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. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 106 cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis.Aims
Methods
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. With informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05.Aims
Methods
Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone. The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety.Aims
Methods
Periprosthetic joint infection (PJI) is a debilitating condition with a substantial socioeconomic burden. A novel autologous blood glue (ABG) has been developed, which can be prepared during surgery and sprayed onto prostheses at the time of implantation. The ABG can potentially provide an antimicrobial coating which will be effective in preventing PJI, not only by providing a physical barrier but also by eluting a well-known antibiotic. Hence, this study aimed to assess the antimicrobial effectiveness of ABG when impregnated with gentamicin and stem cells. Gentamicin elution from the ABG matrix was analyzed and quantified in a time-dependent manner. The combined efficiency of gentamicin and ABG as an anti-biofilm coating was investigated on titanium disks.Aims
Methods
For cementless implants, stability is initially attained by an interference fit into the bone and osteo-integration may be encouraged by coating the implant with bioactive substances. Blood based autologous glue provides an easy, cost-effective way of obtaining high concentrations of growth factors for tissue healing and regeneration with the intention of spraying it onto the implant surface during surgery. The aim of this study was to incorporate nucleated cells from autologous bone marrow (BM) aspirate into gels made from the patient’s own blood, and to investigate the effects of incorporating three different concentrations of platelet rich plasma (PRP) on the proliferation and viability of the cells in the gel. The autologous blood glue (ABG) that constituted 1.25, 2.5, and 5 times concentration PRP were made with and without equal volumes of BM nucleated cells. Proliferation, morphology, and viability of the cells in the glue was measured at days 7 and 14 and compared to cells seeded in fibrin glue.Aims
Methods
Limb salvage in bone tumour patients replaces the bone with massive segmental prostheses where achieving bone integration at the shoulder of the implant through extracortical bone growth has been shown to prevent loosening. This study investigates the effect of multidrug chemotherapy on extracortical bone growth and early radiological signs of aseptic loosening in patients with massive distal femoral prostheses. A retrospective radiological analysis was performed on adult patients with distal femoral arthroplasties. In all, 16 patients were included in the chemotherapy group with 18 patients in the non-chemotherapy control group. Annual radiographs were analyzed for three years postoperatively. Dimensions of the bony pedicle, osseointegration of the hydroxyapatite (HA) collar surface, bone resorption at the implant shoulder, and radiolucent line (RLL) formation around the cemented component were analyzed.Aims
Methods
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. 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).Aims
Methods
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). Cells were isolated from the adipose and bone marrow of juvenile, adult, and previously OVX Wistar rats, and were characterized with flow cytometry, proliferation assays, osteogenic and adipogenic differentiation, and migration to SDF-1. Experiments were repeated with and without intermittent hPTH 1-34.Objectives
Methods
This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis. Mesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats. Cluster of differentiation (CD) marker and CXCR-4 expression was measured using flow cytometry. Cellular proliferation was measured using Alamar Blue, osteogenic differentiation was measured using alkaline phosphatase expression and alizarin red production, and adipogenic differentiation was measured using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF-1. Data was analyzed using a Student’s Objectives
Methods
Increasing innovation in rapid prototyping (RP)
and additive manufacturing (AM), also known as 3D printing, is bringing
about major changes in translational surgical research. This review describes the current position in the use of additive
manufacturing in orthopaedic surgery. Cite this article:
The success of anterior cruciate ligament reconstruction (ACLR)
depends on osseointegration at the graft-tunnel interface and intra-articular
ligamentization. Our aim was to conduct a systematic review of clinical
and preclinical studies that evaluated biological augmentation of
graft healing in ACLR. In all, 1879 studies were identified across three databases.
Following assessment against strict criteria, 112 studies were included
(20 clinical studies; 92 animal studies). Aims
Materials and Methods
Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration. MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts.Objectives
Methods
The Intraosseous Transcutaneous Amputation Prosthesis (ITAP)
may improve quality of life for amputees by avoiding soft-tissue
complications associated with socket prostheses and by improving
sensory feedback and function. It relies on the formation of a seal
between the soft tissues and the implant and currently has a flange
with drilled holes to promote dermal attachment. Despite this, infection
remains a significant risk. This study explored alternative strategies
to enhance soft-tissue integration. The effect of ITAP pins with a fully porous titanium alloy flange
with interconnected pores on soft-tissue integration was investigated.
The flanges were coated with fibronectin-functionalised hydroxyapatite
and silver coatings, which have been shown to have an antibacterial
effect, while also promoting viable fibroblast growth Aims
Materials and Methods
Massive endoprostheses rely on extra-cortical bone bridging (ECBB)
to enhance fixation. The aim of this study was to investigate the
role of selective laser sintered (SLS) porous collars in augmenting
the osseointegration of these prostheses. The two novel designs of porous SLS collars, one with small pores
(Ø700 μm, SP) and one with large pores (Ø1500 μm, LP), were compared
in an ovine tibial diaphyseal model. Osseointegration of these collars
was compared with that of a clinically used solid, grooved design
(G). At six months post-operatively, the ovine tibias were retrieved and
underwent radiological and histological analysis.Aims
Materials and Methods
Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.
There is increasing global awareness of adverse
reactions to metal debris and elevated serum metal ion concentrations
following the use of second generation metal-on-metal total hip
arthroplasties. The high incidence of these complications can be
largely attributed to corrosion at the head-neck interface. Severe
corrosion of the taper is identified most commonly in association
with larger diameter femoral heads. However, there is emerging evidence
of varying levels of corrosion observed in retrieved components
with smaller diameter femoral heads. This same mechanism of galvanic
and mechanically-assisted crevice corrosion has been observed in
metal-on-polyethylene and ceramic components, suggesting an inherent
biomechanical problem with current designs of the head-neck interface. We provide a review of the fundamental questions and answers
clinicians and researchers must understand regarding corrosion of
the taper, and its relevance to current orthopaedic practice. Cite this article:
The aim of this study was to assess the effect
of frictional torque and bending moment on fretting corrosion at
the taper interface of a modular femoral component and to investigate
whether different combinations of material also had an effect. The
combinations we examined were 1) cobalt–chromium (CoCr) heads on
CoCr stems 2) CoCr heads on titanium alloy (Ti) stems and 3) ceramic
heads on CoCr stems. In test 1 increasing torque was imposed by offsetting the stem
in the anteroposterior plane in increments of 0 mm, 4 mm, 6 mm and
8 mm when the torque generated was equivalent to 0 Nm, 9 Nm, 14
Nm and 18 Nm. In test 2 we investigated the effect of increasing the bending
moment by offsetting the application of axial load from the midline
in the mediolateral plane. Increments of offset equivalent to head
+ 0 mm, head + 7 mm and head + 14 mm were used. Significantly higher currents and amplitudes were seen with increasing
torque for all combinations of material. However, Ti stems showed
the highest corrosion currents. Increased bending moments associated
with using larger offset heads produced more corrosion: Ti stems
generally performed worse than CoCr stems. Using ceramic heads did
not prevent corrosion, but reduced it significantly in all loading
configurations. Cite this article:
Arthroplasty registries are important for the
surveillance of joint replacements and the evaluation of outcome. Independent
validation of registry data ensures high quality. The ability for
orthopaedic implant retrieval centres to validate registry data
is not known. We analysed data from the National Joint Registry
for England, Wales and Northern Ireland (NJR) for primary metal-on-metal
hip arthroplasties performed between 2003 and 2013. Records were
linked to the London Implant Retrieval Centre (RC) for validation.
A total of 67 045 procedures on the NJR and 782 revised pairs of
components from the RC were included. We were able to link 476 procedures
(60.9%) recorded with the RC to the NJR successfully. However, 306
procedures (39.1%) could not be linked. The outcome recorded by the
NJR (as either revised, unrevised or death) for a primary procedure
was incorrect in 79 linked cases (16.6%). The rate of registry-retrieval
linkage and correct assignment of outcome code improved over time.
The rates of error for component reference numbers on the NJR were
as follows: femoral head category number 14/229 (5.0%); femoral head
batch number 13/232 (5.3%); acetabular component category number
2/293 (0.7%) and acetabular component batch number 24/347 (6.5%). Registry-retrieval linkage provided a novel means for the validation
of data, particularly for component fields. This study suggests
that NJR reports may underestimate rates of revision for many types
of metal-on-metal hip replacement. This is topical given the increasing
scope for NJR data. We recommend a system for continuous independent
evaluation of the quality and validity of NJR data. Cite this article:
Following the recall of modular neck hip stems
in July 2012, research into femoral modularity will intensify over
the next few years. This review aims to provide surgeons with an
up-to-date summary of the clinically relevant evidence. The development
of femoral modularity, and a classification system, is described.
The theoretical rationale for modularity is summarised and the clinical
outcomes are explored. The review also examines the clinically relevant problems
reported following the use of femoral stems with a modular neck. Joint replacement registries in the United Kingdom and Australia
have provided data on the failure rates of modular devices but cannot
identify the mechanism of failure. This information is needed to
determine whether modular neck femoral stems will be used in the
future, and how we should monitor patients who already have them implanted. Cite this article:
Between 1997 and 2007, 68 consecutive patients underwent replacement of the proximal humerus for tumour using a fixed-fulcrum massive endoprosthesis. Their mean age was 46 years (7 to 87). Ten patients were lost to follow-up and 16 patients died. The 42 surviving patients were assessed using the Musculoskeletal Tumor Society (MSTS) Score and the Toronto Extremity Salvage Score (TESS) at a mean follow-up of five years and 11 months (one year to ten years and nine months). The mean MSTS score was 72.3% (53.3% to 100%) and the mean TESS was 77.2% (58.6% to 100%). Four of 42 patients received a new constrained humeral liner to reduce the risk of dislocation. This subgroup had a mean MSTS score of 77.7% and a mean TESS of 80.0%. The dislocation rate for the original prosthesis was 25.9; none of the patients with the new liner had a dislocation at a mean of 14.5 months (12 to 18). Endoprosthetic replacement for tumours of the proximal humerus using this prosthesis is a reliable operation yielding good results without the documented problems of unconstrained prostheses. The performance of this prosthesis is expected to improve further with a new constrained humeral liner, which reduces the risk of dislocation.
