Effects of a platelet gel on early graft revascularization after anterior cruciate ligament reconstruction: a prospective, randomized, double-blind, clinical trial.

BACKGROUND: Slow graft healing in bone tunnels and a slow graft ligamentization process after anterior cruciate ligament (ACL) reconstruction are some of the reasons for prolonged rehabilitation. AIMS: The purpose of this study was to determine if the use of platelet gel (PG) accelerates early graft revascularization after ACL reconstruction. METHODS: PG was produced from autologous platelet-rich plasma and applied locally. We quantitatively evaluated the revascularization process in the osteoligamentous interface zone in the bone tunnels and in the intra-articular part of the graft by means of contrast-enhanced magnetic resonance imaging (MRI). RESULTS: After 4-6 weeks, the PG-treated group demonstrated a significantly higher level of vascularization in the osteoligamentous interface (0.33 ± 0.09) than the control group (0.16 ± 0.09, p < 0.001). In the intra-articular part of the graft, we found no evidence of revascularization in either group. CONCLUSION: Locally applied PG enhanced early revascularization of the graft in the osteoligamentous interface zone after ACL reconstruction.

Articular cartilage repair by genetically modified bone marrow aspirate in sheep.

Bone marrow presents an attractive option for the treatment of articular cartilage defects as it is readily accessible, it contains mesenchymal progenitor cells that can undergo chondrogenic differentiation and, once coagulated, it provides a natural scaffold that contains the cells within the defect. This study was performed to test whether an abbreviated ex vivo protocol using vector-laden, coagulated bone marrow aspirates for gene delivery to cartilage defects may be feasible for clinical application. Ovine autologous bone marrow was transduced with adenoviral vectors containing cDNA for green fluorescent protein or transforming growth factor (TGF)-beta1. The marrow was allowed to clot forming a gene plug and implanted into partial-thickness defects created on the medial condyle. At 6 months, the quality of articular cartilage repair was evaluated using histological, biochemical and biomechanical parameters. Assessment of repair showed that the groups treated with constructs transplantation contained more cartilage-like tissue than untreated controls. Improved cartilage repair was observed in groups treated with unmodified bone marrow plugs and Ad.TGF-beta1-transduced plugs, but the repaired tissue from TGF-treated defects showed significantly higher amounts of collagen II (P<0.001). The results confirmed that the proposed method is fairly straightforward technique for application in clinical settings. Genetically modified bone marrow clots are sufficient to facilitate articular cartilage repair of partial-thickness defects in vivo. Further studies should focus on selection of transgene combinations that promote more natural healing.

Chondrogenic potential of human synovial mesenchymal stem cells in alginate.

OBJECTIVE: In a recent study, we demonstrated that mesenchymal stem cells (MSCs) derived from the synovial membranes of bovine shoulder joints could differentiate into chondrocytes when cultured in alginate. The purpose of the present study was to establish the conditions under which synovial MSCs derived from aging human donors can be induced to undergo chondrogenic differentiation using the same alginate system. METHODS: MSCs were obtained by digesting the knee-joint synovial membranes of osteoarthritic human donors (aged 59-76 years), and expanded in monolayer cultures. The cells were then seeded at a numerical density of 4x10(6)/ml within discs of 2% alginate, which were cultured in serum-containing or serum-free medium (the latter being supplemented with 1% insulin, transferrin, selenium (ITS). The chondrogenic differentiation capacity of the cells was tested by exposing them to the morphogens transforming growth factor-beta1 (TGF-beta1), TGF-beta2, TGF-beta3, insulin-like growth factor-1 (IGF-1), bone morphogenetic protein-2 (BMP-2) and BMP-7, as well as to the synthetic glucocorticoid dexamethasone. The relative mRNA levels of collagen types I and II, of aggrecan and of Sox9 were determined quantitatively by the real-time polymerase chain reaction (PCR). The extracellular deposition of proteoglycans was evaluated histologically after staining with Toluidine Blue, and that of type-II collagen by immunohistochemistry. RESULTS: BMP-2 induced the chondrogenic differentiation of human synovial MSCs in a dose-dependent manner. The response elicited by BMP-7 was comparable. Both of these agents were more potent than TGF-beta1. A higher level of BMP-2-induced chondrogenic differentiation was achieved in the absence than in the presence of serum. In the presence of dexamethasone, the BMP-2-induced expression of mRNAs for aggrecan and type-II collagen was suppressed; the weaker TGF-beta1-induced expression of these chondrogenic markers was not obviously affected. CONCLUSIONS: We have demonstrated that synovial MSCs derived from the knee joints of aging human donors possess chondrogenic potential. Under serum-free culturing conditions and in the absence of dexamethasone, BMP-2 and BMP-7 were the most potent inducers of this transformation process.

Current concepts in gene therapy of the musculoskeletal system.

The purpose of this article is to review the remarkable progress in the field of musculoskeletal system gene therapy. Since the introduction of this concept 15 years much of the preclinical and clinical data have emerged. The original target, rheumatoid arthritis, has been subjected to clinical phase II efficacy protocol, and osteoarthritis gene therapy efficacy is being thoroughly investigated in various animal models. The most promising area of research in this field however, is the tissue repair, because it doesn't require prolonged period of gene expression, local delivery is reasonably simple and it avoids substantial risk associated with systemic delivery, and levels of gene expression don't need to be so finely regulated. Gene transfer is successfully being used to aid the repair and regeneration of bone, cartilage, ligament tendon, meniscus and intervertebral disc. Other potential applications of gene therapy in musculoskeletal system include osteoporosis, aseptic loosening, genetic diseases and tumors. Highly encouraging data gained from these studies have confirmed that gene therapy is a promising therapeutic solution to treat various musculoskeletal system disorders.

Arthroplasty in treating knee osteoarthritis and proximal tibia stress fracture.

The authors describe two cases of severely angulated tibial non-unions after proximal tibia stress fractures associated with ipsilateral osteoarthritis treated with modular knee endoprosthesis with a long tibial stem to stabilize non-union fragments. During the procedure, no additional osteosynthesis or bone grafting was added. Both non-unions healed after 6 months with no post-operative complications. The authors suggest implantation of modular knee endoprosthesis, as a single procedure, in treatment of proximal tibia non-union after a stress fracture as a result of severe varus/valgus deformity. It provides a solution for osteoarthritis treatment, axis correction and non-union osteosynthesis.

Surgical treatment of extension contractures caused by war injuries to the knee.

Immobilization with external fixation bridging the knee joint in extension is frequently used after sustaining a war injury to the region of the knee joint with femoral and tibial bone fractures. Immobilization of the knee with plaster splints is performed in the same position. This usually prolonged treatment results in extension contractures of the knee joint. From June 1991 until March 1994, 54 patients with extension contractures of the knee caused by war wounds were treated at the Department of Orthopedics, Zagreb University Hospital Center, in Zagreb, Croatia. Results of surgical treatment of 44 patients are presented. The operative procedure consisted of extensive intra- and extra-articular adhesiolysis of the knee. The control group included 30 patients with knee contractures caused by injuries sustained in car crashes or secondary to previous operative procedures. The mean duration of immobilization was 5 months and 6 days. The mean preoperative knee motion amplitude ranged from 5 degrees in extension to 38 degrees in flexion. The mean postoperative knee motion was 98 degrees (range, 2 to 110 degrees). Treatment results did not depend on either duration of preoperative immobilization of the knee or previous infection in the region of injury. Previous knee joint bridging with an external fixator had no impact on the results of extension contracture treatment. Adequate intra- and extra-articular adhesiolysis with appropriate long-term postoperative rehabilitation is essential for the success of the operative treatment for knee joint contracture.

Pulmonary embolism after minor elective orthopedic procedure.

The occurrence of pulmonary embolism, in spite of thromboprophylaxis after a minor elective orthopedic surgery (release of m. rectus femoris tendon) is reported. In case of this severe complication, an early diagnosis is of outmost importance to enable optimal therapy introduction. Deep vein thrombosis and pulmonary embolism are frequent complications after total joint replacement, however, they may also develop after minor surgical orthopedic procedures. The possible causes of pulmonary embolism after release of m. rectus femoris tendon included the history of varicose veins and sclerozation of calf veins, and operative procedure with intraoperative pressure upon large veins of the iliofemoral region, which may and is expected to occur during this procedure. The importance of thrombopropylaxis in orthopedic surgical procedures is emphasized by this case presentation.

[Overuse injury syndromes of the knee]. / Sindromi prenaprezanja u podrucju koljena.

Overuse injuries are frequent in the knee joint. The reason for this is that the knee joint is engaged in all sports activities. Furthermore, the joint area has numerous attachment points for muscles and tendons and numerous bursae. Another reason is that the specific joint between the patella and femur (patellofemoral joint) constitutes a part of the knee joint. Speaking in general terms, all overuse injuries in the knee joint can be divided in four groups according to the aspect: anterior aspect--patellofemoral pain syndrome, patellar tendinitis (jumper's knee), Osgood-Schlatter disease, Sinding Larson Johanson disease, stress fracture of the patella, fat pad syndrome; medial aspect--plica syndrome, semimembranosus tendinitis, pes anserinus tendinitis (bursitis), breaststroker's knee, medial retinaculitis; lateral aspect--Iliotibial band friction syndrome (runner's knee), Popliteal Tendinitis, Bicipital tendinitis; posterior aspect--fabellitis, medial gastrocnemius strain. There are numerous possible reasons for pain caused by overuse injuries around the knee joint, but two are the most frequent: patellar tendinitis (jumper's knee) and Iliotibial band friction syndrome (runner's knee). This paper gives a brief overview of overuse injuries of the knee joint including their definition, anatomy, aetiology, clinical symptoms and signs, and non-operative and surgical treatment.

[Anterior knee pain associated with sports and work]. / Prednja koljenska bol u sportu i radu.

Anterior knee pain is not a disease, but a syndrome with numerous causes. This paper describes its appearance in the patellofemoral joint in sportsmen and in untrained people. Chondromalacia patellae is a condition of the cartilage, not a disease, that is, it is never diagnosed alone. Relative muscular insufficiency, especially of the knee extensors, may occur in children and adolescents, as they grow rapidly. The consequence is a unbalance of active stabilizers and the disturbance of the slippery trail of patella, particularly in the presence of dysplasia of patellofemoral joint. The impingement syndrome pain occurs in sportsmen and people overloading the patellofemoral joint. Other causes of anterior knee pain should be excluded in clinical examination and slippery trail of patella, its position, and signs of instability should be determined. This paper gives an overview of patellar chondromalacia, lateral pressure syndrome, patellar subluxation, patellar acute and recurrent luxation, and idiopathic anterior knee pain. The treatment is basically conservative. Stretching exercises and the strengthening of certain groups of femoral muscles serves to regain the balance, thus normalising the slippery trail and taking off the burden from the patellofemoral joint. If conservative treatment fails, surgery is the alternative.

[Physical procedures in the treatment of overuse injury syndromes of the locomotor system]. / Fizikalne procedure u lijecenju sindroma prenaprezanja sustava za kretanje.

As a rule, the treatment of the overuse syndrome in the locomotor's system is non-surgical, and surgical treatment is needed on rare occasions. Non-surgical treatment should start as soon as possible. The first step is to half or modify sports activities. The treatment includes administration of non-steroidal anti-inflammatory drugs, physical therapy, stretching exercises, and the strengthening of affected muscles. The programme should be adapted to the patient, taking into account the localization and the degree of the injury, as well as his/her sport or work-related activities. The RICE therapeutic programme is important in the treatment of overuse syndromes, especially within the first 72 hours from the occurrence of first symptoms, as it shortens the duration of convalescence for as much as 50%-70%. Beside stabilisation of the joint with optimal loading of antagonistic muscles, stretching exercises have the leading position in prevention and treatment of overuse injuries. During rehabilitation, it is necessary to change activity, its duration and intensity. When a person successfully resumes its sports activities with full load, the rehabilitation is considered completed. No surgical or non-surgical method can warrant a hundred percent recovery for any localization of overuse injury. Prevention, education, and close co-operation between the physician, athlete, and the coach is therefore crucial and is receiving increasing attention.

Regeneration of articular cartilage chondral defects by osteogenic protein-1 (bone morphogenetic protein-7) in sheep.

The efficacy of osteogenic protein-1 (OP-1; BMP-7) in regeneration of articular cartilage was examined by creating knee chondral defects in sheep. With a specially designed instrument in both knees, two 10 mm (diameter) chondral defects were created: one in the trochlea and the other on the femoral condyle. The recombinant BMP was delivered via an extra-articulary positioned mini-osmotic pump, which was fixed to the femoral diaphysis above the knee joint, and connected by a polyethylene tubing to the articular space. Prior to use, the compatibility of OP-1 with mini-osmotic pumps was tested in vitro by measuring aggregation/precipitation and modification of the released protein by size exclusion and reversed phase HPLC. The average amount of aggregation was 15% and about 5% of OP-1 was modified. However, the biological activity of OP-1 released from pumps over a period of 2 weeks at 37 degrees C was equal to ROS cell assay OP-1 standard. Following surgery, a total of 55 microg (low dose) or 170 microg (high dose) OP-1 in acetate buffer (pH 4.5) was slowly released from the pump over a period of 2 weeks. The pumps connected to control knees were filled with acetate buffer as a vehicle. Twelve animals were operated, six of which were treated with the low OP-1 dose, and six with the high OP-1 dose. Three sheep of each group were killed either at 3 or 6 months following surgery, based on arthroscopical evaluation. The chondral defects in the control knees remained empty during the observation period. At 3 months following surgery, defects treated with both OP-1 doses were filled with connective tissue and cartilage. At 6 months following surgery, both doses of OP-1 stimulated regeneration in treated knees. The boundaries between new and old cartilage were well fused and mechanically resisted animals' weight bearing. The regenerated cartilage was rich in proteoglycans and type II collagen, as demonstrated by toluidine blue staining and immunohistochemistry. No signs of endochondral bone formation above the bony tidemark were observed. We suggest that a recombinant bone morphogenctic protein stimulates ingrowth of mesenchymal cells into the chondral defects which then transform into newly formed articular cartilage-like tissue.

Survival of cementless and cemented porous-coated anatomic knee replacements: retrospective cohort study.

AIM: To evaluate the effect of cement use in porous-coated anatomic (PCA) total knee prosthesis on its survival. METHODS: The study was a retrospective analysis of 142 PCA total condylar arthroplasties performed in 124 patients from 1985 to 1991. Uncemented prostheses were used in 87 knees, the prostheses were cemented in 44 knees, and hybrid prosthesis components were used in 11 knees. The average follow-up time was 88 months (range 66-140). The survival of prosthesis was assessed using the Kaplan-Meier's method. The Baltimore score was evaluated as a measure of clinical performance in 115 replacements. RESULTS: The overall cumulative survival rate of a PCA total knee prosthesis was 77% over the average follow-up period of 88 months. No significant differences in survival rates among cementless, cemented, or hybrid fixations could be demonstrated. The survival rate of the prostheses in patients with rheumatoid arthritis (82.5%) was significantly higher than in patients with osteoarthritis (73.8%). Revision was necessary in 29 (20.4%) replacements. CONCLUSION: The survival of PCA endoprosthesis, regardless of the components used for implantation, is not satisfactory.

[Corrective osteotomy in the treatment of degenerative changes in the knee joint]. / Korektivne osteotomije u lijecenju degenerativnih promjena koljenskog zgloba.

Angular deformity of the knee can be corrected by high tibial osteotomy or distal femoral osteotomy. In this research we have analysed effects of corrective osteotomy in knees with varus or valgus deformity. In this research we present a long-term evaluation of 67 patients older than 40 with angular deformity of the knee in which high tibial osteotomy and distal femoral osteotomy were performed at the Department of Orthopaedic Surgery, School of Medicine, University of Zagreb, in the period 1982-1992. Operation was performed bilaterally in 14 patients. There were 66 knees with varus deformity and 15 with valgus deformity out of a total of 81 knees. The most patients with valgus deformity were corrected by supracondylar osteotomy and the most with varus deformity by osteotomy of proximal tibia. The average preoperative duration of symptoms was 6.1 years. The average age was 57.5 at the moment of operation. The mean follow-up was 7 years (range 3-13 years). We assessed the degree of arthrosis according to Ahlböck in five-grade scale. The mean arthrosis was 2.0 preoperatively, 2.2 postoperatively and 2.6 at the last follow-up examination. Although the patients with valgus deformity had smaller degree of arthrosis preoperatively than patients with varus deformity, arthrosis developed equally in both groups despite the fact that the operation was performed. We measured joint tilt according to Shoja and Insall. The patients with varus deformity had joint tilt 7 degrees before operation, -4.3 degrees after operation and -2.4 degrees at the last control. The patients with varus deformity had femurotibial angle of 185 degrees preoperatively, 173 degrees postoperatively, and 175 degrees at the last follow-up examination. The average revarisation of 2 degrees occurred despite overcorrection. The patients with valgus deformity had femurotibial angle of 164 degrees preoperatively, of 178 degrees postoperatively and of 180 degrees at the last follow-up examination. Revarisation progressed 2 degrees on average after varisation osteotomy was performed in the knees with valgus deformity. There was no statistically significant correlation between pain and femurotibial angle and pain and degree of arthrosis preoperatively, postoperatively and at the last follow-up examination. The patients were assessed according to the system developed at the Hospital for Special Surgery (HSS). The mean preoperative HSS score was 2.91 (2.82 varus and 3.33 valgus deformity), and postoperative 4.47 (4.42 varus and 4.47 valgus). The mean score at the last follow-up evaluation was 4.05 (varus 4.03 and valgus 4.13). The patients assessed the improvement themselves and it was 1 to 14 (6.1) years. Although the indications for aloarthroplasty of the knee are more frequent nowadays, the authors recommend not to forget corrective osteotomy in the treatment of angular deformity of the knee with osteoarthritis.

Surgical treatment of infected knee contracture after war injury.

From June 1991 till March 1994, sixteen patients with extension knee contracture as a war injury complication were operatively treated at the Department of Orthopedics, Zagreb University School of Medicine. Infection was present in all patients. During the same period of time, 32 patients with extension knee contracture as a war injury complication and free from the signs of infection were also treated at the Department and served as a control group. The mean age at the time of wounding was 28.3 and 31.8 years in the study and control group, respectively. Operative procedures of extensive intra- and extra-articular adhesiolysis of the knee were performed in all patients. The mean duration of immobilization following injury infliction was 5.5 and 4.9 months in the study and control group, respectively. The mean preoperative knee motion amplitude ranged from 8 degrees in extension to 37 degrees in flexion in the study group, and from 5 degrees in extension to 38 degrees in flexion in the control group. Postoperatively, the mean knee motion amplitude ranged from 2.8 degrees in extension to 97 degrees in flexion in the study group, and from 1.9 degrees in extension to 100 degrees in flexion in the control group. Treatment results did not depend on either the presence of infection in the region of injury or on the duration of preoperative knee immobilization. The treatment of infection was most important for the success of operative treatment of knee contracture. A significant role was also played by adequate intra- and extra-articular adhesiolysis with appropriate intensive postoperative rehabilitation.

Arthroplasty after war injuries to major joints.

From 1992 to 1995, replacement of the joint with an endoprosthesis after serious wounding and major destruction of joint elements was performed in 10 soldiers. Arthroplasty was performed on five knees, three hips, and two shoulders. The age range of the wounded soldiers was 22 to 55 years (mean, 37.7 years). Six soldiers suffered explosive injuries, and 4 were injured by gunfire. Time elapsed from the moment of wounding to the time of total joint replacement was 9 to 42 months. We decided on arthroplasty as the preferred treatment because of the presence of strong contractures and very painful movement. In 8 patients, the results of the treatment, based on a follow-up time of 36 to 48 months, were good. In 2 patients, early septic arthritis developed after arthroplasty of the knee with concomitant loosening of the endoprosthesis. Staphylococcus aureus was detected in both patients. In those 2 patients, therefore, arthrodesis of the knee with external fixation was performed.

Arthroscopic retrieval of metal foreign bodies from the knee joint after war wounds.

From 1991 to 1995 metal bodies were removed from 16 knee joints (in 16 patients) using arthroscopic procedures. In 14 patients the wound resulted from explosive devices and in two from rifle bullets. Nine patients had more than one wound. Arthroscopy was performed on average 8.23 months after the injury took place (ranging from 14 days to 4 years). One metal foreign body was retrieved from 13 patients, two from two and four from one patient. The size of the metal foreign bodies varied from 2 to 24 mm, with an average of 8.61 mm. Different degrees of joint damage were present in all but one patient. The metal bodies were found in the posterolateral angle by the popliteus tendon in four patients, in three of whom the metal bodies went into this position during arthroscopy.

Assessment of femoral neck-shaft and antetorsion angles.

The biplanar (Rippstein/Dunlop) technique is commonly used to radiographically determine the neck-shaft and anteversion angles of the hip. This method is unsuitable for certain groups of patients, such as those with fixed contracture of the hip joint. In these patients we have found the 'sinus wave' method to be preferable. We compared the neck shaft and anteversion angles of 30 hips determined by these two methods. Correlation was good for both the neck shaft (r = 0.972) and anteversion angles (0.69). We also used ultrasound to measure the anteversion but this correlated poorly with the Rippstein/Dunlop technique (r = 0.56). We believe that the sound wave technique is an accurate and practical way to determine the anteversion and neck-shaft angles of the hip.

[Treatment of gonarthrosis with arthroscopic abrasion]. / Lijecenje gonartroze metodom artroskopske abrazije.

From 1988 to 1992 at the Department of orthopaedic surgery, School of medicine, University of Zagreb 21 arthroscopic knee joint abrasions were performed as palliative treatment of osteoarthritis. There were 13 male patients (61.9%) and eight female patients (38.1%); the age of the patients ranged from 17 to 69 years (the average of 42.2 years). The femorotibial angle ranged from -2 to 10 degrees (the average of 5.3 degrees). The average degree of osteoarthritis was 2.1 and of chondromalacia 3.5 degrees. In the majority of cases the abrasion was performed in the medial femoral condyle and the patella; in a smaller number of cases it was performed in the medial tibial condyle, and in the lateral tibial condyle in only one patient. Also, debridement was performed in most of the patients; in four patients cleansing of the medial menisci was made, while in two patients loose joint bodies had to be removed. The average follow-up time was 2.8 years, ranging from 12 months to 5 years. According to HSS score, treatment results were excellent and very good in 15 patients (71.4%), satisfactory in four patients (19.0%) and poor in two patients (9.5%). The authors conclude that the arthroscopic abrasion is good, non-invasive palliative method of treatment of primary knee osteoarthritis. The arthroscopic abrasion method yields good short-term results (from 2 to 5 years) in view of reducing pain and improving joint function.