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The objective of this article was to investigate the safety and regenerative potential of a newly developed biomimetic scaffold when applied to osteochondral defects in an animal model. A new multilayer gradient nano-composite scaffold was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. In the femoral condyles of 12 sheep, 24 osteochondral lesions were created. Animals were randomized into three treatment groups: scaffold alone, scaffold colonized in vitro with autologous chondrocytes and empty defects. Six months after surgery, the animals were sacrificed and the lesions were histologically evaluated. Histologic and gross evaluation of specimens showed good integration of the chondral surface in all groups except for the control group. Significantly better bone regeneration was observed both in the group receiving the scaffold alone and in the group with scaffold loaded with autologous chondrocytes. No difference in cartilage surface reconstruction and osteochondral defect filling was noted between cell-seeded and cell-free groups. In the control group, no bone or cartilage defect healing occurred, and the defects were filled with fibrous tissue. Quantitative macroscopic and histological score evaluations confirmed the qualitative trends observed. The results of the present study showed that this novel osteochondral scaffold is safe and easy to use, and may represent a suitable matrix to direct and coordinate the process of bone and hyaline-like cartilage regeneration. The comparable regeneration process observed with or without autologous chondrocytes suggests that the main mode of action of the scaffold is based on the recruitment of local cells.

A modified hematological index of intoxication was proposed for estimation of the immune system reaction in patients with peritonitis. Critical values of the index are determined, permitting to prognosticate high possibility of lethal outcome.

We report on a 46-year-old athletic patient, previously treated with anterior cruciate ligament reconstruction, with large degenerative chondral lesions of the medial femoral condyle, trochlea and patella, which was successfully treated with a closing-wedge high tibial osteotomy and the implant of a newly developed biomimetic nanostructured osteochondral bioactive scaffold. After 1 year of follow-up the patient was pain-free, had full knee range of motion, and had returned to his pre-operation level of athletic activity. MRI evaluation at 6 months showed that the implant gave a hyaline-like signal as well as a good restoration of the articular surface, with minimal subchondral bone oedema. Subchondral oedema was almost non-visible at 12 months.

Background: The clinical application of the second-generation tissue-engineering approach for the treatment of cartilage lesions has been documented for different types of scaffolds, but systematic information on clinical efficacy and long-term results is not available., Purpose: To analyze and assess the quality of clinical studies on different products in the emerging field of matrix-assisted autologous chondrocyte transplantation. The secondary purpose of this review was to improve the quality assessment of studies by modifying the Coleman methodology score (CMS)., Study Design: Systematic review., Methods: For this review, a literature search was performed to identify all published and unpublished clinical studies of matrix-assisted (second-generation) autologous chondrocyte transplantation using the following medical electronic databases: MEDLINE, MEDLINE preprints, EMBASE, CINAHL, Life Science Citations, and British National Library of Health, including the Cochrane Central Register of Controlled Trials (CENTRAL). The search period was January 1, 1995, to July 1, 2008. To better assess cartilage-related studies, a modification of the CMS was proposed., Results: Eighteen studies were included in the analysis, reporting on 731 patients with an average follow-up of 27.3 months (6.5-60.0 months). Of the 18 studies, 2 were randomized controlled studies, 3 were prospective comparative studies, 11 were prospective cohort studies or prospective case series, and 2 were retrospective case series. Original CMSs for these studies (55.1 +/- 1.6) were significantly higher than those of cartilage repair studies in general (43.5 +/- 1.6, P < .0001) reported in 2005. The statistical analysis indicated that the modified CMS showed higher correlations and lower variability of correlations among 3 reviewers., Conclusion: The quality of the currently available data on second-generation autologous chondrocyte transplantation is still limited by study designs. The modified CMS has demonstrated better sensitivity and reproducibility with respect to the original score, so it can be recommended for cartilage clinical studies evaluation.

The studying of the species and their sensitivity to antibiotics of mostly spread infection factors constitute one of the main trends in intrastationary infection prophylaxis. In 307 patients, suffering the infection processes of various localization, such as purulent wounds, cholecystitis, cholangitis, peritonitis etc., there were studied up the species and sensitivity to antibiotics of the microorganisms determined. Staphylococcus spp. and E. coli were determined most frequently, somewhat rarely--P. aeruginosa, K. pneumoniae, Proteus spp., Enterobacter spp., E. faecalis, S. pyogenes, C. albicans and Citrobacter spp. The factors determined were most sensitive to imipenem (72,09% of sensitive clones), carbenicilline (61.9%), meropenem (60.49%) and ceftriaxone (58.33%).

While examination of 49 patients, in whom peritonitis was diagnosed, the values of 18 leukocyte indices were determined, trustworthy differences of the indices were established in survivors and dead patients. Critical values of the indices, permitting to prognosticate high possibility of lethal outcome occurring, were determined.

Background: There are an increasing number of reports on the hepatitis B virus (HBV) genotype distribution in acute or chronic HBV-infected patients in Japan; however, reports on the HBV genotype of blood donors are few. To compare the HBV genotypes of hepatitis B surface antigen (HBsAg)-positive blood donors with infected patients, all the HBsAg-positive donors' genotypes were determined., Study Design and Methods: Data on Japanese blood donors from October 2006 to September 2007 were obtained from the Japanese Red Cross database. The number of available samples was 1979, and the HBV genotypes were determined in 1887 samples. The six major genotypes of HBV (A-F) were determined by enzyme-linked immunosorbent assay. The presence of the immunoglobulin M (IgM) antibody against the HBV core antigen was determined by enzyme immunoassay among all HBsAg-positive donors., Results: A significant difference in the HBV genotype distribution between donors and patients was in the C/B genotype ratio. The ratios were low in blood donors (2.0-3.9) and high in patients (5.3-18.2). The genotype B ratio increases from 13.8% in teenage donors to 42.4% in those in their 50s; however; the genotype C ratio decreases from 83.1% in teenage donors to 55.1% in those in their 50s. In both IgM antibody against hepatitis B core antigen and nucleic acid test-positive donors, genotypes A and B were restricted to male donors., Conclusions: The age-specific distribution of HBV genotypes in Japanese blood donors was observed in the B/C genotype ratio. The gender-specific distribution of HBV genotype A, which originated from the US or Western countries, was observed in male Japanese donors.

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.

Background: Patellofemoral lesions represent a very troublesome condition to treat for orthopaedic surgeons; however, second-generation autologous chondrocyte implantation (ACI) seems to offer an interesting treatment option with satisfactory results at short-term follow-up., Hypothesis: Hyaluronan-based scaffold seeded with autologous chondrocytes is a viable treatment for the damaged articular surface of the patellofemoral joint., Study Design: Case series; Level of evidence, 4., Methods: Among a group of 38 patients treated for full-thickness patellofemoral chondral lesions with second-generation ACI, we investigated 34 who were available for final follow-up at 5 years. These 34 had chondral lesions with a mean size of 4.45 cm(2). Twenty-one lesions were located on the patella, 9 on the trochlea, and 4 patients had multiple lesions: 3 had patellar and trochlear lesions, and 1 had patellar and lateral femoral condyle lesions. Twenty-six lesions (76.47%) were classified as International Cartilage Repair Society (ICRS) grade IV A or B, 5 lesions (14.70%) were grade IIIC, and 3 (8.82%) were lesions secondary to osteochondritis dissecans (OCD). Results were evaluated using the International Knee Documentation Committee (IKDC) 2000 subjective and objective scores, EuroQol (EQ) visual analog scale (VAS), and Tegner scores at 2 and 5 years. Eight patients had second-look arthroscopy and biopsies., Results: All the scores used demonstrated a statistically significant improvement (P < .0005) at 2 and 5 years' follow-up. Objective preoperative data improved from 8 of 34 (23.52%) normal or nearly normal knees to 32 of 34 (94.12%) at 2 years and 31 of 34 (91.17%) at 5 years after transplantation. Mean subjective scores improved from 46.09 points preoperatively to 77.06 points 2 years after implantation and 70.39 at 5 years. The Tegner score improved from 2.56 to 4.94 and 4.68, and the EQ VAS improved from 56.76 to 81.47 and 78.23 at 2 and 5 years' follow-up, respectively. A significant decline of IKDC subjective and Tegner scores was found in patients with multiple and patellar lesions from 2 to 5 years' follow-up. Second-look arthroscopies in 8 cases revealed the repaired surface to be nearly normal with biopsy samples characterized as hyaline-like in appearance., Conclusion: Hyaluronan-based scaffold seeded with autologous chondrocytes can be a viable treatment for patellofemoral chondral lesions.

Background: Various approaches have been proposed to treat articular cartilage lesions, which are plagued by inherent limited healing potential., Purpose: To compare the clinical outcome of patients treated with second-generation autologous chondrocyte implantation implants with those treated with the microfracture repair technique at 5-year follow-up., Study Design: Cohort study; Level of evidence, 2., Methods: Eighty active patients (mean age, 29.8 years) and grade III to IV cartilage lesions of the femoral condyles or trochlea were treated with arthroscopic second-generation autologous chondrocyte implantation Hyalograft C or microfracture (40 patients per group). Patients achieved a minimum 5-year follow-up and were prospectively evaluated., Results: Both groups showed statistically significant improvement of all clinical scores from preoperative interval to 5-year follow-up. There was a significant improvement for the International Knee Documentation Committee subjective score from pre-operative to 5-year follow-up (Wilcoxon test, P < .001). In the microfracture group, the International Knee Documentation Committee objective score increased from 2.5% normal and nearly normal knees before the operation to 75% normal and nearly normal knees at 5-year follow-up, and the subjective score increased from 41.1 +/- 12.3 preoperatively to 70.2 +/- 14.7 at 5-year follow-up. In the group treated with Hyalograft C, the International Knee Documentation Committee objective score increased from 15% normal and nearly normal knees before the operation to 90% normal and nearly normal knees at 5-year follow-up, and its subjective score increased from 40.5 +/- 15.2 preoperatively to 80.2 +/- 19.1 at 5-year follow-up (Wilcoxon test, P < .001). When comparing the groups, better improvement of the International Knee Documentation Committee objective (P < .001) and subjective (P = .003) scores was observed in the Hyalograft C group at 5-year follow-up. The return to sports at 2 years was similar in both groups and remained stable after 5 years in the Hyalograft C group; it worsened in the microfracture group., Conclusion: Both methods have shown satisfactory clinical outcome at medium-term follow-up. Better clinical results and sport activity resumption were noted in the group treated with second-generation autologous chondrocyte transplantation.

In recent years, regenerative techniques, such as autologous chondrocyte implantation (ACI), have emerged as a potential therapeutic option for the treatment of chondral lesions. However, the good results reported have to be weighed against the number of problems that can be observed with traditional ACI methods. To address these problems, the so-called second generation ACI techniques have been developed. Autologous chondrocyte transplantation on a 3-dimensional matrix was introduced in clinical practice from 1998 to 1999 and results at short to medium-term follow-up are well documented for different types of scaffolds. These techniques may be used for the treatment of large chondral lesions in the young, active population and highly competitive athletes, but long-term and randomized controlled studies will be needed to confirm reliability of these procedures.

Objective: The aim of the study was to investigate the use of a novel hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Two different surgical implantation techniques in a sheep model were evaluated., Methods: Twenty-four skeletally mature sheep were treated with total medial meniscus replacements, while two meniscectomies served as empty controls. The animals were divided into two groups: cell-free scaffold and scaffold seeded with autologous chondrocytes. Two different surgical techniques were compared: in 12 animals, the implant was sutured to the capsule and to the meniscal ligament; in the other 12 animals, also a transtibial fixation of the horns was used. The animals were euthanized after 4 months. The specimens were assessed by gross inspection and histology., Results: All implants showed excellent capsular ingrowth at the periphery. Macroscopically, no difference was observed between cell-seeded and cell-free groups. Better implant appearance and integrity was observed in the group without transosseous horns fixation. Using the latter implantation technique, lower joint degeneration was observed in the cell-seeded group with respect to cell-free implants. The histological analysis indicated cellular infiltration and vascularization throughout the implanted constructs. Cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs., Conclusion: The current study supports the potential of a novel HYAFF/polycaprolactone scaffold for total meniscal substitution. Seeding of the scaffolds with autologous chondrocytes provides some benefit in the extent of fibrocartilaginous tissue repair.

Background: Articular cartilage lesions, with their inherent limited healing potential, remain a challenging problem for orthopaedic surgeons. Various approaches have been proposed to treat these lesions; nevertheless, opinions on indications and clinical efficacy of these techniques are still controversial., Purpose: To evaluate the outcome of osteochondral autografts for treatment of femoral condyle cartilage lesions at a medium-to long-term follow-up., Study Design: Case series; Level of evidence, 4., Methods: We prospectively evaluated 30 patients (mean age, 29.3 years) with full-thickness knee chondral lesions (<2.5 cm(2)) treated with arthroscopic autologous osteochondral transplantation. Thirteen patients underwent previous surgery, while 17 patients were operated on for the first time. In 19 patients, associated procedures were performed. All patients were evaluated at 2- and 7-year follow-up. The International Cartilage Repair Society form, Tegner score, and magnetic resonance imaging were used for clinical evaluation., Results: The International Cartilage Repair Society objective evaluation showed 76.7% of patients had good or excellent results at 7-year follow-up, and International Knee Documentation Committee subjective score significantly improved from preoperative (34.8) to 7-year follow-up (71.8). The Tegner evaluation showed a significant improvement after the surgery at 2- and 7-year follow-up (from 2.9 to 6.2 and 5.6, respectively); however, we noticed reduced sports activity from 2- to 7-year follow-up. Magnetic resonance imaging evaluation showed good integration of the graft in the host bone and complete maintenance of the grafted cartilage in more than 60% of cases., Conclusion: The results of this technique at medium- to long-term follow-up are encouraging. This arthroscopic 1-step surgery appears to be a valid solution for treatment of small, grade III to IV cartilage defects.

The study was conducted to evaluate sensitivity to 44 antibiotics of pathogens isolated from 183 women with genital inflammatory diseases and to offer schemes of antibacterial treatment. The pathogens (66.8%) were in associations. The probability of isolation of main bacteria and sexually transmitted microorganisms in different associations was estimated in the work. Using the methods of clustering analysis all the tested antibiotics were divided into 3 groups, depending on their antimicrobial activity toward bacteria isolated both in monoculture and in associations. Furagin, cefotaxime, gentamicin, cefoperazon, ceftriaxon, ciprofloxacin, pefloxacin, as well as, cefazolin, zoxan, ofloxacin, and lomefloxacin were shown to be the most effective antibiotics in vitro. The least activity was diplayed by ectericid, chlorophillipt, and ampiox. These data should be considered when choosing the antibacterial treatment of genital inflammatory diseases.

Extensive bone loss is still a major problem in orthopedics. A number of different therapeutic approaches have been developed and proposed, but so far none have proven to be fully satisfactory. We used a new tissue engineering approach to treat four patients with large bone diaphysis defects and poor therapeutic alternatives. To obtain implantable three-dimensional (3D) living constructs, cells isolated from the patients' bone marrow stroma were expanded in culture and seeded onto porous hydroxyapatite (HA) ceramic scaffolds designed to match the bone deficit in terms of size and shape. During the surgical session, an Ilizarov apparatus or a monoaxial external fixator was positioned on the patient's affected limb and the ceramic cylinder seeded with cells was placed in the bone defect. Patients were evaluated at different postsurgery time intervals by conventional radiographs and computed tomography (CT) scans. In one patient, an angiographic evaluation was performed at 6.5 years follow-up. In this study we analyze the long-term outcome of these patients following therapy. No major complications occurred in the early or late postoperative periods, nor were major complaints reported by the patients. No signs of pain, swelling, or infection were observed at the implantation site. Complete fusion between the implant and the host bone occurred 5 to 7 months after surgery. In all patients at the last follow-up (6 to 7 years postsurgery in patients 1 to 3), a good integration of the implants was maintained. No late fractures in the implant zone were observed. The present study shows the long-term durability of bone regeneration achieved by a bone engineering approach. We consider the obtained results very promising and propose the use of culture-expanded osteoprogenitor cells in conjunction with porous bioceramics as a real and significant improvement in the repair of critical-sized long bone defects.

A biodegradable, hyaluronian-based biocompatible scaffold was used for autologous chondrocyte transplantation. This prospective study analyzes a clinical outcome of 70 consecutive patients treated by arthroscopic autologous chondrocyte transplantation at minimum 24 months follow up (47 of these patients achieved minimum 36 months follow-up and 21 patients minimum 48 months follow-up) in order to establish clear indication criteria for this type of treatment. 31 of these patients presented isolated chondral lesions, while 39 patients with associated lesions (23 ACL lesions, 28 meniscal lesions, 1 varus knee) were treated during the same surgical procedure with cartilage harvesting. A statistically significant clinical improvement was shown just at 24 months and the second-look arthroscopy demonstrated a complete coverage of the grafted area with a hyaline cartilage-like tissue in 12 of 15 analyzed patients. A better clinical outcome was observed in young, well-trained patients and in traumatic lesions. Other factors, such as defect size, localization, previous and associated surgery did not influence significantly the results. This matrix autologous chondrocyte transplantation procedure simplifies the surgical procedure and can be performed arthroscopically, thus reducing surgical morbidity and recovery time.

Meniscal substitution is a fundamental procedure to prevent osteoarthritis of the knee after massive meniscectomy. Stone, Steadman and Rodkey have developed a bioreadsorbable collagen matrix (CMI) which acts as a scaffold to restore the original medial meniscal. The objective of this study was to prospectively evaluate the results of CMI implantation at a follow up from a minimum of 6 to a maximum of 8 years. Eight patients (mean age 25) were evaluated at a final observation point from 6 to 8 years after CMI implantation. Inclusion criteria were an irreparable meniscal tear or a previous meniscectomy involving the medial meniscus. Follow up evaluation included Cincinnati Knee Rating Scale (CKRS), IKDC, subjective evaluation and X-ray and MRI control. There were no complications related to the device. All patients were able to return to day activities without limitations 3 months after surgery. Both subjective CKRS score and objective IKDC score showed improvement in all cases except one patient with an ACL re-injury. In two cases scores were slightly worse from 2 years after surgery to the final observation point. The other five cases obtained maximum score at final follow-up. In four cases the absence of pain remained until the final observation point, while in four cases a low entity of pain was described at long term follow-up. MRI showed in five cases mixoid degeneration signal, two had normal signal with reduced size, while one patient had no recognizable implant. Six patients had preserved cartilage and articular space, with no changes respect to pre-op control. Arthroscopic second look evaluation has been performed in three cases, revealing in two cases the presence of the implant, although with a reduced size respect to the original one, while in one case the CMI was almost disappeared. Our small series of eight patients prospectively followed from 6 to 8 years of follow-up has shown highly satisfactory results. Although the aspect of the implant was mostly abnormal, the implant may have helped reduce the deterioration of the knee joint at final observation time.

Objective: To identify an appropriate cell source for the generation of meniscus substitutes, among those which would be available by arthroscopy of injured knee joints., Methods: Human inner meniscus cells, fat pad cells (FPC), synovial membrane cells (SMC) and articular chondrocytes (AC) were expanded with or without specific growth factors (Transforming growth factor-beta1, Fibroblast growth factor-2 and Platelet-derived growth factor bb, TFP) and then induced to form three-dimensional cartilaginous tissues in pellet cultures, or using a hyaluronan-based scaffold (Hyaff-11), in culture or in nude mice. Human native menisci were assessed as reference., Results: Cell expansion with TFP enhanced glycosaminoglycan (GAG) deposition by all cell types (up to 4.1-fold) and messenger RNA expression of collagen type II by FPC and SMC (up to 472-fold) following pellet culture. In all models, tissues generated by AC contained the highest fractions of GAG (up to 1.9% of wet weight) and were positively stained for collagen type II (specific of the inner avascular region of meniscus), type IV (mainly present in the outer vascularized region of meniscus) and types I, III and VI (common to both meniscus regions). Instead, inner meniscus, FPC and SMC developed tissues containing negligible GAG and no detectable collagen type II protein. Tissues generated by AC remained biochemically and phenotypically stable upon ectopic implantation., Conclusions: Under our experimental conditions, only AC generated tissues containing relevant amounts of GAG and with cell phenotypes compatible with those of the inner and outer meniscus regions. Instead, the other investigated cell sources formed tissues resembling only the outer region of meniscus. It remains to be determined whether grafts based on AC will have the ability to reach the complex structural and functional organization typical of meniscus tissue.

Background: Tissue engineering has emerged as a potential therapeutic option for cartilage regeneration., Hypothesis: Hyaluronan-based scaffolds seeded with autologous chondrocytes are a viable treatment for damaged articular surface of the patellofemoral joint., Study Design: Case series; Level of evidence, 4., Methods: Thirty-two chondral lesions with a mean size of 4.7 cm(2) were treated with Hyalograft-C. Twenty-two lesions were located in the patella and 10 in the trochlea. Sixteen patients had previous trauma, 3 had osteochondritis dissecans, and 13 had degenerative changes. Transplantations were carried out arthroscopically or through a miniarthrotomy incision. Eight patients had concomitant procedures, including patellar realignment (2), lateral release (3), and meniscectomy (3). Results were evaluated using the International Cartilage Repair Society-International Knee Documentation Committee scale, EuroQol EQ-5D form, and magnetic resonance imaging scans at 12 and 24 months. Six patients had second-look arthroscopy and biopsies. Statistical analysis was performed using the paired t test and Wilcoxon signed rank test., Results: The International Cartilage Repair Society-International Knee Documentation Committee and EuroQol EQ-5D scores demonstrated a statistically significant improvement (P < .0001). Objective preoperative data improved from 6/32 (18.8%) with International Knee Documentation Committee A or B to 29/32 (90.7%) at 24 months after transplantation. Mean subjective scores improved from 43.2 points preoperatively to 73.6 points 24 months after implantation. Magnetic resonance imaging studies at 24 months revealed 71% to have an almost normal cartilage with positive correlation to clinical outcomes. Second-look arthroscopies in 6 cases revealed the repaired surface to be nearly normal with biopsy samples characterized as hyaline-like in appearance., Conclusion: Biodegradable scaffolds seeded with autologous chondrocytes can be a viable treatment for chondral lesions. The type of tissue repair achieved demonstrated histologic characteristics similar to normal articular cartilage. Long-term investigations are needed to determine the durability of the repair produced with this technique.

Objective: Regeneration of the meniscal tissue occurs to a limited extent, and the loss of meniscal tissue leads to osteoarthritis. A new biomaterial consisting of hyaluronic acid and polycaprolactone was used as a meniscus substitute in sheep to evaluate the properties of the implant material with regard to size, biomechanical stability, tissue ingrowth, and integration., Methods: Eight sheep (right stifle joints) were treated with three total and three partial meniscus replacements while two meniscectomies served as empty controls. The animals were euthanized after 6 weeks. The specimens were assessed by gross inspection and histology, and compared with the nonoperated left joints., Results: The surgical technique was found to be feasible. The implants remained in position, did not tear, and showed excellent tissue ingrowth to the capsule. Tissue integration was also observed between the original meniscus and the implant. However, graft compression and extrusion occurred. The histological investigation revealed tissue formation, cellular infiltration and vascularization. Cartilage degeneration was more severe in the operated joints., Conclusion: The present study shows promising results concerning the qualities of this biomaterial with regard to implantation technique, stability and tissue ingrowth.

The regeneration of damaged organs requires that engineered tissues mature when implanted at sites of injury or disease. We have used new analytic techniques to determine the extent of tissue regeneration after treatment of knee injury patients with a novel cartilage tissue engineering therapy and the effect of pre-existing osteoarthritis on the regeneration process. We treated 23 patients, with a mean age of 35.6 years, presenting with knee articular cartilage defects 1.5 cm2 to 11.25 cm2 (mean, 5.0 cm2) in area. Nine of the patients had X-ray evidence of osteoarthritis. Chondrocytes were isolated from healthy cartilage removed at arthroscopy. The cells were cultured for 14 days, seeded onto esterified hyaluronic acid scaffolds (Hyalograft C), and grown for a further 14 days before implantation. A second-look biopsy was taken from each patient after 6 to 30 months (mean, 16 months). After standard histological analysis, uncut tissue was further analyzed using a newly developed biochemical protocol involving digestion with trypsin and specific, quantitative assays for type II collagen, type I collagen, and proteoglycan, as well as mature and immature collagen crosslinks. Cartilage regeneration was observed as early as 11 months after implantation and in 10 out of 23 patients. Tissue regeneration was found even when implants were placed in joints that had already progressed to osteoarthrosis. Cartilage injuries can be effectively repaired using tissue engineering, and osteoarthritis does not inhibit the regeneration process.

Adequacy and effectiveness of empirical antibacterial therapy of severe nosocomial infections with meropenem vs. combined regimens of antibacterial therapy were investigated and the ratio of the cost and effectiveness of the compared regimens was evaluated. A prospective, randomized, open, comparative study of two initiative regimens of empirical antibacterial therapy of severe nosocomial infections was performed: meropenem in a daily dose of 1.5-3 g and the standard regimen with the use of betalactams and fluoroquinolones in combination with aminoglycosides and/or metronidazole. Patients with recorded diagnosis of nosocomial pneumonia (including the ventilator-associated one) or abdominal infection with the signs of severe sepsis and severity of APACHE II > 14 were enrolled. The patients were stratified into 2 groups subject to the disease severity, i.e. APACHE II 15-20 and APACHE II 21-25. One hundred thirty five out of 166 patients with recorded nosocomial infection were included into the final estimate of the therapy adequacy and effectiveness (Protocol Analysis): 62 patients were treated with meropenem and in the treatment of 73 patients the standard antibacterial therapy was used. In the group of the patients treated with meropenem there were stated significantly higher clinical effectiveness (recovery in 80.6% of the patients vs. the control of 46.6%, p < 0.01) and pathogen eradication (89.6 and 48.1% respectively, p < 0.01). The difference in the clinical and bacteriological effectiveness of meropenem and the standard therapy was more evident in the subgroups of more severe patients (APACHE > 20). With the use of meropenem the probability of recovery from nosocomial infection was significantly higher (RR 1.73-1.94, p < 0.001) vs. the control. Meropenem provided significantly higher eradication of the pathogens: P. aeruginosa (88 and 40% respectively, p = 0.007), E. coli (100 and 46.7%, p = 0.003), Acinetobacter spp. (90.9 and 40%, p = 0.02). The antibacterial therapy with the use of meropenem was assessed as adequate in 51 out of 56 patients (91.1%), that was 3 times as frequent as with the use of the standard antibacterial therapy (33.9%). The cost-effectiveness coefficient with the use of meropenem was 2.2 times lower vs. the control. Therefore, the empirical therapy of severe nosocomial infections with meropenem proved to be more adequate and from the economic viewpoint more advantageous vs. the standard combined regimens of antibacterial therapy, that was evident from significantly higher clinical and bacteriological efficacy of the treatment and decrease of the terms of the patients hospitalization in intensive care units (on the average by 5 days).

Objective: To compare the respective performance and effectiveness of autologous chondrocyte implantation (ACI) and mosaicplasty at resurfacing local full-thickness chondral defects of the knee., Design: Randomized clinical trial., Setting: Multicenter trial at orthopedic clinics and university hospitals conducted from 1997 to 2000., Patients: A population of patients selected according to eligibility criteria of age, traumatic origin of the defect, its localization, size, and gravity, and above all, no previous surgical treatment of the lesion. Forty-seven patients were randomly assigned to ACI or mosaicplasty and subjected to arthroscopic debridement of the lesion at the time of enrollment. They were called for surgery 6 months after the initial debridement., Main Outcome: Improved knee functionality as assessed by repeated clinical evaluation based on the International Knee Documentation Committee Scale and the Lysholm Knee Scoring Scale., Results: Fourteen patients (31.8%) experienced substantial improvement following the initial debridement and, being clinically cured, received no further treatment. Seven patients (15.9%) were lost to follow-up. Among the 23 patients (52.3%) who could effectively be evaluated, a complete recovery (ie, Lysholm Knee Scoring Scale score, 90-100) was observed upon clinical examination in 88% of the mosaicplasty-treated patients and in 68% of the ACI-treated ones (P = 0.093)., Conclusions: Although the low power of our study prevents definitive conclusions, ACI and mosaicplasty are cartilage repair techniques that are clinically equivalent and similar in performance. The high percentage of spontaneous improvement ((1/3) of the patients) observed after simple debridement calls into question the need for prompt surgical treatment of patients with lesions similar to those included in this clinical trial. Moreover, this finding warrants further investigation, ideally through randomized clinical trials in which patients subjected to debridement alone are compared with patients undergoing reconstructive surgery.

Unlabelled: The use of tissue engineering for cartilage repair has emerged as a potential therapeutic option and has led to the development of Hyalograft C, a tissue-engineered graft composed of autologous chondrocytes grown on a scaffold entirely made of HYAFF 11, an esterified derivative of hyaluronic acid. Here we present the results of an ongoing multicenter clinical study conducted with the primary objective to investigate the subjective symptomatic, functional and health-related quality of life outcomes of patients treated with Hyalograft C. Clinical results on the cohort of 141 patients with followup assessments ranging from 2 to 5 years (average followup time: 38 months), are reported. At followup 91.5% of patients improved according to the International Knee Documentation Committee subjective evaluation; 76% and 88% of patients had no pain and mobility problems respectively assessed by the EuroQol-EQ5D measure. Furthermore, 95.7% of the patients had their treated knee normal or nearly normal as assessed by the surgeon; cartilage repair was graded arthroscopically as normal or nearly normal in 96.4% of the scored knees; the majority of the second-look biopsies of the grafted site histologically were assessed as hyaline-like. Importantly, a very limited complication rate was recorded in this study. The positive clinical results obtained indicate that Hyalograft C is a safe and effective therapeutic option for the treatment of articular cartilage lesions., Level of Evidence: Therapeutic study, Level III-2 (retrospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

Purpose: To prospectively evaluate the mosaicplasty technique for treatment of femoral condyle cartilage lesions (Outerbridge grade IV) less than 2.5 cm2 in homogeneous group of young active patients., Type of Study: Case series., Methods: Thirty-seven patients (10 female, 27 male; mean age, 29.5 years) with full-thickness knee chondral lesions were treated by the arthroscopic mosaicplasty technique. All patients practiced sports. There were 12 ACL reconstructions, 11 medial meniscectomies, and 8 lateral meniscectomies associated; 10 meniscectomies, 9 ACL reconstructions, and 5 cartilage reparative operations had been previously performed. All patients were evaluated at a 2-year follow-up. The International Cartilage Repair Society (ICRS) form, return to sports, computed tomography, or magnetic resonance imaging were used for clinical evaluation. In some cases, second-look arthroscopy was performed., Results: The ICRS showed 78.3% good and excellent results; 27 patients returned to sports at the same level and 5 at a lower level, but 5 were not able to resume sports. Results in the lateral condyles were significantly better than those in medial condyles, and younger patients had a better clinical outcome than did older patients. Cases with associated surgery had better clinical results; previous surgery did not significantly influence the clinical outcome., Conclusions: The results of this technique at medium-term follow-up are encouraging with 78.3% clinically satisfactory results. Better results can be obtained in young patients with associated surgery, with localized grade 4 lesions of the lateral condyles. This arthroscopic 1-step surgery appears to be a valid solution for the treatment of grade III-IV cartilage defects not more than 2.5 cm2., Level of Evidence: Level IV, Case Series.

Hyalograft C is an innovative tissue-engineering approach for the treatment of knee cartilage defects involving the implantation of laboratory expanded autologous chondrocytes grown on a three-dimensional hyaluronan-based scaffold. This technique has recently been introduced into clinical practice, with more than 600 patients treated so far. Because no periosteal coverage is required to keep the graft in place, surgical time and morbidity are reduced, and handling of the graft is much simpler than currently available autologous chondrocyte implantation techniques. The safety profile of the treatment appears positive, with a limited number of adverse events reported. Here we discuss the clinical, arthroscopic and histological results from a cohort of 67 patients treated with Hyalograft C (mean follow-up time from implantation of 17.5 months). Results are reported based on four endpoints: patients' subjective evaluation of knee conditions (97% of patients improved) and quality of life (94% improved), surgeons' knee functional test (87% of patients with the best scores), arthroscopic evaluation of cartilage repair (96.7% biologically acceptable) and histological assessment of the grafted site (majority of specimens hyaline-like). The positive clinical results obtained indicate that Hyalograft C may be a viable therapeutic option for the treatment of acute cartilage lesions.

A tissue engineering, cell-based therapeutic approach could be essential for extensive bone or cartilage reconstruction. This article is divided in two chapters and describes new cell-based surgical techniques for cartilage and bone reconstruction. The second part of the article, regarding cartilage repair, describes a new arthroscopic surgical technique for tissue engineered cartilage grafting. A 3-dimensional hyaluronic acid support is used for autologous chondrocyte culturing. The technique reduces morbidity of classic autologous implant avoiding open surgery and periosteal flap use. With this technique is possible to reduce the patient morbidity, time and cost of surgery.

A tissue engineering, cell-based therapeutic approach could be essential for extensive bone or cartilage reconstruction. This article is divided in two chapters and describes new cell-based surgical techniques for cartilage and bone reconstruction. In the first part on bone reconstruction, marrow-derived osteogenic progenitor cells combined with hydroxyapatite were utilized. The validity of this model has been shown for the repair of critical size bone defects in large size animal models. We used this cell-based therapeutic approach to treat 3 patients with large bone defects, achieving bone reconstruction.

This prospective study examined 50 patients who underwent ACL surgery using hamstring tendons with a modification including intra- and extra-articular reconstruction. All patients were athletes competing at a high level in various sports. Full return to sports was allowed at 4 months. IKDC score and KT-2000 were used for assessing clinical outcome at a mean of 6.4 years (5-7 years) Resumption of sport, Tegner activity score, and isokinetic test were also used. The IKDC score showed 92% of normal or nearly normal knees. Of the 50 patients 48 regained full extension, and only two had extension deficit between 0 degrees and 3 degrees. KT evaluation was less than 3 mm in 38 cases (76%), 3-5 mm in 9 (18%), and more than 5 mm in 3 (6%). In 90% of cases the patient resumed sport at the same level. The mean Tegner activity score was 8.1 (5-10). The isokinetic test showed no deficit for hamstring and quadriceps muscles. Removal of staples was necessary in eight cases (16%) due to femoral lateral bursitis. Acute reconstruction had significantly better clinical assessment of abnormal laxity and KT value. Men had significantly better results then women. This technique demonstrated a high reliability, low morbidity, low functional deficit and fast recovery using hamstring grafts.

We describe an arthroscopic surgical technique for tissue engineered cartilage grafting. A three-dimensional hyaluronic acid support is used for autologous chondrocyte culturing. The technique reduces morbidity of classic autologous implant and avoids open surgery and the use of a periosteal flap. The procedure includes the advantages of arthroscopic osteochondral grafting without donor site morbidity. With this technique is possible to reduce the patient morbidity, time and cost of surgery.

The ability of marrow-derived osteoprogenitor cells to promote repair of critical-size tibial gaps upon autologous transplantation on a hydroxyapatite ceramic (HAC) carrier was tested in a sheep model. Conditions for in vitro expansion of sheep bone marrow stromal cells (BMSC) were established and the osteogenic potential of the expanded cells was validated. Ectopic implantation of sheep BMSC in immunocompromised mice led to extensive bone formation. When used to repair tibial gaps in sheep, cell-loaded implants (n = 2) conducted a far more extensive bone formation than did cell-free HAC cylinders (n = 2) over a 2-month period. In cell-loaded implants, bone formation was found to occur both within the internal macropore space and around the HAC cylinder while in control cell-free implants, bone formation was limited mostly to the outer surface and was not observed in most of the inner pores. As tested in an indentation assay, the stiffness of the complex HAC-bone material was found to be higher in cell-loaded implants compared to controls. Our pilot study on a limited number of large-sized animals suggests that the use of autologous BMSC in conjunction with HAC-based carriers results in faster bone repair compared to HAC alone. Potentially this combination could be used clinically in the treatment of extensive long bone defects., (Copyright 2000 John Wiley & Sons, Inc.)

This study reports on 13 patients (mean age: 31 years) with a femoral condyle defect >1.5 cm2 who underwent treatment with an osteochondral graft of the same size obtained from the superior aspect of the lateral condyle, preserving the patellar groove. Mean follow-up was 61.5 months (range: 13-141 months). Twelve results were rated clinically as satisfactory with patients able to resume their normal pre-injury level of activity, and 1 case was rated as poor. No patient reported any patellar problems. Radiographic and computed tomographic evaluation demonstrated good integration of the graft in the host bone. The results of this technique at relatively long-term follow-up are encouraging, with a high percentage of subjective satisfaction. This technique appears to be reliable and provides a valid solution for treatment of wide cartilage defects when other techniques are too complex or inadequate.

The capacity of hydroxyapatite (HA) implants to support large defect repair in weight-bearing long bones of large size animals was investigated. Diaphyseal resections 3.5 cm of the tibia were performed in five adult sheep. They were substituted with HA macroporous ceramic cylinders anatomically shaped, and an external fixator was assembled. The sheep were sacrificed at 20, 40, 60, 120, and 270 days after surgery, respectively. Histology and micro X-ray study of resected implants and adjacent tissues showed proper integration of ceramic with newly formed periosteal bone as early as 20 days after surgery. In one sheep, the external fixator was removed 5 months after surgery. The animal gained the ability to walk with no functional impairment until it was sacrificed 4 months later. At this time, extensive integration of ceramic with bone was detected radiographically and confirmed by a morphological study of the resected sample. Our data indicate that large defects in a weight-bearing long bone can be repaired to the extent necessary for full functional recovery in large animals. These data set the stage for further intervention on material properties as well as for preliminary attempts to use ceramic prostheses for reconstruction of large bone defects in humans.

Overweight patients are often considered poor candidates for total knee arthroplasty (TKA). A retrospective study of this was done on 47 osteoarthritic knees treated by TKA without patella resurfacing between March 1991 and June 1993. The Hospital for Special Surgery (HSS) rating system was used for clinical evaluation, and radiographs to study the degree of osteoarthritis and radiolucency. Correlations between overweight, range of motion (ROM) and stage of patellar damage and other measured variables (HSS score, patellar pain and radiolucency) were studied. Overweight was not correlated with HSS score, radiolucency or patellar pain. ROM was significantly correlated with patellar pain and HSS score, with better results in patients with ROM between 90 degrees and 110 degrees. Therefore, we believe that TKA in osteoarthritic knees can lead to successful results, even in active or overweight patients.