Aims. The aims of this study were to develop an automatic system capable of calculating four radiological measurements used in the diagnosis and monitoring of cerebral palsy (CP)-related hip disease, and to demonstrate that these measurements are sufficiently accurate to be used in clinical practice. Methods. We developed a machine-learning system to automatically measure Reimer’s migration percentage (RMP), acetabular index (ACI), head shaft angle (HSA), and neck shaft angle (NSA). The system automatically locates points around the femoral head and acetabulum on pelvic radiographs, and uses these to calculate measurements. The system was evaluated on 1,650 pelvic radiographs of children with CP (682 females and 968 males, mean age 8.3 years (SD 4.5)). Each radiograph was manually measured by five clinical experts. Agreement between the manual clinical measurements and the automatic system was assessed by mean absolute deviation (MAD) from the mean manual measurement, type 1 and type 2 intraclass correlation coefficients (ICCs), and a linear mixed-effects model (LMM) for assessing bias. Results. The MAD scores were 5.7% (SD 8.5%) for RMP, 4.3° (SD 5.4°) for
Hip arthroscopy has gained prominence as a primary surgical intervention for symptomatic femoroacetabular impingement (FAI). This study aimed to identify radiological features, and their combinations, that predict the outcome of hip arthroscopy for FAI. A prognostic cross-sectional cohort study was conducted involving patients from a single centre who underwent hip arthroscopy between January 2013 and April 2021. Radiological metrics measured on conventional radiographs and magnetic resonance arthrography were systematically assessed. The study analyzed the relationship between these metrics and complication rates, revision rates, and patient-reported outcomes.Aims
Methods
The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI). This single-centre study focused on a cohort of 24 patients with cam- or pincer-type FAI, full-thickness femoral or acetabular chondral lesions, or osteochondral lesions ≥ 2 cm2, who underwent surgical hip dislocation for FAI correction in combination with AMIC between March 2009 and February 2016. Baseline data were retrospectively obtained from patient files. Mid-term outcomes were prospectively collected at a follow-up in 2020: cartilage repair tissue quality was evaluated by MRI using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Patient-reported outcome measures (PROMs) included the Oxford Hip Score (OHS) and Core Outcome Measure Index (COMI). Clinical examination included range of motion, impingement tests, and pain.Aims
Methods
Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury. A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm2) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations.Aims
Methods
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.
Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67phox was involved in suramin-enhanced chondrocyte phenotype maintenance.Aims
Methods
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. 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.Aims
Methods
The high prevalence of osteoarthritis (OA), as well as the current lack of disease-modifying drugs for OA, has provided a rationale for regenerative medicine as a possible treatment modality for OA treatment. In this editorial, the current status of regenerative medicine in OA including stem cells, exosomes, and genes is summarized along with the author’s perspectives. Despite a tremendous interest, so far there is very little evidence proving the efficacy of this modality for clinical application. As symptomatic relief is not sufficient to justify the high cost associated with regenerative medicine, definitive structural improvement that would last for years or decades and obviate or delay the need for joint arthroplasty is essential for regenerative medicine to retain a place among OA treatment methods. Cite this article:
Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model. Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone.Aims
Methods
The aim of this study was to report the outcome of femoral condylar fresh osteochondral allografts (FOCA) with concomitant realignment osteotomy with a focus on graft survivorship, complications, reoperation, and function. We identified 60 patients (16 women, 44 men) who underwent unipolar femoral condylar FOCA with concomitant realignment between 1972 and 2012. The mean age of the patients was 28.9 years (10 to 62) and the mean follow-up was 11.4 years (2 to 35). Failure was defined as conversion to total knee arthroplasty, revision allograft, or graft removal. Clinical outcome was evaluated using the modified Hospital for Special Surgery (mHSS) score.Aims
Patients and Methods
This systematic review examines the current literature regarding surgical techniques for restoring articular cartilage in the hip, from the older microfracture techniques involving perforation to the subchondral bone, to adaptations of this technique using nanofractures and scaffolds. This review discusses the autologous and allograft transfer systems and the autologous matrix-induced chondrogenesis (AMIC) technique, as well as a summary of the previously discussed techniques, which could become common practice for restoring articular cartilage, thus reducing the need for total hip arthroplasty. Using the
The aim of this study was to evaluate antegrade autologous bone
grafting with the preservation of articular cartilage in the treatment
of symptomatic osteochondral lesions of the talus with subchondral
cysts. The study involved seven men and five women; their mean age was
35.9 years (14 to 70). All lesions included full-thickness articular
cartilage extending through subchondral bone and were associated
with subchondral cysts. Medial lesions were exposed through an oblique
medial malleolar osteotomy, and one lateral lesion was exposed by
expanding an anterolateral arthroscopic portal. After refreshing
the subchondral cyst, it was grafted with autologous cancellous
bone from the distal tibial metaphysis. The fragments of cartilage
were fixed with 5-0 nylon sutures to the surrounding cartilage.
Function was assessed at a mean follow-up of 25.3 months (15 to
50), using the American Orthopaedic Foot and Ankle Society (AOFAS)
ankle-hindfoot outcome score. The radiological outcome was assessed
using MRI and CT scans.Aims
Patients and Methods
The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation MSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 μg, high-dose: 40 μg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium. A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 μg/kg of G-CSF daily, the high-dose group (n = 10) received 50 μg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically.Objectives
Methods
Mesenchymal stem cells have the ability to differentiate into various cell types, and thus have emerged as promising alternatives to chondrocytes in cell-based cartilage repair methods. The aim of this experimental study was to investigate the effect of bone marrow derived mesenchymal stem cells combined with platelet rich fibrin on osteochondral defect repair and articular cartilage regeneration in a canine model. Osteochondral defects were created on the medial femoral condyles of 12 adult male mixed breed dogs. They were either treated with stem cells seeded on platelet rich fibrin or left empty. Macroscopic and histological evaluation of the repair tissue was conducted after four, 16 and 24 weeks using the International Cartilage Repair Society macroscopic and the O’Driscoll histological grading systems. Results were reported as mean and standard deviation (Objectives
Methods
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 August 2015 Research Roundup360 looks at: Lightbulbs, bleeding and procedure durations; Infection and rheumatoid agents; Infection rates and ‘bundles of care’ revisited;
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:
Cartilage defects of the hip cause significant
pain and may lead to arthritic changes that necessitate hip replacement.
We propose the use of fresh osteochondral allografts as an option
for the treatment of such defects in young patients. Here we present
the results of fresh osteochondral allografts for cartilage defects
in 17 patients in a prospective study. The underlying diagnoses
for the cartilage defects were osteochondritis dissecans in eight
and avascular necrosis in six. Two had Legg-Calve-Perthes and one
a femoral head fracture. Pre-operatively, an MRI was used to determine
the size of the cartilage defect and the femoral head diameter.
All patients underwent surgical hip dislocation with a trochanteric
slide osteotomy for placement of the allograft. The mean age at
surgery was 25.9 years (17 to 44) and mean follow-up was 41.6 months
(3 to 74). The mean Harris hip score was significantly better after
surgery (p <
0.01) and 13 patients had fair to good outcomes.
One patient required a repeat allograft, one patient underwent hip
replacement and two patients are awaiting hip replacement. Fresh
osteochondral allograft is a reasonable treatment option for hip
cartilage defects in young patients. Cite this article:
Osteochondral lesions (OCLs) occur in up to 70%
of sprains and fractures involving the ankle. Atraumatic aetiologies have
also been described. Techniques such as microfracture, and replacement
strategies such as autologous osteochondral transplantation, or
autologous chondrocyte implantation are the major forms of surgical
treatment. Current literature suggests that microfracture is indicated
for lesions up to 15 mm in diameter, with replacement strategies
indicated for larger or cystic lesions. Short- and medium-term results
have been reported, where concerns over potential deterioration
of fibrocartilage leads to a need for long-term evaluation. Biological augmentation may also be used in the treatment of
OCLs, as they potentially enhance the biological environment for
a natural healing response. Further research is required to establish
the critical size of defect, beyond which replacement strategies
should be used, as well as the most appropriate use of biological augmentation.
This paper reviews the current evidence for surgical management
and use of biological adjuncts for treatment of osteochondral lesions
of the talus. Cite this article:
The management of failed autologous chondrocyte
implantation (ACI) and matrix-assisted autologous chondrocyte implantation
(MACI) for the treatment of symptomatic osteochondral defects in
the knee represents a major challenge. Patients are young, active
and usually unsuitable for prosthetic replacement. This study reports
the results in patients who underwent revision cartilage transplantation
of their original
The December 2013 Knee Roundup360 looks at: Conflict of interest and hyaluronic acid; Will time indeed tell in microfracture?; Contralateral knee pain and joint replacement outcomes; Patient satisfaction and knee replacement?; Hope in the cytokines for painful TKRs?; Pain severity, cytokines and osteoarthritis?; Quadriceps weakness and pain; and spontaneous osteonecrosis of the knee
The treatment of osteochondral lesions and osteoarthritis
remains an ongoing clinical challenge in orthopaedics. This review
examines the current research in the fields of cartilage regeneration,
osteochondral defect treatment, and biological joint resurfacing, and
reports on the results of clinical and pre-clinical studies. We
also report on novel treatment strategies and discuss their potential
promise or pitfalls. Current focus involves the use of a scaffold
providing mechanical support with the addition of chondrocytes or mesenchymal
stem cells (MSCs), or the use of cell homing to differentiate the
organism’s own endogenous cell sources into cartilage. This method
is usually performed with scaffolds that have been coated with a
chemotactic agent or with structures that support the sustained
release of growth factors or other chondroinductive agents. We also
discuss unique methods and designs for cell homing and scaffold
production, and improvements in biological joint resurfacing. There
have been a number of exciting new studies and techniques developed
that aim to repair or restore osteochondral lesions and to treat
larger defects or the entire articular surface. The concept of a
biological total joint replacement appears to have much potential. Cite this article:
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.
Matrix-assisted autologous chondrocyte transplantation (MACT)
has been developed and applied in the clinical practice in the last
decade to overcome most of the disadvantages of the first generation
procedures. The purpose of this systematic review is to document
and analyse the available literature on the results of MACT in the
treatment of chondral and osteochondral lesions of the knee. All studies published in English addressing MACT procedures were
identified, including those that fulfilled the following criteria:
1) level I-IV evidence, 2) measures of functional or clinical outcome,
3) outcome related to cartilage lesions of the knee cartilage.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.
We analysed whether a high body mass index (BMI)
had a deleterious effect on outcome following autologous chondrocyte
implantation (ACI) or matrix-carried autologous chondrocyte implantation
(MACI) for the treatment of full-thickness chondral defects of the
knee from a subset of patients enrolled in the
The August 2012 Knee Roundup. 360. looks at: meniscal defects and a polyurethane scaffold; which is best between a single or double bundle; OA of the knee; how to resolve anterior knee pain; whether yoga can be bad for your menisci; metal ions in the serum; whether
The June 2012 Knee Roundup. 360. looks at:
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
Matrix-induced autologous chondrocyte implantation
(MACI) is an established technique used to treat osteochondral lesions
in the knee. For larger osteochondral lesions (>
5 cm2)
deeper than approximately 8 mm we have combined the use of two MACI
membranes with impaction grafting of the subchondral bone. We report
our results of 14 patients who underwent the ‘bilayer collagen membrane’
technique (BCMT) with a mean follow-up of 5.2 years (2 to 8). There
were 12 men and two women with a mean age of 23.6 years (16 to 40).
The mean size of the defect was 7.2 cm2 (5.2 to 12 cm2)
and were located on the medial (ten) or lateral (four) femoral condyles.
The mean modified Cincinnati knee score improved from 45.1 (22 to
70) pre-operatively to 82.8 (34 to 98) at the most recent review
(p <
0.05). The visual analogue pain score improved from 7.3
(4 to 10) to 1.7 (0 to 6) (p <
0.05). Twelve patients were considered
to have a good or excellent clinical outcome. One graft failed at
six years. The BCMT resulted in excellent functional results and durable
repair of large and deep osteochondral lesions without a high incidence
of graft-related complications.
We attempted to characterise the biological quality
and regenerative potential of chondrocytes in osteochondritis dissecans
(OCD). Dissected fragments from ten patients with OCD of the knee
(mean age 27.8 years (16 to 49)) were harvested at arthroscopy.
A sample of cartilage from the intercondylar notch was taken from
the same joint and from the notch of ten patients with a traumatic
cartilage defect (mean age 31.6 years (19 to 52)). Chondrocytes
were extracted and subsequently cultured. Collagen types 1, 2, and
10 mRNA were quantified by polymerase chain reaction. Compared with
the notch chondrocytes, cells from the dissecate expressed similar
levels of collagen types 1 and 2 mRNA. The level of collagen type
10 message was 50 times lower after cell culture, indicating a loss
of hypertrophic cells or genes. The high viability, retained capacity
to differentiate and metabolic activity of the extracted cells suggests
preservation of the intrinsic repair capability of these dissecates.
Molecular analysis indicated a phenotypic modulation of the expanded
dissecate chondrocytes towards a normal phenotype. Our findings
suggest that cartilage taken from the dissecate can be reasonably
used as a cell source for chondrocyte implantation procedures.
The aim of this study was to evaluate the cultivation potential of cartilage taken from the debrided edge of a chronic lesion of the articular surface. A total of 14 patients underwent arthroscopy of the knee for a chronic lesion on the femoral condyles or trochlea. In addition to the routine cartilage biopsy, a second biopsy of cartilage was taken from the edge of the lesion. The cells isolated from both sources underwent parallel cultivation as monolayer and three-dimensional (3D) alginate culture. The cell yield, viability, capacity for proliferation, morphology and the expressions of typical cartilage genes (collagen I, COL1; collagen II, COL2; aggrecan, AGR; and versican, VER) were assessed. The cartilage differentiation indices (COL2/COL1, AGR/VER) were calculated. The control biopsies revealed a higher mean cell yield (1346 cells/mg Our results suggest that the cultivation of chondrocytes solely from the edges of the lesion cannot be recommended for use in autologous chondrocyte implantation.
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.
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.
We compared the quality of debridement of chondral lesions performed by four arthroscopic (SH, shaver; CU, curette; SHCU, shaver and curette; BP, bipolar electrodes) and one open technique (OPEN, scalpel and curette) which are used prior to autologous chondrocyte implantation (ACI). The ex vivo simulation of all five techniques was carried out on six juvenile equine stifle joints. The OPEN, SH and SHCU techniques were tested on knees harvested from six adult human cadavers. The most vertical walls with the least adjacent damage to cartilage were obtained with the OPEN technique. The CU and SHCU methods gave inferior, but still acceptable results whereas the SH technique alone resulted in a crater-like defect and the BP method undermined the cartilage wall. The subchondral bone was severely violated in all the equine samples which might have been peculiar to this model. The predominant depth of the debridement in the adult human samples was at the level of the calcified cartilage. Some minor penetrations of the subchondral end-plate were induced regardless of the instrumentation used. Our study suggests that not all routine arthroscopic instruments are suitable for the preparation of a defect for
We present a prospective review of the two-year functional outcome of 37 Avon patellofemoral joint replacements carried out in 29 patients with a mean age of 66 years (30 to 82) between October 2002 and March 2007. No patients were lost to follow-up. This is the first independent assessment of this prosthesis using both subjective and objective analysis of outcome. At two years the median Oxford knee score was 39 (interquartile range 32 to 44), the median American Knee Society objective score was 95 (interquartile range 90 to 100), the median American Knee Society functional score was 85 (interquartile range 60 to 100), and the median Melbourne Knee score was 28 (interquartile range 21 to 30). Two patients underwent further surgery. Only one patient reported an unsatisfactory outcome. We conclude that the promising early results observed by the designing centre are reproducible and provide further support for the role of patellofemoral joint replacement.
Smoking is known to have an adverse effect on wound healing and musculoskeletal conditions. This case-controlled study looked at whether smoking has a deleterious effect in the outcome of autologous chondrocyte implantation for the treatment of full thickness chondral defects of the knee. The mean Modified Cincinatti Knee score was statistically significantly lower in smokers (n = 48) than in non-smokers (n = 66) both before and after surgery (p <
0.05). Smokers experienced significantly less improvement in the knee score two years after surgery (p <
0.05). Graft failures were only seen in smokers (p = 0.016). There was a strong negative correlation between the number of cigarettes smoked and the outcome following surgery (Pearson’s correlation coefficient −0.65, p = 0.004). These results suggest that patients who smoke have worse pre-operative function and obtain less benefit from this procedure than non-smokers. The counselling of patients undergoing autologous chondrocyte implantation should include smoking, not only as a general cardiopulmonary risk but also because poorer results can be expected in smokers following this procedure.
Autologous chondrocyte implantation is an option in the treatment of full-thickness chondral or osteochondral injuries which are symptomatic. The goal of surgery and rehabilitation is the replacement of damaged cartilage with hyaline or hyaline-like cartilage, producing improved levels of function and preventing early osteoarthritis. The intermediate results have been promising in terms of functional and clinical improvement. Our aim was to explore the hypothesis that the histological quality of the repair tissue formed after autologous chondrocyte implantation improved with increasing time after implantation. In all, 248 patients who had undergone autologous chondrocyte implantation had biopsies taken of the repair tissue which then underwent histological grading. Statistical analysis suggested that with doubling of the time after implantation the likelihood of a favourable histological outcome was increased by more than fourfold (p <
0.001).
Perilesional changes of chronic focal osteochondral defects were assessed in the knees of 23 sheep. An osteochondral defect was created in the main load-bearing region of the medial condyle of the knees in a controlled, standardised manner. The perilesional cartilage was evaluated macroscopically and biopsies were taken at the time of production of the defect (T0), during a second operation one month later (T1), and after killing animals at three (T3; n = 8), four (T4; n = 8), and seven (T7; n = 8) months. All the samples were histologically assessed by the International Cartilage Repair Society grading system and Mankin histological scores. Biopsies were taken from human patients (n = 10) with chronic articular cartilage lesions and compared with the ovine specimens. The ovine perilesional cartilage presented with macroscopic and histological signs of degeneration. At T1 the International Cartilage Repair Society ‘Subchondral Bone’ score decreased from a mean of 3.0 ( The perilesional cartilage in the animal model became chronic at one month and its histological appearance may be considered comparable with that seen in human osteochondral defects after trauma.
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.
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.
We describe the outcome at a mean follow-up of 8.75 years (7.6 to 9.8) of seven patients who had undergone osteochondral autologous transplantation for full-thickness cartilage defects of the shoulder between 1998 and 2000. These patients have been described previously at a mean of 32.6 months when eight were included. One patient has been lost to follow-up. The outcome was assessed by the Constant shoulder score and the Lysholm knee score to assess any donor-site morbidity. Standard radiographs and MR scores were obtained and compared with the pre-operative findings and the results from the previous review. No patient required any further surgery on the shoulder. The mean Constant score improved significantly until the final follow-up (p = 0.018). The Lysholm score remained excellent throughout. There was a significant progression of osteoarthritic changes from the initial surgery to the first and final follow-up but this did not appear to be related to the size of the defect, the number of cylinders required or the Constant score (p = 0.016). MRI showed that all except one patient had a congruent joint surface at the defect with full bony integration of all osteochondral cylinders. The results have remained satisfactory over a longer period with very good objective and subjective findings.
We report the effects of local administration of osteogenic protein-1 on the biomechanical properties of the overstretched anterior cruciate ligament in an animal model. An injury in the anterior cruciate ligament was created in 45 rabbits. They were divided into three equal groups. In group 1, no treatment was applied, in group II, phosphate-buffered saline was applied around the injured ligament, and in group III, 12.5 μg of osteogenic protein-1 mixed with phosphate-buffered saline was applied around the injured ligament. A control group of 15 rabbits was assembled from randomly-selected injured knees from among the first three groups. Each rabbit was killed at 12 weeks. The maximum load and stiffness of the anterior cruciate ligament was found to be significantly greater in group III than either group 1 (p = 0.002, p = 0.014) or group II (p = 0.032, p = 0.025). The tensile strength and the tangent modulus of fascicles from the ligament were also significantly greater in group III than either group I (p = 0.002, p = 0.0174) or II (p = 0.005, p = 0.022). The application of osteogenic protein-1 enhanced the healing in the injured anterior cruciate ligament, but compared with the control group the treated ligament remained lengthened. The administration of osteogenic protein-1 may have a therapeutic role in treating the overstretched anterior cruciate ligament.
Implantation of autologous chondrocytes and matrix autologous chondrocytes are techniques of cartilage repair used in the young adult knee which require harvesting of healthy cartilage and which may cause iatrogenic damage to the joint. This study explores alternative sources of autologous cells. Chondrocytes obtained from autologous bone-marrow-derived cells and those from the damaged cartilage within the lesion itself are shown to be viable alternatives to harvest-derived cells. A sufficient number and quality of cells were obtained by the new techniques and may be suitable for autologous chondrocyte and matrix autologous chondrocyte implantation.
Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous ‘chondrocyte-fibrin’ construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis. All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC,
