medial femoral condyles of ten skeletally mature dogs. The implants were mounted on special devices which ensured stable weight-loading during each gait cycle. All implants were initially surrounded by a 0.75 mm gap and were coated with TCP ceramic. Each animal received two implants, one with 0.3 μg rhTGF-β1 adsorbed on the ceramic surface and the other without growth factor. Histological analysis showed that bone ongrowth was significantly increased from 22 ± 5.6% bone-implant contact in the control group to 36 ± 2.9% in the rhTGF-β stimulated group, an increase of 59%. The volume of bone in the gap was increased by 16% in rhTGF-β1-stimulated TCP-coated implants, but this difference was not significant. Mechanical push-out tests showed no difference in fixation of the implant between the two groups. Our study suggests that rhTGF-β1 adsorbed on TCP-ceramic-coated implants can enhance bone ongrowth

We report the finding of sodium- and phosphorus-based crystallisation in abnormal human articular cartilage. We prepared five chondromalacic, five osteoarthritic and four macroscopically normal specimens of patellar cartilage by a cryofracturing technique and examined them in a scanning electron microscope. An energy-dispersive X-ray microanalysis system was used to identify the crystals, which were found in only three of the five chondromalacic specimens. Star-shaped crystals were seen either individually or in clusters in the matrix of the cartilage. They consisted of sodium and phosphorus, and we have found no previous reports of such findings. The calcified zone, the bone, and the articular surface were free from crystals.

A prospective single-cohort study was designed to include 20 patients with enchondromas but was stopped because of poor early results. Four patients with an enchondroma, three in the proximal humerus and one in the distal femur, were treated by curettage and filling of the defect with Norian SRS cement. Clinical and radiological follow-up including CT and MRI was carried out for 18 months. All three patients with lesions in the proximal humerus had severe pain and limited movement of the shoulder. The radiological and CT appearances of the cement were unchanged at follow-up. There were characteristic appearances of synovitis and periosteitis on MRI in two patients. Since the cement induces a soft-tissue reaction the bony cavity should be sealed with the curetted and burred bone after curettage and introduction of Norian cement, especially in sites where a tourniquet cannot be applied.

Aims. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing. Methods. A mouse fracture model was initially established by surgical means. Exosomes were isolated from BMSCs from mice. The endocytosis of the mouse osteoblast MC3T3-E1 cell line was analyzed. CCK-8 and disodium phenyl phosphate microplate methods were employed to detect cell proliferation and alkaline phosphatase (ALP) activity, respectively. The binding of miR-136-5p to low-density lipoprotein receptor related protein 4 (LRP4) was analyzed by dual luciferase reporter gene assay. HE staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry were performed to evaluate the healing of the bone tissue ends, the positive number of osteoclasts, and the positive expression of β-catenin protein, respectively. Results. miR-136-5p promoted fracture healing and osteoblast proliferation and differentiation. BMSC-derived exosomes exhibited an enriched miR-136-5p level, and were internalized by MC3T3-E1 cells. LRP4 was identified as a downstream target gene of miR-136-5p. Moreover, miR-136-5p or exosomes isolated from BMSCs (BMSC-Exos) containing miR-136-5p activated the Wnt/β-catenin pathway through the inhibition of LRP4 expression. Furthermore, BMSC-derived exosomes carrying miR-136-5p promoted osteoblast proliferation and differentiation, thereby promoting fracture healing. Conclusion. BMSC-derived exosomes carrying miR-136-5p inhibited LRP4 and activated the Wnt/β-catenin pathway, thus facilitating fracture healing. Cite this article: Bone Joint Res 2021;10(12):744–758

Objectives. X-linked hypophosphataemic rickets (XLHR) is a disease of impaired bone mineralization characterized by hypophosphataemia caused by renal phosphate wasting. The main clinical manifestations of the disorder are O-shaped legs, X-shaped legs, delayed growth, and bone pain. XLHR is the most common inheritable form of rickets, with an incidence of 1/20 000 in humans. It accounts for approximately 80% of familial cases of hypophosphataemia and serves as the prototype of defective tubular phosphate (PO4. 3+. ) transport, due to extra renal defects resulting in unregulated FGF23 activity. XLHR is caused by loss-of-function mutations in the PHEX gene. The aim of this research was to identify the genetic defect responsible for familial hypophosphataemic rickets in a four-generation Chinese Han pedigree and to analyze the function of this mutation. Methods. The genome DNA samples of all members in the pedigree were extracted from whole blood. We sequenced all exons of the PHEX and FGF23 genes, as well as the adjacent splice site sequence with Sanger sequencing. Next, we analyzed the de novo mutation c.1692 del A of the PHEX gene with an online digital service and investigated the mutant PHEX with SWISS-MODEL, immunofluorescence, and protein stability detection. Results. Through Sanger sequencing, we found a de novo mutation, c.1692 del A, in exon 16 of the PHEX gene in this pedigree. This mutation can make the PHEX protein become unstable and decay rapidly, which results in familial XLHR. Conclusion. We have found a de novo loss-of-function mutation, c.1692 del A, in exon 16 of the PHEX gene that can cause XLHR. Cite this article: J. Huang, X. Bao, W. Xia, L. Zhu, J. Zhang, J. Ma, N. Jiang, J. Yang, Q. Chen, T. Jing, J. Liu, D. Ma, G. Xu. Functional analysis of a de novo mutation c.1692 del A of the PHEX gene in a Chinese family with X-linked hypophosphataemic rickets. Bone Joint Res 2019;8:405–413. DOI: 10.1302/2046-3758.88.BJR-2018-0276.R1

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. Results. The expression of SLC20A2 in MUT group was similar to WT group. The Pi concentration in the medium of cells in MUT group was significantly higher than WT group, which meant the SLC20A2 mutation inhibited Pi uptake in ATDC5 chondrocytes. The proliferation rate of ATDC5 chondrocytes in MUT group was greater than WT group. The expression of aggrecan (Acan), α-1 chain of type II collagen (COL2A1), and SRY-box transcription factor 9 (SOX9) were higher in MUT group than WT group. However, the expression of Runt-related transcription factor 2 (Runx2), α-1 chain of type X collagen (COL10A1), and matrix metallopeptidase 13 (MMP13) was significantly decreased in the MUT group. Similar results were obtained by Alcian blue and Alizarin red staining. The expression of Ihh and PTHrP in MUT group was higher than WT group. An inhibitor (cyclopamine) of Ihh/PTHrP signalling pathway inhibited the proliferation and restored the differentiation of chondrocytes in MUT group. Conclusion. A mutation in SLC20A2 (c.C1948T) decreases Pi uptake in ATDC5 chondrocytes. SLC20A2 mutation promotes chondrocyte proliferation while inhibiting chondrocyte differentiation. The Ihh/PTHrP signalling pathway may play an important role in this process. Cite this article: Bone Joint Res 2020;9(11):751–760

The continual cycle of bone formation and resorption is carried out by osteoblasts, osteocytes, and osteoclasts under the direction of the bone-signaling pathway. In certain situations the host cycle of bone repair is insufficient and requires the assistance of bone grafts and their substitutes. The fundamental properties of a bone graft are osteoconduction, osteoinduction, osteogenesis, and structural support. Options for bone grafting include autogenous and allograft bone and the various isolated or combined substitutes of calcium sulphate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. Not all bone grafts will have the same properties. As a result, understanding the requirements of the clinical situation and specific properties of the various types of bone grafts is necessary to identify the ideal graft. We present a review of the bone repair process and properties of bone grafts and their substitutes to help guide the clinician in the decision making process. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):6–9

Aims. The purpose of this study was to evaluate the in vitro effects of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase (NOX) and a downregulator of intracellular reactive oxygen species (ROS), on high glucose-induced oxidative stress on tenocytes. Methods. Tenocytes from normal Sprague-Dawley rats were cultured in both control and high-glucose conditions. Apocynin was added at cell seeding, dividing the tenocytes into four groups: the control group; regular glucose with apocynin (RG apo+); high glucose with apocynin (HG apo+); and high glucose without apocynin (HG apo–). Reactive oxygen species production, cell proliferation, apoptosis and messenger RNA (mRNA) expression of NOX1 and 4, and interleukin-6 (IL-6) were determined in vitro. Results. Expression of NOX1, NOX4, and IL-6 mRNA in the HG groups was significantly higher compared with that in the RG groups, and NOX1, NOX4, and IL-6 mRNA expression in the HG apo+ group was significantly lower compared with that in the HG apo– group. Cell proliferation in the RG apo+ group was significantly higher than in the control group and was also significantly higher in the HG apo+ group than in the HG apo– group. Both the ROS accumulation and the amounts of apoptotic cells in the HG groups were greater than those in the RG groups and were significantly less in the HG apo+ group than in the HG apo– group. Conclusion. Apocynin reduced ROS production and cell death via NOX inhibition in high-glucose conditions. Apocynin is therefore a potential prodrug in the treatment of diabetic tendinopathy. Cite this article:Bone Joint Res 2020;9(1):23–28

Aims. The aims of this study were to compare the mean duration of antibiotic release and the mean zone of inhibition between vancomycin-loaded porous tantalum cylinders and antibiotic-loaded bone cement at intervals, and to evaluate potential intrinsic antimicrobial properties of tantalum in an in vitro medium environment against methicillin-sensitive Staphylococcus aureus (MSSA). Materials and Methods. Ten porous tantalum cylinders and ten cylinders of cement were used. The tantalum cylinders were impregnated with vancomycin, which was also added during preparation of the cylinders of cement. The cylinders were then placed on agar plates inoculated with MSSA. The diameter of the inhibition zone was measured each day, and the cylinders were transferred to a new inoculated plate. Inhibition zones were measured with a Vernier caliper and using an automated computed evaluation, and the intra- and interobserver reproducibility were measured. The mean inhibition zones between the two groups were compared with Wilcoxon’s test. Results. MSSA was inhibited for 12 days by the tantalum cylinders and for nine days by the cement cylinders. At day one, the mean zone of inhibition was 28.6 mm for the tantalum and 19.8 mm for the cement group (p < 0.001). At day ten, the mean zone of inhibition was 3.8 mm for the tantalum and 0 mm for the cement group (p < 0.001). The porous tantalum cylinders soaked only with phosphate buffered solution showed no zone of inhibition. Conclusion. Compared with cement, tantalum could release antibiotics for longer. Further studies should assess the advantages of using antibiotic-loaded porous tantalum implants at revision arthroplasty. Cite this article: Bone Joint J 2019;101-B:848–851

We undertook a multicentre, prospective study of a series of 112 unstable trochanteric fractures in order to evaluate if internal fixation with a sliding screw device combined with augmentation using a calcium phosphate degradable cement (Norian SRS) could improve the clinical, functional and radiological outcome when compared with fractures treated with a sliding screw device alone. Pain, activities of daily living, health status (SF-36), the strength of the hip abductor muscles and radiological outcome were analysed. Six weeks after surgery, the patients in the augmented group had significantly lower global and functional pain scores (p < 0.003), less pain after walking 50 feet (p < 0.01), and a better return to the activities of daily living (p < 0.05). At follow-up at six weeks and six months, those in the augmented group showed a significant improvement compared with the control group in the SF-36 score. No other significant differences were found between the groups. We conclude that augmentation with calcium phosphate cement in unstable trochanteric fractures provides a modest reduction in pain and a slight improvement in the quality of life during the course of healing when compared with conventional fixation with a sliding screw device alone

Aim. Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model. Materials and Methods. Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 10. 6. MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II. Results. Within the PBS injection (control group), typical progressive degenerative changes were revealed in the various knee structures. In the single MSC injection (single group), osteoarthritic changes were attenuated, but still appeared, especially in the medial compartments involving fibrillation of the articular cartilage, osteophyte formation in the medial plateau, and longitudinal tear of the meniscus. In the multiple-injections group, the smoothness and texture of the articular cartilage and meniscus were improved. Histologically, absence or reduction in matrix staining and cellularity were noticeable in the control and single-injection groups, respectively, in contrast to the multiple-injections group, which showed good intensity of matrix staining and chondrocyte distribution in the various cartilage zones. Osteoarthritis Research Society International (OARSI) scoring showed significantly better results in the multiple-injections group than in the other groups. Immunohistochemically, collagen I existed superficially in the medial femoral condyle in the single group, while collagen II was more evident in the multiple-injections group than the single-injection group. Conclusion. A single injection of MSCs was not enough to restore the condition of osteoarthritic joints. This is in contrast to multiple injections of MSCs, which had the ability to replace lost cells, as well as reducing inflammation. Cite this article: Bone Joint J 2019;101-B:824–831

Objectives. To assess the structure and extracellular matrix molecule expression of osteogenic cell sheets created via culture in medium with both dexamethasone (Dex) and ascorbic acid phosphate (AscP) compared either Dex or AscP alone. Methods. Osteogenic cell sheets were prepared by culturing rat bone marrow stromal cells in a minimal essential medium (MEM), MEM with AscP, MEM with Dex, and MEM with Dex and AscP (Dex/AscP). The cell number and messenger (m)RNA expression were assessed in vitro, and the appearance of the cell sheets was observed after mechanical retrieval using a scraper. β-tricalcium phosphate (β-TCP) was then wrapped with the cell sheets from the four different groups and subcutaneously implanted into rats. Results. After mechanical retrieval, the osteogenic cell sheets from the MEM, MEM with AscP, and MEM with Dex groups appeared to be fragmented or incomplete structures. The cell sheets cultured with Dex/AscP remained intact after mechanical retrieval, without any identifiable tears. Culture with Dex/AscP increased the mRNA and protein expression of extracellular matrix proteins and cell number compared with those of the other three groups. More bridging bone formation was observed after transplantation of the β-TCP scaffold wrapped with cell sheets cultured with Dex/AscP, than in the other groups. Conclusions. These results suggest that culture with Dex/AscP improves the mechanical integrity of the osteogenic cell sheets, allowing retrieval of the confluent cells in a single cell sheet structure. This method may be beneficial when applied in cases of difficult tissue reconstruction, such as nonunion, bone defects, and osteonecrosis. Cite this article: M. Akahane, T. Shimizu, T. Kira, T. Onishi, Y. Uchihara, T. Imamura, Y. Tanaka. Culturing bone marrow cells with dexamethasone and ascorbic acid improves osteogenic cell sheet structure. Bone Joint Res 2016;5:569–576. DOI: 10.1302/2046-3758.511.BJR-2016-0013.R1

Aims

The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment.

Cite this article: Bone Joint Res 2024;13(12):725–740.

The April 2012 Research Roundup. 360 . looks at who is capable of being an arthroscopist, bupivacaine, triamcinolone and chondrotoxicity, reducing scarring in injured skeletal muscle, horny Goat Weed and the repair of osseous defects, platelet-derived growth factor and fracture healing, the importance of the reserve zone in a child’s growth plate, coping with advanced arthritis, hydroxyapatite and platelet-rich plasma for bone defects, and calcium phosphate and bone regeneration

Aims

Orthopaedic surgery requires grafts with sufficient mechanical strength. For this purpose, decellularized tissue is an available option that lacks the complications of autologous tissue. However, it is not widely used in orthopaedic surgeries. This study investigated clinical trials of the use of decellularized tissue grafts in orthopaedic surgery.

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.

Aims

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

Aim. Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage. Patients and Methods. Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results. We identified 1265 differentially methylated genes, of which 145 are associated with significant changes in gene expression, such as DLX5, NCOR2 and AXIN2 (all p-values of both DNA methylation and mRNA expression < 0.05). Pathway enrichment analysis identified 26 OA-associated pathways, such as mitogen-activated protein kinase (MAPK) signalling pathway (p = 6.25 × 10-4), phosphatidylinositol (PI) signalling system (p = 4.38 × 10-3), hypoxia-inducible factor 1 (HIF-1) signalling pathway (p = 8.63 × 10-3 pantothenate and coenzyme A (CoA) biosynthesis (p = 0.017), ErbB signalling pathway (p = 0.024), inositol phosphate (IP) metabolism (p = 0.025), and calcium signalling pathway (p = 0.032). Conclusion. We identified a group of genes and biological pathwayswhich were significantly different in both DNA methylation and mRNA expression profiles between patients with OA and controls. These results may provide new clues for clarifying the mechanisms involved in the development of OA. Cite this article: A. He, Y. Ning, Y. Wen, Y. Cai, K. Xu, Y. Cai, J. Han, L. Liu, Y. Du, X. Liang, P. Li, Q. Fan, J. Hao, X. Wang, X. Guo, T. Ma, F. Zhang. Use of integrative epigenetic and mRNA expression analyses to identify significantly changed genes and functional pathways in osteoarthritic cartilage. Bone Joint Res 2018;7:343–350. DOI: 10.1302/2046-3758.75.BJR-2017-0284.R1

Aims

A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach.

We describe a case of oncogenic osteomalacia in an adult male who presented with low back pain and bilateral hip pain. Extensive investigations had failed to find a cause. A plain pelvic radiograph showed Looser’s zones in both femoral necks. MRI confirmed the presence of insufficiency fractures bilaterally in the femoral head and neck. Biochemical investigations confirmed osteomalacia which was unresponsive to treatment with vitamin D and calcium. A persistently low serum phosphate level suggested a diagnosis of hypophosphataemic osteomalacia. The level of fibroblast growth factor-23 was highly raised, indicating the cause as oncogenic osteomalacia. This was confirmed on positron-emission tomography, MRI and excision of a benign fibrous histiocytoma following a rapid recovery. The diagnosis of oncogenic osteomalacia may be delayed due to the non-specific presenting symptoms. Subchondral insufficiency fractures of the femoral head may be missed unless specifically looked for

Aims

Proximal humeral fractures are the third most common fracture among the elderly. Complications associated with fixation include screw perforation, varus collapse, and avascular necrosis of the humeral head. To address these challenges, various augmentation techniques to increase medial column support have been developed. There are currently no recent studies that definitively establish the superiority of augmented fixation over non-augmented implants in the surgical treatment of proximal humeral fractures. The aim of this systematic review and meta-analysis was to compare the outcomes of patients who underwent locking-plate fixation with cement augmentation or bone-graft augmentation versus those who underwent locking-plate fixation without augmentation for proximal humeral fractures.

Aims

This study aims to determine the rate of and risk factors for total knee arthroplasty (TKA) after operative management of tibial plateau fractures (TPFs) in older adults.

Aims

Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects.

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There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV.

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Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

Objectives. There is increasing application of bone morphogenetic proteins (BMPs) owing to their role in promoting fracture healing and bone fusion. However, an optimal delivery system has yet to be identified. The aims of this study were to synthesise bioactive BMP-2, combine it with a novel α-tricalcium phosphate/poly(D,L-lactide-co-glycolide) (α-TCP/PLGA) nanocomposite and study its release from the composite. Methods. BMP-2 was synthesised using an Escherichia coli expression system and purified. In vitro bioactivity was confirmed using C2C12 cells and an alkaline phosphatase assay. The modified solution-evaporation method . was used to fabricate α-TCP/PLGA nanocomposite and this was characterised using X-ray diffraction and scanning electron microscopy. Functionalisation of α-TCP/PLGA nanocomposite by adsorption of BMP-2 was performed and release of BMP-2 was characterised using an enzyme-linked immunosorbent assay (ELISA). Results. Alkaline phosphatase activity of C2C12 cells was increased by the presence of all BMP-2/nanocomposite discs compared with the presence of a blank disc (p = 0.0022), and increased with increasing incubation concentrations of BMP-2, showing successful adsorption and bioactivity of BMP-2. A burst release profile was observed for BMP-2 from the nanocomposite. . Conclusions. Functionalisation of α-TCP/PLGA with BMP-2 produced osteoinduction and was dose-dependent. This material therefore has potential application as an osteoinductive agent in regenerative medicine

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

Objectives. The need for bone tissue supplementation exists in a wide range of clinical conditions involving surgical reconstruction in limbs, the spine and skull. The bone supplementation materials currently used include autografts, allografts and inorganic matrix components; but these pose potentially serious side-effects. In particular the availability of the autografts is usually limited and their harvesting causes surgical morbidity. Therefore for the purpose of supplementation of autologous bone graft, we have developed a method for autologous extracorporeal bone generation. Methods. Human osteoblast-like cells were seeded on porous granules of tricalcium phosphate and incubated in osteogenic media while exposed to mechanical stimulation by vibration in the infrasonic range of frequencies. The generated tissue was examined microscopically following haematoxylin eosin, trichrome and immunohistochemical staining. Results. Following 14 days of incubation the generated tissue showed histological characteristics of bone-like material due to the characteristic eosinophilic staining, a positive staining for collagen trichrome and a positive specific staining for osteocalcin and collagen 1. Macroscopically, this tissue appeared in aggregates of between 0.5 cm and 2 cm. . Conclusions. We present evidence that the interaction of the cellular, inorganic and mechanical components in vitro can rapidly generate three-dimensional bone-like tissue that might be used as an autologous bone graft

We have developed an animal model to examine the formation of heterotopic ossification using standardised muscular damage and implantation of a beta-tricalcium phosphate block into a hip capsulotomy wound in Wistar rats. The aim was to investigate how cells originating from drilled femoral canals and damaged muscles influence the formation of heterotopic bone. The femoral canal was either drilled or left untouched and a tricalcium phosphate block, immersed either in saline or a rhBMP-2 solution, was implanted. These implants were removed at three and 21 days after the operation and examined histologically, histomorphometrically and immunohistochemically. Bone formation was seen in all implants in rhBMP-2-immersed, whereas in those immersed in saline the process was minimal, irrespective of drilling of the femoral canals. Bone mineralisation was somewhat greater in the absence of drilling with a mean mineralised volume to mean total volume of 18.2% (. sd. 4.5) versus 12.7% (. sd. 2.9, p < 0.019), respectively. Our findings suggest that osteoinductive signalling is an early event in the formation of ectopic bone. If applicable to man the results indicate that careful tissue handling is more important than the prevention of the dissemination of bone cells in order to avoid heterotopic ossification

Aims

Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections.

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The aim of this study was to report the patterns of symptoms and insufficiency fractures in patients with tumour-induced osteomalacia (TIO) to allow the early diagnosis of this rare condition.

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To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants.

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Isolated acetabular liner exchange with a highly crosslinked polyethylene (HXLPE) component is an option to address polyethylene wear and osteolysis following total hip arthroplasty (THA) in the presence of a well-fixed acetabular shell. The liner can be fixed either with the original locking mechanism or by being cemented within the acetabular component. Whether the method used for fixation of the HXLPE liner has any bearing on the long-term outcomes is still unclear.

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The aim of this study was to compare the pattern of initial fixation and changes in periprosthetic bone mineral density (BMD) between patients who underwent total hip arthroplasty (THA) using a traditional fully hydroxyapatite (HA)-coated stem (T-HA group) and those with a newly introduced fully HA-coated stem (N-HA group).

Aims

Electromagnetic induction heating has demonstrated in vitro antibacterial efficacy over biofilms on metallic biomaterials, although no in vivo studies have been published. Assessment of side effects, including thermal necrosis of adjacent tissue, would determine transferability into clinical practice. Our goal was to assess bone necrosis and antibacterial efficacy of induction heating on biofilm-infected implants in an in vivo setting.

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The aim of this study was to evaluate the radiological outcome of patients with large bone defects in the femur and tibia who were treated according to the guidelines of the diamond concept in our department (Centre for Orthopedics, Trauma Surgery, and Paraplegiology).

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The survival of humeral hemiarthroplasties in patients with relatively intact glenoid cartilage could theoretically be extended by minimizing the associated postoperative glenoid erosion. Ceramic has gained attention as an alternative to metal as a material for hemiarthroplasties because of its superior tribological properties. The aim of this study was to assess the in vitro wear performance of ceramic and metal humeral hemiarthroplasties on natural glenoids.

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The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI.

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Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP.

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Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

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The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA.

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To investigate health-related quality of life (HRQoL) of older adults (aged ≥ 60 years) after tibial plateau fracture (TPF) compared to preinjury and population matched values, and what aspects of treatment were most important to patients.

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Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

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The incidence of limb fractures in patients living with HIV (PLWH) is increasing. However, due to their immunodeficiency status, the operation and rehabilitation of these patients present unique challenges. Currently, it is urgent to establish a standardized perioperative rehabilitation plan based on the concept of enhanced recovery after surgery (ERAS). This study aimed to validate the effectiveness of ERAS in the perioperative period of PLWH with limb fractures.

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This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

The role of bone-graft extenders in impaction revision surgery is becoming increasingly important. Tricalcium phosphate and hydroxyapatite have been shown to be both biocompatible and osteoconductive, yet many surgeons remain reluctant to use them. The difficulty in handling bone-graft extenders can be partly alleviated by using porous particles and adding clotted blood. In an in vitro model we measured the cohesive properties of various impaction graft mixes. Several factors were evaluated including the use of pure bone graft compared with mixes with extender, washing the bone and the addition of clotted blood. Our findings showed that pure allograft bone particles had significantly higher cohesion than when mixed with extender (p < 0.001). Washing had no effect on cohesion. The addition of clotted blood significantly increased the cohesion of both pure bone (p < 0.019) and mixes with pure bone and with porous graft extender (p < 0.044)

The alkaline phosphatase activity of pre-osseous tibial cartilage of rachitic bone stored in the deep freeze for two weeks at -25 degrees centigrade was only slightly less than that of fresh controls from the same animals. The deep frozen pre-osseous tissue did not calcify in in vitro calcifying media containing either inorganic phosphorus or organic phosphate ester. The fresh controls calcified equally well in both media. In addition, after deep-freeze storage the tissue hydrolysed the organic phosphate to the same degree as did the fresh tissue. Bones heated at 65 degrees centigrade will calcify in vitro after calcium chloride treatment despite the destruction of phosphatase activity. It appears unlikely that a relationship exists between alkaline phosphatase and the minimal system required for calcification of pre-osseous cartilage in vitro. These findings do not exclude the possibility that alkaline phosphatase plays some critical role in vivo

The changes in serum adjusted ionised calcium and parathyroid hormone (PTH) were prospectively studied in 32 patients with isolated tibial fractures, treated conservatively. We measured serum albumin, adjusted total calcium, phosphate, pH, adjusted ionised calcium and PTH at intervals until the fractures had healed. The mean ionised calcium adjusted for pH fell within 24 hours of injury, and then rose to a peak at between four and six weeks. These changes cannot be explained by changes in serum pH or PTH. The restoration of normal ionised calcium levels after fracture coincided with the period when the callus was being calcified. Analysis of the changes in ionised calcium, phosphate and PTH suggests that PTH levels alter in response to changes in ionised calcium levels. PTH is highest immediately after fracture and lowest, often not recordable, at six weeks. The cause of the changes in the ionised calcium level has yet to be elucidated

Aims

Bone regeneration during treatment of staphylococcal bone infection is challenging due to the ability of Staphylococcus aureus to invade and persist within osteoblasts. Here, we sought to determine whether the metabolic and extracellular organic matrix formation and mineralization ability of S. aureus-infected human osteoblasts can be restored after rifampicin (RMP) therapy.

Aims

Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders.

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).

Aims

Our objective was to conduct a systematic review and meta-analysis, to establish whether differences arise in clinical outcomes between autologous and synthetic bone grafts in the operative management of tibial plateau fractures.

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed. . In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups. After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate. Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes. Cite this article: Bone Joint J 2014; 96-B:845–50

Aims

BoneMaster is a thin electrochemically applied hydroxyapatite (HA) coating for orthopaedic implants that is quickly resorbed during osseointegration. Early stabilization is a surrogacy marker of good survival of femoral stems. The hypothesis of this study was that a BoneMaster coating yields a fast early and lasting fixation of stems.

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This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D.

Aims

Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood.

Impacted morsellised allografts have been used successfully to address the problem of poor bone stock in revision surgery. However, there are concerns about the transmission of pathogens, the high cost and the shortage of supply of donor bone. Bone-graft extenders, such as tricalcium phosphate (TCP) and hydroxyapatite (HA), have been developed to minimise the use of donor bone. In a human cadaver model we have evaluated the surgical and mechanical feasibility of a TCP/HA bone-graft extender during impaction grafting revision surgery. A TCP/HA allograft mix increased the risk of producing a fissure in the femur during the impaction procedure, but provided a higher initial mechanical stability when compared with bone graft alone. The implications of the use of this type of graft extender in impaction grafting revision surgery are discussed

Osteoarthritis (OA) is a degenerative disease resulting from progressive joint destruction caused by many factors. Its pathogenesis is complex and has not been elucidated to date. Advanced glycation end products (AGEs) are a series of irreversible and stable macromolecular complexes formed by reducing sugar with protein, lipid, and nucleic acid through a non-enzymatic glycosylation reaction (Maillard reaction). They are an important indicator of the degree of ageing. Currently, it is considered that AGEs accumulation in vivo is a molecular basis of age-induced OA, and AGEs production and accumulation in vivo is one of the important reasons for the induction and acceleration of the pathological changes of OA. In recent years, it has been found that AGEs are involved in a variety of pathological processes of OA, including extracellular matrix degradation, chondrocyte apoptosis, and autophagy. Clearly, AGEs play an important role in regulating the expression of OA-related genes and maintaining the chondrocyte phenotype and the stability of the intra-articular environment. This article reviews the latest research results of AGEs in a variety of pathological processes of OA, to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment.

Cite this article: Bone Joint Res 2022;11(5):292–300.

Objectives. Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts. Methods. Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays. Results. After six weeks, the area of mineralisation was significantly higher for the transplanted osteophytes than for the cancellous bone (43803 μm. 2. , . sd. 14660 versus 9421 μm. 2. , . sd. 5032, p = 0.0184, one-way analysis of variance). Compared with cancellous bone, the conditioned medium prepared using osteophytes contained a significantly higher amounts of transforming growth factor (TGF)-β1 (471 pg/ml versus 333 pg/ml, p = 0.0001, Wilcoxon rank sum test), bone morphogenetic protein (BMP)-2 (47.75 pg/ml versus 32 pg/ml, p = 0.0214, Wilcoxon rank sum test) and insulin-like growth factor (IGF)-1 (314.5 pg/ml versus 191 pg/ml, p = 0.0418, Wilcoxon rank sum test). The stronger effects of osteophytes towards osteoblasts in terms of a higher proliferation rate, upregulation of gene expression of differentiation markers such as alpha-1 type-1 collagen and alkaline phosphate, and higher migration, compared with cancellous bone, was confirmed. Conclusion. We provide evidence of favourable features of osteophytes for bone mineralisation through a direct effect on osteoblasts. The acceleration in metabolic activity of the osteophyte provides justification for future studies evaluating the clinical use of osteophytes as autologous bone grafts. Cite this article: K. Ishihara, K. Okazaki, T. Akiyama, Y. Akasaki, Y. Nakashima. Characterisation of osteophytes as an autologous bone graft source: An experimental study in vivo and in vitro. Bone Joint Res 2017;6:73–81. DOI: 10.1302/2046-3758.62.BJR-2016-0199.R1

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.

Aims

This study investigates head-neck taper corrosion with varying head size in a novel hip simulator instrumented to measure corrosion related electrical activity under torsional loads.

Aims

Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA.

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This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients.

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Acquired heterotopic ossification (HO) is a debilitating disease characterized by abnormal extraskeletal bone formation within soft-tissues after injury. The exact pathogenesis of HO remains unknown. It was reported that BRD4 may contribute to osteoblastic differentiation. The current study aims to determine the role of BRD4 in the pathogenesis of HO and whether it could be a potential target for HO therapy.

Aims

A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing.

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Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components.

Aims

To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities.

Periprosthetic joint infection (PJI) is one of the most dreaded complications after arthroplasty surgery; thus numerous approaches have been undertaken to equip metal surfaces with antibacterial properties. Due to its antimicrobial effects, silver is a promising coating for metallic surfaces, and several types of silver-coated arthroplasty implants are in clinical use today. However, silver can also exert toxic effects on eukaryotic cells both in the immediate vicinity of the coated implants and systemically. In most clinically-used implants, silver coatings are applied on bulk components that are not in direct contact with bone, such as in partial or total long bone arthroplasties used in tumour or complex revision surgery. These implants differ considerably in the coating method, total silver content, and silver release rates. Safety issues, such as the occurrence of argyria, have been a cause for concern, and the efficacy of silver coatings in terms of preventing PJI is also controversial. The application of silver coatings is uncommon on parts of implants intended for cementless fixation in host bone, but this option might be highly desirable since the modification of implant surfaces in order to improve osteoconductivity can also increase bacterial adhesion. Therefore, an optimal silver content that inhibits bacterial colonization while maintaining osteoconductivity is crucial if silver were to be applied as a coating on parts intended for bone contact. This review summarizes the different methods used to apply silver coatings to arthroplasty components, with a focus on the amount and duration of silver release from the different coatings; the available experience with silver-coated implants that are in clinical use today; and future strategies to balance the effects of silver on bacteria and eukaryotic cells, and to develop silver-coated titanium components suitable for bone ingrowth.

Cite this article: Bone Joint J 2021;103-B(3):423–429.

A small proportion of the total phosphate in normal bone salt occurs in the form of pyrophosphate. The deposit formed in vitro on incubation of rachitic cartilage with a calcifying medium does not contain pyrophosphate unless ATP is added to the medium, in which case the proportion of pyrophosphate is of the same order as that found in normal bone

1. A case of symmetrical bilateral calcareous bursitis at the elbow is described. 2. Metabolic and neurotrophic factors played a role in its genesis. 3. Chemical analysis showed a similarity between the ratio of calcium phosphate and calcium carbonate in dystrophic calcification and in the fluid in the bursal cavity. 4. An inflammatory reaction was seen around the calcium appearing interstitially: this was probably not a consequence of chemical stimuli

Aims

Here we introduce a wide and complex study comparing effects of growth factors used alone and in combinations on human mesenchymal stem cell (hMSC) proliferation and osteogenic differentiation. Certain ways of cell behaviour can be triggered by specific peptides – growth factors, influencing cell fate through surface cellular receptors.

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Vertebrates have adapted to life on Earth and its constant gravitational field, which exerts load on the body and influences the structure and function of tissues. While the effects of microgravity on muscle and bone homeostasis are well described, with sarcopenia and osteoporosis observed in astronauts returning from space, the effects of shorter exposures to increased gravitational fields are less well characterized. We aimed to test how hypergravity affects early cartilage and skeletal development in a zebrafish model.

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Tourniquets have potential adverse effects including postoperative thigh pain, likely caused by their ischaemic and possible compressive effects. The aims of this preliminary study were to determine if it is possible to directly measure intramuscular pH in human subjects over time, and to measure the intramuscular pH changes resulting from tourniquet ischaemia in patients undergoing knee arthroscopy.

Aims

Platelet concentrates, like platelet-rich plasma (PRP) and platelet lysate (PL), are widely used in regenerative medicine, especially in bone regeneration. However, the lack of standard procedures and controls leads to high variability in the obtained results, limiting their regular clinical use. Here, we propose the use of platelet-derived extracellular vesicles (EVs) as an off-the-shelf alternative for PRP and PL for bone regeneration. In this article, we evaluate the effect of PL-derived EVs on the biocompatibility and differentiation of mesenchymal stromal cells (MSCs).

Throughout this work data have been gathered favouring the concept that the metaphysial vascular arrangement is primarily related to the process of enchondral ossification, and has very limited, if any, responsibility for the nourishment of the growth cartilage. The present evidence favours the suggestion that when the chondrocytes of the column have become too far separated from their source of nourishment (the epiphysial vessels) they and their surrounding matrix suffer changes which prepare them for the process of calcification. At least calcium and phosphate ions will be required for this to take place. The proximity of the vessel and also the fact that it is not isolated by a membrane at its very end suggests a profuse interchange of fluids with the surrounding area

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The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis.

In vitamin D-fed chicks 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were implanted into experimentally-produced fractures of the mid-tibia. The mechanical and biochemical properties of the tibia were evaluated for two weeks, including torsion tests, measurement of alkaline phosphatase activity, 45Ca incorporation, and Ca2+ content. Both dihydroxylated metabolites of vitamin D3 had a direct effect on endochondral bone formation. 24,25(OH)2D3 strengthened the callus, and raised alkaline phosphate activity in the first seven days after fracture. 1,25(OH)2D3 decreased the strength of the callus concomitant with a reduction in 45Ca incorporation. It is suggested that local application of 24,25(OH)2D3 into fractures may accelerate healing and prevent non-union

1. Three cases of localised deposition of calcium salts deep to the origin of the common extensors of the forearm with acute symptoms clinically indistinguishable from "tennis elbow" are described. 2. Reports of nine similar cases have been found in the literature. 3. It is suggested that "tennis elbow" is caused by a lesion, probably an adventitial bursa, in the tissue space between the tendon of origin of the forearm extensors and the capsule of the radio-humeral joint; and that it is the sudden precipitation of calcium phosphate at this site which causes the lesion here described. 4. Acute calcification near the elbow joint is compared with the similar calcification which may occur in the insertion of the supraspinatus tendon. 5. Operative treatment is advised

We have studied in vitro the effect of a hydroxyapatite (HA) tricalcium phosphate material coated with hepatocyte growth factor (HA-HGF) on cell growth, collagen synthesis and secretion of metalloproteinases (MMPs) by human osteoblasts. Cell proliferation was stimulated when osteoblasts were incubated with untreated HA and was further increased after exposure to HA-HGF. The uptake of [. 3. H]-proline was increased after treatment with HA. When osteoblasts were exposed to HA-HGF, collagen synthesis was increased with respect to HA. The secretion of MMPs in control cells was undetectable, but in HA and HA-HGF cells MMP 2 and MMP 9 were clearly synthesised. Our results suggest that HA can promote osteoblast activity and that HGF can further increase its bioactivity

Synthetic bone substitutes provide an alternative to autograft but do not give equivalent clinical results. Their performance may be enhanced by adding osteogenic growth factors. In this study, TGFβ1 was absorbed on to a carrier of β tricalcium phosphate and Gelfoam® and used to fill a defect around a tibial implant in a rat model of revision arthoplasty. We added 0.0, 0.02 μg, 0.1 μg or 1.0 μg of TGFβ1 to the carrier and then implanted it around an hydroxyapatite-coated stainless-steel pin in the proximal tibia of rats. The tibiae were harvested at three, six or 26 weeks and the amount of bone formation and ceramic resorption were assessed. TGFβ1 had no effect on the amount of bone in the defect, the amount of fluorescent label incorporated or the rate of mineral apposition. The growth factor did not significantly affect the amount of β TCP remaining in the tissue at any of the time points

Miller-Galante II total knee arthroplasty (MG II TKA) was performed on 32 knees in 30 patients. On both the femoral and tibial components, the fibre-metal area was plasma-sprayed with hydroxyapatite-tricalcium phosphate (HA-TCP). The clinical and radiographic outcome was evaluated. A mean pre-operative knee score of 26.0 ± 18.6 (SD) increased to 97.5 ± 3.5 and a mean pre-operative functional score of 21.7 ± 15.0 (SD) increased to 83.4 ± 12.4 at follow-up of seven years. Clear zones were common around the components at one month post-operatively but had completely disappeared after six months. An autopsy of a patient who underwent MG II TKA with HA-TCP two years previously, showed osteogenesis in all parts of the fibre-metal, and bone tissue comprised 77.7% of the interface. This coated prosthesis has good early fixation which is maintained at seven years with good clinical and radiographic outcomes

1. The process of repair after fracture of the humerus of the growing rat has been studied by histological, histochemical and biochemical methods. 2. Both periosteal and surrounding mesenchymal cells take part in the process of repair. 3. The primary framework of collagen bridging the gap is mainly formed by the mesenchymal cells, while calcification and ossification of the framework is largely a function of the periosteum. 4. The mucopolysaccharide content rises rapidly in the first week after injury, and is followed by a rise in the collagen content during the second week. The deposition of calcium phosphate during the third and fourth weeks causes an apparent fall in the collagen content during that period. The collagen content tends to return to normal during the phase of remodelling in the fifth and sixth weeks. 5. The tensile strength of the healing bone bears a close relation to its collagen content

A model of tourniquet ischaemia was developed in the hind limb of the rat, and the metabolic changes that occurred in the calf muscles were monitored by the non-invasive technique of phosphorus-31 nuclear magnetic resonance spectroscopy. During ischaemia the intramyocellular pH became acidic as the level of phosphocreatine declined and that of inorganic phosphate rose. Phosphocreatine was no longer detectable after approximately 2 hours and ATP was depleted after approximately 3.5 hours. Metabolic recovery was rapid (1 hour) if ATP was present when the tourniquet was released but was prolonged (3 or more hours) if ATP was depleted. Hourly release of the tourniquet for 10 minutes ensured the maintenance of ATP and rapid metabolic recovery. Release for intervals of only 5 minutes did not have the same protective effect and in fact worsened tissue pH during the period of tourniquet ischaemia. Heparin and corticosteroids were without effect during and after periods of tourniquet ischaemia

Aims

We report the medium-term outcomes of a consecutive series of 118 Zenith total ankle arthroplasties (TAAs) from a single, non-designer centre.

Ceramics have many properties which might make them suitable alternatives to bone grafts. This present study was done to find a suitable biodegradable porous ceramic for human bone replacement. Three different porous ceramics (calcium aluminate, calcium hydroxyapatite and tricalcium phosphate), with interlinked pores of two size ranges (150 to 210 micron), were implanted into the skulls of rats and rabbits for up to six months; the interaction with surrounding bone, which is virtually devoid of bone marrow, was then assessed. The ceramics caused no adverse biological response. Tissue ingrowth into pores throughout the implant was seen in all three types and in both pore sizes of ceramic, but the density of the penetrating tissue was far less for calcium aluminate than for calcium hydroxyapatite or tricalcium phosphate. For each type of ceramic, the soft-tissue ingrowth was more dense with the larger pore size, and with a longer period of implantation. Bone ingrowth was not usually seen within the pores of any ceramic. There were no differences in the histological findings between the rats and the rabbits. The results demonstrate that it is possible to produce ceramic materials with a porous structure which allows ingrowth of tissue and biological fluids

The role of three genetically distinct collagen types in the formation of endochondral bone and in calcification and resorption of cartilage has been assessed. Using antibodies specific to types I, II and III collagen we have demonstrated in the embryonic chick tibia that endochondral bone formation began with deposition of type III collagen in lacunae of hypertropic chondrocytes by invading bone-marrow-derived cells. This was followed by the deposition of type I collagen, which is the collagenous constituent of endochondral osteoid. At later stages of development endochondral osteoid was found in the epiphysial growth plate in apparently intact lacunae of hypertrophic chondrocytes; this indicated that the latter might contribute to the synthesis of osteoid type I collagen. Immuno-histological staining for collagen types, and von Kossa staining for calcium phosphate on parallel sections, demonstrated that type I and type II collagen matrices were substrates for calcification. Endochondral bone (with type I collagen) was found on scaffolding of both uncalcified and calcified cartilage (with type II collagen), indicating that calcification of endochondral osteoid and of the underlying cartilage occurred independentyl. Spicules of endochondral cancellous bone of a four-week-old chick contained a core of calcified type II collagen

Aims

Aneurysmal bone cysts (ABCs) are locally aggressive lesions typically found in the long bones of children and adolescents. A variety of management strategies have been reported to be effective in the treatment of these lesions. The purpose of this review was to assess the effectiveness of current strategies for the management of primary ABCs of the long bones.

Objectives

Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1).

Aims

This combined clinical and in vitro study aimed to determine the incidence of liner malseating in modular dual mobility (MDM) constructs in primary total hip arthroplasties (THAs) from a large volume arthroplasty centre, and determine whether malseating increases the potential for fretting and corrosion at the modular metal interface in malseated MDM constructs using a simulated corrosion chamber.

Aims

The diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF.

Aims

We propose a state-of-the-art temporary spacer, consisting of a cobalt-chrome (CoCr) femoral component and a gentamicin-eluting ultra-high molecular weight polyethylene (UHMWPE) tibial insert, which can provide therapeutic delivery of gentamicin, while retaining excellent mechanical properties. The proposed implant is designed to replace conventional spacers made from bone cement.