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:
We have reviewed 22 patients from a total of 135 treated by autologous chondrocyte implantation (ACI) who had undergone further surgery for pain in the knee and mechanical symptoms after a mean of 10.5 months. There were 31 grafted lesions. At operation the findings included lifting (24/31) and detachment (3/31) of periosteal patches for which arthroscopic shaving was performed. Chondroplasty was undertaken on two new lesions, another required an
In order to determine the usefulness of MRI in assessing autologous chondrocyte implantation (ACI) the first 57 patients (81 chondral lesions) with a 12-month review were evaluated clinically and with specialised MRI at three and 12 months. Improvement 12 months after operation was found subjectively (37.6 to 51.9) and in knee function levels (from 85% International Cartilage Repair Society (ICRS) III/IV to 61% I/II). The International Knee Documentation Committee (IKDC) scores showed an initial deterioration at three months (56% IKDC A/B) but marked improvement at 12 months (88% A/B). The MRI at three months showed 82% of patients with at least 50% defect fill, 59% with a normal or nearly normal signal at repair sites, 71% with a mild or no effusion and 80% with a mild or no underlying bone-marrow oedema. These improved at 12 months to 93%, 93%, 94% and 91%, respectively. The overall MR score at 12 months suggested production of normal or nearly normal cartilage in 82%, corresponding to a subjective improvement in 81% of patients and 88% IKDC A/B scores. Second-look surgery and biopsies in 15 patients (22 lesions) showed a moderate correlation of MRI with visual scoring; 70% of biopsies showed hyaline and hyaline-like cartilage. Thus, MRI at 12 months is a reasonable non-invasive means of assessment of
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
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:
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
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
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
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.
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 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:
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:
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.
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.