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Aims. To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs). Methods. Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 10. 6. ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed. Results. In the graft reseeded with ACL-derived cells, a large number of elongated cells that integrated into the matrix were evident at day 3 and day 7. However, in the graft reseeded with ADMSCs, only a small number of elongated cells were found integrated into the matrix. Immunofluorescence for Ki-67 and type I collagen confirmed the pronounced production of type I collagen by Ki-67-positive ACL-derived cells integrated into the ECM. A messenger RNA (mRNA) expression assay demonstrated significantly higher gene expression levels of types I (p = 0.013) and III (p = 0.050) collagen in the composites reseeded with ACL-derived cells than ADMSCs. Conclusion. ACL-derived cells, when reseeded to acellularized tendon graft, demonstrated earlier better survival and integration in the tendon ECM and resulted in higher gene expression levels of collagen, which may be essential to the normal ligamentization process compared to ADMSCs. Cite this article: Bone Joint Res 2022;11(11):777–786


Bone & Joint Research
Vol. 12, Issue 3 | Pages 179 - 188
7 Mar 2023
Itoh M Itou J Imai S Okazaki K Iwasaki K

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. Methods. Using the ClinicalTrials.gov (CTG) and the International Clinical Trials Registry Platform (ICTRP) databases, we comprehensively surveyed clinical trials of decellularized tissue use in orthopaedic surgeries registered before 1 September 2022. We evaluated the clinical results, tissue processing methods, and commercial availability of the identified products using academic literature databases and manufacturers’ websites. Results. We initially identified 4,402 clinical trials, 27 of which were eligible for inclusion and analysis, including nine shoulder surgery trials, eight knee surgery trials, two ankle surgery trials, two hand surgery trials, and six peripheral nerve graft trials. Nine of the trials were completed. We identified only one product that will be commercially available for use in knee surgery with significant mechanical load resistance. Peracetic acid and gamma irradiation were frequently used for sterilization. Conclusion. Despite the demand for decellularized tissue, few decellularized tissue products are currently commercially available, particularly for the knee joint. To be viable in orthopaedic surgery, decellularized tissue must exhibit biocompatibility and mechanical strength, and these requirements are challenging for the clinical application of decellularized tissue. However, the variety of available decellularized products has recently increased. Therefore, decellularized grafts may become a promising option in orthopaedic surgery. Cite this article: Bone Joint Res 2023;12(3):179–188


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

Aims

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

Methods

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


Bone & Joint Research
Vol. 12, Issue 3 | Pages 155 - 164
1 Mar 2023
McCarty CP Nazif MA Sangiorgio SN Ebramzadeh E Park S

Aims

Taper corrosion has been widely reported to be problematic for modular total hip arthroplasty implants. A simple and systematic method to evaluate taper damage with sufficient resolution is needed. We introduce a semiquantitative grading system for modular femoral tapers to characterize taper corrosion damage.

Methods

After examining a unique collection of retrieved cobalt-chromium (CoCr) taper sleeves (n = 465) using the widely-used Goldberg system, we developed an expanded six-point visual grading system intended to characterize the severity, visible material loss, and absence of direct component contact due to corrosion. Female taper sleeve damage was evaluated by three blinded observers using the Goldberg scoring system and the expanded system. A subset (n = 85) was then re-evaluated following destructive cleaning, using both scoring systems. Material loss for this subset was quantified using metrology and correlated with both scoring systems.


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

Aims

Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up.

Methods

A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery.


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

Aims

There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN).

Methods

The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites.


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

Aims

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

Methods

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


Bone & Joint Research
Vol. 7, Issue 5 | Pages 357 - 361
1 May 2018
Shin T Lim D Kim YS Kim SC Jo WL Lim YW

Objectives. Laser-engineered net shaping (LENS) of coated surfaces can overcome the limitations of conventional coating technologies. We compared the in vitro biological response with a titanium plasma spray (TPS)-coated titanium alloy (Ti6Al4V) surface with that of a Ti6Al4V surface coated with titanium using direct metal fabrication (DMF) with 3D printing technologies. Methods. The in vitro ability of human osteoblasts to adhere to TPS-coated Ti6Al4V was compared with DMF-coating. Scanning electron microscopy (SEM) was used to assess the structure and morphology of the surfaces. Biological and morphological responses to human osteoblast cell lines were then examined by measuring cell proliferation, alkaline phosphatase activity, actin filaments, and RUNX2 gene expression. Results. Morphological assessment of the cells after six hours of incubation using SEM showed that the TPS- and DMF-coated surfaces were largely covered with lamellipodia from the osteoblasts. Cell adhesion appeared similar in both groups. The differences in the rates of cell proliferation and alkaline phosphatase activities were not statistically significant. Conclusions. The DMF coating applied using metal 3D printing is similar to the TPS coating, which is the most common coating process used for bone ingrowth. The DMF method provided an acceptable surface structure and a viable biological surface. Moreover, this method is automatable and less complex than plasma spraying. Cite this article: T. Shin, D. Lim, Y. S. Kim, S. C. Kim, W. L. Jo, Y. W. Lim. The biological response to laser-aided direct metal-coated Titanium alloy (Ti6Al4V). Bone Joint Res 2018;7:357–361. DOI: 10.1302/2046-3758.75.BJR-2017-0222.R1


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

Aims

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

Methods

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


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

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

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


Bone & Joint Research
Vol. 10, Issue 4 | Pages 277 - 284
1 Apr 2021
Funk GA Menuey EM Ensminger WP Kilway KV McIff TE

Aims

Poly(methyl methacrylate) (PMMA)-based bone cements are the industry standard in orthopaedics. PMMA cement has inherent disadvantages, which has led to the development and evaluation of a novel silorane-based biomaterial (SBB) for use as an orthopaedic cement. In this study we test both elution and mechanical properties of both PMMA and SBB, with and without antibiotic loading.

Methods

For each cement (PMMA or SBB), three formulations were prepared (rifampin-added, vancomycin-added, and control) and made into pellets (6 mm × 12 mm) for testing. Antibiotic elution into phosphate-buffered saline was measured over 14 days. Compressive strength and modulus of all cement pellets were tested over 14 days.


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

Aims

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

Methods

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


Bone & Joint Research
Vol. 9, Issue 6 | Pages 293 - 301
1 Jun 2020
Hexter AT Hing KA Haddad FS Blunn G

Aims

To evaluate graft healing of decellularized porcine superflexor tendon (pSFT) xenograft in an ovine anterior cruciate ligament (ACL) reconstruction model using two femoral fixation devices. Also, to determine if pSFT allows functional recovery of gait as compared with the preoperative measurements.

Methods

A total of 12 sheep underwent unilateral single-bundle ACL reconstruction using pSFT. Two femoral fixation devices were investigated: Group 1 (n = 6) used cortical suspensory fixation (Endobutton CL) and Group 2 (n = 6) used cross-pin fixation (Stratis ST). A soft screw was used for tibial fixation. Functional recovery was quantified using force plate analysis at weeks 5, 8, and 11. The sheep were euthanized after 12 weeks and comprehensive histological analysis characterized graft healing at the graft-bone interface and the intra-articular graft (ligamentization).


Bone & Joint Research
Vol. 8, Issue 11 | Pages 518 - 525
1 Nov 2019
Whitaker S Edwards JH Guy S Ingham E Herbert A

Objectives

This study investigated the biomechanical performance of decellularized porcine superflexor tendon (pSFT) grafts of varying diameters when utilized in conjunction with contemporary ACL graft fixation systems. This aimed to produce a range of ‘off-the-shelf’ products with predictable mechanical performance, depending on the individual requirements of the patient.

Methods

Decellularized pSFTs were prepared to create double-bundle grafts of 7 mm, 8 mm, and 9 mm diameter. Femoral and tibial fixation systems were simulated utilizing Arthrex suspension devices and interference screws in bovine bone, respectively. Dynamic stiffness and creep were measured, followed by ramp to failure from which linear stiffness and load at failure were measured. The mechanisms of failure were also recorded.


Bone & Joint Research
Vol. 9, Issue 1 | Pages 23 - 28
1 Jan 2020
Kurosawa T Mifune Y Inui A Nishimoto H Ueda Y Kataoka T Yamaura K Mukohara S Kuroda R

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.


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.


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

Objectives

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

Methods

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


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

Objectives

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

Methods

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


Bone & Joint Research
Vol. 7, Issue 8 | Pages 524 - 538
1 Aug 2018
Zhao S Arnold M Ma S Abel RL Cobb JP Hansen U Boughton O

Objectives

The ability to determine human bone stiffness is of clinical relevance in many fields, including bone quality assessment and orthopaedic prosthesis design. Stiffness can be measured using compression testing, an experimental technique commonly used to test bone specimens in vitro. This systematic review aims to determine how best to perform compression testing of human bone.

Methods

A keyword search of all English language articles up until December 2017 of compression testing of bone was undertaken in Medline, Embase, PubMed, and Scopus databases. Studies using bulk tissue, animal tissue, whole bone, or testing techniques other than compression testing were excluded.


Bone & Joint Research
Vol. 7, Issue 4 | Pages 318 - 324
1 Apr 2018
González-Quevedo D Martínez-Medina I Campos A Campos F Carriel V

Objectives

Recently, the field of tissue engineering has made numerous advances towards achieving artificial tendon substitutes with excellent mechanical and histological properties, and has had some promising experimental results. The purpose of this systematic review is to assess the efficacy of tissue engineering in the treatment of tendon injuries.

Methods

We searched MEDLINE, Embase, and the Cochrane Library for the time period 1999 to 2016 for trials investigating tissue engineering used to improve tendon healing in animal models. The studies were screened for inclusion based on randomization, controls, and reported measurable outcomes. The RevMan software package was used for the meta-analysis.