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Objectives: Aim of this study is to analyze the clinical outcome of an osteochondral scaffold implanted into chondral and osteohondral lesions located at the patella, site that is commonly considered as one of the more difficult to treat successfully. Methods: Forty-four patients were treated by implanting a collagenhydroxyapatite osteochondral scaffold and prospectively evaluated at initial time, then at 6, 12 and 24 months of follow-up, using the IKDC Knee documentation form and the Kujala score. They were 26 male and 18 female. Mean age was 33.2 (16–59) years, mean BMI 24.0 ± 3.0. Size of the defects was 3.3 ± 3.0 cm2. Fifteen Patients were operated for the first time and 23 of them requested combined procedures due to comorbidities. Four of them had multiple lesions. Etiology was degenerative in 29 cases, 10 traumatic and 5 were OCDs. Results: A statistically significant improvement and function recovery were recorded up to 24 months. IKDC subj score increased from 39.3 ± 15.1 to 62.6 ± 18.6 and 68.9 ± 17.8 at the 1 year and final evaluation respectively (p\0.05). Tegner score increased from 1.8 ± 1.1 to 3.6 ± 1.3 at 2 years’ follow-up (p\0.05). Three patients failed, being re-operated for the same lesion. Conclusions: The use of this biomimetic cell-free scaffold for osteochondral lesions of the patella allows to obtain function recovery and a good clinical outcome at short-term follow-up, even if lower than previously reported for other site locations. These results have to be confirmed at longer follow-up to determine the possible benefit of addressing also the subchondral bone disease.

The regeneration of extended bone defects is a serious concern and the number of patients affected by bone diseases is ever increasing. The continuous progress in materials science and nanotechnology is providing novel approaches to developing new porous materials with structures that are able to mimic the morphological and mechanical features of bone, thus achieving improved assistance to the regenerative processes. This chapter provides an overview of the technologies that have recently been developed for use in manufacturing porous ceramics and composites for bone scaffolding, including the new biomorphic processes that, by transforming ligneous sources into hierarchically organized hydroxyapatite, may provide solutions to assist the regeneration of long segmental bones. © 2014 Woodhead Publishing Limited. All rights reserved.

Objectives: This prospective clinical study tested the mid-term follow- up of a one-step procedure using a cell-free biomimetic multilayered scaffold for the treatment of osteochondral lesions of the knee. Methods: 27 patients (9F, 18 M, mean age 34.9 yy) affected by symptomatic ICRS grade III-IV chondral lesions of the knee were treated. Patients were analyzed prospectively up to 72 months using the ICRS Cartilage Standard Evaluation Form, and high resolution MRI. Sites of the defects were: 7 MFC, 5 LFC, 11 patellae, 7 trochleae, and 2 lateral tibial plateaus. Five patients had multiple lesions. Defect area was 2.9 ± 1.3 cm2. Etiology was traumatic in 5 cases, microtraumatic/degenerative in 16 and OCD in 6 cases. Results: Function recovery and a significant clinical improvement were detected. Mean IKDC subjective increased from 40.0 ± 14.7 to 77.4 ± 19.6 at final evaluation, showing the significant improvement stable over time. Mean pre-injury Tegner score increased from 1.6 ± 1.1 pre-operative to 4.0 ± 1.8 at 12 months and 3.9 ± 1.8 (n.s.) at final follow-up. Despite the significant improvement (p\0.05) at 1 year, the final sport activity was lower than the preinjury level. MRI evaluation revealed a good integration of the scaffold and a satisfactory filling of the defect. Conclusions: This one-step surgery seems to be an easy and effective procedure for chondral and osteochondral lesions of the knee. Results show satisfactory outcomes even in large osteochondral lesions or complex cases. MRI improves over time but abnormal findings are still present at mid-term 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±2.7cm(2); range 3.0-12.5cm(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

Different techniques have been proposed across the years to treat osteochondral diseases: minimally invasive bone marrow stimulation techniques aimed at favoring the healing process in the injured area through the migration of stem cells from the subchondral bone; on the other side, some more aggressive techniques are based on autologous or allogenic tissue transplant. Unfortunately, both the high specialization and the low healing potential of the cartilage tissue still make the treatment of cartilage defects a challenge for the orthopedic surgeon. Bioengineered scaffolds or polymeric matrices implanted in the injured area showed promising results. The range of scaffolds in use for chondral or osteochondral repair is very wide; they differ not only with respect to the type of the materials used for their realization but also for the presence or absence of one or more cell lines – either chondrogenic or osteogenic. When approaching big chondral lesions, the subchondral bone is often involved and it also needs to be treated in order to have a correct restoration of the most superficial layers of the joint. In our opinion the smartest treatment choice could be a cell-free osteochondral scaffold, an off-the-shelf product, thus immediately available, avoiding the double surgical time. Following this rationale, after preclinical in vitro and animal studies and under the approval of the local ethics committee, we introduced the use of a newly developed nanostructured biomimetic scaffold in a clinical pilot study to treat chondral and osteochondral lesions of the knee. Its safety and manageability, as much as the surgical procedure reproducibility and the clinical outcome, have been evaluated up to 36 months’ follow-up in order to test its intrinsic potential without any cells culture aid.

PRP cryopreservation remains a controversial point. Our purpose was to investigate the effect of freezing/thawing on PRP molecule release, and its effects on the metabolism of chondrocytes and synoviocytes. PRP was prepared from 10 volunteers, and a half volume underwent one freezing/thawing cycle. IL-1β, HGF, PDGF AB/BB, TGF-β1, and VEGF were assayed 1 hour and 7 days after activation. Culture media of chondrocytes and synoviocytes were supplemented with fresh or frozen PRP, and, at 7 days, proliferation, gene expression, and secreted proteins levels were evaluated. Results showed that in the freeze-thawed PRP the immediate and delayed molecule releases were similar or slightly lower than those in fresh PRP. TGF-β1 and PDGF AB/BB concentrations were significantly reduced after freezing both at 1 hour and at 7 days, whereas HGF concentration was significantly lower in frozen PRP at 7 days. In fresh PRP IL-1βand HGF concentrations underwent a significant further increase after 7 days. Similar gene expression was found in chondrocytes cultured with both PRPs, whereas in synoviocytes HGF gene expression was higher in frozen PRP. PRP cryopreservation is a safe procedure, which sufficiently preserves PRP quality and its ability to induce proliferation and the production of ECM components in chondrocytes and synoviocytes.

Objectives: Platelet Rich Plasma (PRP) is a biological compound rich of growth factors able to support healing processes, and it represents a fascinating tool for clinicians. However results on its potentiality as intra-articular treatment for cartilage degenerative lesions in osteoarthritis (OA) are still controversial, due to the lack of well designed studies and the differences in the preparation procedures. The aim of this study was to analyze the modifications induced by two different PRP preparations on chondrocytes and sinoviocytes in culture, by documenting changes in proliferations, gene expression, and extracellular matrix components deposition. Methods: Blood collected from 10 volunteers was used to obtain two PRP preparations derived respectively from a ‘‘one-spinning procedure’’, to obtain a pure platelet concentrate without leukocytes but with a limited number of platelets (P-PRP), and by a ‘‘two-spinning approach’’, producing a product characterized by a higher platelet concentration and the presence of leukocytes (L-PRP). Results: Our data showed that L-PRP contains higher levels of growth factors and cytokines compared to P-PRP. Both PRPs stimulate chondrocytes proliferation during all the culture period evaluated; a significant enhancement in cell growth was induced by P-PRP respect to L-PRP only at day 7. Moreover, P-PRP stimulates chondrocyte anabolism as demonstrated by the expression of collagen type II and aggrecan, while L-PRP promotes catabolic pathways in which some different cytokines are involved. Interesting, L-PRP induces a higher expression of hyaluronic acid synthase-2 and hyaluronan compared to P-PRP. On sinoviocytes, L-PRP is able to sustain the up-regulation of proinflammatory factors, such as IL-1beta, IL-8 and FGF-2, together with a down modulation of HGF and TIMP-4 expression, two factors that have been recognized as anti-catabolic mediators in cartilage, whereas P-PRP was not able to exert a differential pattern of biological effect compared to PPP. Conclusions: Our study highlights that the two PRPs induce distinct effects on cultured human chondrocytes and sinoviocytes. This is due to the different content in PRP of platelets, leukocytes, growth factors and molecules that act synergically to regulate several biological processes which could influence the regeneration of a functional tissue.

Objectives: To successfully treat osteochondral defects is a real challenge for the orthopaedic surgeon, since only the formation of fibrocartilage and poor subchondral regeneration have yet been proved with the techniques currently available. Preclinical tests demonstrated that this new biomaterial (obtained by enucleating equine collagen type 1 fibrils with hydroxyapatite nanoparticles in 3 different layers with 3 different gradient ratios at physiological conditions) induced an ‘‘in situ’’ cartilage regeneration into the defect site, exploiting the self-regenerative potential due to the stem cells incoming from the bone marrow. The first pilot clinical study confirmed safety and manageability of the procedure, showing good and stable results over time on 30 patients. Methods: 99 patients (75 M, 24 F, mean age 32.9 yy) were treated for a total of 113 chondral/osteochondral lesions of the knee (36 medial femoral condyles, 25 lateral femoral condyles, 23 patellae, 23 femoral throcleas and 6 tibial plateaux). Mean size of the lesions was 3.4 ± 2.6 cm2. All patients and their clinical outcome were analyzed prospectively at 6, 12 and 24 months using the Cartilage standard Evaluation Form as proposed by ICRS. An high resolution MRI was performed and the MOCART scoring scale was used to analyze the repaired tissue. Results: A statistically significant improvement and function recovery comparing the pre-operative were recorded up to 24 months. IKDC subj score increased from 45.6 ± 16.2 to 69.9 ± 18.9 and 74 ± 18.6 at the 1 year and final evaluation respectively (p\0.05). Tegner score increased from 2.6 ± 2.0 to 4.2 ± 1.6 at 2 years’ follow-up (p\0.05). A tendency to a better clinical outcome was detected for OCD lesions. MRI evaluation confirmed the good results, showing a good filling in most of the lesions treated. Three patients failed, being re-operated for the same reason. Conclusions: The use of this biomimetic cell-free scaffold for osteochondral lesions of the knee allows to obtain function recovery and a good clinical outcome at short-time follow-up. Better results are recorded in case of OCDs. These promising results have to be proven at longer follow-up.

The subchondral bone plays a key role in the integrity and repair of the entire osteochondral unit. Its unique anatomical structure is well suited to support the articular cartilage, even providing nutrition for its basal layers. The subchondral bone becomes a problem in reconstructive cartilage surgery when violated, for example, following osteochondral fractures or in osteochondritis dissecans (OCD), thus leading to an osteochondral lesion. Such osteochondral defects are difficult to treat because the subchondral bone and the articular cartilage have very dissimilar intrinsic healing capacities (Huey et al., 2012; Hunziker, 1999; Hunziker, 2009). Recent clinical evidence also pointed to the role of subchondral bone alterations in the course of spontaneous and surgical cartilage repair. In the treatment of cartilage defects, it is imperative to establish the etiology of the subchondral bone lesion and then address the specific pathology accordingly. This chapter will focus on the subchondral bone and its relevance for reconstructive cartilage surgery. It is based on individual presentations from the Instructional Course Lecture “Subchondral bone and reason for surgery” (Table 1).

Knee injuries are among the most common clinical conditions treated everyday by orthopaedic clinicians and sport medicine doctors. A single joint can be affected by a large variety of pathology, ranging from ligament lesions to cartilage defects and many others. As a consequence, this is a field of intense basic and clinical research, and there is a growing interest in better understanding how to evaluate knee condition at the moment of injury and after conservative or surgical treatments. Therefore it has been observed a great interest over time in developing clinical scores in order to make correlations with objective findings and give the clinician a suitable instrument for the assessment of the therapy outcome. In the past years it has been observed a progressive trend from clinician-based outcome tools to patient-reported outcome measures. The necessity of assessing the knee condition in the most effective way possible is one of the peculiar aspects justifying this growing interest; moreover, it must be also considered the drastic increase in patient consciousness about health and expected outcome after therapies and lastly, the interest by health insurers to better evaluate the expense concerning knee injuries and their recovery1. These outcome evaluation instruments are patient-oriented2, strenghtening this way the importance of patient perception, which must be considered prevalent over the mere surgical result. Some studies have proved that patient satisfaction is strictly linked to outcome scores concerning subjective symptoms and function3. On the opposite side, some clinicians are not sure about the validity of this patient-reported tests, arguing that their subjective nature is a weak point, especially if compared to the more objective clinician-based findings4,5; even in this case, recent studies have proved that these clinical scores are often superior than the aforementioned clinical “objective” measures6-10. In this chapter we will discuss in detail the scores employed in clinical studies focusing on knee treatments, in order to help the orthopedic surgeon in the choice of the most accurate evaluation tool according to the specific procedure performed.

Objectives: The management of post-traumatic and degenerative osteochondral defects of the proximal tibia represents a challenge for the orthopedic surgeon. In fact, some studies reported how this kind of injuries often imply in the long term an early secondary post-traumatic osteoarthritis,which requires a total knee replacement. In this context and given the young age of patients affected by these lesions, treatments should have as main objective to restore the articular surface thus permitting a complete restoration of the joint functionality.With this aimwe treated patients affected by complex defects of the tibial plateau with an osteochondral three-layer biomimetic scaffold. Methods: 11 patients (13 lesions) enrolled between 2007 and 2010 affected by post-traumatic osteochondral lesion of the tibial plateau and treated with the implantation of an osteochondral three-layer biomimetic scaffold. Patients were evaluated clinically up to 24 months of follow-up by the International Documentation Committee (IKDC) scores and Tegner score Results: A statistically significant improvement of all clinical scores was obtained from basal evaluation to the final evaluation at 24 months. The subjective IKDC improved from 42.5 ± 10.2 at basal evaluation to 68.4 ± 17.0 at 24 months of follow-up. Tegner score improves from 2.3 ± 2.1 pre-operative to 4.4 ± 1.9 at 24 months of follow-up. Three patients referred postoperative fever and swelling, that resolved within 1 month after surgery. Conclusions: Encouraging results have been registered in the present study, with a significant improvement of symptoms and functionality at short term follow-up, thus delaying the need of joint replacement for these complex patients.

Chondral lesions are a challenging problem for the orthopaedic surgeon, and regenerative techniques have been widely studied in this field as ambitious solutions to restore the articular surface. Even though the clinical efficacy of autologous chondrocyte implantation (ACI) has been well demonstrated in the literature long-term follow-up, this technique presents some biological and surgical drawbacks. Second-generation ACI procedures have been developed to address these shortcomings. Different types of scaffolds have been applied clinically in numerous studies with promising results, but well-designed studies with long-term evaluation are still lacking. The versatility of the second-generation ACI approach has been shown by several studies that have successfully applied this procedure not only in the management of cartilage damage in young, active patients, but also in patients with OCD, patients over 40 years old, or in cases of degenerative lesions. However, besides overall good results, its superiority with respect to other surgical approaches is still controversial. Further studies are necessary to support the potential of second-generation ACI and to define better the correct indications for those patients who can have a real benefit from this regenerative treatment.

The modern regenerative procedures demonstrated to offer the replacement of the articular surface with a hyaline-like tissue, but the properties of healthy cartilage tissue are still unmatched by any available substitute. Moreover, the treatment of osteochondral lesions is even more biologically challenging since two different tissues are involved (bone and articular cartilage) with a distinctly different intrinsic healing capacity. For the repair of the entire osteochondral unit, several authors have highlighted the need for biphasic scaffolds, to reproduce the different biological and functional requirements for guiding the growht of the two tissues, and different specific scaffolds have been developed for the treatment of large chondral or osteochondral articular defects. At the time being, among these only two scaffols used for osteochondral regeneration are commercialized for clinical application. One is a bilayer porous PLGA-calcium-sulphate biopolymer. The second osteochondral scaffold is a nanostructured biomimetic HA-collagen scaffold with a porous 3-D tri-layer composite structure, mimicking the whole osteochonfral anatomy. Other osteochondral scaffolds are still under preclinical investigation. In this chapter we focus on reviewing the available evidence on the clinical outcome of these osteochondral scaffolds, as well as on reporting the new biomaterials developed and tested in preclinical studies that show to be promising for osteochondral regeneration.

Background:Young patients with osteoarthritic knees are a challenging population because of a combination of high functional demands and limited indication for joint replacement.Purpose:To analyze the potential of the cartilage regenerative approach by documenting the results and failures of matrix-assisted autologous chondrocyte transplantation (MACT) at midterm follow-up.Study Design:Case series; Level of evidence, 4.Methods:Forty-four patients affected by cartilage lesions in osteoarthritic knees underwent MACT as a salvage procedure. The mean age at surgery was 42 years (range, 20-58 years), and the average defect size was 4 cm2(range, 1.5-9 cm2). Patients were prospectively evaluated with the subjective International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner scores preoperatively; at 1, 2, and 5 years; and at a final assessment at 9 years’ mean follow-up. Adverse events and failures were also reported.Results:A statistically significant improvement was observed in all scores from the initial evaluation to the final follow-up. The mean ± standard deviation IKDC subjective score improved from 38.0 ± 15.8 to 67.0 ± 18.3 at 2 years ( P < .0005), with a subsequent decrease to 57.8 ± 20.6 at the final follow-up ( P = .012). The same trend was confirmed by the EQ-VAS score. The activity level revealed by the Tegner score improved at all follow-ups but without achieving the preinjury level. The analysis of the influencing factors showed the importance of the meniscus condition, revealing a significantly inferior outcome in knees with previous or combined partial meniscectomy procedures. During the study period, 12 patients had failed results, producing a cumulative failure rate of 27.3%. At the last evaluation, half of the patients considered their condition not better than before the treatment, and 39% would not repeat the treatment considering the results obtained.Conclusion:Despite a statistically significant improvement, the clinical outcome was poor. A higher improvement could be obtained in patients who had not undergone previous or combined meniscectomies, but this was limited over time. The failure rate was also high, regardless of the degree of osteoarthritis. Tissue-engineered cartilage implantation is questionable for this indication, and the limits of this scaffold-based procedure have to be considered if it is used as a salvage procedure for young patients affected by knee osteoarthritis.

URPOSE: The purpose of this study was to evaluate the efficacy of multiple platelet-rich plasma (PRP) injections on the healing of chronic refractory patellar tendinopathy, and report the quality and duration of the clinical improvement up to a medium-term follow-up. METHODS: Forty-three patients (mean age, 30.6 years; mean BMI, 24.7; 42 men, one woman) affected by chronic patellar proximal tendinopathy were enrolled in this trial. Eleven patients were affected by bilateral tendinopathy. They underwent three ultrasound guided intra-tendinous injections of five millilitres PRP, two weeks apart from each other. Patients were prospectively evaluated initially, then after two, six, and up to mean 48.6 ± 8.1 months of follow-up (minimum evaluation at 36 months). The following evaluation tools were used: Blanzina, VISA-P, EQ-VAS for general health, and Tegner scores. Patients' overall satisfaction and time to return to sport were also reported. RESULTS: Good and stable results were documented over time, with the VISA-P score increasing from 44.1 ± 15.6 at baseline to 61.4 ± 22.2 at two months, 76.6 ± 25.4 at six months, and 84.3 ± 21.6 at four years' follow-up. The same trend was confirmed by the other scores used, and 80 % of the patients were satisfied and returned to previous sports activities. Significantly poorer results were obtained in patients with a longer history of symptoms, and poor results were also observed in bilateral lesions. No correlation between ultrasonographic and clinical findings could be found. CONCLUSIONS: Multiple injections of PRP provided a good clinical outcome for the treatment of chronic recalcitrant patellar tendinopathy with stable results up to medium-term follow-up. Patients affected by bilateral pathology and presenting a long history of pain obtained significantly poorer results.

PURPOSE: Although traditionally not indicated for the treatment of osteoarthritis (OA), regenerative procedures are becoming a focus of increased interest due to their potential to provide pain relief and alter the progression of degenerative diseases. The purpose of this study was to assess whether a combined biomechanical and biological approach could offer good results in unicompartmental OA, thus delaying the need for unicompartmental arthroplasty in patients too young or refusing metal resurfacing. METHODS: Forty-three patients (mean age = 40.1 ± 11 years, 33 men and 10 women, mean BMI = 25 ± 3) affected by unicompartmental OA (Kellegren-Lawrence score = 3) in stable joints were enrolled and treated consecutively. Fifteen patients were treated with osteotomy and osteochondral biomimetic scaffold implant (3 of them also with meniscal substitution), 11 with osteotomy and meniscal scaffold implant, 9 with osteotomy and meniscal allograft implant, and 8 with both cartilage and meniscal reconstruction, depending on the specific joint compartment main requirements. Clinical evaluation was performed at 3-year (2-4) median follow-up using the following scoring systems: IKDC subjective and objective, VAS for pain, and Tegner scores. Failures, adverse events, and complications were also reported. RESULTS: The IKDC subjective score improved from 47.3 to 79.6 at the final evaluation (p < 0.0005), VAS improved from 6.1 to 2.3 (p < 0.0005), and also sport activity level evaluated with the Tegner score showed a significant improvement, from 2 (1-5) to 4 (3-10; p < 0.0005), even if without achieving the pre-injury level (6, p = 0.001). A further subanalysis confirmed the positive outcome obtained in all the treatment subgroups and showed a higher clinical improvement in patients under the age of 40 years (IKDC subjective 84.4 ± 13.2 vs 76.5 ± 17.3; p = 0.03). CONCLUSION: This integrated biological and biomechanical approach produced a marked improvement at short-medium follow-up in patients affected by unicompartmental OA. Even though a good outcome was achieved at all ages, patients under the age of 40 years presented a greater clinical and subjective improvement. Longer follow-up studies are needed to show results over time and confirm this approach as an effective alternative to unicompartmental implants.

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.

BACKGROUND AIMS: An extensive debate about the clinical benefits of autologous platelet concentrates used as a treatment option for patients with orthopedic injuries is ongoing. The aim of this study was to determine whether different compositions of platelet concentrates may affect the osteogenic differentiation of bone marrow stromal cells (BMSC). METHODS: Pure platelet-rich plasma (P-PRP) and leukocyte-PRP (L-PRP) were characterized for platelet and leukocyte content. As an indicative marker of the delivery of growth factors (GFs), the release of basic fibroblast growth factor (bFGF) from platelet gel (PG) was measured at 1, 18, 48 and 72 h and at 7 d. The ability of different PGs to induce proliferation and differentiation of BMSC was evaluated by using bioactivity assays. RESULTS: The platelet recovery was significantly higher in L-PRP, either fresh or frozen. PGs derived from L-PRP and P-PRP showed significant differences in terms of bFGF release and biological activity. bFGF release was faster both in fresh and frozen L-PRP preparations. Moreover, L-PRP samples were able to induce a significantly higher proliferation of BMSC compared with P-PRP or PPP samples. Even though all PG preparations allowed the deposition of mineral nodules in BMSC cultures, the mineralization activity correlated significantly with bFGF levels. CONCLUSIONS: The biological activity of platelet concentrates differs according to preparation technique, which affects platelet and leukocyte content and GF availability. Because GF levels are not always optimal in subjects with defective bone healing, composition and bioactivity of PRP should be analyzed to test the reliability and potential effectiveness of the regenerative treatment. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved

Osteochondritis dissecans (OCD) is an acquired lesion of the subchondral bone that may lead to the separation and instability of the overlying articular cartilage.

Background:Osteochondritis dissecans (OCD) is an acquired lesion of the subchondral bone that may result in separation and instability of the overlying articular cartilage. Unstable lesions must be treated surgically to reestablish the joint surface as anatomically as possible.Hypothesis/Purpose:The aim of this study was to evaluate the potential of a biomimetic osteochondral scaffold to treat OCD by analyzing the results obtained at 2-year follow-up. The hypothesis was that this scaffold, which was developed to treat the entire osteochondral unit, might restore the articular surface and improve symptoms and function in patients affected by knee OCD.Study Design:Case series; Level of evidence, 4.Methods:Twenty-seven consecutive patients (19 men, 8 women; age [mean ± SD], 25.5 ± 7.7 years) who were affected by symptomatic knee OCD of the femoral condyles (average defect size 3.4 ± 2.2 cm2), grade 3 or 4 on the International Cartilage Repair Society (ICRS) scale, were enrolled and treated with the implantation of a 3-layer collagen-hydroxyapatite scaffold. Patients were prospectively evaluated by subjective and objective International Knee Documentation Committee (IKDC) and Tegner scores preoperatively and at 1- and 2-year follow-up. An MRI was also performed at the 2 follow-up times.Results:A statistically significant improvement in all clinical scores was obtained at 1 year, and a further improvement was found the following year. At the 2-year follow-up, the IKDC subjective score had increased from 48.4 ± 17.8 preoperatively to 82.3 ± 12.2, the IKDC objective evaluation from 40% to 85% of normal knees, and the Tegner score from 2.4 ± 1.7 to 4.5 ± 1.6. The MRI evaluations showed good defect filling and implant integration but also inhomogeneous regenerated tissue and subchondral bone changes in most patients at both follow-up times. No correlation between the MOCART (magnetic resonance observation of cartilage repair tissue) score and clinical outcome was found.Conclusion:This biomimetic osteochondral scaffold seems to be a valid treatment option for knee OCD, showing a good clinical outcome at 2-year follow-up. Moreover, the improvement was not correlated with lesion size, so large lesions can benefit from this implant. Less favorable findings were obtained with MRI evaluation.

Background Platelet 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). Methods 109 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. Results Only 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). Conclusions Results 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.

Purpose The aim of this study is to evaluate the safety and clinical efficacy of this novel polyurethane meniscal scaffold to treat partial meniscal loss. Methods Eighteen patients (11 men and 7 women, mean age: 45 years) affected by irreparable acute meniscal tears requiring partial meniscectomy or chronic prior loss of meniscal tissue were enrolled in the study. They underwent arthroscopic polyurethane meniscal scaffold implantation (13 medial and 5 lateral) and, in case of presence of other comorbidities, concurrent procedures were also performed. Patients were prospectively evaluated up to 2 years of follow-up through IKDC objective, IKDC subjective, and Tegner scores. Furthermore, MRI evaluation of the meniscal scaffold was performed. Results No major adverse events were observed. A statistically significant increase in all the clinical parameters considered was found. The IKDC objective score increased from 61 % of normal or nearly normal knees at basal evaluation to 94 % at 2 years of follow-up (p = 0.01). There was also a significant increase in the IKDC subjective score both at 6‐12 months of follow-up (p = 0.03 and p \ 0.005), which was confirmed at 24 months. The Tegner score also showed a significant increase from the pre-operative level (median value 2, range 1‐5) to final evaluation (median value 3, range 2‐5; p = 0.005), albeit not reaching the pre-injury sports activity level. Conclusions The implantation of this novel polyurethane scaffold proved to be a safe and potentially effective procedure to treat partial meniscal loss with encouraging results at short-term follow-up. Further high-quality studies with larger numbers of patients and longer evaluation times are needed to confirm these preliminary data. Level of evidence Case series, Level IV.

n the last decade, huge steps forward have been made in the field of cartilage regeneration. The most recent trend for treating chondral/ osteochondral lesions is based on the application of smart biomaterials that could lead to "in situ" regeneration of not only cartilage, but also subchondral bone, preferably through a single step procedure to reduce the costs and the morbidity for the patient. This innovative approach is currently under investigation as several "scaffolds" have been proposed in clinical practice, with or without the aid of cells, with the opportunity, in the second case, of bypassing the strict limits imposed by cell manipulation regulations. Furthermore, the fascinating potential of mesenchymal stem cells has recently opened new paths of research to discover how and whether these powerful entities can really contribute to tissue regeneration. The first clinical trials have been published but further high quality research is needed to understand their mechanisms of action, their limits, and their clinical efficacy.

Regenerative procedures aim to recreate a hyaline-like tissue, thus restoring a biologically and biomechanically valid articular surface with durable clinical results. Autologous chondrocyte implantation (ACI) has been developed two decades ago, and both the production of a hyaline-like articular surface and a satisfactory clinical outcome have been documented at medium-long follow-up. Bioengineering technology further improved this regenerative treatment approach to include matrix-assisted ACI (MACI) techniques. These procedures have been introduced in the clinical practice one decade ago, showing similar results while at the same time overcoming most of the concerns related to the first-generation ACI. The use of scaffolds to create a cartilage-like tissue in a three-dimensional culture system allows for the optimization of the procedure from both the biological and surgical point of view. However, despite thousands of treated patients and many published studies suggesting good clinical results and durability of these procedures, the properties of healthy, normal articular cartilage are still unmatched by any available substitute. Both indications and results of these substitutes are still controversial. The role of many variables that may influence the final outcome still need to be clarified to further improve the potential benefits of these biological regenerative procedures.

The aim of the study was to investigate the use of a hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Eighteen skeletally mature sheep were treated. The animals were divided into three groups: cell-free scaffold, scaffold seeded with autologous chondrocytes, and meniscectomy alone. The implant was sutured to the capsule and to the meniscal ligament. At a 12-month gross assessment, histology and histomorphometry were used to assess the meniscus implant, knee joint, and osteoarthritis development. All implants showed excellent capsular ingrowth at the periphery. The implant gross assessment showed significant differences between cell-seeded and cell-free groups (p = 0.011). The histological analysis indicated a cellular colonization throughout the implanted constructs. Avascular cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs. Joint gross assessment showed that sheep treated with scaffold implantation achieved a significant higher score than those underwent meniscectomy (p < 0.0005), and the Osteoarthritis Research Society International score showed that osteoarthritic changes were significantly less in the cell-seeded group than in the meniscectomy group (p = 0.047), even though results were not significantly superior to those of the cell-free scaffold. Seeding of the scaffold with autologous chondrocytes increases its tissue regeneration capacity, providing a better fibrocartilaginous tissue formation. The study suggests the potential of the novel hyaluronic acid/polycaprolactone scaffold for total meniscal substitution, although this approach has to be further improved before being applied into clinical practice.

BACKGROUND: Osteochondritis dissecans is a relatively common cause of knee pain. The aim of this study was to describe the outcomes of five different surgical techniques in a series of sixty patients with osteochondritis dissecans. METHODS: Sixty patients (age 22.4 ± 7.4 years, sixty-two knees) with osteochondritis dissecans of a femoral condyle (forty-five medial and seventeen lateral) were treated with osteochondral autologous transplantation, autologous chondrocyte implantation with bone graft, biomimetic nanostructured osteochondral scaffold (MaioRegen) implantation, bone-cartilage paste graft, or a "one-step" bone-marrow-derived cell transplantation technique. Preoperative and follow-up evaluation included the International Knee Documentation Committee (IKDC) score, the EuroQol visual analog scale (EQ-VAS) score, radiographs, and magnetic resonance imaging. RESULTS: The global mean IKDC score improved from 40.1 ± 14.3 preoperatively to 77.2 ± 21.3 (p < 0.0005) at 5.3 ± 4.7 years of follow-up, and the EQ-VAS improved from 51.7 ± 17.0 to 83.5 ± 18.3 (p < 0.0005). No influence of age, lesion size, duration of follow-up, or previous surgical procedures on the result was found. The only difference among the results of the surgical procedures was a trend toward better results following autologous chondrocyte implantation (p = 0.06). CONCLUSIONS: All of the techniques were effective in achieving good clinical and radiographic results in patients with osteochondritis dissecans, and the effectiveness of autologous chondrocyte implantation was confirmed at a mean follow-up of five years. Newer techniques such as MaioRegen implantation and the "one-step" transplantation technique are based on different rationales; the first relies on the characteristics of the scaffold and the second on the regenerative potential of mesenchymal cells. Both of these newer procedures have the advantage of being minimally invasive and requiring a single operation.

Objectives: Autologous chondrocyte implantation (ACI) was developed two decades ago, and both the production of a hyaline-like articular surface and a satisfactory clinical outcome have been documented; the development of the Matrix-assisted Autologous Chondrocyte Transplantation (MACT) techniques further improved the potential of this regenerative treatment approach with bothbiological and surgical advantages. However, indication criteria of these procedures are still controversial. The aim of this study is to determine patient characteristics that could influence the results, in order to improve them and help to select patients that may benefit from this regenerative treatment with a better clinical outcome. Methods: 194 consecutive patients, 142 men and 52 women with a mean age of 29.0 ± 10.4 years, affected by knee chondral lesions, were enrolled and treated with implantation of a hyaluronic acid based bioengineered tissue (141 underwent an arthroscopic procedure, in the other cases a mini-open approach was used). All the patients were evaluated prospectively yearly for a minimum follow-up of 5 years with IKDC, EQ-VAS, and Tegner scores. Complications, failures, and patient satisfaction were also documented. Results: A statistically significant improvement was observed in all scores from the basal evaluation to the final follow-up. The IKDC subjective score increased from 39.0 ± 14.1 to 76.0 ± 21.6 at 5 years (p\0.0005); a similar improvement was documented with the EQ-VAS score, passing from 58.1 ± 19.7 to 83.8 ± 15.3 (p\0.0005), and also the activity level evaluated with Tegner score showed a marked improvement, from 1.7 ± 1.2 to 5.1 ± 2.5 (p\0.0005), even if without achieving the pre-injury level (6.7 ± 2.0, p\0.0005). A better outcome was obtained in young active men affected by traumatic chondral lesions of the medial femoral condyle, whereas the worst results were found in degenerative lesions, in lesions of other joint sites, or when previous surgery had been performed. Conclusions: This study demonstrates the influence of various factors on clinical outcome at 5 years follow-up after MACT. Age, sex, activity level, as well as etiology, site and previous patient’s history, are important aspects to be considered when treating knee chondral lesions. The understanding of all influencing factors and their mechanism of action will help to better select the treatment strategy and to further improve the potential and clinical outcome of cartilage regenerative procedures.

Purpose: The aim of this study was to analyze the clinical outcome obtained with arthroscopic second generation autologous chondrocyte implantation (ACI) associated with bone grafting for the treatment of knee osteochondritis dissecans (OCD) at medium term follow-up. Methods: Thirty-four knees affected by symptomatic OCD grade III or IV on the ICRS (International Cartilage Repair Society) scale were treated and prospectively evaluated at 12, 24 months of follow-up, and at a final mean 6 +/- 1 years of follow-up. The mean age at treatment was 21 +/- 6 years. The average size of the defects was 3 +/- 1 cm(2). Patients were evaluated with IKDC, EQ-VAS, and Tegner scores. Results: A statistically significant improvement in all scores was observed after the treatment. The IKDC subjective score improved from 38 +/- 13 to 81 +/- 20, and 91% of the knees were rated as normal or nearly normal in the objective IKDC at the final evaluation. EQ-VAS and Tegner scores showed a statistically significant linear trend of improvement over time passing from 52 +/- 18 to 83 +/- 14 and from 2 +/- 1 to 5 +/- 3, respectively, at 6 years' follow-up. A better outcome was obtained in men, sport active patients, and smaller lesions. Conclusions: Second generation ACI associated with bone grafting is a valid treatment option for knee OCD and may offer a good and stable clinical outcome at mean 6 years of follow-up. Further studies are needed to confirm the results over time, and determine if there is only a symptomatic improvement, or if this procedure may also prevent or delay further knee degeneration.

Osteochondritis, Dissecans, Knee, Cartilage Fractures

The use of scaffolds in combination with autologous chondrocytes is well established in clinical practice in Europe (even if not yet available in the US). The rationale for using a scaffold is to have a temporary three dimensional structure of biodegradable polymers for the growth of living cells. An ideal scaffold should mimic biology and the architectural and structural properties of the native tissue, thus facilitating cell infiltration, attachment, proliferation and differentiation. Other important properties include biocompatibility and biodegradability through safe biochemical pathways at suitable time intervals to support the first phases of tissue formation and gradual replacement by regenerating tissue. There is increasing interest in utilising various biomaterials in clinical practice, not only to deliver expanded autologous chondrocytes for tissue regeneration, but also as a new treatment approach, which involves the implant of various biomaterials for "in situ" cartilage repair exploiting bone marrow stem cell differentiation induced by the scaffold properties. In fact, some scaffolds may have a potential themselves to promote chondral or osteochondral regeneration by exploiting the self-regenerative potential of the body. An ideal graft would be an off-the-shelf product from both a surgical and commercial standpoint. The possibility to produce a cell-free implant that is "smart" enought to provide the joint with the appropriate stimuli to induce orderly and durable tissue regeneration is realy attractive, and new, different biomaterials have recently been proposed to induce "in situ" cartilage regeneration after direct transplantation onto the defect site both in research and in clinical practice.

Le tecniche ACI cosiddette “di II generazione” sono state sviluppate con l’obiettivo di superare i limiti della tecnica ACI tradizionale grazie all’impiego di tessuti bioingegnerizzati di vario genere sotto forma di scaffold solido (Fig. 1), in grado di fornire un supporto biocompatibile e biodegradabile capace di mantenere il fenotipo differenziato dei condrociti e permetterne una maggior adesione al sito di impianto. Inoltre alcuni di questi supporti permettono la possibilità di utilizzare tecniche artroscopiche, diminuendo tempi e morbidità della procedura chirurgica; rimangono però limitate le conoscenze sulla stabilità a lungo termine di alcuni di questi impianti.

To compare the safety and efficacy of two different approaches of platelet-rich plasma (PRP) production methods as intra-articular injection treatment for knee cartilage degenerative lesions and osteoarthritis (OA). The study involved 144 symptomatic patients affected by cartilage degenerative lesions and OA. Seventy-two patients were treated with 3 injections of platelet concentrate prepared with a single-spinning procedure (PRGF), the other 72 with 3 injections of PRP obtained with a double-spinning approach. The patients were evaluated prospectively at the enrollment and at 2, 6, and 12 months' follow-up with IKDC, EQ-VAS and Tegner scores; adverse events and patient satisfaction were also recorded. Both treatment groups presented a statistically significant improvement in all the scores evaluated at all the follow-up times. Better results were achieved in both groups in younger patients with a lower degree of cartilage degeneration. The comparative analysis showed similar improvements with the two procedures: in particular, IKDC subjective evaluation increased from 45.0 +/- A 10.1 to 59.0 +/- A 16.2, 61.3 +/- A 16.3, and 61.6 +/- A 16.2 at 2, 6, and 12 months in the PRGF group, and from 42.1 +/- A 13.5 to 60.8 +/- A 16.6, 62.5 +/- A 19.9, and 59.9 +/- A 20.0 at 2, 6, and 12 months in the PRP group, respectively. Concerning adverse events, more swelling (P = 0.03) and pain reaction (P = 0.0005), were found after PRP injections. Although PRP injections produced more pain and swelling reaction with respect to that produced by PRGF, similar results were found at the follow-up times, with a significant clinical improvement with respect to the basal level. Better results were achieved in younger patients with a low degree of cartilage degeneration.

Background:Loss of knee meniscal tissue often leads to increased pain and decreased function.Hypothesis:At a minimum 2-year follow-up, patients receiving a lateral collagen meniscus implant (CMI) would show improved knee function and decreased pain compared with their preoperative status.Study Design:Case series; Level of evidence, 4.Methods:Twenty-four patients with irreparable lateral meniscal tears (n = 7) or previous partial lateral meniscectomy (n = 17) underwent arthroscopic lateral collagen meniscus implantation. Clinical evaluation was performed preoperatively, at 6 months, and at a minimum 2-year follow-up with Lysholm, visual analog scale (VAS) for pain, Tegner, objective International Knee Documentation Committee (IKDC), and EuroQol 5 dimensions (EQ-5D) scores. A magnetic resonance imaging (MRI) evaluation was performed preoperatively and at final follow-up using the modified Yulish score for cartilage and the Genovese score for implant size and signal intensity.Results:All clinical scores significantly improved from preoperative evaluation to final follow-up. Average Lysholm scores improved from 64.0 ± 16.2 to 92.7 ± 13.8 ( P < .0001), VAS for pain from 55.2 ± 29.4 to 19.5 ± 25.6 ( P < .0001), Tegner from 3 (interquartile range, 2-4) to 5 (interquartile range, 4-7) ( P = .0062), objective IKDC from 6A, 14B, 4C to 20A, 3B, 1D ( P = .0002), and EQ-5D from 0.58 ± 0.28 to 0.89 ± 0.14 ( P < .0001). Good to excellent (A + B) objective IKDC scores improved from 83% preoperatively to 96% at 2-year follow-up. The Tegner index (the percentage of the lost activity level that was regained as a result of the treatment intervention) was 47% at 6-month follow-up and 79% at 2-year follow-up: this improvement was statistically significant ( P = .0062). The MRI evaluations for tibial and femoral modified Yulish scores for cartilage remained similar over the course of the study; 87.5% of implants were reduced in size, and in 3 cases (12.5%), they were completely resorbed; 50% of the implants had a slightly hyperintense signal (relative to the normal meniscus), and signal intensity changes suggested that full maturation had occurred in 37.5% at final follow-up (based on the Genovese scores).Conclusion:The lateral CMI demonstrated that it was safe in this population study, with decreased pain and improved knee function in 96% of patients with excellent/good Lysholm results in 87% of patients at a minimum 2-year follow-up. The MRI scans demonstrated a decreased implant size relative to a normal meniscus.

Large cartilage lessions in patients over 60 years old are mainly associated with a degenerative environment and can be included in the definition of osteoarthritis (OA). OA is the most common cause of chronic disability in older adults: it leads to articular cartilage degeneration and ends in joint destruction. While in advanced OA unicompartimental or total arthroplasty remain the main choice for the orthopaedic surgeon, for the treatment of early stages with limited cartilage damage, numerous more conservative approaches have been proposed, such as pharmaceuticals or surgical techniques less invasive than a prosthesis.

Negli ultimi anni è notevolmente accresciuto l’interesse rivolto all’importanza dell’osso subcondrale e del suo ruolo patogenetico nel danno delle superfici articolari; parallelamente sono state sviluppate nuove tecniche specifiche per il trattamento di questo tipo di patologia. Attualmente due soli scaffolds sono stati impiegati in clinica per il trattamento di lesioni osteocondrali: TruFit® (Smith & Nephew, Andover, MA) e Maioregen® (Fin-Ceramica S.p.A., Faenza, Italy). Sebbene i risultati a livello di studi preliminari siano ancora controversi, l’utilizzo di questa tipologia di scaffold per trattare difetti della cartilagine e dell’osso sottostante sembra essere promettente.

A biodegradable, hyaluronian-based biocompatible scaff old is used for autologous chondrocyte implantation (ACI) for the treatment of articular cartilage lesions. This procedure consists of two steps: the fi rst one is an arthroscopic biopsy of healthy cartilage for chondrocyte cell culture. After 6 weeks, the bioengineered tissue obtained can be implanted trough a mini-open procedure or arthroscopic technique.

Objective: Complex fractures of the tibial plateau are difficult to treat and present a high complication rate. The goal of this report is to describe a combined biological and mechanical approach to restore all morphological and functional knee properties. Methods: We treated a 50-year-old woman, who was affected by a posttraumatic osteochondral lesion and depression of the lateral tibial plateau with knee valgus deviation. The mechanical axis was corrected with a lateral tibial plateau elevation osteotomy, the damaged joint surface was replaced by a recently developed biomimetic osteochondral scaffold, and a hinged dynamic external fixator was applied to protect the graft and at the same time to allow postoperative joint mobilization. Results: A marked clinical improvement was documented at 12 months and further improved up to 5 years, with pain-free full range of motion and return to previous activities. The MRI evaluation at 12 and 24 months showed that the implant remained in site with a hyaline-like signal and restoration of the articular surface. Conclusion: This case report describes a combined surgical approach for complex knee lesions that could represent a treatment option to avoid or at least delay posttraumatic osteoarthritis and more invasive procedures.