Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears. Cite this article:
The aim of this study was to report the incidence
of arthrofibrosis of the knee and identify risk factors for its development
following a fracture of the tibial plateau. We carried out a retrospective
review of 186 patients (114 male, 72 female) with a fracture of
the tibial plateau who underwent open reduction and internal fixation.
Their mean age was 46.4 years (19 to 83) and the mean follow-up
was16.0 months (6 to 80). A total of 27 patients (14.5%) developed arthrofibrosis requiring
a further intervention. Using multivariate regression analysis,
the use of a provisional external fixator (odds ratio (OR) 4.63,
95% confidence interval (CI) 1.26 to 17.7, p = 0.021) was significantly
associated with the development of arthrofibrosis. Similarly, the
use of a continuous passive movement (CPM) machine was associated
with significantly less development of arthrofibrosis (OR = 0.32,
95% CI 0.11 to 0.83, p = 0.024). The effect of time in an external
fixator was found to be significant, with each extra day of external
fixation increasing the odds of requiring manipulation under anaesthesia
(MUA) or quadricepsplasty by 10% (OR = 1.10, p = 0.030). High-energy
fracture, surgical approach, infection and use of tobacco were not
associated with the development of arthrofibrosis. Patients with
a successful MUA had significantly less time to MUA (mean 2.9 months; Based our results, CPM following operative fixation for a fracture
of the tibial plateau may reduce the risk of the development of
arthrofibrosis, particularly in patients who also undergo prolonged
provisional external fixation. Cite this article:
The incidence of acute and chronic conditions
of the tendo Achillis appear to be increasing. Causation is multifactorial
but the role of inherited genetic elements and the influence of
environmental factors altering gene expression are increasingly
being recognised. Certain individuals’ tendons carry specific variations
of genetic sequence that may make them more susceptible to injury.
Alterations in the structure or relative amounts of the components
of tendon and fine control of activity within the extracellular
matrix affect the response of the tendon to loading with failure
in certain cases. This review summarises present knowledge of the influence of
genetic patterns on the pathology of the tendo Achillis, with a
focus on the possible biological mechanisms by which genetic factors
are involved in the aetiology of tendon pathology. Finally, we assess
potential future developments with both the opportunities and risks
that they may carry. Cite this article:
This article reviews the current knowledge of
the intervertebral disc (IVD) and its association with low back
pain (LBP). The normal IVD is a largely avascular and aneural structure
with a high water content, its nutrients mainly diffusing through
the end plates. IVD degeneration occurs when its cells die or become
dysfunctional, notably in an acidic environment. In the process
of degeneration, the IVD becomes dehydrated and vascularised, and
there is an ingrowth of nerves. Although not universally the case,
the altered physiology of the IVD is believed to precede or be associated
with many clinical symptoms or conditions including low back and/or
lower limb pain, paraesthesia, spinal stenosis and disc herniation. New treatment options have been developed in recent years. These
include biological therapies and novel surgical techniques (such
as total disc replacement), although many of these are still in
their experimental phase. Central to developing further methods
of treatment is the need for effective ways in which to assess patients
and measure their outcomes. However, significant difficulties remain
and it is therefore an appropriate time to be further investigating
the scientific basis of and treatment of LBP.
Orthopaedic surgery is in an exciting transitional period as modern surgical interventions, implants and scientific developments are providing new therapeutic options. As advances in basic science and technology improve our understanding of the pathology and repair of musculoskeletal tissue, traditional operations may be replaced by newer, less invasive procedures which are more appropriately targeted at the underlying pathophysiology. However, evidence-based practice will remain a basic requirement of care. Orthopaedic surgeons can and should remain at the forefront of the development of novel therapeutic interventions and their application. Progression of the potential of bench research into an improved array of orthopaedic treatments in an effective yet safe manner will require the development of a subgroup of specialists with extended training in research to play an important role in bridging the gap between laboratory science and clinical practice. International regulations regarding the introduction of new biological treatments will place an additional burden on the mechanisms of this translational process, and orthopaedic surgeons who are trained in science, surgery and the regulatory environment will be essential. Training and supporting individuals with these skills requires special consideration and discussion by the orthopaedic community. In this paper we review some traditional approaches to the integration of orthopaedic science and surgery, the therapeutic potential of current regenerative biomedical science for cartilage repair and ways in which we may develop surgeons with the skills required to translate scientific discovery into effective and properly assessed orthopaedic treatments.
Platelet-leucocyte gel (PLG), a new biotechnological blood product, has hitherto been used primarily to treat chronic ulcers and to promote soft-tissue and bone regeneration in a wide range of medical fields. In this study, the antimicrobial efficacy of PLG against Staphylococcus aureus (ATCC 25923) was investigated in a rabbit model of osteomyelitis. Autologous PLG was injected into the tibial canal after inoculation with Staph. aureus. The prophylactic efficacy of PLG was evaluated by microbiological, radiological and histological examination. Animal groups included a treatment group that received systemic cefazolin and a control group that received no treatment. Treatment with PLG or cefazolin significantly reduced radiological and histological severity scores compared to the control group. This result was confirmed by a significant reduction in the infection rate and the number of viable bacteria. Although not comparable to cefazolin, PLG exhibited antimicrobial efficacy in vivo and therefore represents a novel strategy to prevent bone infection in humans.
Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline. The platelet α granules are rich in growth factors that play an essential role in tissue healing, such as
Chondral damage to the knee is common and, if left untreated, can proceed to degenerative osteoarthritis. In symptomatic patients established methods of management rely on the formation of fibrocartilage which has poor resistance to shear forces. The formation of hyaline or hyaline-like cartilage may be induced by implanting autologous, cultured chondrocytes into the chondral or osteochondral defect. Autologous chondrocyte implantation may be used for full-thickness chondral or osteochondral injuries which are painful and debilitating with the aim of replacing damaged cartilage with hyaline or hyaline-like cartilage, leading to improved function. The intermediate and long-term functional and clinical results are promising. We provide a review of autologous chondrocyte implantation and describe our experience with the technique at our institution with a mean follow-up of 32 months (1 to 9 years). The procedure is shown to offer statistically significant improvement with advantages over other methods of management of chondral defects.
Platelet-rich plasma is a new inductive therapy which is being increasingly used for the treatment of the complications of bone healing, such as infection and nonunion. The activator for platelet-rich plasma is a mixture of thrombin and calcium chloride which produces a platelet-rich gel. We analysed the antibacterial effect of platelet-rich gel Zones of inhibition produced by platelet-rich gel ranged between 6 mm and 24 mm (mean 9.83 mm) in diameter. Platelet-rich gel inhibited the growth of
We carried out a prospective study to determine whether the addition of a recombinant human bone morphogenetic protein (rhBMP-2) to a machined allograft spacer would improve the rate of intervertebral body fusion in the spine. We studied 77 patients who were to undergo an interbody fusion with allograft and instrumentation. The first 36 patients received allograft with adjuvant rhBMP-2 (allograft/rhBMP-2 group), and the next 41, allograft and demineralised bone matrix (allograft/demineralised bone matrix group). Each patient was assessed clinically and radiologically both pre-operatively and at each follow-up visit using standard methods. Follow-up continued for two years. Every patient in the allograft/rhBMP-2 group had fused by six months. However, early graft lucency and significant (>
10%) subsidence were seen radiologically in 27 of 55 levels in this group. The mean graft height subsidence was 27% (13% to 42%) for anterior lumbar interbody fusion, 24% (13% to 40%) for transforaminal lumbar interbody fusion, and 53% (40% to 58%) for anterior cervical discectomy and fusion. Those who had undergone fusion using allograft and demineralised bone matrix lost only a mean of 4.6% (0% to 15%) of their graft height. Although a high rate of fusion (100%) was achieved with rhBMP-2, significant subsidence occurred in more than half of the levels (23 of 37) in the lumbar spine and 33% (6 of 18) in the cervical spine. A 98% fusion rate (62 of 63 levels) was achieved without rhBMP-2 and without the associated graft subsidence. Consequently, we no longer use rhBMP-2 with allograft in our practice if the allograft has to provide significant structural support.
External fixation of distal tibial fractures is often associated with delayed union. We have investigated whether union can be enhanced by using recombinant bone morphogenetic protein-7 (rhBMP-7). Osteoinduction with rhBMP-7 and bovine collagen was used in 20 patients with distal tibial fractures which had been treated by external fixation (BMP group). Healing of the fracture was compared with that of 20 matched patients in whom treatment was similar except that rhBMP-7 was not used. Significantly more fractures had healed by 16 (p = 0.039) and 20 weeks (p = 0.022) in the BMP group compared with the matched group. The mean time to union (p = 0.002), the duration of absence from work (p = 0.018) and the time for which external fixation was required (p = 0.037) were significantly shorter in the BMP group than in the matched group. Secondary intervention due to delayed healing was required in two patients in the BMP group and seven in the matched group. RhBMP-7 can enhance the union of distal tibial fractures treated by external fixation.
We isolated multilineage mesenchymal progenitor cells from haematomas collected from fracture sites. After the haematoma was manually removed from the fracture site it was cut into strips and cultured. Homogenous fibroblastic adherent cells were obtained. Flow cytometry revealed that the adherent cells were consistently positive for mesenchymal stem-cell-related markers CD29, CD44, CD105 and CD166, and were negative for the haemopoietic markers CD14, CD34, CD45 and CD133 similar to bone-marrow-derived mesenchymal stem cells. In the presence of lineage-specific induction factors the adherent cells could differentiate Our results indicate that haematomas found at a fracture site contain multilineage mesenchymal progenitor cells and play an important role in bone healing. Our findings imply that to enhance healing the haematoma should not be removed from the fracture site during osteosynthesis.
The efficacy of β-tricalcium phosphate (β-TCP) loaded with bone morphogenetic protein-2 (BMP-2)-gene-modified bone-marrow mesenchymal stem cells (BMSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in goats. Bilateral early-stage osteonecrosis was induced in adult goats three weeks after ligation of the lateral and medial circumflex arteries and delivery of liquid nitrogen into the femoral head. After core decompression, porous β-TCP loaded with BMP-2 gene- or β-galactosidase (gal)-gene-transduced BMSCs was implanted into the left and right femoral heads, respectively. At 16 weeks after implantation, there was collapse of the femoral head in the untreated group but not in the BMP-2 or β-gal groups. The femoral heads in the BMP-2 group had a normal density and surface, while those in the β-gal group presented with a low density and an irregular surface. Histologically, new bone and fibrous tissue were formed in the macropores of the β-TCP. Sixteen weeks after implantation, lamellar bone had formed in the BMP-2 group, but there were some empty cavities and residual fibrous tissue in the β-gal group. The new bone volume in the BMP-2 group was significantly higher than that in the β-gal group. The maximum compressive strength and Young’s modulus of the repaired tissue in the BMP-2 group were similar to those of normal bone and significantly higher than those in the β-gal group. Our findings indicate that porous β-TCP loaded with BMP-2-gene-transduced BMSCs are capable of repairing early-stage, experimentally-induced osteonecrosis of the femoral head and of restoring its mechanical function.
The reduced stability of hydroxyapatite (HA)-coated implants in osteopenic conditions is considered to be a major problem. We therefore developed a model of a boosted cementless implantation in osteopenic rats. Twelve-week-old rats were either ovariectomised (OVX) or sham-operated (SO), and after 24 weeks plain or HA-coated implants were inserted. They were treated with either a prostaglandin EP4 receptor agonist (ONO-4819) or saline for one month. The EP4 agonist considerably improved the osteoporosis in the OVX group. Ultrastructural analysis and mechanical testing showed an improvement in the implant-bone attachment in the HA-coated implants, which was further enhanced by the EP4 agonist. Although the stability of the HA-coated implants in the saline-treated OVX rats was less than in the SO normal rats, the administration of the EP4 agonist significantly compensated for this shortage. Our results showed that the osteogenic effect of the EP4 agonist augmented the osteoconductivity of HA and significantly improved the stability of the implant-bone attachment in the osteoporotic rat model.
