One-step surgery with multipotent stem cells and Hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45 years.

PURPOSE: The aim of this study is to prospectively evaluate the medium-term effectiveness and regenerative capability of autologous adult mesenchymal stem cells, harvested as bone marrow aspirate concentrate (BMAC), along with a hyaluronan-based scaffold (Hyalofast) in the treatment of ICRS grade 4 chondral lesions of the knee joint, in patients older than 45 years. METHODS: A study group of 20 patients with an age >45 years (mean 50.0 ± 4.1 years) was compared to a control group of 20 patients with an age <45 years (mean 36.6 ± 5.0). Patients were prospectively evaluated for 4 years. All patients were evaluated with MRI, KOOS, IKDC, VAS and Tegner scores preoperatively and at two-year and final follow-up. RESULTS: At final follow-up, all scores significantly improved (P < 0.001) as follows: all KOOS score categories; Tegner 2 (range 0-4) to 6 (range 4-8) and 3 (range 0-6) to 6 (range 3-10); IKDC subjective (39.2 ± 16.5 to 82.2 ± 8.9) and (40.8 ± 13.9 to 79.4 ± 14.6), in the study and control group respectively. In addition, we show that results are affected by lesion size and number but not from concomitant surgical procedures. MRI showed complete filling in 80 % of patients in the study group and 71 % of patients in the control group. Histological analysis conducted in three patients from the study and two patients from the control group revealed good tissue repair with a variable amount of hyaline-like tissue. CONCLUSION: Treatment of cartilage lesions with BMAC and Hyalofast is a viable and effective option that is mainly affected by lesion size and number and not by age. In particular, it allows to address the >45 years population with functional outcomes that are comparable to younger patients at final follow-up. LEVEL OF EVIDENCE: Prospective cohort study, Level II.

Postoperative Infection After Anterior Cruciate Ligament Reconstruction.

CONTEXT: Infection after anterior cruciate ligament reconstruction (ACLR) is uncommon; if it occurs, it can lead to disastrous complications. OBJECTIVE: To analyze post-ACLR infections and identify related complications to provide the most effective treatment protocol. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: Among approximately 1850 ACLRs performed by a single surgeon over the past 20 years, 7 cases of post-ACLR infection were identified (incidence, 0.37%). Five patients presenting with low-severity infection were successfully treated without any complication or residual functional disability. The remaining 2 patients, although successfully treated, presented with minor residual limitations. From a literature review, 16 studies including 246 cases of infection were reported among 35,795 ACLRs, making the rate of infection 0.68% (range, 0.14%-2.6%). CONCLUSION: With proper treatment protocols, post-ACLR infection is rare but can compromise outcomes.

Cartilage Repair in the Inflamed Joint: Considerations for Biological Augmentation Toward Tissue Regeneration.

Cartilage repair/regeneration procedures (e.g., microfracture, autologous chondrocyte implantation [ACI]) typically result in a satisfactory outcome in selected patients. However, the vast majority of patients with chronic symptoms and, in general, a more diseased joint, do not benefit from these surgical techniques. The aims of this work were to (1) review factors negatively influencing the joint environment; (2) review current adjuvant therapies that can be used to improve results of cartilage repair/regeneration procedures in patients with more diseased joints, (3) outline future lines of research and promising experimental approaches. Chronicity of symptoms and advancing patient age appear to be the most relevant factors negatively affecting clinical outcome of cartilage repair/regeneration. Preliminary experience with hyaluronic acid, platelet-rich plasma, and mesenchymal stem cell has been positive but there is no strong evidence supporting the use of these products and this requires further assessment with high-quality, prospective clinical trials. The use of a Tissue Therapy strategy, based on more mature engineered tissues, holds promise to tackle limitations of standard ACI procedures. Current research has highlighted the need for more targeted therapies, and (1) induction of tolerance with granulocyte colony-stimulating factor (G-CSF) or by preventing IL-6 downregulation; (2) combined IL-4 and IL-10 local release; and (3) selective activation of the prostaglandin E2 (PGE2) signaling appear to be the most promising innovative strategies. For older patients and for those with chronic symptoms, adjuvant therapies are needed in combination with microfracture and ACI.

Matrix-Induced Autologous Chondrocyte Implantation versus Multipotent Stem Cells for the Treatment of Large Patellofemoral Chondral Lesions: A Nonrandomized Prospective Trial.

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

The effects of repeated intra-articular PRP injections on clinical outcomes of early osteoarthritis of the knee.

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

One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee.

BACKGROUND: Chondral lesions in athletically active patients cause considerable morbidity, and treatment with existing cell-based therapies can be challenging. Bone marrow has been shown as a possible source of multipotent stem cells (MSCs) with chondrogenic potential and is easy to harvest during the same surgical procedure. PURPOSE: To investigate the clinical outcome in a group of active patients with large full-thickness chondral defects of the knee treated with 1-step surgery using bone marrow-derived MSCs and a second-generation matrix. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: From January 2007 to February 2010, 25 patients (average age, 46.5 years) with symptomatic large chondral defects of the knee (International Cartilage Repair Society grade 4) who underwent cartilage transplantation with MSCs and a collagen type I/III matrix were followed up for a minimum of 3 years. The average lesion size was 8.3 cm(2). Coexisting injuries were treated during the same surgical procedure in 18 patients. All patients underwent a standard postoperative rehabilitation program. Preoperative and postoperative evaluations at 1-year, 2-year, and final follow-up included radiographs, magnetic resonance imaging (MRI), and visual analog scale (VAS) for pain, International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm, Marx, and Tegner scores. Seven patients underwent second-look arthroscopic surgery, with 4 consenting to a tissue biopsy. RESULTS: No patients were lost at final follow-up. The average preoperative values for the evaluated scores were significantly improved at final follow-up (P < .001): VAS, 5.4 ± 0.37 to 0.48 ± 0.19; IKDC subjective, 37.92 ± 4.52 to 81.73 ± 2.42; KOOS pain, 61.04 ± 3.95 to 93.32 ± 1.92; KOOS symptoms, 55.64 ± 3.23 to 89.32 ± 2.32; KOOS activities of daily living, 63.96 ± 4.48 to 91.20 ± 2.74; KOOS sports, 34.20 ± 5.04 to 80.00 ± 3.92; KOOS quality of life, 32.20 ± 4.43 to 83.04 ± 3.37; Lysholm, 46.36 ± 2.25 to 86.52 ± 2.73; Marx, 3.00 ± 0.79 to 9.04 ± 0.79; and Tegner, 2.12 ± 0.32 to 5.64 ± 0.26. Patients younger than 45 years of age and those with smaller or single lesions showed better outcomes. The MRI scans showed good stability of the implant and complete filling of the defect in 80% of patients, and hyaline-like cartilage was found in the histological analysis of the biopsied tissue. No adverse reactions or postoperative complications were noted. CONCLUSION: The treatment of large chondral defects with MSCs is an effective procedure and can be performed routinely in clinical practice. Moreover, it can be achieved with 1-step surgery, avoiding a previous surgical procedure to harvest cartilage and subsequent chondrocyte cultivation.

Symptomatic Early Osteoarthritis of the Knee Treated With Pulsed Electromagnetic Fields: Two-Year Follow-up.

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

Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes.

PURPOSE: Microfracture is a well-established treatment procedure for chondral defects in high-demand population with good short-term results. The purpose of our study was to evaluate long-term clinical outcome of microfracture treatment in athletes with full-thickness chondral defects. METHODS: Between 1991 and 2001, 170 patients were treated with microfracture for full-thickness knee chondral lesions at our institute and 67 of them were included in this study and prospectively followed up. Sixty-one athletes (91%) were available at final follow-up (average 15.1 years). Average lesion size was 401 ± 27 mm2. Lysholm, Tegner and International Knee Documentation Committee (IKDC) (subjective-objective) scores were utilized pre-operatively and at 2-year, 5-year and final follow-up; Knee injury and Osteoarthritis Outcome Score (KOOS), visual analog scale (VAS) and Marx scores were also collected at final follow-up. RESULTS: IKDC, Lysholm and Tegner scores increased significantly at 2 years, but gradually deteriorated at long term; however, average scores were significantly above baseline at final follow-up. Seven patients (11%) were considered as failures as they underwent another operation because of reinjury or persistent pain during the first 5 years. Pain and swelling during strenuous activities was reported only in nine patients by the end of 2 years and in 35 patients at final follow-up. Patients with smaller lesions (≤400 mm²) and younger patients (≤30 years) showed significantly better results in KOOS, VAS and Marx scores. Radiographs performed at final follow-up showed evidence of progression of osteoarthritis changes in 40% of the knees, with higher rate in older patients with large or multiple lesions (p < 0.05). CONCLUSIONS: Microfracture when applied in young patients with smaller lesions can offer good clinical results at short- and long-term follow-up; lesion size is more important prognostic factor of outcome than age. Deterioration of the clinical outcome should be expected after 2 and 5 years post-treatment, and degenerative changes are present at long-term follow-up, with higher rate in older athletes with large, multiple lesions. LEVEL OF EVIDENCE: IV.

Platelet-rich plasma treatment in symptomatic patients with knee osteoarthritis: preliminary results in a group of active patients.

BACKGROUND: With increasing frequency, platelet-rich plasma (PRP) preparations have been used to treat cartilage lesions to regenerate tissue homeostasis and retard the progression of knee osteoarthritis (OA). PURPOSE: To determine the effectiveness of intra-articular PRP injections in active patients with knee OA and to evaluate clinical outcomes in patients with and without previous surgical treatment for cartilage lesions. STUDY DESIGN: Case series. MATERIALS AND METHODS: Fifty patients with knee OA were followed for a minimum of 12 months. All were treated with 2 intra-articular injections of autologous PRP. Twenty-five patients had undergone a previous operative intervention for cartilage lesions, whereas 25 had not. Operated patients had undergone either cartilage shaving or microfracture. Multiple evaluative scores were collected at pretreatment and at 6 and 12 months posttreatment. The required sample of patients was determined beforehand by using statistical power analysis; International Knee Documentation Committee (subjective) score was defined as the primary parameter. A P value of less than 0.05 was considered statistically significant. General linear model-repeated measure test evaluated within-time improvement for each variable for all patients. Post hoc test with Bonferroni adjustment for multiple comparisons was performed to investigate the significance in improvement within time evaluations for each variable for the total sample. The differences in improvement between operated and nonoperated patients were also investigated, as were those between sexes. RESULTS: All patients showed significant improvement in all scores at 6 and 12 months (P < 0.01) and returned to previous activities. No significant difference in improvement was found between the evaluated subgroups (P < 0.01). CONCLUSIONS: The PRP treatment showed positive effects in patients with knee OA. Operated and nonoperated patients showed significant improvement by means of diminishing pain and improved symptoms and quality of life. CLINICAL RELEVANCE: There are only a few studies of PRP treatment for cartilage on osteoarthritic knees. Different PRP products might be more or less appropriate to treat different types of tissues and pathologies. The clinical efficacy of PRP remains under debate, and a standardized protocol has not yet been established.

Single- versus double-bundle ACL reconstruction: is there any difference in stability and function at 3-year followup?

BACKGROUND: Despite a number of studies comparing postoperative stability and function after anatomic double-bundle and single-bundle anterior cruciate ligament reconstruction (ACLR), it remains unclear whether double-bundle reconstruction improves stability or function. QUESTIONS/PURPOSES: We therefore asked whether patients having single- and double-bundle ACLR using semitendinosus (ST) alone differed with regard to (1) postoperative stability; (2) ROM; and (3) five functional scores. METHODS: We prospectively followed 60 patients with an isolated anterior cruciate ligament (ACL) injury. Thirty patients underwent single-bundle and 30 patients underwent double-bundle ACL reconstruction. Clinically we assessed stability and range of motion (ROM); anteroposterior stability was assessed by Rolimeter and rotational stability by a pivot shift test. Function was assessed by IKDC, Noyes, Lysholm, Marx, and Tegner activity scales. The minimum followup was 36 months (mean, 46.2 months; range, 36-60 months). RESULTS: Residual anteroposterior laxity at 3 years postoperatively was similar in both groups: 1.4 ± 0.3 mm versus 1.4 ± 0.2 mm, respectively. We observed no difference in the pivot shift test. ROM was similar in both groups, although double-bundle patients required more physical therapy sessions to gain full ROM. IKDC, Noyes, Lysholm, Marx, and Tegner scores were similar at final followup. CONCLUSION: Double-bundle reconstruction of the ACL did not improve function or stability compared with single-bundle reconstruction. LEVEL OF EVIDENCE: Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Tibial plateau fracture after primary anatomic double-bundle anterior cruciate ligament reconstruction: a case report.

Tibial plateau fracture after primary anatomic double-bundle anterior cruciate ligament (ACL) reconstruction is rare. To our knowledge, this is the first case report of a tibial plateau fracture after primary anatomic double-bundle ACL reconstruction. In our patient the tibial plateau fracture occurred after a torsional injury to the involved extremity. The fracture occurred 4.5 years after the ACL reconstruction. The fracture was intra-articular Schatzker type IV and had a significant displacement. The patient was treated operatively by open reduction-internal fixation. He recovered well.

One-Step Cartilage Repair with Bone Marrow Aspirate Concentrated Cells and Collagen Matrix in Full-Thickness Knee Cartilage Lesions: Results at 2-Year Follow-up.

OBJECTIVE: The purpose of our study was to determine the effectiveness of cartilage repair utilizing 1-step surgery with bone marrow aspirate concentrate (BMAC) and a collagen I/III matrix (Chondro-Gide, Geistlich, Wolhusen, Switzerland). MATERIALS AND METHODS: We prospectively followed up for 2 years 15 patients (mean age, 48 years) who were operated for grade IV cartilage lesions of the knee. Six of the patients had multiple chondral lesions; the average size of the lesions was 9.2 cm(2). All patients underwent a mini-arthrotomy and concomitant transplantation with BMAC covered with the collagen matrix. Coexisting pathologies were treated before or during the same surgery. X-rays and MRI were collected preoperatively and at 1 and 2 years' follow-up. Visual analog scale (VAS), International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm, Marx, SF-36 (physical/mental), and Tegner scores were collected preoperatively and at 6, 12, and 24 months' follow-up. Four patients gave their consent for second-look arthroscopy and 3 of them for a concomitant biopsy. RESULTS: Patients showed significant improvement in all scores at final follow-up (P < 0.005). Patients presenting single lesions and patients with small lesions showed higher improvement. MRI showed coverage of the lesion with hyaline-like tissue in all patients in accordance with clinical results. Hyaline-like histological findings were also reported for all the specimens analyzed. No adverse reactions or postoperative complications were noted. CONCLUSION: This study showed that 1-step surgery with BMAC and collagen I/III matrix could be a viable technique in the treatment of grade IV knee chondral lesions.