Treatment of knee cartilage by cultured stem cells and three dimensional scaffold: a phase I/IIa clinical trial.

PURPOSE: Damage of the knee cartilage is a common condition manifesting itself mainly by pain and/or swelling that may substantially reduce the quality of life while ultimately leading to osteoarthritis in affected patients. Here, we aimed to evaluate the safety and efficacy of cultured autologous bone marrow mesenchymal stem cells (BM-MSCs) attached to the 3D Chondrotissue® scaffold by autologous blood plasma coagulation (BiCure® ortho MSCp) in the treatment of knee cartilage defects. METHODS: The primary endpoint of this phase I/IIa clinical trial was to evaluate the safety of the treatment. The secondary objective was to determine the short-to-medium-term therapeutic outcomes by standardized scoring questionnaires including Lysholm Knee Scoring Scale (Lysholm score), Knee Injury and Osteoarthritis Outcome Score (KOOS), and pain Visual Analogue Scale (VAS) systems and imaging (X-ray and magnetic resonance imaging, MRI). A total of six patients were included and followed for 12 months after the surgery. RESULTS: BiCure® ortho MSCp was well tolerated with no adverse events associated with the investigational medicinal product. Significant improvements were observed in Lysholm scores and KOOS while X-ray showed no deterioration of the arthritis and MRI revealed a persistent filling of the chondral defects by the implant. CONCLUSION: Overall, our data demonstrate the safety of the tested investigational medicinal product. The function of the treated knee improved within one year after surgery in all enrolled patients. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: EudraCT No.: 2018-004,067-31; October 18 2018.

Predictors of radiographic outcomes of conservative and surgical treatment of Legg-Calvé-Perthes disease.

PURPOSE: Treatment outcomes of conservative and surgical treatment of Legg-Calvé-Perthes disease (LCPD) have been shown to be conditioned by a number of factors that may vary across different populations. This retrospective study aimed to evaluate factors affecting radiographically assessed treatment outcomes in patients treated surgically or conservatively for LCPD at Faculty Hospital Motol, Prague, Czech Republic, between the years 2006 and 2019. METHODS: Data of forty-seven children comprising 52 hips were analysed. Treatment outcomes were evaluated according to Stulberg classification. Predictors included the initial stage of fragmentation of the hip joint according to Herring classification, type of treatment (conservative or surgical), age at the time of diagnosis and sex. RESULTS: Older age and severity of LCPD according to Herring classification but not the type of treatment were the strongest factors determining treatment outcomes. Treatment outcomes were comparable in patients treated conservatively or surgically both across the whole cohort of patients and a group of young children < six years of age. CONCLUSIONS: Results strengthen the roles of severity of the LCPD at onset of treatment and age of the patient in predicting treatment outcomes in patients with LCPD. Conservative and surgical treatments appear to yield similar treatment outcomes irrespective of age of patients.

Meniscus transplantation-prospective assessment of clinical results in two, five and ten year follow-up.

PURPOSE: The authors present clinical results in patients following transplantation of deep-frozen menisci within ten years following the surgery. METHODS: A cohort of 46 patients who were transplanted altogether 49 menisci was subject to prospective study following six months, two, five and ten years after meniscus transplantation. For subjective assessment, we used KOOS, IKDC and Lysholm scores; objective assessment was based on load X-ray examination of the operated knee at two, five and ten years after the surgery, MRI examination of 34 patients in the interval of two and ten years after the operation, control arthroscopy was performed in 23 patients eight of whom suffered a new injury. RESULTS: All 38 patients who have completed ten year follow-up without any new injury of the operated joint demonstrated statistically significant improvement of mobility in the period of six months and two, five and ten years following the meniscal transplantation. Further follow-up demonstrated different results in patients with a new injury and without a new injury of the operated knee joint. In eight patients (17.3%), the follow-up was disturbed by a new injury of the operated joint within three to eight years after the meniscal transplantation. In three patients with the damaged meniscal transplant, a cartilage deterioration from degree II to degree IIIa was found. In second-look arthroscopy, the patients with no injury showed signs of the improved condition of cartilage by one degree according to ICRS classification on average. The MRI imaging showed relatively frequent (47%) extrusion of the anterior and medial part of meniscus (2.5-3.8 mms) without the followed-up dynamics of changes at two and ten years after the surgery. CONCLUSION: All patients in the selected cohort proved the positive benefit of meniscus transplant when it comes to the improvement of clinical symptoms and improvement of mobility of the operated knee joint. The higher mobility following the transplantation compared to the activity prior to the surgery could have contributed to a new injury of the operated joint in 17% of the patients in the cohort.

Paediatric pelvic injuries: a retrospective epidemiological study from four level 1 trauma centers.

AIM OF THE STUDY: Epidemiologic evaluation of pelvic ring injuries in children. METHODS: Retrospective analysis over a period of 13 years, excluding pathological fractures. AO/OTA type, epidemiological data, type of treatment, and complications were recorded. Data were assessed using Fisher's exact test and Wilcoxon test. RESULTS: 243 boys, 115 girls, mean age (SD) 14.1 ± 3.0 years, AO/OTA types: 281 A, 52 B, 25 C. Multiple trauma: 62, combined trauma: 59, mono-trauma: 237. 281 patients were treated non-operatively, 97 surgically. ETIOLOGY: traffic accidents 88, falls from a great height 37, crushing injuries four, and sports injuries 192, simple falls 30, others seven. High-energy mechanisms prevailed in types B and C. Low-energy mechanism in type A (p < 0.0001). Similar differences were found between type A (p = 0.0009) and in case type C requiring surgery and cases treated non-operatively (p < 0.0001). Twenty-six patients (7.3%) had complications (pelvic asymmetry 5, neurological deficits 5, non-union 1, ectopic calcification 4, others 7). Higher complication rates were associated with types B and C (p = 0.0015), with surgically treated cases (p < 0.0001) and multiple trauma (p = 0.0305). DISCUSSION: Results of this trial were comparable with other studies. CONCLUSION: Sports injuries accounted for most type A injuries, while types B and C tended to be associated with high-energy trauma. Complications were associated with the severity of pelvic trauma, more common in surgically treated group of patients; this is primarily linked to the surgical cases being more serious as well as the associated injuries.

Hip arthroscopy learning curve: a prospective single-surgeon study.

PURPOSE: Arthroscopy of the hip joint is considered a demanding procedure with long learning curve. There are only a few studies that concentrate on this topic. This prospective clinical study evaluates the learning curve of the hip arthroscopy based on clinical outcomes, surgical time, and complication rate. MATERIALS: In this study, we first evaluated 150 hip arthroscopy procedures performed by a single surgeon. The patient group consisted of 86 females and 64 males with mean age 37 years (range 16-69). Study cohorts were divided into groups of 50 patients. Surgical time, complication rate and clinical results based on NAHS score were recorded for each group. Statistical analysis of differences between groups was performed using the ANOVA method and paired t-test. RESULTS: We found a statistically significant decrease of complication rate with more procedures performed. There were significantly better clinical outcomes after at least 100 procedures. No difference in surgical time was found, but towards the end of the learning curve, more complex procedures were performed. The only statistical difference was the portal setup time. The learning curves were constructed based on these results. CONCLUSIONS: Hip arthroscopy provides very good clinical outcomes if precisely indicated and performed. It is, however, a demanding procedure with many possible pitfalls and complications. According to our study, at least 100 procedures are needed to gain basic technical and indication skills. The presence of a more skilled surgeon in the beginning of the learning curve is advised to reduce the complication rate.

[Femoroacetabular impingement treatment options]. / Femoroacetabulární impingement a moznosti jeho resení.

Femoroacetabular impingement syndrome is a very common hip pathology that is responsible for hip pain in patients under 40 years of age. Anatomic changes in hip joint cause labral tears and cartilage dysfunction, both of these conditions cause severe hip pain and often lead to hip arthritis. This syndrome is very common in the population, but very often misdiagnosed and undertreated.The main treatment option is surgical treatment; conservative treatment alone is not successful. There are many surgical procedures that may be chosen according to the degree of hip pathology. In this article we present treatment options for femoroacetabular impingement syndrome and our results. Recently one of the main treatment options is hip arthroscopy we have very good experience and results with this method.

[Primary malignant bone tumors in children possibilities of limb-saving surgery using allografts]. / Primární maligní nádory kostí u detí moznosti záchovné chirurgie s vyuzitím alostepu.

Therapy of primary malignant bone tumors is always multimodal and requires close cooperation of oncologist, orthopedic surgeon, radiologist and others. In our article, we provide a brief overview of the most common malignant bone tumors in pediatric patients and summarize the commonly used therapeutic procedures. Despite advances in cancer treatment radical surgical resection of the tumor is still necessary. If possible, it should be complete removal of the affected structures, made in terms of the so-called limb-saving (limb-sparing) surgery that preserves the shape and function of the affected limb to the fullest extent possible. In addition the resection must be done at the same time with substitution of the removed bone. Bone grafts, both autografts and allografts, are used in majority of solutions. We also discuss the comparison of different approaches of limb-saving surgery compared to ablative procedures.

[Avascular necrosis of the femoral head]. / Avaskulární nekróza hlavice femuru.

Avascular necrosis of the femoral head in adults is not common, but not too rare diseases. In orthopedic practice, it is one of the diseases that are causing implantation of hip replacement at a relatively early age. In the early detection and initiation of therapy can delay the implantation of prosthesis for several years, which is certainly more convenient for the patient and beneficial. This article is intended to acquaint the reader with the basic diagnostic procedures and therapy.

A comparison of ACL reconstruction using patellar tendon versus hamstring autograft in female patients: a prospective randomised study.

PURPOSE: The incidence of an anterior cruciate ligament (ACL) tear is highest in female patients; however, it is not apparent whether graft choice affects clinical results. The aim of this prospective randomised study was to evaluate clinical results of an ACL reconstruction using patellar tendon [bone-patellar tendon-bone (BTB)] or hamstring graft (HS) in female patients. METHODS: Inclusion criteria were traumatic instability, no signs of osteoarthritis, no previous instability and no contralateral knee instability. Inclusion criteria were met in 150 patients, mean age 26 (17-47) years. Patients were randomised into two groups of 75 patients according to graft type; all had the same rehabilitation protocol. Tegner Lysholm knee score and stability were evaluated pre-operatively and one and two years postoperatively. The difference between groups was statistically evaluated using unpaired t test. RESULTS: Of the 150 patients, all completed one year follow-up; three were lost to follow-up at two years. There was no significant difference in functional scores and knee stability between groups. The HS group had significantly less anterior knee pain in the first six months postoperatively. CONCLUSION: ACL reconstruction significantly improves clinical results and stability of the knee. Difference in Lysholm score and stability between groups was not significant. Neither group showed higher tendency to graft failure within two years. Graft choice for reconstruction in female patients should be surgeon specific and individualised, as both grafts studied achieved comparable results.

Human multipotent mesenchymal stem cells improve healing after collagenase tendon injury in the rat.

BACKGROUND: Mesenchymal stromal cells attract much interest in tissue regeneration because of their capacity to differentiate into mesodermal origin cells, their paracrine properties and their possible use in autologous transplantations. The aim of this study was to investigate the safety and reparative potential of implanted human mesenchymal stromal cells (hMSCs), prepared under Good Manufacturing Practice (GMP) conditions utilizing human mixed platelet lysate as a culture supplement, in a collagenase Achilles tendon injury model in rats. METHODS: Eighty-one rats with collagenase-induced injury were divided into two groups. The first group received human mesenchymal stromal cells injected into the site of injury 3 days after lesion induction, while the second group received saline. Biomechanical testing, morphometry and semiquantitative immunohistochemistry of collagens I, II and III, versican and aggrecan, neovascularization, and hMSC survival were performed 2, 4, and 6 weeks after injury. RESULTS: Human mesenchymal stromal cell-treated rats had a significantly better extracellular matrix structure and a larger amount of collagen I and collagen III. Neovascularization was also increased in hMSC-treated rats 2 and 4 weeks after tendon injury. MTCO2 (Cytochrome c oxidase subunit II) positivity confirmed the presence of hMSCs 2, 4 and 6 weeks after transplantation. Collagen II deposits and alizarin red staining for bone were found in 6 hMSC- and 2 saline-treated tendons 6 weeks after injury. The intensity of anti-versican and anti-aggrecan staining did not differ between the groups. CONCLUSIONS: hMSCs can support tendon healing through better vascularization as well as through larger deposits and better organization of the extracellular matrix. The treatment procedure was found to be safe; however, cartilage and bone formation at the implantation site should be taken into account when planning subsequent in vivo and clinical trials on tendinopathy as an expected adverse event.

Comparison of conservative against surgical treatment of anterior-superior iliac spine avulsion fractures in children and adolescents.

PURPOSE: Avulsion fracture of the anterior-superior iliac spine is an uncommon injury. It is mostly seen in adolescent sprinters, distance runners and soccer players. Most cases are unilateral. We present a cohort of patients and the strategy for their treatment. METHODS: During the period 2005-2012, we treated 23 (19 male, four female) patients with an average age of 15.1 years (4-17). Ten patients with minimally displaced fractures were treated conservatively, and 13 patients with greater fragment dislocation were treated surgically. All patients underwent the standardised rehabilitation protocol. We evaluated range of motion (ROM), X-ray six weeks and one year postoperatively, length of bed rest, return to activity and complication rates (infection, heterotopic ossification). RESULTS: All patients returned to sports at the preinjury level. Surgically treated patients showed faster recovery and better compliance with rehabilitation protocols. The time interval for X-ray union was comparable between groups, as was full recovery. There was no deep infection; however, there were five minor heterotopic ossifications, none of which required further treatment. CONCLUSION: We emphasise that the indication for surgical treatment is mainly determined by the grade of fragment displacement and the patient's sporting activity. Although long-term results were comparable between treatment methods, surgery carries the risk of higher complication rates and the need for osteosynthetic material extraction.

A Review on Additive Manufacturing Methods for NiTi Shape Memory Alloy Production.

The NiTi alloy, known as Nitinol, represents one of the most investigated smart alloys, exhibiting a shape memory effect and superelasticity. These, among many other remarkable attributes, enable its utilization in various applications, encompassing the automotive industry, aviation, space exploration, and, notably, medicine. Conventionally, Nitinol is predominantly produced in the form of wire or thin sheets that allow producing many required components. However, the manufacturing of complex shapes poses challenges due to the tenacity of the NiTi alloy, and different processing routes at elevated temperatures have to be applied. Overcoming this obstacle may be facilitated by additive manufacturing methods. This article provides an overview of the employment of additive manufacturing methods, allowing the preparation of the required shapes of Nitinol products while retaining their exceptional properties and potential applications.

Hypothermic Storage of 3D Cultured Multipotent Mesenchymal Stromal Cells for Regenerative Medicine Applications.

The regulatory requirements in cell processing, in the choice of a biomaterial scaffold and in quality control analysis, have to be followed in the clinical application of tissue-engineered grafts. Confirmation of sterility during quality control studies requires prolonged storage of the cell-based construct. After storage, preservation of the functional properties of the cells is an important prerequisite if the cells are to be used for cell-based tissue therapies. The study presented here shows the generation of 3D constructs based on Wharton's jelly multipotent mesenchymal stromal cells (WJ-MSCs) and the clinically-acceptable HyaloFast® scaffold, and the effect of two- and six-day hypothermic storage of 3D cell-based constructs on the functional properties of populated cells. To study the viability, growth, gene expression, and paracrine secretion of WJ-MSCs within the scaffolds before and after storage, xeno-free culture conditions, metabolic, qPCR, and multiplex assays were applied. The WJ-MSCs adhered and proliferated within the 3D HyaloFast®. Our results show different viability of the cells after the 3D constructs have been stored under mild (25 °C) or strong (4 °C) hypothermia. At 4 °C, the significant decrease of metabolic activity of WJ-MSCs was detected after 2 days of storage, with almost complete cell loss after 6 days. In mild hypothermia (25 °C) the decrease in metabolic activity was less remarkable, confirming the suitability of these conditions for cell preservation in 3D environment. The significant changes were detected in gene expression and in the paracrine secretion profile after 2 and 6 days of storage at 25 °C. The results presented in this study are important for the rapid transfer of tissue engineering approaches into clinical applications.

Concurrence of High Corrosion Resistance and Strength with Excellent Ductility in Ultrafine-Grained Mg-3Y Alloy.

In the field of magnesium-based degradable implantable devices, the Mg-Y-RE-Zr alloying system (WE-type) has gained popularity due to its satisfying degradation rate together with mechanical strength. However, utilization of RE and Zr in the WE-type alloys was originally driven to improve Mg-based alloys for high-temperature applications in the industry, while for medical purposes, there is a question of whether the amount of alloying elements may be further optimized. For this reason, our paper presents the Mg-3Y (W3) magnesium alloy as an alternative to the WE43 alloy. This study shows that the omission of RE and Zr elements did not compromise the corrosion resistance and the degradation rate of the W3 alloy when compared with the WE43 alloy; appropriate biocompatibility was preserved as well. It was shown that the decrease in the mechanical strength caused by the omission of RE and Zr from the WE43 alloy could be compensated for by severe plastic deformation, as achieved in this study, by equal channel angular pressing. Ultrafine-grained W3 alloy exhibited compression yield strength of 362 ± 6 MPa and plastic deformation at maximum stress of 18 ± 1%. Overall, the early results of this study put forward the motion of avoiding RE elements and Zr in magnesium alloy as a suitable material for biodegradable applications and showed that solo alloying of yttrium is sufficient for maintaining desirable properties of the material at once.

The anterior talo-fibular ligament reconstruction in surgical treatment of chronic lateral ankle instability.

Chronic lateral ankle instability causes significant problems in physical activity and accelerates development of osteoarthritic changes. The results of treatment for chronic ankle instability are often meets controversial. A surgical reconstruction of ATFL as described in this paper was performed during the period 1997-2005 on 47 patients (26 male, 21 female), with a mean age of 29.3 years. The average follow-up period was 46.2 months. All patients had clinical examination, X-ray and MRI. The mean values of the Good score improved from an average 3.32 prior to surgery to 1.19 one year after the operation. Paired t-tests showed improvements of great significance (p < 10(-28)). The Good score prior to surgery ranged from 2-4, whereas the scores one year after surgery were either 1 or 2, with a score of 1 being recorded in 38 cases (81%). In the postoperative follow-up, MRI showed a newly-formed ligament structure in all cases. The authors describe their own technique for a reconstruction of lateral ankle instability using remnants of the former ATFL. The scar tissue seems to be sufficient to form a new duplicated structure providing good stability. MRI proved to be a sensitive and specific method for identifying the extent of talo-fibular ligament injury.

Irreducible dislocation of the hip in cerebral palsy patients treated by Schanz proximal femoral valgus osteotomy.

Palliative Schanz proximal femoral valgus osteotomy is considered a common option for treatment of irreducible hip dislocation in cerebral palsy. From 1992 to 2005, Schanz osteotomy was indicated on 55 occasions in 35 nonambulatory patients with the quadriplegic form of cerebral palsy aged 9-18. Postoperatively, the main emphasis focussed on clinical presentation, improvement of hip range of motion, and pain relief. X-rays were carried out at three, six, and 12 months postoperatively with subsequent average follow up 98 +/- 4.5 months. In all patients, the range of hip abduction and flexion increased. In 54 (98.2%) cases painful symptoms significantly improved. One patient (1.8%) had a subsequent femoral head excision because of persistent hip pain. Transient hip pain persisted in four patients (7.3%). Schanz valgus osteotomy improves the hip range of motion, relieves pain, and facilitates care of the patient. Schanz femoral osteotomy is a less invasive method compared to proximal femoral excision and should preferably be used in older children with neurogenic hip dislocation in whom reconstructive surgery is not indicated.

Manipulation of pediatric supracondylar fractures of humerus in prone position under general anesthesia.

BACKGROUND: Displaced pediatric supracondylar fractures are usually treated with manipulation and fixation with Kirschner wires. The procedure is commonly performed with the patient in supine position. Reducing and stabilizing the fracture with the patient in supine position are associated with various risks and technical difficulties. METHODS: We describe a technique of manipulative reduction and fixation of pediatric supracondylar fractures by positioning the patient prone. RESULTS: We have used this technique in 455 patients and prefer it to the commonly described method of fracture reduction and stabilization with the patient supine. CONCLUSIONS: Positioning the patient prone simplifies the reduction and provides adequate exposure to insert Kirschner wires safely from both medial and lateral aspects. Positioning the C-arm is easily achieved, and good radiographs are obtained without disturbing the reduced fracture. LEVEL OF EVIDENCE: Level III.

Histologic and immunohistochemical characteristics of failed articular cartilage resurfacing procedures for osteochondritis of the knee: a case series.

BACKGROUND: The histologic appearance of the repair tissue after articular cartilage resurfacing procedures in humans is not well documented. HYPOTHESIS: The histologic and immunohistochemical appearance of the repair tissues in failed articular cartilage resurfacing procedures will be similar, regardless of the procedure that was done, and will not resemble normal articular cartilage. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Graft tissue from 10 patients who underwent an autologous chondrocyte implantation (n = 6), microfracture (n = 3), or periosteal transplantation (n = 1) procedure to treat symptomatic osteochondritis dissecans of the medial femoral condyle was processed for histologic examination after failure of the articular cartilage resurfacing procedure. Serial sections from all slabs were stained with hematoxylin and eosin and toluidine blue and were immunostained using antibodies directed against types I, II, and X collagen. RESULTS: Specimens from all 3 types of repair procedures were composed primarily of fibrous connective tissue and fibrocartilage. None of the sections stained positively for type X collagen. All 10 cases stained positively for type I collagen (range, 7%-97% of tissue area). Staining for type II collagen was positive in 4 of 6 autologous chondrocyte implantation cases, 3 of 3 microfracture cases, and the periosteal transplant case (range, 2%-65% of tissue area). In 8 of 10 cases, the percentage of the section area exhibiting positive staining for type I collagen was higher than for type II collagen (6 of 6 autologous chondrocyte implantation; 1 of 3 microfracture; 1 periosteal transplant). CONCLUSION: The histologic appearance of the repair tissue of 3 different failed articular cartilage resurfacing procedures was similar and did not resemble normal articular cartilage.