Francesco Perdisa

Clinical Results and MRI Evolution of a Nano-Composite Multilayered Biomaterial for Osteochondral Regeneration at 5 Years

Background: Several cartilage lesions involve the subchondral bone, and there is a need for biphasic scaffolds to treat the entire osteochondral unit to reproduce the different biological and functional requirements and guide the growth of the 2 tissues. Purpose: To evaluate the results of a cell-free collagen-hydroxyapatite osteochondral scaffold at midterm, and to use magnetic resonance imaging (MRI) analysis to document the imaging evolution of the tissue regeneration process through 5 years of follow-up. Study Design: Case series; Level of evidence, 4. Methods: Twenty-seven patients (9 women, 18 men; mean age, 34.9 ± 10.2 years) treated for knee chondral or osteochondral lesions (size, 1.5-6 cm2) were followed for 2 and 5 years and were clinically evaluated using the International Knee Documentation Committee (IKDC) and Tegner scores. An MRI evaluation was performed at both follow-ups in 23 lesions, and the magnetic resonance observation of cartilage repair tissue (MOCART) score and specific subchondral bone parameters (bone regeneration, bone signal quality, osteophytes or upcoming bone front, sclerotic areas, and edema) were analyzed. Results: A statistically significant improvement in all clinical scores was observed from the initial evaluation to the 2- and 5-year follow-ups, and the results were stable over time. The mean IKDC subjective score improved from 40.0 ± 15.0 to 76.5 ± 14.5 (2-year follow-up) and 77.1 ± 18.0 (5-year follow-up) and the mean Tegner score from 1.6 ± 1.1 to 4.0 ± 1.8 (2-year follow-up) and 4.1 ± 1.9 (5-year follow-up). The MRI evaluation showed a significant improvement in both the MOCART score and subchondral bone status from 2 to 5 years. At 5 years, complete filling of the cartilage was shown in 78.3% of the lesions, complete integration of the graft was detected in 69.6% of cases, the repair tissue surface was intact in 60.9%, and the structure of the repair tissue was homogeneous in 60.9% of the cases. No correlation was found between MRI findings and clinical outcome. Conclusion: This osteochondral scaffold was used for the treatment of chondral and osteochondral knee defects with a single-step procedure. The study results highlighted the safety and potential of this procedure, which offered a good clinical outcome with stable results at midterm follow-up. Although the MRI findings improved over time, some abnormalities persisted, but no correlation was found between the imaging and clinical results.

Matrix assisted autologous chondrocyte transplantation for cartilage treatment: A systematic review

Objectives 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. Methods 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. Results The literature analysis showed a progressively increasing number of articles per year. A total of 51 articles were selected: three randomised studies, ten comparative studies, 33 case series and five case reports. Several scaffolds have been developed and studied, with good results reported at short to medium follow-up. Conclusions MACT procedures are a therapeutic option for the treatment of chondral lesions that can offer a positive outcome over time for specific patient categories, but high-level studies are lacking. Systematic long-term evaluation of these techniques and randomised controlled trials are necessary to confirm the potential of this treatment approach, especially when comparing against less ambitious traditional treatments.

Stem cells in articular cartilage regeneration

BackgroundMesenchymal stem cells (MSCs) have emerged as a promising option to treat articular chondral defects and early OA stages. However, their potential and limitations for clinical use remain controversial. Thus, the aim of this systematic review was to examine MSCs treatment strategies in order to summarize the current clinical evidence for the treatment of cartilage lesions and OA. MethodsA systematic review of the literature was performed on the PubMed database using the following string: “cartilage treatment” AND “mesenchymal stem cells”. The filters included publications on the clinical use of MSCs for cartilage defects and OA in English language up to 2015. ResultsOur search identified 1639 papers: 60 were included in the analysis, with an increasing number of studies published on this topic over time. Seven were randomized, 13 comparative, 31 case series, and 9 case reports; 26 studies reported the results after injective administration, whereas 33 used surgical implantation. One study compared the 2 different modalities. With regard to the cell source, 20 studies concerned BMSCs, 17 ADSCs, 16 BMC, 5 PBSCs, 1 SDSCs, and 1 compared BMC vs PBSCs. ConclusionsThe available studies allow to draw some indications. First, no major adverse events related to the treatment or to the cell harvest have been reported. Second, a clinical benefit of using MSCs therapies has been reported in most of the studies, regardless of cell-source, indication or administration method. Third, young age, lower BMI, smaller lesion size for focal lesions and earlier stages of OA joints, have been shown to correlate with better outcomes, even though the available data strength doesn’t allow to define clear cutoff values.

Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence

Among the current therapeutic approaches for the regeneration of damaged articular cartilage, none has yet proven to offer results comparable to those of native hyaline cartilage. Recently, it has been claimed that the use of mesenchymal stem cells (MSCs) provides greater regenerative potential than differentiated cells, such as chondrocytes. Among the different kinds of MSCs available, adipose-derived mesenchymal stem cells (ADSCs) are emerging due to their abundancy and easiness to harvest. However, their mechanism of action and potential for cartilage regeneration are still under investigation, and many other aspects still need to be clarified. The aim of this systematic review is to give an overview of in vivo studies dealing with ADSCs, by summarizing the main evidence for the treatment of cartilage disease of the knee.

Clinical results of multilayered biomaterials for osteochondral regeneration

Several techniques have been used during the years to treat chondral and osteochondral lesions. Among them, the emerging trend in the field of osteochondral regeneration is to treat the entire osteochondral unit by implanting cell-free scaffolds, which provide a three-dimensional support for the cell growth and may act themselves as stimuli for an “in situ” tissue regeneration. Various multi-layered products have been proposed that mimic both the subchondral bone and the cartilaginous layer. Among these, three have currently been reported in the literature. One has been widely investigated: it is a nanocomposite three-layered collagen-hydroxyapatite scaffold, which is showing promising results clinically and by MRI even at mid-term follow-up. The second is a PLGA-calcium-sulfate bilayer scaffold: however, the literature findings are still controversial and only short-term outcomes of limited case-series have been published. The most recent one is a solid aragonite-based scaffold, which seems to give promising clinical and MRI outcomes, even if the literature is still lacking more in-depth evaluations.Even though the Literature related to this topic is quickly increasing in number, the clinical evidence it is still limited to some case series, and high-level studies are needed to better demonstrate their real effectiveness.

Arthroscopic mosaicplasty: Long-term outcome and joint degeneration progression

BACKGROUND This study aims to document the long-term results in a group of patients treated with arthroscopic mosaicplasty for knee cartilage lesions, both in terms of clinical outcome and joint degeneration progression, evaluated by radiographs. METHODS 26 patients (19 men and 7 women, mean age 29 years, mean BMI 23) treated arthroscopically with mosaicplasty for cartilage defects of the femoral condyles (mean/median/mode size 1.9 standard deviation, SD 0.6 cm(2)) were prospectively evaluated at 12 years follow-up. The clinical outcome was analyzed with IKDC and Tegner scores. Range of motion, transpatellar and suprapatellar circumferences were also measured. Radiographs with weight-bearing antero-posterior and Rosenberg projections were used for radiological evaluation in 18 patients, applying both Kellgren-Lawrence score and a direct joint line measurement to assess osteoarthritis. RESULTS A significant improvement in all clinical scores was obtained from the basal evaluation to the 12-year follow-up (IKDC subjective score from 36.8 standard deviation, SD 13.0 to 77.3 standard deviation, SD 20.6, P<0.0005; Tegner score from 2.9 standard deviation, SD 1.3 to 5.2 standard deviation, SD 2.5, P<0.0005), and better results in patients with a higher pre-injury activity level and those requiring fewer plugs. The radiographic evaluation showed significantly poorer Kellgren-Lawrence scores and a reduction of the joint line in the treated compartments. Knees with 3-4 plugs presented a significantly higher joint degeneration level with respect to those implanted with 1-2 plugs. CONCLUSIONS Mosaicplasty is an effective surgical option for small lesions of the femoral condyles. Although joint degeneration progression was present at 12 years, this did not affect significantly the clinical outcome which was satisfactory at long-term follow-up.

Tibial plateau lesions. Surface reconstruction with a biomimetic osteochondral scaffold: Results at 2 years of follow-up

INTRODUCTION Tibial plateau articular pathology caused by post-traumatic or degenerative lesions is a challenge for the orthopaedic surgeon and can lead to early osteoarthritis. The aim of the present study was to evaluate the results of treatment of these complex defects with implantation of an osteochondral scaffold, which is designed to target the cartilage surface and to reconstruct joint anatomy by addressing the entire osteochondral unit. MATERIALS AND METHODS Eleven patients (5 female and 6 male) with a mean age of 37.3 ± 11.0 years and osteochondral lesions of the tibial plateau (mean 5.1 ± 2.7 cm(2); range 3.0-12.5 cm(2)) were treated with the implantation of an osteochondral biomimetic collagen-hydroxyapatite scaffold (Maioregen(®), Fin-Ceramica, Faenza, Italy). Comorbidities were addressed taking care to restore the correct limb alignment. Patients were evaluated pre-operatively and prospectively followed-up for 2 years using the International Knee Documentation Committee (IKDC) subjective and objective scores; activity level was documented using the Tegner score. RESULTS Three patients experienced minor adverse events. No patients required further surgery for treatment failure during the study follow-up period, and 8 patients (72.7%) reported a marked improvement. The IKDC subjective score improved from 42.5 ± 10.2 before treatment to 69.8 ± 19.0 at 12 months (p<0.05), with stable results at 24 months. The IKDC objective score increased from 27.3% normal and nearly normal knees before treatment to 85.7% normal and nearly normal knees at 24 months of follow-up. The Tegner score increased from 2.3 ± 2.1 before treatment to 4.8 ± 2.4 at 12 months (p<0.05), and was stable at the final follow-up. CONCLUSION The present study on the implantation of an osteochondral scaffold for the treatment of tibial plateau lesions showed a promising clinical outcome at short-term follow-up, which indicates that this procedure can be considered as a possible treatment option, even in these complex defects, when comorbidities are concomitantly addressed.

Platelet rich plasma: a valid augmentation for cartilage scaffolds? a systematic review

It has been shown that modern regenerative scaffold-based procedures for the treatment of articular cartilage defects offer good clinical results, although the properties of native healthy cartilage have not yet been matched by any substitute. Several implants have been tested and clinically used over the years to promote articular surface restoration, some of them producing a hyaline-like reparative tissue. There has been an increase in the number of new biological strategies, alone and in combination with scaffolds, to enhance the clinical outcome in patients with chondral disease. Among these innovative methods, one of the most widely used is Platelet-rich Plasma (PRP), based on the rationale of using the growth factors contained in platelet alpha granules to promote tissue regeneration. The aim of the present manuscript is to review systematically the current evidence in pre-clinical and clinical studies for the use of PRP augmented scaffolds to treat chondral or osteochondral disorders.

Meniscal Scaffolds - Preclinical Evidence to Support their Use: A Systematic Review

Arthroscopic meniscal treatment is the most common procedure performed in the orthopedic practice. Current management of meniscal pathology relies on different therapeutic options, ranging from selective meniscectomy, suturing, and to meniscal replacement by using either allografts or scaffolds. The progresses made in the field of regenerative medicine and biomaterials allowed to develop several meniscal substitutes, some of those currently used in the clinical practice. Before reaching the clinical application, these devices necessarily undergo accurate testing in the animal model: the aim of the present manuscript is to systematically review the scientific evidence derived by animal model results for the use of meniscal scaffolds, in order to understand the current state of research in this particular field and to identify the trends at preclinical level that may influence in the near future the clinical practice. Thirty-four papers were included in the present analysis. In 12 cases the meniscal scaffolds were used with cells to further stimulate tissue regeneration. With the exception of some negative reports regarding dacron-based scaffolds, the majority of the trials highlighted that biomaterials and bio-engineered scaffolds are safe and could play a beneficial role in stimulating meniscal healing and in chondral protection. With regard to the benefits of cell augmentation, the evidence is limited to a small number of studies and no conclusive evidence is available. However, preclinical evidence seems to suggest that cells could enhance tissue regeneration with respect to the use of biomaterials alone, and further research should confirm the translational potential of cell-based approach.

One-Step Treatment for Patellar Cartilage Defects With a Cell-Free Osteochondral Scaffold: A Prospective Clinical and MRI Evaluation:

Background: The treatment of symptomatic cartilage defects of the patella is particularly challenging, and no gold standard is currently available. Purpose: To evaluate the clinical results of a biphasic cell-free collagen-hydroxyapatite scaffold and to evaluate osteochondral tissue regeneration with magnetic resonance imaging (MRI). Study Design: Case series; Level of evidence, 4. Methods: Thirty-four patients (18 men and 16 women; mean ± SD: age, 30.0 ± 10 years) were treated by scaffold implantation for knee chondral or osteochondral lesions of the patella (area, 2.1 ± 1 cm2). The clinical evaluation was performed prospectively at 12 and 24 months via the IKDC (International Knee Documentation Committee; objective and subjective) and Tegner scores. MRI evaluation was performed at both follow-ups in 18 lesions through the MOCART score (magnetic resonance observation of cartilage repair tissue) and specific subchondral bone parameters. Results: A statistically significant improvement in all the scores was observed at 12- and 24-month follow-up as compared with the basal evaluation. The IKDC subjective score improved from 39.5 ± 14.5 to 61.9 ± 14.5 at 12 months (P > .0005) with a further increase to 67.6 ± 17.4 at 24 months of follow-up (12-24 months, P = .020). The MRI evaluation showed a stable value of the MOCART score between 12 and 24 months, with a complete filling of the cartilage in 87.0% of the lesions, complete integration of the graft in 95.7%, and intact repair tissue surface in 69.6% at final follow-up. The presence of osteophytes or more extensive bony overgrowth was documented in 47.8% of the patients of this series, but no correlation was found between MRI findings and clinical outcome. Conclusion: The implantation of a cell-free collagen-hydroxyapatite osteochondral scaffold provided a clinical improvement at short-term follow-up for the treatment of patellar cartilage defects. Women had lower outcomes, and the need for realignment procedures led to a slower recovery. MRI evaluation showed some abnormal findings with the presence of bone overgrowth, but no correlation has been found with the clinical outcome.