Alessandro Di Martino

Platelet-riCh plasma: New clinical application A pilot study for treatment of jumper's knee

This study describes a simple, low-cost, minimally invasive way to apply PRP growth factors to chronic patellar tendinosis; 20 male athletes with a mean history of 20.7 months of pain received treatment, and outcomes were prospectively evaluated at 6 months follow-up. No severe adverse events were observed, and statistically significant improvements in all scores were recorded. The results suggest that this method may be safely used for the treatment of jumpers knee, by aiding the regeneration of tissue which otherwise has low healing potential.

Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial

BackgroundPlatelet Rich Plasma (PRP), a blood-derived product rich in growth factors, is a promising treatment for cartilage defects but there is still a lack of clinical evidence. The aim of this study is to show, through a randomized double blind prospective trial, the efficacy of this procedure, by comparing PRP to Hyaluronic Acid (HA) injections for the treatment of knee chondropathy or osteoarthritis (OA).Methods109 patients (55 treated with HA and 54 with PRP) were treated and evaluated at 12 months of follow-up. The patients were enrolled according to the following inclusion criteria: age> 18 years, history of chronic (at least 4 months) pain or swelling of the knee and imaging findings of degenerative changes of the joint (Kellgren-Lawrence Score up to 3). A cycle of 3 weekly injections was administered blindly. All patients were prospectively evaluated before and at 2, 6, and 12 months after the treatment by: IKDC, EQ-VAS, TEGNER, and KOOS scores. Range of motion and knee circumference changes were measured over time. Adverse events and patient satisfaction were also recorded.ResultsOnly minor adverse events were detected in some patients, such as mild pain and effusion after the injections, in particular in the PRP group, where a significantly higher post-injective pain reaction was observed (p=0.039). At the follow-up evaluations, both groups presented a clinical improvement but the comparison between the two groups showed a not statistically significant difference in all scores evaluated. A trend favorable for the PRP group was only found in patients with low grade articular degeneration (Kellgren-Lawrence score up to 2).ConclusionsResults suggest that PRP injections offer a significant clinical improvement up to one year of follow-up. However, conversely to what was shown by the current literature, for middle-aged patients with moderate signs of OA, PRP results were not better than those obtained with HA injections, and thus it should not be considered as first line treatment. More promising results are shown for its use in low grade degeneration, but they still have to be confirmed.

Novel Nano-composite Multilayered Biomaterial for Osteochondral Regeneration A Pilot Clinical Trial

Background: In recent years, there has been an increasing interest in and awareness of the importance of subchondral bone, for its role in the pathogenesis of articular surface damage and for the care that should be taken when treating such damage. Purpose: The objective of this pilot clinical study was to test the safety and performance of a newly developed type I collagen-hydroxyapatite nanostructured biomimetic osteochondral scaffold that aims to regenerate cartilage and subchondral bone. Study Design: Case series; Level of evidence, 4. Methods: A multilayer gradient nano-composite scaffold was obtained by nucleating collagen type I fibrils with hydroxyapatite nanoparticles. Thirty patients (9 female, 21 male; mean age, 29.3 years) with knee chondral or osteochondral lesions were treated with scaffold implantation. Lesion size varied from 1.5 cm2 to 6.0 cm2. Twenty-eight patients were followed for 2 years and were clinically evaluated using the International Knee Documentation Committee and Tegner scores. At final follow-up, magnetic resonance imaging evaluation was performed in 24 patients, and they were evaluated with the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score. Results: The Tegner and International Knee Documentation Committee objective and subjective scores improved significantly from the baseline evaluation to the 6-, 12-, and 24-month follow-ups. Further analysis showed a slower recovery but the same results for patients who presented with adverse events, for older patients, for patients who underwent previous surgery, and for those with patellar lesions. In contrast, a faster recovery was observed in active patients. At magnetic resonance imaging evaluation, complete filling of the cartilage and complete integration of the graft was shown in 70% of the lesions. However, the subchondral lamina and bone were considered intact in a minority of cases (7% and 47%, respectively). Conclusion: This open 1-step procedure was used for the treatment of chondral and osteochondral knee defects. The present pilot study highlighted the safety and potential clinical benefit of the graded biomimetic osteochondral scaffold in promoting bone and cartilage tissue restoration by itself and with good clinical and magnetic resonance imaging results at the 2-year follow-up.

Platelet-rich plasma (PRP) to treat sports injuries: evidence to support its use

Tissue repair in musculoskeletal lesions is often a slow and sometimes incomplete process. In sports patients or professional athletes, the impact of musculoskeletal lesions on life and work is great, and the fast recovery of full efficiency and return to competition is of primary importance. The clinical improvement offered by available treatments is not always sufficient for highly demanding patients to return to their previous level of activity. The search for a minimally invasive solution to improve the status of the chondral surface of the injured joint is therefore highly desirable, especially in these patients. Platelet-rich plasma (PRP) is a procedure that allows to obtain a natural concentration of autologous growth factors. The attractive possibility to use the patients’ own growth factors to enhance reparative process in tissues with low healing potential, the promising preliminary clinical findings and the safety of these methods, explain the wide application of this biological approach. The aim of this review is to analyse the existing published studies to look for scientific evidence in preclinical studies or in the results obtained through PRP application in humans that supports the efficacy of PRP and its use for the treatment of tendinous, ligamentous, cartilaginous and muscular injuries. The analysis of the literature shows promising preclinical results but contradictory clinical findings for the treatment of sport injuries. High-quality studies are required to confirm these preliminary results and provide scientific evidence to support its use.

Arthroscopic Second-Generation Autologous Chondrocyte Implantation: A Prospective 7-Year Follow-up Study

Background: Regenerative techniques, such as autologous chondrocyte implantation (ACI), have emerged as a potential therapeutic option for the treatment of chondral lesions, aiming to recreate a hyaline-like tissue in the damaged articular surface. The clinical application of the regenerative approach is well documented for different types of scaffold but mostly with an evaluation of the clinical outcome at short-term follow-up. Purpose: This study was conducted to analyze the clinical outcome obtained with arthroscopic second-generation ACI up to 7 years’ follow-up, to assess the durability of the results, and understand its real potential over time. Study Design: Case series; Level of evidence, 4. Methods: Sixty-two consecutive patients, 48 men and 14 women with a mean age of 28.1 ± 11.4 years, affected by chondral lesions of the femoral condyles were enrolled and treated with arthroscopic implantation of the bioengineered tissue Hyalograft C. The average size of the defects was 2.5 ± 1.0 cm2. Patients were evaluated with International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner scores every year for 7 years, and a magnetic resonance imaging evaluation was performed. Results: A statistically significant improvement was observed in all scores from the basal evaluation to the 84 months’ follow-up. The IKDC subjective score increased from 39.6 ± 15.0 to 73.6 ± 18.8 at 12 months; a further slight improvement was observed at 24 months’ follow-up (76.5 ± 20.7), and then the results were stable and reached a final 7-year value of 77.3 ± 21.5. Seven cases (11%) failed. A better outcome was obtained in young active men, whereas the worst results were found in degenerative lesions or when previous surgery had been performed. Postoperative magnetic resonance imaging studies in 42 cases revealed a complete filling of the cartilage defect in 57% of the lesions, complete integration of the graft in 62% of cases, intact repair tissue surface in 50%, homogeneous repair tissue structure in 43%, and a graft signal-intensity score that was isointense with the adjacent native cartilage in 43% and 48% of the cases in dual T2–fast spin echo and 3-dimensional gradient echo with fat suppression sequences, respectively. Conclusion: The analysis of this group of homogeneous patients, prospectively evaluated every year for 7 years, shows that this bioengineered approach with the proper indications may offer good and stable clinical results over time.

Scaffold-Based Repair for Cartilage Healing: A Systematic Review and Technical Note

PURPOSE The aim of this systematic review was to address the treatment of chondral and osteochondral knee lesions through the use of scaffolds, by showing surgical options and results of this scaffold-based repair approach for the healing of the articular surface. METHODS All studies published in English addressing cartilage scaffold-based treatment were identified, including those that fulfilled the following criteria: (1) Levels I to IV evidence addressing the outlined areas of interest, (2) measures of functional or clinical outcome, (3) knee cartilage lesions, and (4) minimum of 2 years of follow-up. RESULTS The analysis showed a progressively increasing number of articles per year from 1995 to February 2012. The number of selected articles was 51, with 40 focusing on 2-step procedures and 11 focusing on 1-step procedures. The evaluation of evidence level showed 3 randomized studies, 10 comparative studies, 33 case series, and 5 case reports. CONCLUSIONS Regenerative scaffold-based procedures are emerging as a therapeutic option for the treatment of chondral lesions, but well-designed studies are lacking. Systematic long-term evaluation of these techniques and randomized studies are necessary to confirm the potential of this treatment approach, especially compared with the available traditional treatments. Different 1-step scaffold-based strategies are emerging to simplify the procedure and reduce costs. LEVEL OF EVIDENCE Level IV, systematic review of Level I to IV studies.

Platelet-Rich Plasma Intra-articular Knee Injections Show No Superiority Versus Viscosupplementation A Randomized Controlled Trial

Background: Osteoarthritis (OA) is a common disease that will affect almost half the population at some point in their lives through pain and decreased functional capacity. New nonoperative options are being proposed to treat earlier stages of joint degeneration to provide symptomatic relief and delay surgical intervention. Purpose: To evaluate the benefit provided by platelet-rich plasma (PRP) injections to treat knee joint degeneration in comparison with hyaluronic acid (HA), the most common injective treatment currently adopted for this condition. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 443 patients were screened, and 192 of them were enrolled in the study according to the following inclusion criteria: (1) unilateral symptomatic knee with history of chronic pain (at least 4 months) or swelling and (2) imaging findings of degenerative changes (Kellgren-Lawrence score of 0-3 at radiographs or MRI evidence of degenerative chondropathy). Patients underwent 3 weekly intra-articular injections of either PRP or HA. Patients were prospectively evaluated at baseline and then at 2, 6, and 12 months of follow-up using the International Knee Documentation Committee (IKDC) subjective score (main outcome), Knee injury and Osteoarthritis Outcome Score, EuroQol visual analog scale, and Tegner score. Range of motion, transpatellar circumference, patient satisfaction, and adverse events were also recorded. Results: Two patients reported severe pain and swelling after HA injections, while no major adverse events were noted in the PRP group. However, PRP presented overall significantly more postinjection swelling and pain. Both treatments proved to be effective in improving knee functional status and reducing symptoms: the IKDC score in the PRP group rose from 52.4 ± 14.1 to 66.2 ± 16.7 at 12 months (P < .0005), and in the HA group it rose from 49.6 ± 13.0 to 64.2 ± 18.0 at 12 months (P < .0005). A similar trend was observed for all the clinical scores used. The comparative analysis of the 2 treatments showed no significant intergroup difference at any follow-up evaluation in any of the clinical scores adopted. Conclusion: PRP does not provide a superior clinical improvement with respect to HA, and therefore it should not be preferred to viscosupplementation as injective treatment of patients affected by knee cartilage degeneration and OA.

Osteochondral tissue engineering approaches for articular cartilage and subchondral bone regeneration

PurposeOsteochondral defects (i.e., defects which affect both the articular cartilage and underlying subchondral bone) are often associated with mechanical instability of the joint and therefore with the risk of inducing osteoarthritic degenerative changes. This review addresses the current surgical treatments and most promising tissue engineering approaches for articular cartilage and subchondral bone regeneration.MethodsThe capability to repair osteochondral or bone defects remains a challenging goal for surgeons and researchers. So far, most clinical approaches have been shown to have limited capacity to treat severe lesions. Current surgical repair strategies vary according to the nature and size of the lesion and the preference of the operating surgeon. Tissue engineering has emerged as a promising alternative strategy that essentially develops viable substitutes capable of repairing or regenerating the functions of damaged tissue.ResultsAn overview of novel and most promising osteochondroconductive scaffolds, osteochondroinductive signals, osteochondrogenic precursor cells, and scaffold fixation approaches are presented addressing advantages, drawbacks, and future prospectives for osteochondral regenerative medicine.ConclusionTissue engineering has emerged as an excellent approach for the repair and regeneration of damaged tissue, with the potential to circumvent all the limitations of autologous and allogeneic tissue repair.Level of evidenceSystematic review, Level III.

Second-Generation Autologous Chondrocyte Implantation: Results in Patients Older Than 40 Years

Background Aging is responsible for degenerative changes in all cartilage elements, thus impairing its properties and healing potential. Most studies on surgical procedures for cartilage focus on young patients because these procedures are generally not considered suitable for older patients. Purpose To analyze the clinical outcome of cartilage lesion treatment using second-generation autologous chondrocyte implantation (ACI) techniques in patients more than 40 years old with no clear signs of osteoarthritis, to understand their real potential in relation to aging, the failure rate, and complications in older patients. Study Design Case series; Level of evidence, 4. Methods Sixty-one patients with grade III to IV cartilaginous lesions of the condyles with no clear signs of osteoarthritis and a minimum age of 40 years were treated with second-generation ACI and prospectively evaluated at 5 years’ follow-up. Twenty-two patients were treated with arthroscopic Hyalograft C implantation, and 39 underwent the open Chondro-Gide MACI procedure. Results A significant improvement in both subjective and objective evaluations was observed. The International Knee Documentation Committee (IKDC) subjective score improved from 36.8 ± 8.4 to 68.1 ± 21.8 at the final evaluation. The failure rate was 20%. A faster improvement was observed in the group treated with the arthroscopic Hyalograft C technique, whereas similar scores were found at the 24-month follow-up and final evaluation. Conclusion A clinical improvement was found in patients more than 40 years old, who in most cases benefited from second-generation ACI with good results lasting at medium-term follow-up. However, the results were inferior with respect to those previously found for younger populations, and the failure rate at medium-term follow-up was also higher. These findings were consistent in the 2 treatment groups. The only difference was the faster recovery when the arthroscopic approach was used.

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.