Asode Ananthram Shetty

Novel repair technique for articular cartilage defect using a fibrin and hyaluronic acid mixture

We evaluated the cartilage repair potential of a hyaluronic acid and fibrin mixture when transplanted into cartilage defects. Circular, articular, cartilage defects 4-mm in diameter were made in the trochlear region in 21 New Zealand white rabbits divided into three groups. The seven rabbits in the control group underwent microfracture (M group), the seven rabbits in the experimental group underwent microfracture with subsequent injection of hyaluronic acid mixed with fibrin (MH group), and seven rabbits in the other experimental group underwent microfracture followed by injection of bone marrow concentrate and hyaluronic acid mixed with fibrin (MBH group). At week 12 following surgery, the cartilage was observed and histologically compared in the three groups. The surface of the newly generated cartilage was very smooth and even, and we noticed that the entire area was completely regenerated in both experimental groups. The control group showed incomplete and irregular cartilage formation in the defect. In histologic scoring, comparison of the MBH group (M= 2.333) and the M group (M= 9.000) differed significantly (P= 0.046). Therefore, injection of a mixture of bone marrow concentrate, hyaluronic acid and fibrin to treat articular cartilage defects of the knee appears to be an effective method of cartilage regeneration.

Autologous bone-marrow mesenchymal cell induced chondrogenesis: Single-stage arthroscopic cartilage repair

We describe a single stage arthroscopic procedure for the treatment of articular cartilage defects in the knee. The novel procedure involves microfracture and application of bone marrow aspirate concentrate cells (BMAC) with hyaluronic acid and fibrin gel. The aim of the study was to evaluate the clinical and radiological outcomes at 2 years. A prospective study of 30 patients with symptomatic ICRS grade III/IV chondral defects, ranging from 2–9 cm2, who were assessed clinically and radiologically. The surgical procedure involved debridement of the lesion, microfracture and application of concentrated BMAC with HA and fibrin gel under CO2 insufflation. Patients underwent morphological MRI, quantitative T2*-mapping and d-GEMRIC scan. Clinical assessment used the Lysholm, IKDC and KOOS scores. Radiological assessment used the MOCART score. At 2 year follow-up, Lysholm score was 80.1, as compared to 50.8 pre-operatively (p < 0.05). KOOS (symptomatic) was 92.1, as compared to 65.7 pre-operatively. IKDC (subjective) was 83, up from 39 preoperatively. The mean T2* relaxation-times for the repair tissue and native cartilage were 29.1 and 29.9 respectively. Average MOCART score for all lesions was 72. Our technique shows encouraging clinical results at 2 year follow-up. Clinical outcome scores show significant benefit. The morphological MRI shows good cartilage defect filling and the biochemical MRI (T2*-mapping) suggests hyaline like repair tissue.

Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC)

Degenerative and traumatic articular cartilage defects are common, difficult to treat, and progressive lesions that cause significant morbidity in the general population. There have been multiple approaches to treat such lesions, including arthroscopic debridement, microfracture, multiple drilling, osteochondral transplantation and autologous chondrocyte implantation (ACI) that are currently being used in clinical practice. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) is a single-staged arthroscopic procedure. This method combines a modified microfracture technique with the application of a bone marrow aspirate concentrate (BMAC), hyaluronic acid and fibrin gel to treat articular cartilage defects. We reviewed the current literatures and surgical techniques for mesenchymal cell induced chondrogenesis.

The effect of platelet rich plasma combined with microfracture for the treatment of chondral defect in a rabbit knee

Recently, many clinical studies have been published regarding platelet-rich plasma (PRP) injection for early degenerative joint disease. We evaluated the cartilage repair potential of platelet-rich plasma when injected into the knee joint. Articular, cartilage defects 4 mm in diameter and circular in shape were made in the trochlear region of 20 knees in 10 New Zealand white rabbits who were divided into two groups. The left knees in the control group underwent microfracture, and the right knees in the experimental group underwent microfracture with subsequent injection of platelet-rich plasma. At week 12 following the surgery, the cartilage was observed macroscopically and histologically compared in the two groups. The control group showed incomplete and irregular fibrous tissue formation in the defect. The experimental group showed nearly complete defect coverage with neo-cartilage. In the histologic scoring, comparison of the control group and the experimental group differed significantly (p < 0.05).Therefore, injection of platelet-rich plasma used to treat articular cartilage defects of the knee appears to have some effect for cartilage regeneration.

Comparison between total knee arthroplasty and MCIC (autologous bone marrow mesenchymal-cell-induced-chondrogenesis) for the treatment of osteoarthritis of the knee

Total knee arthroplasty (TKA) is the gold standard of treatment for advanced osteoarthritis of the knee. The technical methods of cartilage regeneration procedures are now well-developed. Indications for this procedure are being expanded to the treatment of osteoarthritis. We compared data from 42 patients who underwent TKA and from 52 patients who underwent MCIC (autologous bone marrow mesenchymal-cell-induced-chondrogenesis). All patients were over 50 years of age and showed grade IV of the Kellgren-Lawrence classification. The TKA patients were older and predominantly female, compared to the MCIC patients. There was no difference between the two groups regarding the patient satisfaction. Clinical evaluation of the two groups showed significant mean improvement in the tKSS-A (pain) and tKSS-B (function) scores throughout the postoperative follow-up period. The monetary cost of TKA was relatively higher than that of MCIC. Therefore, considering the patient age and quality of life, MCIC is a potential treatment option for osteoarthritis as it thus delays the disease progression.

Treatment of osteonecrosis in the knee joint of a rabbit using autologous cultured osteoblasts

BACKGROUND [corrected] To develop a successful treatment modality for osteonecrosis, an appropriate animal model is essential. We have proposed a new osteonecrosis model that shows the total amount of necrosis and in which we observed new bone formation after transplanting autologous cultured osteoblasts. MATERIALS AND METHODS The femoral condyles of the right knees of New Zealand white rabbits were exposed after dissecting the ligaments surrounding the distal femur. After which, the metaphyseal-diaphyseal junction was cut using a saw, and the entire femoral condyle was isolated. After three liquid nitrogen treatments, the isolated femoral condyle was internally fixated to the femoral shaft using two or three Kirschner wires. Bone marrow isolated from the iliac crest was cultivated to differentiate it into osteoblasts, and the cultured cells were then injected into the necrotic bone. RESULTS Viable osteocytes with well-stained nuclei were not present in the necrotic areas at any stage of the development of the osteonecrosis model within 24 wk after osteonecrosis induction. However, new bone formation with osteocytes and blood vessels was observed in the necrotic bone 12 wk after transplanting the autologous cultured osteoblasts. CONCLUSIONS The distal femoral condyle of the rabbit is an appropriate model for demonstrating osteonecrosis and treatment evaluation owing to its easy reproducibility and treatment interpretation. Therefore, autologous cultured osteoblast treatment would seem to be a potentially successful treatment modality for osteonecrosis.

Autologous collagen induced chondrogenesis (ACIC: Shetty–Kim technique) – A matrix based acellular single stage arthroscopic cartilage repair technique

The defects of articular cartilage in the knee joint are a common degenerative disease and currently there are several established techniques to treat this problem, each with their own advantages and shortcomings. Autologous chondrocyte implantation is the current gold standard but the technique is expensive, time-consuming and most versions require two stage procedures and an arthrotomy. Autologous collagen induced chondrogenesis (ACIC) is a single-stage arthroscopic procedure and we developed. This method uses microfracture technique with atelocollagen mixed with fibrin gel to treat articular cartilage defects. We introduce this ACIC techniques and its scientific background.

Gel ACI (GACI): Articular Cartilage Repair Technique

As articular cartilage has only limited ability to regenerate, various treatment options have been developed during the past several decades to treat symptomatic articular cartilage injuries [1, 2]. Among these treatment options available, autologous chondrocyte implantation (ACI), an advanced, cell-based, biologic technology, has become a standard technique used to repair symptomatic, full-thickness, chondral injuries [2]. The traditional ACI technique involves injection of cultured autologous chondrocyte cells into the prepared cartilage defect covered by a periosteal flap. This was the first generation of ACI. However, complications such as periosteal hypertrophy and, less commonly, calcification and delamination have been encountered when periosteum is used as a cover material [3]. Furthermore, improvements in tissue engineering have resulted in a new generation of ACI techniques in which cells are combined with bioactive resorbable biomaterials such as a bilayer type I/III collagen membranes, hyaluronan polymer, and copolymers of polylactin and polyglactin [3]. However, all these techniques require open arthrotomy for the second stage of cell implantation, which has associated patient morbidity and complications [4].

A critical analysis of the paper - Single-step scaffold-based cartilage repair in the knee: A systematic review.

1. This paper failed to describe the details of criteria for inclusion and exclusion of the patients in this study. The study has excluded papers with patient sample size less than 50 which according to us is too farfetched. Many important studies get excluded and hence alter the results here. 2. The mean age group of their cases is relatively young (31–40 years). There are ample of recent publications showing that these procedures are being carried out even in older patients with cutoff up to 65 years of age. Hence, the authors did not explain the exclusion reasons for these study groups. 3. The authors have included OCD as an operative indication but have not mentioned anything about the need of additional bone grafting in some of these cases, with significant bone loss. We believe that in such cases growing cartilage on the defect is like building a ‘tower on the sand,’ which will eventually fail quickly. 4. It is not clear which single staged procedures were done by arthroscopy and by arthrotomy and what criteria were used for making this decision. This could be of relevance in the outcomes as the rehabilitation time is extended in arthrotomy cases and could also be associated with higher risk of infection. 5. A serious shortcoming of this study is short term follow-up of their patients and has serious clinical implications as it is known that cartilage takes at least 18 months to show its full growth. Moreover, no postoperative assessment of the quality of cartilage was done by imaging or arthroscopically making us suspicious about the ‘success’ of these procedures. 6. Systematic reviews and RCTs are considered excellent evidence as they stand high up in the hierarchy of evidence. But, the

Mesenchymal Stem Cell Induced Chondrogenesis (MCIC

In 1743 William Hunter [1] stated, ‘an ulcerated cartilage is a troublesome problem and once destroyed, it never repairs’. This statement holds true even today, in spite of new advances in the field of tissue engineering. Cartilage injuries are common in the knee joint and if untreated can become symptomatic and progressively lead to premature arthritis [2] (Ref Wong et al.). Galen observed and wrote about premature arthritis in athletes.