The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student Objectives
Methods
Stem cells are a key component of regenerative medicine strategies. Particular areas of musculoskeletal application include cartilage and bone regeneration in arthritis and trauma. There are several types of stem cell and this article will focus on the adult derived cells. The review includes current issues and future developments.
We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry.Objectives
Materials and Methods
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. 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 Objectives
Methods
Currently, there is no animal model in which
to evaluate the underlying physiological processes leading to the heterotopic
ossification (HO) which forms in most combat-related and blast wounds.
We sought to reproduce the ossification that forms under these circumstances
in a rat by emulating patterns of injury seen in patients with severe
injuries resulting from blasts. We investigated whether exposure
to blast overpressure increased the prevalence of HO after transfemoral
amputation performed within the zone of injury. We exposed rats
to a blast overpressure alone (BOP-CTL), crush injury and femoral
fracture followed by amputation through the zone of injury (AMP-CTL)
or a combination of these (BOP-AMP). The presence of HO was evaluated
using radiographs, micro-CT and histology. HO developed in none
of nine BOP-CTL, six of nine AMP-CTL, and in all 20 BOP-AMP rats.
Exposure to blast overpressure increased the prevalence of HO. This model may thus be used to elucidate cellular and molecular
pathways of HO, the effect of varying intensities of blast overpressure,
and to evaluate new means of prophylaxis and treatment of heterotopic
ossification. Cite this article:
The repair of chondral lesions associated with
femoroacetabular impingement requires specific treatment in addition
to that of the impingement. In this single-centre retrospective
analysis of a consecutive series of patients we compared treatment
with microfracture (MFx) with a technique of enhanced microfracture
autologous matrix-induced chondrogenesis (AMIC). Acetabular grade III and IV chondral lesions measuring between
2 cm2 and 8 cm2 in 147 patients were treated
by MFx in 77 and AMIC in 70. The outcome was assessed using the
modified Harris hip score at six months and one, two, three, four
and five years post-operatively. The outcome in both groups was
significantly improved at six months and one year post-operatively.
During the subsequent four years the outcome in the MFx group slowly deteriorated,
whereas that in the AMIC group remained stable. Six patients in
the MFx group subsequently required total hip arthroplasty, compared
with none in the AMIC group We conclude that the short-term clinical outcome improves in
patients with acetabular chondral damage following both MFx and
AMIC. However, the AMIC group had better and more durable improvement,
particularly in patients with large (≥ 4 cm2) lesions. Cite this article:
Chronic conditions of the wrist may be difficult to manage because
pain and psychiatric conditions are correlated with abnormal function
of the hand. Additionally, intra-articular inflammatory cytokines
may cause pain. We aimed to validate the measurement of inflammatory cytokines
in these conditions and identify features associated with symptoms. The study included 38 patients (18 men, 20 women, mean age 43
years) with a chronic condition of the wrist who underwent arthroscopy.
Before surgery, the Self-Rating Depression Scale (SDS), Hand20 questionnaire
and a visual analogue scale (VAS) for pain were used. Cytokine and
chemokine levels in the synovial fluid of the wrist were measured
using enzyme-linked immunosorbent assays and correlations between
the levels with pain were analysed. Gene expression profiles of
the synovial membranes were assessed using quantitative polymerase
chain reaction.Aims
Patients and Methods
The treatment of osteochondral lesions is of
great interest to orthopaedic surgeons because most lesions do not heal
spontaneously. We present the short-term clinical outcome and MRI
findings of a cell-free scaffold used for the treatment of these
lesions in the knee. A total of 38 patients were prospectively evaluated
clinically for two years following treatment with an osteochondral
nanostructured biomimetic scaffold. There were 23 men and 15 women; the
mean age of the patients was 30.5 years (15 to 64). Clinical outcome
was assessed using the Knee Injury and Osteoarthritis Outcome Score
(KOOS), the Tegner activity scale and a Visual Analgue scale for
pain. MRI data were analysed based on the Magnetic Resonance Observation
of Cartilage Repair Tissue (MOCART) scoring system at three, 12
and 24 months post-operatively. There was a continuous significant
clinical improvement after surgery. In two patients, the scaffold
treatment failed (5.3%) There was a statistically significant improvement
in the MOCART precentage scores. The repair tissue filled most of
the defect sufficiently. We found subchondral laminar changes in all
patients. Intralesional osteophytes were found in two patients (5.3%).
We conclude that this one-step scaffold-based technique can be used
for osteochondral repair. The surgical technique is straightforward,
and the clinical results are promising. The MRI aspects of the repair
tissue continue to evolve during the first two years after surgery.
However, the subchondral laminar and bone changes are a concern. 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.
Osteochondritis Dissecans (OCD) is a condition
for which the aetiology remains unknown. It affects subchondral bone
and secondarily its overlying cartilage and is mostly found in the
knee. It can occur in adults, but is generally identified when growth
remains, when it is referred to as juvenile OCD. As the condition
progresses, the affected subchondral bone separates from adjacent
healthy bone, and can lead to demarcation and separation of its associated
articular cartilage. Any symptoms which arise relate to the stage
of the disease. Early disease without separation of the lesion results
in pain. Separation of the lesion leads to mechanical symptoms and
swelling and, in advanced cases, the formation of loose bodies. Early identification of OCD is essential as untreated OCD can
lead to the premature degeneration of the joint, whereas appropriate
treatment can halt the disease process and lead to healing. Establishing
the stability of the lesion is a key part of providing the correct
treatment. Stable lesions, particularly in juvenile patients, have
greater propensity to heal with non-surgical treatment, whereas
unstable or displaced lesions usually require surgical management. This article discusses the aetiology, clinical presentation and
prognosis of OCD in the knee. It presents an algorithm for treatment,
which aims to promote healing of native hyaline cartilage and to
ensure joint congruity. Take home message: Although there is no clear consensus as to
the best treatment of OCD, every attempt should be made to retain
the osteochondral fragment when possible as, with a careful surgical
technique, there is potential for healing even in chronic lesions Cite this article:
The April 2012 Research Roundup360 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
The April 2013 Research Roundup360 looks at: when the ‘residency cake’ is done; steroids, stem cells and tendons; what exactly is osteoarthritis; platelet-rich plasma; CRPS; d-Dimer for DVT; reducing bacterial adhesion; and fin or limb?
Autologous chondrocyte implantation (ACI) and
mosaicplasty are methods of treating symptomatic articular cartilage
defects in the knee. This study represents the first long-term randomised
comparison of the two techniques in 100 patients at a minimum follow-up
of ten years. The mean age of the patients at the time of surgery was
31.3 years (16 to 49); the mean duration of symptoms pre-operatively
was 7.2 years (9 months to 20 years). The lesions were large with
the mean size for the ACI group being 440.9 mm2 (100
to 1050) and the mosaicplasty group being 399.6 mm2 (100
to 2000). Patients had a mean of 1.5 previous operations (0 to 4)
to the articular cartilage defect. Patients were assessed using
the modified Cincinnati knee score and the Stanmore-Bentley Functional Rating
system. The number of patients whose repair had failed at ten years
was ten of 58 (17%) in the ACI group and 23 of 42 (55%) in the mosaicplasty
group (p <
0.001). The functional outcome of those patients with a surviving graft
was significantly better in patients who underwent ACI compared
with mosaicplasty (p = 0.02).
Peri-tendinous injection of local anaesthetic,
both alone and in combination with corticosteroids, is commonly performed
in the treatment of tendinopathies. Previous studies have shown
that local anaesthetics and corticosteroids are chondrotoxic, but
their effect on tenocytes remains unknown. We compared the effects
of lidocaine and ropivacaine, alone or combined with dexamethasone,
on the viability of cultured bovine tenocytes. Tenocytes were exposed
to ten different conditions: 1) normal saline; 2) 1% lidocaine;
3) 2% lidocaine; 4) 0.2% ropivacaine; 5) 0.5% ropivacaine; 6) dexamethasone
(dex); 7) 1% lidocaine+dex; 8) 2% lidocaine+dex; 9) 0.2% ropivacaine+dex;
and 10) 0.5% ropivacaine+dex, for 30 minutes. After a 24-hour recovery
period, the viability of the tenocytes was quantified using the
CellTiter-Glo viability assay and fluorescence-activated cell sorting
(FACS) for live/dead cell counts. A 30-minute exposure to lidocaine
alone was significantly toxic to the tenocytes in a dose-dependent
manner, but a 30-minute exposure to ropivacaine or dexamethasone
alone was not significantly toxic. Dexamethasone potentiated ropivacaine tenocyte toxicity at higher
doses of ropivacaine, but did not potentiate lidocaine tenocyte
toxicity. As seen in other cell types, lidocaine has a dose-dependent
toxicity to tenocytes but ropivacaine is not significantly toxic.
Although dexamethasone alone is not toxic, its combination with
0.5% ropivacaine significantly increased its toxicity to tenocytes.
These findings might be relevant to clinical practice and warrant
further investigation.
Osteochondral injuries, if not treated adequately, often lead
to severe osteoarthritis. Possible treatment options include refixation
of the fragment or replacement therapies such as Pridie drilling,
microfracture or osteochondral grafts, all of which have certain
disadvantages. Only refixation of the fragment can produce a smooth
and resilient joint surface. The aim of this study was the evaluation
of an ultrasound-activated bioresorbable pin for the refixation of
osteochondral fragments under physiological conditions. In 16 Merino sheep, specific osteochondral fragments of the medial
femoral condyle were produced and refixed with one of conventional
bioresorbable pins, titanium screws or ultrasound-activated pins.
Macro- and microscopic scoring was undertaken after three months. Objectives
Methods
Hyaline articular cartilage has been known to
be a troublesome tissue to repair once damaged. Since the introduction
of autologous chondrocyte implantation (ACI) in 1994, a renewed
interest in the field of cartilage repair with new repair techniques
and the hope for products that are regenerative have blossomed.
This article reviews the basic science structure and function of
articular cartilage, and techniques that are presently available
to effect repair and their expected outcomes.
The August 2012 Research Roundup360 looks at: PRP and chondrogenic differentiation; basic fibroblast growth factor; whether glucosamine works; randomised trials; ossification of the ligamentum flavum; treadmill running; inhibiting BMP antagonists; and whether NSAIDs delay union after all.
Fibrin glue, also known as fibrin sealant, is now established as a haemostatic agent in surgery, but its role in orthopaedic surgery is neither well known nor clearly defined. Although it was originally used over 100 years ago, concerns about transmission of disease meant that it fell from favour. It is also available as a slow-release drug delivery system and as a substrate for cellular growth and tissue engineering. Consequently, it has the potential to be used in a number of ways in orthopaedic surgery. The purpose of this review is to address its use in surgery of the knee in which it appears to offer great promise.
Treatment for osteoarthritis (OA) has traditionally
focused on joint replacement for end-stage disease. An increasing number
of surgical and pharmaceutical strategies for disease prevention
have now been proposed. However, these require the ability to identify
OA at a stage when it is potentially reversible, and detect small
changes in cartilage structure and function to enable treatment
efficacy to be evaluated within an acceptable timeframe. This has
not been possible using conventional imaging techniques but recent
advances in musculoskeletal imaging have been significant. In this
review we discuss the role of different imaging modalities in the
diagnosis of the earliest changes of OA. The increasing number of
MRI sequences that are able to non-invasively detect biochemical
changes in cartilage that precede structural damage may offer a
great advance in the diagnosis and treatment of this debilitating
condition. Cite this article:
Treatment strategies for osteoarthritis most commonly involve the removal or replacement of damaged joint tissue. Relatively few treatments attempt to arrest, slow down or reverse the disease process. Such options include peri-articular osteotomy around the hip or knee, and treatment of femoro-acetabular impingement, where early intervention may potentially alter the natural history of the disease. A relatively small proportion of patients with osteoarthritis have a clear predisposing factor that is both suitable for modification and who present early enough for intervention to be deemed worthwhile. This paper reviews recent advances in our understanding of the pathology, imaging and progression of early osteoarthritis.
