We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy.Objectives
Materials and Methods
The August 2015 Research Roundup360 looks at: Lightbulbs, bleeding and procedure durations; Infection and rheumatoid agents; Infection rates and ‘bundles of care’ revisited; ACI: new application for a proven technology?; Hydrogel coating given the thumbs up; Hydroxyapatite as a smart coating?
We reviewed 59 bone graft substitutes marketed
by 17 companies currently available for implantation in the United Kingdom,
with the aim of assessing the peer-reviewed literature to facilitate
informed decision-making regarding their use in clinical practice.
After critical analysis of the literature, only 22 products (37%)
had any clinical data. Norian SRS (Synthes), Vitoss (Orthovita),
Cortoss (Orthovita) and Alpha-BSM (Etex) had Level I evidence. We question
the need for so many different products, especially with limited
published clinical evidence for their efficacy, and conclude that
there is a considerable need for further prospective randomised
trials to facilitate informed decision-making with regard to the
use of current and future bone graft substitutes in clinical practice. Cite this article:
Revision knee arthroplasty presents a number
of challenges, not least of which is obtaining solid primary fixation
of implants into host bone. Three anatomical zones exist within
both femur and tibia which can be used to support revision implants.
These consist of the joint surface or epiphysis, the metaphysis
and the diaphysis. The methods by which fixation in each zone can
be obtained are discussed. The authors suggest that solid fixation
should be obtained in at least two of the three zones and emphasise
the importance of pre-operative planning and implant selection. Cite this article:
We conducted a case-control study to examine
the merit of silver-coated tumour prostheses. We reviewed 85 patients
with Agluna-treated (silver-coated) tumour implants treated between
2006 and 2011 and matched them with 85 control patients treated
between 2001 and 2011 with identical, but uncoated, tumour prostheses. In all, 106 men and 64 women with a mean age of 42.2 years (18.4
to 90.4) were included in the study. There were 50 primary reconstructions
(29.4%); 79 one-stage revisions (46.5%) and 41 two-stage revisions
for infection (24.1%). The overall post-operative infection rate of the silver-coated
group was 11.8% compared with 22.4% for the control group (p = 0.033,
chi-square test). A total of seven of the ten infected prostheses
in the silver-coated group were treated successfully with debridement,
antibiotics, and implant retention compared with only six of the
19 patients (31.6%) in the control group (p = 0.048, chi-square
test). Three patients in the silver-coated group (3.5%) and 13 controls
(15.3%) had chronic periprosthetic infection (p = 0.009, chi-square
test). The overall success rates in controlling infection by two-stage
revision in the silver-coated group was 85% (17/20) compared with
57.1% (12/21) in the control group (p = 0.05, chi-square test).
The Agluna-treated endoprostheses were associated with a lower rate
of early periprosthetic infection. These silver-treated implants
were particularly useful in two-stage revisions for infection and
in those patients with incidental positive cultures at the time
of implantation of the prosthesis. Debridement with antibiotic treatment and retention of the implant
appeared to be more successful with silver-coated implants. Cite this article:
Fresh-frozen allograft bone is frequently used
in orthopaedic surgery. We investigated the incidence of allograft-related
infection and analysed the outcomes of recipients of bacterial culture-positive
allografts from our single-institute bone bank during bone transplantation.
The fresh-frozen allografts were harvested in a strict sterile environment
during total joint arthroplasty surgery and immediately stored in
a freezer at -78º to -68º C after packing. Between January 2007
and December 2012, 2024 patients received 2083 allografts with a
minimum of 12 months of follow-up. The overall allograft-associated
infection rate was 1.2% (24/2024). Swab cultures of 2083 allografts
taken before implantation revealed 21 (1.0%) positive findings.
The 21 recipients were given various antibiotics at the individual
orthopaedic surgeon’s discretion. At the latest follow-up, none
of these 21 recipients displayed clinical signs of infection following
treatment. Based on these findings, we conclude that an incidental positive
culture finding for allografts does not correlate with subsequent
surgical site infection. Additional prolonged post-operative antibiotic
therapy may not be necessary for recipients of fresh-frozen bone
allograft with positive culture findings. Cite this article:
Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies.
A clinical investigation into a new bone void filler is giving
first data on systemic and local exposure to the anti-infective
substance after implantation. A total of 20 patients with post-traumatic/post-operative bone
infections were enrolled in this open-label, prospective study.
After radical surgical debridement, the bone cavity was filled with
this material. The 21-day hospitalisation phase included determination
of gentamicin concentrations in plasma, urine and wound exudate, assessment
of wound healing, infection parameters, implant resorption, laboratory
parameters, and adverse event monitoring. The follow-up period was
six months. Objective
Method
Bacterial infection in orthopaedic surgery can be devastating, and is associated with significant morbidity and poor functional outcomes, which may be improved if high concentrations of antibiotics can be delivered locally over a prolonged period of time. The two most widely used methods of doing this involve antibiotic-loaded polymethylmethacrylate or collagen fleece. The former is not biodegradable and is a surface upon which secondary bacterial infection may occur. Consequently, it has to be removed once treatment has finished. The latter has been used successfully as an adjunct to systemic antibiotics, but cannot effect a sustained release that would allow it to be used on its own, thereby avoiding systemic toxicity. This review explores the newer biodegradable carrier systems which are currently in the experimental phase of development and which may prove to be more effective in the treatment of osteomyelitis.
We have assessed the different adhesive properties
of some of the most common bacteria associated with periprosthetic
joint infection on various types of ultra high molecular Weight
Polyethylene (UHMWPE). Quantitative Cite this article:
In a rabbit model we investigated the efficacy of a silk fibroin/hydroxyapatite (SF/HA) composite on the repair of a segmental bone defect. Four types of porous SF/HA composites (SF/HA-1, SF/HA-2, SF/HA-3, SF/HA-4) with different material ratios, pore sizes, porosity and additives were implanted subcutaneously into Sprague-Dawley rats to observe biodegradation. SF/HA-3, which had characteristics more suitable for a bone substitite based on strength and resorption was selected as a scaffold and co-cultured with rabbit bone-marrow stromal cells (BMSCs). A segmental bone defect was created in the rabbit radius. The animals were randomised into group 1 (SF/HA-3 combined with BMSCs implanted into the bone defect), group 2 (SF/HA implanted alone) and group 3 (nothing implanted). They were killed at four, eight and 12 weeks for visual, radiological and histological study. The bone defects had complete union for group 1 and partial union in group 2, 12 weeks after operation. There was no formation of new bone in group 3. We conclude that SF/HA-3 combined with BMSCs supports bone healing and offers potential as a bone-graft substitute.
The December 2012 Spine Roundup360 looks at: the Japanese neck disability index; adjacent segment degeneration; sacroiliac loads determined by limb length discrepancy; whether epidural steroids improve outcome in lumbar disc herniation; spondylodiscitis in infancy; total pedicle screws; and iliac crest autograft complications.
Trabecular metal (TM) augments are a relatively
new option for reconstructing segmental bone loss during acetabular
revision. We studied 34 failed hip replacements in 34 patients that
were revised between October 2003 and March 2010 using a TM acetabular
shell and one or two augments. The mean age of the patients at the
time of surgery was 69.3 years (46 to 86) and the mean follow-up
was 64.5 months (27 to 107). In all, 18 patients had a minor column
defect, 14 had a major column defect, and two were associated with
pelvic discontinuity. The hip centre of rotation was restored in
27 patients (79.4%). The Oxford hip score increased from a mean
of 15.4 points (6 to 25) before revision to a mean of 37.7 (29 to
47) at the final follow-up. There were three aseptic loosenings
of the construct, two of them in the patients with pelvic discontinuity.
One septic loosening also occurred in a patient who had previously
had an infected hip replacement. The augments remained stable in
two of the failed hips. Whenever there was a loose acetabular component
in contact with a stable augment, progressive metal debris shedding
was evident on the serial radiographs. Complications included another
deep infection treated without revision surgery. Good clinical and
radiological results can be expected for bone-deficient acetabula
treated by a TM cup and augment, but for pelvic discontinuities
this might not be a reliable option. Cite this article:
Alumina–alumina bearings are among the most resistant
to wear in total hip replacement. Examination of their surfaces
is one way of comparing damage caused by wear of hip joints simulated We found that long-term alumina wear in association with a loose
acetabular component could be categorised into three groups. Of
20 specimens, four had ‘low wear’, eight ‘crescent wear’ and eight
‘severe wear’, which was characterised by a change in the physical
shape of the bearing and a loss of volume. This suggests that the
wear in alumina–alumina bearings in association with a loose acetabular
component may be variable in pattern, and may explain, in part,
why the wear of a ceramic head
In an interdisciplinary project involving electronic
engineers and clinicians, a telemetric system was developed to measure
the bending load in a titanium internal femoral fixator. As this
was a new device, the main question posed was: what clinically relevant
information could be drawn from its application? As a first clinical
investigation, 27 patients (24 men, three women) with a mean age
of 38.4 years (19 to 66) with femoral nonunions were treated using the
system. The mean duration of the nonunion was 15.4 months (5 to
69). The elasticity of the plate-callus system was measured telemetrically
until union. Conventional radiographs and a CT scan at 12 weeks
were performed routinely, and healing was staged according to the
CT scans. All nonunions healed at a mean of 21.5 weeks (13 to 37).
Well before any radiological signs of healing could be detected,
a substantial decrease in elasticity was recorded. The relative
elasticity decreased to 50% at a mean of 7.8 weeks (3.5 to 13) and
to 10% at a mean of 19.3 weeks (4.5 to 37). At 12 weeks the mean
relative elasticity was 28.1% (0% to 56%). The relative elasticity
was significantly different between the different healing stages
as determined by the CT scans. Incorporating load measuring electronics into implants is a promising
option for the assessment of bone healing. Future application might
lead to a reduction in the need for exposure to ionising radiation
to monitor fracture healing.
A 70-year-old man with an uncemented metal-on-polyethylene
total hip prosthesis underwent revision arthroplasty 33 months later
because of pain, swelling and recurrent dislocation. There appeared
to be corrosion and metal release from the prosthetic head, resulting
in pseudotumour formation and severe local soft-tissue destruction.
The corrosion occurred at the junction between the titanium-molybdenum-zirconium-iron
taper and the cobalt-chrome-molybdenum head, but the mechanism was unproven.
The introduction of a trabecular tantalum rod
has been proposed for the management of early-stage osteonecrosis of
the femoral head but serves as a single-point of support of the
necrotic lesion. We describe a technique using two or three 4.2
mm (or later 4.7 mm) tantalum pegs for the prevention of collapse
of the necrotic lesion. We prospectively studied 21 patients (26
hips) with non-traumatic osteonecrosis of the femoral head treated
in this manner. Of these, 21 patients (24 hips) were available for
radiological and clinical evaluation at a mean follow-up of 46 months
(18 to 67). Radiological assessment showed that only eight hips
deteriorated according to the Association Research Circulation Osseous
classification, and four hips according to the Classification of
the Japanese Investigation Committee of Health and Welfare. Functional
improvement was obtained with an improvement in the mean Harris
hip score from 65.2 (33.67 to 95) to 88.1 (51.72 to 100), the mean
Merle D’Aubigné-Postel score from 13 (6 to 18) to 16 (11 to 18),
a mean visual analogue score for pain from 5.2 (0 to 9.5) to 2.6
(0 to 7), and the mean Short-Form 36 score from 80.4 (56.8 to 107.1)
to 92.4 (67.5 to 115.7). Of these 24 hips followed for a minimum
of 18 months, three were considered as failures at the final follow-up,
having required total hip replacement. One of the hips without full
follow-up was also considered to be a failure. In more than two-thirds
of the surviving hips a satisfactory clinical outcome was achieved
with promising radiological findings. The estimated mean implant
survival was 60 months (95% confidence interval 53.7 to 66.3).
Between October 2001 and September 2009 we lengthened 242 lower-limb segments in 180 patients using the Intramedullary Skeletal Kinetic Distractor (ISKD). Mechanical failure was defined either as breakage of the ISKD or failure of the internal mechanism to activate. Retrieved nails which failed mechanically were examined by the manufacturer for defects. In all, 15 ISKDs in 12 patients (13 limbs) failed mechanically representing an overall failure rate of 6.2%, with fracture of the device occurring in ten of the 15 failures. Two nails in one patient failed to lengthen and had to be replaced. The manufacturer detected an error in the assembly of the nail, which prompted a wide recall. One nail jammed after being forcefully inserted, and two nails failed to lengthen fully. Lengthening was achieved in all 12 patients, although three required a second operation to exchange a defective nail for a new, functioning device. The ISKD is a complex mechanical device which lengthens by the oscillation of two telescopic sections connected by a threaded rod. The junction between these sections is surrounded by a keyring collar. This keyring collar is the weakest part of the device.
A silver-containing hydroxyapatite (Ag-HA) coating has been developed using thermal spraying technology. We evaluated the osteoconductivity of this coating on titanium (Ti) implants in rat tibiae in relation to bacterial infection in joint replacement. At 12 weeks, the mean affinity indices of bone formation of a Ti, an HA, a 3%Ag-HA and a 50%Ag-HA coating were 97.3%, 84.9%, 81.0% and 40.5%, respectively. The mean affinity indices of bone contact of these four coatings were 18.8%, 83.7%, 77.2% and 40.5%, respectively. The indices of bone formation and bone contact around the implant of the 3%Ag-HA coating were similar to those of the HA coating, and no significant differences were found between them (bone formation, p = 0.99; bone contact, p = 0.957). However, inhibition of bone formation was observed with the 50%Ag-HA coating. These results indicate that the 3%Ag-HA coating has low toxicity and good osteoconductivity, and that the effect of silver toxicity on osteoconductivity depends on the dose.
Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks. In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.