BACKGROUND The refinement of the use of platelet-derived growth factors that has occurred over the last decade has led to a broadening of the fields of use, in particular for new treatments in orthopaedics aimed at improving tissue regeneration. MATERIALS AND METHODS Twenty-seven patients, aged between 18 and 81 years, with a diagnosis of degenerative joint disease lasting for more than 1 year were treated. The patients were divided into two groups, one with arthritis of the knee, the other with degenerative cartilage disease of the knee. Both groups were treated with a therapeutic protocol consisting of a cycle of three infiltrations of platelet-rich plasma at weekly intervals.The extemporaneous preparation was made from a sample of about 8 mL of venous whole blood collected into a specific Fibrin Polymer 2 test-tube from RegenLab(®) and centrifuged before addition of calcium gluconate.During the initial pre-treatment evaluation, specific questionnaires were administered, the Numerical Rating Scale (NRS) for subjective measurement of pain and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); these assessments were repeated 7 days after the end of the treatment and at 6 months during the follow-up. RESULTS The parameters evaluated improved in both groups after treatment and there was a further improvement after 6 months of follow-up; furthermore, there was a substantial decrease in pain right after the first infiltration. DISCUSSION The patients were treated on an out-patient basis by a specifically created multidisciplinary team comprising a transfusion specialist, an orthopaedist and a radiologist, who collaborate in a symbiotic manner. The out-patient protocol exploits the regenerative properties of platelet-rich plasma, which is a low cost treatment; in practice, a diagnostic-therapeutic programme of lower intensity, but of high technical and professional quality is created. The strategy also reduces both the number of hospital services and the pharmacological support required, thereby optimising the use of health care resources.

Background: Platelet-rich plasma (PRP) has recently been postulated as a treatment for osteoarthritis (OA). Although anabolic effects of PRP on chondrocytes are well documented, no reports are known addressing effects on cartilage degeneration. Since OA is characterized by a catabolic and inflammatory joint environment, the authors investigated whether PRP was able to counteract the effects of such an environment on human osteoarthritic chondrocytes. Hypothesis: Platelet-rich plasma inhibits inflammatory effects of interleukin-1 (IL-1) beta on human osteoarthritic chondrocytes. Study Design: Controlled laboratory study. Methods: Human osteoarthritic chondrocytes were cultured in the presence of IL-1 beta to mimic an osteoarthritic environment. Medium was supplemented with 0%, 1%, or 10% PRP releasate (PRPr, the active releasate of PRP). After 48 hours, gene expression of collagen type II alpha 1 (COL2A1), aggrecan (ACAN), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, ADAMTS5, matrix metalloproteinase (MMP)13, and prostaglandin-endoperoxide synthase (PTGS)2 was analyzed. Additionally, glycosaminoglycan (GAG) content, nitric oxide (NO) production, and nuclear factor kappa B (NFκB) activation were studied. Results: Platelet-rich plasma releasate diminished IL-1 beta-induced inhibition of COL2A1 and ACAN gene expression. The PRPr also reduced IL-1 beta-induced increase of ADAMTS4 and PTGS2 gene expression. ADAMTS5 gene expression and GAG content were not influenced by IL-1 beta or additional PRPr. Matrix metalloproteinase 13 gene expression and NO production were upregulated by IL-1 beta but not affected by added PRPr. Finally, PRPr reduced IL-1 beta-induced NFκB activation to control levels containing no IL-1 beta. Conclusion: Platelet-rich plasma releasate diminished multiple inflammatory IL-1 beta-mediated effects on human osteoarthritic chondrocytes, including inhibition of NFκB activation. Clinical Relevance: Platelet-rich plasma releasate counteracts effects of an inflammatory environment on genes regulating matrix degradation and formation in human chondrocytes. Platelet-rich plasma releasate decreases NFκB activation, a major pathway involved in the pathogenesis of OA. These results encourage further study of PRP as a treatment for OA.

PURPOSE The aim of our study is to compare the efficacy of platelet-rich plasma (PRP) and viscosupplementation (hyaluronic acid [HA]) intra-articular injections for the treatment of knee cartilage degenerative lesions and osteoarthritis (OA). METHODS The study involved 150 patients affected by cartilage degenerative lesions and early and severe OA. Fifty symptomatic patients were treated with 3 autologous PRP intra-articular injections and were evaluated prospectively at enrollment and at 2- and 6-month follow-up. The results obtained were compared with 2 homogeneous groups of patients treated with HA injections. One group was treated with injections of high-molecular weight HA; the other group was treated with low-molecular weight (LW) HA. International Knee Documentation Committee and EQ VAS scores were used for clinical evaluation; adverse events and patient satisfaction were also recorded. RESULTS At 2 months' follow-up, the PRP and LW HA groups showed a similar improvement, with higher results compared with the high-molecular weight HA group (P <.005). At 6 months' follow-up, better results were observed in the PRP group (P <.005). PRP and LW HA treatments offered similar results in patients aged over 50 years and in the treatment of advanced OA. PRP showed a better performance compared with HA in younger patients affected by cartilage lesions or early OA. CONCLUSIONS Autologous PRP injections showed more and longer efficacy than HA injections in reducing pain and symptoms and recovering articular function. Better results were achieved in younger and more active patients with a low degree of cartilage degeneration, whereas a worse outcome was obtained in more degenerated joints and in older patients, in whom results similar to those of viscosupplementation have been observed. LEVEL OF EVIDENCE Level II, prospective comparative study.

PURPOSE: The purpose is to describe a noninvasive arthroscopic procedure as an alternative to open surgery for avascular necrosis of the hip. METHODS: Patients with grade I or IIA avascular necrosis of the hip are treated by core decompression performed by drilling under fluoroscopic guidance. Liquid platelet-rich plasma (PRP) is delivered through a trocar, saturating the necrotic area. In more severe conditions, the necrotic bone is decompressed and debrided, through a cortical window at the head-neck junction. A composite graft made of autologous bone and PRP is delivered by impactation through the core decompression track. Fibrin membranes are applied to enhance healing of the head-neck window and arthroscopic portals. Platelet-rich plasma is infiltrated in the central compartment. RESULTS: This arthroscopic approach aids in making diagnosis of the labrum and articular cartilage and permits intra-operative treatment decisions. Visual control permits the precise localization and treatment for the necrotic area allowing cartilage integrity to be preserved. CONCLUSIONS: Arthroscopic management of avascular necrosis of the femoral head is viable and has significant advantages. Clinical studies should justify the theoretical additional benefits of this approach.

BACKGROUND Diced-cartilage grafts have been used for dorsal nasal augmentation for several years with good results. However, compounds such as Surgicel and temporalis fascia used as a wrap have inherent problems associated with them, predominantly inflammation and graft resorption. An autologous carrier could provide stabilization of cartilage grafts while avoiding the complications seen with earlier techniques. METHODS In our patients, a malleable construct was used for dorsal nasal augmentation in which autologous diced-cartilage grafts were stabilized with autologous tissue glue (ATG) created from platelet-rich plasma (platelet gel) and platelet-poor plasma (fibrin glue). RESULTS A prospective analysis of 68 patients, who underwent dorsal nasal augmentation utilizing ATG and diced-cartilage grafts between 2005 and 2008, were included in the study. Although there was notable maintenance of the dorsal height, no complications occurred that required explantation over a mean follow-up of 15 months. CONCLUSION The use of ATG to stabilize diced-cartilage grafts is a safe, reliable technique for dorsal nasal augmentation. The platelet gel provides growth factors while the fibrin glue creates a scaffold that allows stabilization and diffusion of nutrients to the cartilage graft.

Little is know about the pathophysiology of acute and degenerative tendon injuries. Although most lesions are uncomplicated, treatment is long and unsatisfactory in a considerable number of cases. Besides the common growth factors that were shown to be relevant for tendon integrity more recently protection against oxidative stress was shown to promote tendon healing. To improve tendon regeneration, many have advocated the use of platelet-rich plasma (PRP), a thrombocyte concentrate that can serve as an autologous source of growth factors. In this study, we investigated the effect of platelet-released growth factors (PRGF) on tenocytes. Tenocytes were isolated from the Achilles tendon of postnatal rats. Tenocyte cell cultures were stimulated with PRGF. We used a CyQuant assay and WST assay to analyse tendon cell growth and viability in different concentrations of PRGF. Migration and proliferation of cells grown in PRGF were assessed by a scratch test. A dual-luciferase assay was used to demonstrate the activation of the anti-oxidant response element (ARE) in tenocytes. A positive effect of PRGF could be shown on tendon cell growth and migratory capacity. PRGF activated the Nrf2-ARE pathway in a dose-dependent manner. Here, we provide evidence of a biological effect of PRGF on tenocytes by the promotion of tenocyte growth and activation of the Nrf2-ARE pathway. This is a novel aspect of the action of platelet concentrates on tendon growth.

Catabolic inflammatory cytokines are prevalent in osteoarthritis (OA). The purpose of this study was to evaluate an autologous protein solution (APS) as a potential chondroprotective agent for OA therapy. APS was prepared from platelet-rich plasma (PRP). The APS solution contained both anabolic (bFGF, TGF-β1, TGF-β2, EGF, IGF-1, PDGF-AB, PDGF-BB, and VEGF) and anti-inflammatory (IL-1ra, sTNF-RI, sTNF-RII, IL-4, IL-10, IL-13, and IFNγ) cytokines but low concentrations of catabolic cytokines (IL-1α, IL-1β, TNFα, IL-6, IL-8, IL-17, and IL-18). Human articular chondrocytes were pre-incubated with the antagonists IL-1ra, sTNF-RI, or APS prior to the addition of recombinant human IL-1β or TNFα. Following exposure to inflammatory cytokines, the levels of MMP-13 in the culture medium were evaluated by ELISA. MMP-13 production stimulated in chondrocytes by IL-1β or TNFα was reduced by rhIL-1ra and sTNF-RI to near basal levels. APS was also capable of inhibiting the production of MMP-13 induced by both IL-1β and TNFα. The combination of anabolic and anti-inflammatory cytokines in the APS created from PRP may render this formulation to be a potential candidate for the treatment of inflammation in patients at early stages of OA.

Trauma, malposition and age-related degeneration of articular cartilage often result in severe lesions that do not heal spontaneously. Many efforts over the last centuries have been undertaken to support cartilage healing, with approaches ranging from symptomatic treatment to structural cartilage regeneration. Microfracture and matrix-associated autologous chondrocyte transplantation (MACT) can be regarded as one of the most effective techniques available today to treat traumatic cartilage defects. Research is focused on the development of new biomaterials, which are intended to provide optimized physical and biochemical conditions for cell proliferation and cartilage synthesis. New attempts have also been undertaken to replace chondrocytes with cells that are more easily available and cause less donor site morbidity, e.g. adipose derived stem cells (ASC). The number of in vitro studies on adult stem cells has rapidly increased during the last decade, indicating that many variables have yet to be optimized to direct stem cells towards the desired lineage. The present review gives an overview of the difficulties of cartilage repair and current cartilage repair techniques. Moreover, it reviews new fields of cartilage tissue engineering, including stem cells, co-cultures and platelet-rich plasma (PRP).

BACKGROUND: Full-thickness chondral defects and early osteoarthritis continue to present major challenges for the patient and the orthopaedic surgeon as a result of the limited healing potential of articular cartilage. The use of bioactive growth factors is under consideration as a potential therapy to enhance healing of chondral injuries and modify the arthritic disease process. QUESTIONS/PURPOSES: We reviewed the role of growth factors in articular cartilage repair and identified specific growth factors and combinations of growth factors that have the capacity to improve cartilage regeneration. Additionally, we discuss the potential use of platelet-rich plasma, autologous-conditioned serum, and bone marrow concentrate preparations as methods of combined growth factor delivery. METHODS: A PubMed search was performed using key words cartilage or chondrocyte alone and in combination with growth factor. The search was open for original manuscripts and review papers and open for all dates. From these searches we selected manuscripts investigating the effects of growth factors on extracellular matrix synthesis and excluded those investigating molecular mechanisms of action. RESULTS: By modulating the local microenvironment, the anabolic and anticatabolic effects of a variety of growth factors have demonstrated potential in both in vitro and animal studies of cartilage injury and repair. Members of the transforming growth factor-β superfamily, fibroblast growth factor family, insulin-like growth factor-I, and platelet-derived growth factor have all been investigated as possible treatment augments in the management of chondral injuries and early arthritis. CONCLUSIONS: The application of growth factors in the treatment of local cartilage defects as well as osteoarthritis appears promising; however, further research is needed at both the basic science and clinical levels before routine application.

PURPOSE Platelet-rich plasma (PRP) therapy is a simple, low-cost and minimally invasive method that provides a natural concentrate of autologous blood growth factors (GFs) that can be used to enhance tissue regeneration. In a previous analysis of a 12-month follow-up study, promising results were obtained when treating patients affected by knee degeneration with PRP intra-articular injections. The main purpose of this study was to investigate the persistence of the beneficial effects observed. METHODS Of the 91 patients evaluated in the previous 12-month follow-up study, 90 were available for the 2-year follow-up (24 patients presented a bilateral lesion, in a total of 114 knees treated). All of the patients presented a chronic knee degenerative condition and were treated with three intra-articular PRP injections. IKDC and EQ-VAS scores were used for clinical evaluation. Complications, adverse events and patient satisfaction were also recorded. RESULTS All of the evaluated parameters worsened at the 24-month follow-up: these parameters were at significantly lower levels with respect to the 12-month evaluation (the IKDC objective evaluation fell from 67 to 59% of normal and nearly normal knees; the IKDC subjective score fell from 60 to 51), even if they remained higher than the basal level. Further analysis showed better results in younger patients (P = 0.0001) and lower degrees of cartilage degeneration (P < 0.0005). The median duration of the clinical improvement was 9 months. CONCLUSIONS These findings indicate that treatment with PRP injections can reduce pain and improve knee function and quality of life with short-term efficacy. Further studies are needed to confirm these results and understand the mechanism of action, and to find other application modalities, with different platelet and GF concentrations and injection timing, which provide better and more durable results.

PURPOSE The aim of our study is to compare the efficacy of platelet-rich plasma (PRP) and viscosupplementation (hyaluronic acid [HA]) intra-articular injections for the treatment of knee cartilage degenerative lesions and osteoarthritis (OA). METHODS The study involved 150 patients affected by cartilage degenerative lesions and early and severe OA. Fifty symptomatic patients were treated with 3 autologous PRP intra-articular injections and were evaluated prospectively at enrollment and at 2- and 6-month follow-up. The results obtained were compared with 2 homogeneous groups of patients treated with HA injections. One group was treated with injections of high-molecular weight HA; the other group was treated with low-molecular weight (LW) HA. International Knee Documentation Committee and EQ VAS scores were used for clinical evaluation; adverse events and patient satisfaction were also recorded. RESULTS At 2 months' follow-up, the PRP and LW HA groups showed a similar improvement, with higher results compared with the high-molecular weight HA group (P <.005). At 6 months' follow-up, better results were observed in the PRP group (P <.005). PRP and LW HA treatments offered similar results in patients aged over 50 years and in the treatment of advanced OA. PRP showed a better performance compared with HA in younger patients affected by cartilage lesions or early OA. CONCLUSIONS Autologous PRP injections showed more and longer efficacy than HA injections in reducing pain and symptoms and recovering articular function. Better results were achieved in younger and more active patients with a low degree of cartilage degeneration, whereas a worse outcome was obtained in more degenerated joints and in older patients, in whom results similar to those of viscosupplementation have been observed. LEVEL OF EVIDENCE Level II, prospective comparative study.

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.

PURPOSE: 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). METHODS: 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. RESULTS: 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 ± 10.1 to 59.0 ± 16.2, 61.3 ± 16.3, and 61.6 ± 16.2 at 2, 6, and 12 months in the PRGF group, and from 42.1 ± 13.5 to 60.8 ± 16.6, 62.5 ± 19.9, and 59.9 ± 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. CONCLUSIONS: 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. LEVEL OF EVIDENCE: II.

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 jumper's knee, by aiding the regeneration of tissue which otherwise has low healing potential.

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, 24months of follow-up, and at a final mean 6±1years of follow-up. The mean age at treatment was 21±6years. The average size of the defects was 3±1cm(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 6years' 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 6years 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.

PURPOSE: Degenerative cartilage lesions present a negative joint environment, which may have a negative effect on the process of cartilage regeneration. The aim of this study is to analyze the clinical outcome obtained with the treatment for isolated degenerative knee cartilage lesions by second-generation arthroscopic autologous chondrocyte implantation (ACI). METHODS: Fifty-eight consecutive patients affected by focal degenerative chondral lesions of the femoral condyles and trochlea were treated by second-generation arthroscopic ACI. The mean age at surgery was 34.7 ± 9.1 years and the average defect size was 2.3 ± 0.9 cm(2). The patients were prospectively evaluated with IKDC, EQ-VAS, and Tegner scores preoperatively, at 2 and 6 years. RESULTS: A statistically significant improvement was observed in all scores from the basal evaluation to the final follow-up. The IKDC subjective score improved from 39.3 ± 13.6 to 68.8 ± 22.7 and 68.5 ± 23.9 at the 2- and 6-year follow-ups, respectively, with a significant improvement (P < 0.0005) and stable results over time; the same trend was confirmed by the EQ-VAS and Tegner scores. The worst results were found in patients with a low physical activity level, women, and those having undergone previous surgery, whereas the symptom duration before surgery did not influence the final outcome. The failure rate was 18.5%. CONCLUSIONS: Despite a significant improvement, the results were lower with respect to the outcome reported in different study populations, and the number of failures was markedly higher, too. Tissue-engineered cartilage implantation is a promising approach for the treatment of degenerative chondral lesions, but graft properties, besides mechanical and biochemical joint environment, have to be improved. LEVEL OF EVIDENCE: Case series, Level IV.

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 cm(2). 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.

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.

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 cm(2) to 6.0 cm(2). 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.