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Nakamura N.,Osaka University | Hui J.,National University of Singapore | Koizumi K.,Osaka University | Yasui Y.,Osaka University | And 4 more authors.
Operative Techniques in Orthopaedics | Year: 2014

In order to overcome potential problems associated with autologous chondrocyte implantation, mesenchymal stem cell-based therapies could be potential alternatives. Conventional stem cell-based therapy accompanies the separation of cells from tissue followed by monolayer culture for the expansion of cell numbers. On the other hand, the cost of cell culture under quality control is high, which could be a potential barrier for industrialization. In order to reduce the cost associated cell culture, culture-free cell-based therapies have been investigated with the use of bone marrow aspirate. In this chapter, we will introduce the three stem cell-based therapies in cartilage repair. The first two procedures are using cell culture methods and the last one with cell-free method. All the three methods have been into the stage of clinical trials and their surgical procedures as well as their preliminary results will be reported. © 2014 Elsevier Inc.


Zaslav K.,Advanced Orthopedic Technologies | McAdams T.,Stanford University | Scopp J.,Peninsula Orthopedic Associates | Theosadakis J.,University of Arizona | And 2 more authors.
Cartilage | Year: 2012

Objective: Articular cartilage injury is common after athletic injury and remains a difficult treatment conundrum both for the surgeon and athlete. Although recent treatments for damage to articular cartilage have been successful in alleviating symptoms, more durable and complete, long-term articular surface restoration remains the unattained goal. In this article, we look at both new ways to prevent damage to articular surfaces as well as new techniques to recreate biomechanically sound and biochemically true articular surfaces once an athlete injures this surface. This goal should include reproducing hyaline cartilage with a well-integrated and flexible subchondral base and the normal zonal variability in the articular matrix. Results: A number of nonoperative interventions have shown early promise in mitigating cartilage symptoms and in preclinical studies have shown evidence of chondroprotection. These include the use of glucosamine, chondroitin, and other neutraceuticals, viscosupplementation with hyaluronic acid, platelet-rich plasma, and pulsed electromagnetic fields. Newer surgical techniques, some already in clinical study, and others on the horizon offer opportunities to improve the surgical restoration of the hyaline matrix often disrupted in athletic injury. These include new scaffolds, single-stage cell techniques, the use of mesenchymal stem cells, and gene therapy. Conclusion: Although many of these treatments are in the preclinical and early clinical study phase, they offer the promise of better options to mitigate the sequelae of athletically induced cartilage. © SAGE Publications 2012.


PubMed | Stanford University, OASI Bioresearch Foundation, Peninsula Orthopedic Associates, University of Arizona and Advanced Orthopedic Technologies
Type: Journal Article | Journal: Cartilage | Year: 2015

Articular cartilage injury is common after athletic injury and remains a difficult treatment conundrum both for the surgeon and athlete. Although recent treatments for damage to articular cartilage have been successful in alleviating symptoms, more durable and complete, long-term articular surface restoration remains the unattained goal. In this article, we look at both new ways to prevent damage to articular surfaces as well as new techniques to recreate biomechanically sound and biochemically true articular surfaces once an athlete injures this surface. This goal should include reproducing hyaline cartilage with a well-integrated and flexible subchondral base and the normal zonal variability in the articular matrix.A number of nonoperative interventions have shown early promise in mitigating cartilage symptoms and in preclinical studies have shown evidence of chondroprotection. These include the use of glucosamine, chondroitin, and other neutraceuticals, viscosupplementation with hyaluronic acid, platelet-rich plasma, and pulsed electromagnetic fields. Newer surgical techniques, some already in clinical study, and others on the horizon offer opportunities to improve the surgical restoration of the hyaline matrix often disrupted in athletic injury. These include new scaffolds, single-stage cell techniques, the use of mesenchymal stem cells, and gene therapy.Although many of these treatments are in the preclinical and early clinical study phase, they offer the promise of better options to mitigate the sequelae of athletically induced cartilage.


PubMed | San Raffaele Hospital, OASI Bioresearch Foundation, Instituto Ortopedico Rizzoli and University of Insubria
Type: Journal Article | Journal: Cartilage | Year: 2016

The aim of this study was to compare the effectiveness of 2 different meniscal scaffolds in treating patients with irreparable partial medial meniscal tear and patients complaining of pain in the medial compartment of the knee due to a previous partial medial meniscectomy. Based on previous studies, we hypothesized that both the scaffolds are effective in improving clinical outcomes in these patient populations.Twenty-eight patients underwent collagen-based medial meniscus implantation (CMI-Menaflex) and 25 with a second-generation scaffold (Actifit). All patients were assessed with Lysholm, Tegner scale, and MRI evaluation-preoperatively, at 6 months, at 12 moths, and followed-up for a minimum of 2 years. Second look arthroscopy and concomitant biopsy were performed in 7 and 12 patients of CMI and Actifit groups, respectively.The CMI group at final follow-up showed improvement in Lysholm score from 58.4 17.3 to 94.5 6.0, while the Actifit group showed improvement from 67.0 15.7 to 90.3 13.1; the improvement was statistically significant in both the groups but intergroup difference was not statistically significant (P = 0.1061). Tegner Activity Scale score improved in both the groups, but intergroup difference was not statistically significant (P = 0.5918). MRI evaluation showed in situ scaffold and no progression of degenerative arthritis in both the groups at final follow-up. Histological evaluation showed more fibrous tissue with blood vessels in the CMI group and the Actift group showed avascular cartilaginous features.Both the scaffolds are effective in improving patients symptoms and joint function at short-term follow-up.


Gobbi A.,Oasi Bioresearch Foundation | Lad D.,Oasi Bioresearch Foundation | Petrera M.,Oasi Bioresearch Foundation | Karnatzikos G.,Oasi Bioresearch Foundation
Cartilage | Year: 2014

Objective: In vitro and in vivo studies have proven a pro-anabolic and anti-catabolic activity within cartilage with the use of pulsed electromagnetic fields (PEMFs). This has piqued interest of sports physicians for its use in the treatment of early osteoarthritis (OA). The aim was to determine if the use of PEMFs in patients with early OA of the knee would lead to an improved clinical outcome. Study design: Prospective case series. Methods: Twenty-two patients aged between 30 and 60 years who underwent treatment with PEMFs (4-hour treatment per day, duration 45 days) were included. All patients presented with symptomatic early OA with grade 0-2 changes (Kellgren-Lawrence classification) at the pretreatment evaluation. Patients were evaluated before treatment, at 1- and 2-year follow-up using visual analogue scale for pain, International Knee Documentation Committee objective, Tegner, and Knee Injury and Osteoarthritis Outcome Scores. Results: A significant improvement in all scores was observed at 1-year follow-up (P = 0.008). At 2-year follow-up, results deteriorated but were still superior to pretreatment levels (P = 0.02). No adverse reactions or side effects were seen. Conclusions: This study showed that the use of PEMFs in patients with symptomatic early OA of the knee led to significant improvement in symptoms, knee function, and activity at 1-year follow-up. There was a significant decline in all the scores at 2-year follow-up. © The Author(s) 2013.


Gobbi A.,Oasi Bioresearch Foundation | Lad D.,Oasi Bioresearch Foundation | Karnatzikos G.,Oasi Bioresearch Foundation
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2015

Purpose: To assess the outcome of intra-articular platelet-rich plasma (PRP) injections into the knee in patients with early stages of osteoarthritis (OA) and to determine whether cyclical dosing would affect the end result. Methods: This is a prospective, randomized study in which 93 patients (119 knees) were followed up for a minimum of 2 years. Fifty knees were randomly selected prior to the first injection, to receive a second cycle at the completion of 1 year. A cycle consisted of three injections, each given at a monthly interval. The outcome was assessed using Knee Injury and Osteoarthritis Outcome Score (KOOS), Visual Analogue Scale (VAS), Tegner and Marx scoring systems, recorded prior to the first injection and then at 12, 18 and 24 months. Results: There was a significant improvement in all scores over time compared to the pre-treatment value (p < 0.001). At 12 months, both groups showed similar and significant improvement. At 18 months, except for KOOS (Symptoms) and Tegner score, all other parameters showed a significant difference between the two groups in favour of the patients who had received the second cycle (p < 0.001). At 2 years, the scores declined in both groups but remained above the pre-treatment value with no significant difference between the groups despite the patients with two cycles showing higher mean values for all the scores. Conclusion: Intra-articular PRP injections into the knee for symptomatic early stages of OA are a valid treatment option. There is a significant reduction in pain and improvement in function after 12 months, which can be further improved at 18 months by annual repetition of the treatment. Although the beneficial effects are ill sustained at 2 years, the results are encouraging when compared to the pre-treatment function. Level of evidence: II. © 2014, Springer-Verlag Berlin Heidelberg.


Gobbi A.,Oasi Bioresearch Foundation | Chaurasia S.,Oasi Bioresearch Foundation | Karnatzikos G.,Oasi Bioresearch Foundation | Nakamura N.,Health Science University
Cartilage | Year: 2015

Objective. To compare the outcome of matrix-induced autologous chondrocyte implantation (MACI) and bone marrow aspirate concentrate (BMAC)–derived multipotent stem cells (MSCs) implantation in patellofemoral chondral lesions, using the same HYAFF11 scaffold. Methods. From January 2005 to December 2010, 37 patients with patellofemoral chondral lesions were prospectively followed up, for a minimum of 3 years; 19 of these patients were treated with MACI and 18 with BMAC. Radiographs, magnetic resonance imaging, and clinical scores (International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, visual analog scale, and Tegner) were collected preoperatively, at 2-year and final follow-up. Five patients of MACI and 6 of the BMAC group underwent second-look arthroscopy; 4 patients of each group consented to a concomitant biopsy. Results. No adverse reactions or postoperative infections were noted. Baseline characteristics were similar in both groups (P > 0.05). Both groups showed significant improvement in all scores, from preoperative to final follow-up (P = 0.001), but there was no significant difference in improvement between the 2 groups, except for the IKDC subjective score (P = 0.015), which favored the BMAC group. Deterioration in MACI and improvement in BMAC group scores were noticed, from 2-year to final follow-up, but was nonsignificant. MACI patients with trochlear lesions showed better results than patellar lesions, while location was not a prognostic factor in the BMAC group. MRI showed complete filling of the defects in 76% of patients in MACI and 81% of patients in BMAC, and histological analysis revealed hyaline-like features. Conclusion. Both techniques are viable and effective for large patellofemoral chondral lesions at minimum 3-year follow-up. © The Author(s) 2014


PubMed | Health Science University and Oasi Bioresearch Foundation
Type: Journal Article | Journal: Cartilage | Year: 2015

To compare the outcome of matrix-induced autologous chondrocyte implantation (MACI) and bone marrow aspirate concentrate (BMAC)-derived multipotent stem cells (MSCs) implantation in patellofemoral chondral lesions, using the same HYAFF11 scaffold.From January 2005 to December 2010, 37 patients with patellofemoral chondral lesions were prospectively followed up, for a minimum of 3 years; 19 of these patients were treated with MACI and 18 with BMAC. Radiographs, magnetic resonance imaging, and clinical scores (International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, visual analog scale, and Tegner) were collected preoperatively, at 2-year and final follow-up. Five patients of MACI and 6 of the BMAC group underwent second-look arthroscopy; 4 patients of each group consented to a concomitant biopsy.No adverse reactions or postoperative infections were noted. Baseline characteristics were similar in both groups (P > 0.05). Both groups showed significant improvement in all scores, from preoperative to final follow-up (P = 0.001), but there was no significant difference in improvement between the 2 groups, except for the IKDC subjective score (P = 0.015), which favored the BMAC group. Deterioration in MACI and improvement in BMAC group scores were noticed, from 2-year to final follow-up, but was nonsignificant. MACI patients with trochlear lesions showed better results than patellar lesions, while location was not a prognostic factor in the BMAC group. MRI showed complete filling of the defects in 76% of patients in MACI and 81% of patients in BMAC, and histological analysis revealed hyaline-like features.Both techniques are viable and effective for large patellofemoral chondral lesions at minimum 3-year follow-up.


PubMed | Oasi Bioresearch Foundation
Type: Journal Article | Journal: Cartilage | Year: 2015

In vitro and in vivo studies have proven a pro-anabolic and anti-catabolic activity within cartilage with the use of pulsed electromagnetic fields (PEMFs). This has piqued interest of sports physicians for its use in the treatment of early osteoarthritis (OA). The aim was to determine if the use of PEMFs in patients with early OA of the knee would lead to an improved clinical outcome.Prospective case series.Twenty-two patients aged between 30 and 60 years who underwent treatment with PEMFs (4-hour treatment per day, duration 45 days) were included. All patients presented with symptomatic early OA with grade 0-2 changes (Kellgren-Lawrence classification) at the pretreatment evaluation. Patients were evaluated before treatment, at 1- and 2-year follow-up using visual analogue scale for pain, International Knee Documentation Committee objective, Tegner, and Knee Injury and Osteoarthritis Outcome Scores.A significant improvement in all scores was observed at 1-year follow-up (P = 0.008). At 2-year follow-up, results deteriorated but were still superior to pretreatment levels (P = 0.02). No adverse reactions or side effects were seen.This study showed that the use of PEMFs in patients with symptomatic early OA of the knee led to significant improvement in symptoms, knee function, and activity at 1-year follow-up. There was a significant decline in all the scores at 2-year follow-up.


PubMed | Oasi Bioresearch Foundation
Type: Journal Article | Journal: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA | Year: 2015

To assess the outcome of intra-articular platelet-rich plasma (PRP) injections into the knee in patients with early stages of osteoarthritis (OA) and to determine whether cyclical dosing would affect the end result.This is a prospective, randomized study in which 93 patients (119 knees) were followed up for a minimum of 2years. Fifty knees were randomly selected prior to the first injection, to receive a second cycle at the completion of 1year. A cycle consisted of three injections, each given at a monthly interval. The outcome was assessed using Knee Injury and Osteoarthritis Outcome Score (KOOS), Visual Analogue Scale (VAS), Tegner and Marx scoring systems, recorded prior to the first injection and then at 12, 18 and 24months.There was a significant improvement in all scores over time compared to the pre-treatment value (p<0.001). At 12months, both groups showed similar and significant improvement. At 18months, except for KOOS (Symptoms) and Tegner score, all other parameters showed a significant difference between the two groups in favour of the patients who had received the second cycle (p<0.001). At 2years, the scores declined in both groups but remained above the pre-treatment value with no significant difference between the groups despite the patients with two cycles showing higher mean values for all the scores.Intra-articular PRP injections into the knee for symptomatic early stages of OA are a valid treatment option. There is a significant reduction in pain and improvement in function after 12months, which can be further improved at 18months by annual repetition of the treatment. Although the beneficial effects are ill sustained at 2years, the results are encouraging when compared to the pre-treatment function.II.

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