Analysis of the Initial Learning Curve for Robotic-Assisted Total Knee Arthroplasty Using the ROSA® Knee System.

Background/Objectives: Total knee arthroplasty (TKA) is a frequent procedure in orthopedic surgery. Advances in TKA include the development of robotic-assisted systems. Training in raTKA entails a learning curve to achieve proficiency comparable to conventional manual TKA (maTKA). Methods: We conducted a prospective study of the learning curve in raTKA using the Robotic Surgical Assistant (ROSA) Knee System. The study included 180 patients (90 raTKAs; 90 maTKAs) and three surgeons (one with >15 years of experience in maTKA). The cumulative sum control chart method (CUSUM) was used to define the transition from the learning phase to the mastered phase in raTKA. Results: The learning curves were 43 cases (experienced surgeons) and 61 cases (all surgeons). Mean operative times for both phases in raTKA were longer than in maTKA (p < 0.001). In raTKA, operative times in the learning phase were longer compared to those in the mastered phase (p < 0.001). Operative times in the learning and mastered phases for all surgeons in raTKA were significantly longer compared to those in maTKA (p < 0.001); however, operative times of the experienced surgeon in the mastered phase of raTKA and in maTKA showed no differences. Conclusions: The learning curve in raTKA is dependent upon the surgeon's previous experience in maTKA.

Genome-Wide Association Screens for Anterior Cruciate Ligament Tears.

BACKGROUND: The etiopathogenesis of ACL rupture is not clarified. The aim of this study is to identify genomic regions and genetic variants relevant to anterior cruciate ligament injury susceptibility that could be involved in non-contact anterior cruciate ligament ruptures. METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with a PRISMA checklist and algorithm. A search of PubMed, MEDLINE, CINAHL, Cochrane, EMBASE, and Google Scholar databases was conducted using combinations of the terms "anterior cruciate ligament", "ACL", "rupture", "genetics", "single nucleotide polymorphisms", and "SNP" since the inception of the databases until 2021. RESULTS: Twenty-three studies were included. A total of 7724 patients were analyzed. In total, 3477 patients had ACL ruptures and 4247 patients were controls. Genetic variants in genes encoding for collagens, elastin, fibrillin, matrix metalloproteinases, proteoglycans, angiogenesis-associated signaling cascade proteins, growth differentiation factors, tissue inhibitors of metalloproteases, interleukins, and fibrinogen were analyzed. CONCLUSION: Findings regarding the association between genes encoding for collagen (COL3A1, COL1A1, and COL12A1), aggrecan (ACAN), decorin (DCN), matrix metalloproteinase (MMP3), interleukin 6 (IL-6), vascular endothelial growth factor A (VEGFA), biglycan (BGN), fibrinogen (FGB), and ACL injuries were found to be inconclusive. Additional evidence is required in order to establish substantial conclusions regarding the association between genetic variants and ACL rupture.

Intraosseous injection of mesenchymal stem cells for the treatment of osteonecrosis of the immature femoral head and prevention of head deformity: A study in a pig model.

BACKGROUND: Cell therapy has been proposed as part of the therapeutic arsenal to assist bone formation and remodeling in the early stages of osteonecrosis of the femoral head. The purpose of this study is to determine the effects of intraosseous inoculation of mesenchymal stem cells on bone formation and remodeling in an established experimental model of osteonecrosis of the femoral head in immature pigs. METHODS: Thirty-one 4-week-old immature Yorkshire pigs were used. Experimental osteonecrosis of the femoral head was created in the right hip of all included animals (n = 31). The month after surgery, hip and pelvis radiographs were taken to confirm osteonecrosis of the femoral head. Four animals were excluded following surgery. Two groups were established: (A) mesenchymal stem cell-treated group (n = 13) and (B) saline-treated group (n = 14). One month after surgery the mesenchymal stem cell-group received an intraosseous injection of 10 × 106 mesenchymal stem cell (5 cc) and the saline-treated group of 5 cc of physiological saline solution. Osteonecrosis of the femoral head progression was assessed by monthly X-rays (1-, 2-, 3- and 4-months post-surgery). The animals were sacrificed 1 or 3 months following the intraosseous injection. Repair tissue and osteonecrosis of the femoral head were histologically evaluated immediately after sacrifice. RESULTS: At time of sacrifice, radiographic images showed evident osteonecrosis of the femoral head with associated severe femoral head deformity in 11 of the 14 animals (78%) in the saline group and in only 2 of the 13 animals (15%) in the mesenchymal stem cell group. Histologically, the mesenchymal stem cell group showed less osteonecrosis of the femoral head and less flattening. In the saline group, there was pronounced femoral head flattening and the damaged epiphyseal trabecular bone was largely replaced with fibrovascular tissue. CONCLUSION: Intraosseous mesenchymal stem cells inoculation improved bone healing and remodeling in our immature pig osteonecrosis of the femoral head model. This work supports further investigation to determine whether mesenchymal stem cells enhance the healing process in immature osteonecrosis of the femoral head.

Early Identification and Treatment of Trochlear Knee Dysplasia.

A shallow sulcus characterizes trochlear dysplasia (TD) of the femoral trochlea, which can lead to chronic pain or instability of the patellofemoral joint. Breech presentation at birth has been identified as a risk factor for developing this condition, which an ultrasound can identify early. Early treatment could be considered at this stage, given the potential for remodelling in these skeletally immature patients. Newborns with breech presentation at birth who meet the inclusion criteria will be enrolled and randomised in equal proportions between treatment with the Pavlik harness and observation. The primary objective is to determine the difference in the means of the sulcus angle between the two treatment arms at two months. Ours is the first study protocol to evaluate an early non-invasive treatment for TD in the newborn with breech presentation at birth using a Pavlik harness. We hypothesised that trochlear dysplasia could be reverted when identified and treated early in life with a simple harness, as it is done with developmental dysplasia of the hip.

Relationship of the Cruciate and Meniscofemoral Ligaments with the Knee Osteology. An Anatomical Study.

Objective To analyze the dimensions of the posterior cruciate ligament (PCL), anterior cruciate ligament (ACL), the presence of meniscus-femoral ligaments MFLs in human knees, and the correlation with the dimensions of the knee skeleton. Methods Anatomical study on 29 specimens of human knees in which we measured the length and width of the cruciate and meniscus-femoral ligaments and the dimensions of femoral and tibia condyles and the femoral notch. The ACL length was calculated with different degrees of knee flexion. The relationship between the ligaments and bone dimensions were analyzed. Results The length of the ACL and the PCL were similar. Posterior MFL was more frequent and longer than the anterior MFL. We found the posterior MFL in the 72.41% of the knees and anterior MFL in 20.69%. The ACL presented 30% of its maximum length up to 60°, approximately half of its length between 90° and 120°, reaching its maximum length at 170°. We found a strong correlation between the length of the ACL and that of the PCL ( p = 0.001). However, the lengths of the ACL and PCL were not related with the bone dimensions. Conclusion We have found no correlations between the cruciate and MFLs and the anatomical dimensions of the intercondylar notch and the proximal tibia and distal femur. The presence of the posterior MFL was more frequent and longer than that of the anterior ligament.

Variation in Juvenile Long Bone Properties as a Function of Age: Mechanical and Compositional Characterization.

Bone is a heterogeneous, hierarchical biocomposite material made of an organic matrix filled with a mineral component, which plays an important role in bone strength. Although the effect of the mineral/matrix ratio on the mechanical properties of bone during aging has been intensively investigated, the relationship between the mechanical properties and the chemical composition of bone with age requires additional research in juvenile individuals. In this study, bone coupons from bovine and ovine animal species were machined from cortical areas of long bones to quantify whether the variation in mechanical properties at different stages of development is related to the change in the composition of bone tissue. An energy-dispersive X-ray detector (EDX) attached to a scanning electron microscope (SEM) was used to perform a compositional analysis of the tissue. In addition, nanoindentation analyses were carried out to address how the elastic modulus changed with age. Nonparametric statistical analyses found significant differences (p < 0.05) in Ca content and elastic modulus between species, but no differences were found within each species with development. A multiple linear regression model found that the elastic modulus was significantly related to the decrease in P and C in the samples, to the animal species (larger in bovine), and development, although not linearly. This model also found an interaction between Ca and development that could explain the lack of significance of the relationship between the elastic modulus and development in the univariate models.

Relationship of the Cruciate and Meniscofemoral Ligaments with the Knee Osteology. An Anatomical Study / Relação dos ligamentos cruzados e meniscofemorais com a osteologia do joelho: Um estudo anatômico

Abstract Objective To analyze the dimensions of the posterior cruciate ligament (PCL), anterior cruciate ligament (ACL), the presence of meniscus-femoral ligaments MFLs in human knees, and the correlation with the dimensions of the knee skeleton. Methods Anatomical study on 29 specimens of human knees in which we measured the length and width of the cruciate and meniscus-femoral ligaments and the dimensions of femoral and tibia condyles and the femoral notch. The ACL length was calculated with different degrees of knee flexion. The relationship between the ligaments and bone dimensions were analyzed. Results The length of the ACL and the PCL were similar. Posterior MFL was more frequent and longer than the anterior MFL. We found the posterior MFL in the 72.41% of the knees and anterior MFL in 20.69%. The ACL presented 30% of its maximum length up to 60°, approximately half of its length between 90° and 120°, reaching its maximum length at 170°. We found a strong correlation between the length of the ACL and that of the PCL (p= 0.001). However, the lengths of the ACL and PCL were not related with the bone dimensions. Conclusion We have found no correlations between the cruciate and MFLs and the anatomical dimensions of the intercondylar notch and the proximal tibia and distal femur. The presence of the posterior MFL was more frequent and longer than that of the anterior ligament.

Resumo Objetivo Analisar as dimensões do ligamento cruzado posterior (LCP), do ligamento cruzado anterior (LCA), a presença de ligamentos meniscofemorais (LMFs) em joelhos humanos e a correlação com as dimensões do esqueleto do joelho. Métodos Estudo anatômico em 29 espécimes de joelhos humanos nos quais medimos o comprimento e a largura dos ligamentos cruzado e meniscofemoral e as dimensões dos côndilos femorais e tibiais e do entalhe femoral. O comprimento do LCA foi calculado com diferentes graus de flexão do joelho. Analisou-se a relação entre os ligamentos e as dimensões ósseas. Resultados O comprimento do LCA e do LCP foram semelhantes, LMF posterior foi mais frequente e mais longo do que o LMF anterior. Foram encontradas LMF posterior em 72,41% dos joelhos e LMF anterior em 20,69%. O LCA apresentou 30% de seu comprimento máximo até 60°, aproximadamente metade de seu comprimento entre 90° e 120°, atingindo seu comprimento máximo com flexão de 170°. Encontramos uma forte correlação entre o comprimento do LCA e do LCP (p= 0,001). No entanto, os comprimentos do LCA e do LCP não estavam relacionados com as dimensões ósseas. Conclusão Não encontramos correlações entre os ligamentos cruzado e meniscofemoral e as dimensões anatômicas do entalhe intercondilar e da tíbia proximal e do fêmur distal. A presença do LMF posterior foi mais frequente e maior que a do ligamento anterior.

Safety of International Professional Sports Competitions During the COVID-19 Pandemic: The Association Football Experience.

Major sporting events were suspended during the most acute phase of the COVID-19 pandemic. Competitions are resuming with enhanced hygiene protocols and altered mechanics. While risks for players and staff have been studied, the impact of large-scale tournaments on the communities that host them remains largely unstudied. CONMEBOL Copa América is one of the first wide-scale international tournaments to be conducted in its original format since the beginning of the COVID-19 pandemic. The tournament saw 10 national teams compete in four Brazilian cities during a period of heightened viral transmission. The analysis of over 28,000 compulsory PCR tests showed that positive cases did not lead to the uncontrolled spread of the disease among staff and players. More importantly, the data indicate that locally hired staff were not exposed to increased risk while working. The Copa América experience shows that international sporting competitions can be conducted safely even under unfavourable epidemiological situations.

Treatment of Chondral Knee Lesions with Autologous Chondrocytes Embedded in a Fibrin Scaffold. Clinical and Functional Assessment.

Objective The aim of our study is to analyze the clinical and functional results obtained using autologous chondrocytes embedded in a fibrin scaffold in knee joint injuries. Methods We included 56 patients, 36 men and 20 women, with a mean age 36 years. Six of the patients were professional athletes, with single knee injuries that were either chondral or osteochondral (43 chondral, 9 osteochondral, 2 cases of osteochondritis dissecans and 2 osteochondral fractures), 2 to 10 cm 2 in size and ≤ 10 mm deep, with no signs of osteoarthritis. The location of the injury was in the patella (8), the medial femoral condyle (40) and lateral femoral condyle (7) and one in the trochlea. The mean follow-up was 3 (range: 1-6) years. The clinical course was assessed using the Cincinnati and Knee Injury and Osteoarthritis Outcome (KOOS) scores, 6 and 12 months after surgery. The paired Student t-test was used to compare pre-and postoperative results. Results Six months after the implant, patients resumed their everyday activities. On the assessment scores, their condition was improving in comparison with their presurgical state ( p < 0.05). They were also able to carry out their sporting activities more easily than prior to surgery ( p < 0.05). Conclusion The seeding of chondrocytes in fibrin may provide a favorable micro-environment for the synthesis of extracellular matrix and improved the clinical condition and activity of the patients 1 year after surgery.

Treatment of Chondral Knee Lesions with Autologous Chondrocytes Embedded in a Fibrin Scaffold. Clinical and Functional Assessment / Tratamento de lesões condrais no joelho com condrócitos autólogos embebidos em arcabouço de fibrina. Avaliação clínica e funcional

Abstract Objective The aim of our study is to analyze the clinical and functional results obtained using autologous chondrocytes embedded in a fibrin scaffold in knee joint injuries. Methods We included 56 patients, 36 men and 20 women, with a mean age 36 years. Six of the patients were professional athletes, with single knee injuries that were either chondral or osteochondral (43 chondral, 9 osteochondral, 2 cases of osteochondritis dissecans and 2 osteochondral fractures), 2 to 10 cm2 in size and ≤ 10 mm deep, with no signs of osteoarthritis. The location of the injury was in the patella (8), the medial femoral condyle (40) and lateral femoral condyle (7) and one in the trochlea. The mean follow-up was 3 (range: 1-6) years. The clinical course was assessed using the Cincinnati and Knee Injury and Osteoarthritis Outcome (KOOS) scores, 6 and 12 months after surgery. The paired Student t-test was used to compare pre-and postoperative results. Results Six months after the implant, patients resumed their everyday activities. On the assessment scores, their condition was improving in comparison with their presurgical state (p < 0.05). They were also able to carry out their sporting activities more easily than prior to surgery (p < 0.05). Conclusion The seeding of chondrocytes in fibrin may provide a favorable microenvironment for the synthesis of extracellular matrix and improved the clinical condition and activity of the patients 1 year after surgery.

Resumo Objetivo O objetivo do nosso estudo é analisar os resultados clínicos e funcionais do tratamento de lesões nas articulações do joelho com condrócitos autólogos embebidos em arcabouço de fibrina. Métodos O estudo foi realizado com 56 pacientes (36 homens e 20 mulheres) com idade média de 36 anos; 6 indivíduos eram atletas profissionais. Os pacientes apresentavam lesões únicas, condrais ou osteocondrais (43 condrais, nove osteocondrais, 2 casos de osteocondrite dissecante e duas fraturas osteocondrais) no joelho, com 2 a 10 cm2 de tamanho e ≤ 10 mm de profundidade, sem sinais de osteoartrite. As lesões estavam localizadas na patela (8), no côndilo femoral medial (40), no côndilo femoral lateral (7) e na tróclea (1). O período médio de acompanhamento foi de 3 anos (faixa de 1-6 anos). A evolução clínica foi avaliada pelos escores de Cincinnati e Knee Injury and Osteoarthritis Outcome (KOOS), 6 e 12 meses após a cirurgia. O teste t de Student pareado foi utilizado para comparação dos achados pré e pós-operatórios. Resultados Os pacientes retomaram suas atividades diárias 6 meses após o implante. Os escores avaliados demonstraram a melhora em comparação ao estado pré-cirúrgico (p < 0,05). Além disso, os pacientes conseguiram realizar suas atividades esportivas com mais facilidade do que antes da cirurgia (p < 0,05). Conclusão A cultura de condrócitos em fibrina pode proporcionar um microambiente favorável para a síntese de matriz extracelular e melhorar a condição clínica e a atividade dos pacientes 1 ano após a cirurgia

Arthroscopic Tenotomy of the Long Head of the Biceps Tendon and Section of the Anterior Joint Capsule Produce Moderate Osteoarthritic Changes in an Experimental Sheep Model.

Osteoarthritis (OA) of the glenohumeral (GH) joint is a common cause of shoulder pain, resulting in considerable invalidity. Unfortunately, the study of its pathogenesis is challenging. Models of OA are necessary to identify specific targets for therapy and to be able to interfere with the development and evolution of OA. This study aims to assess the effect of an arthroscopic tenotomy of the long head of the biceps tendon (LHBT) and section of the anterior glenohumeral joint capsule on the ovine glenohumeral joint. In addition, the authors aim to validate and evaluate the reliability of a modified semi-quantitative MRI score to assess joint degeneration in a sheep's shoulder. Eight skeletally mature sheep received an arthroscopic tenotomy of the LHBT and section of the anterior joint capsule and were euthanized four months after surgery. All animals tolerated the surgery well, and no complication was recorded for six weeks. Moderate degenerative changes to the ovine shoulder joint were found on MRI and histological evaluation. The arthroscopic tenotomy of the LHBT and the anterior glenohumeral joint capsule section caused moderate degenerative changes to the ovine shoulder joint.

Deep deltoid ligament injury is related to rotational instability of the ankle joint: a biomechanical study.

PURPOSE: In the athletic population, the prevalence of isolated syndesmotic lesions is high. To detect potential instability of the ankle is crucial to define those lesions in need of surgical management. The aim was to define how the extent of tibio-fibular syndesmotic ligament injury influences the overall stability of the ankle joint in a cadaver model. METHODS: Twenty fresh-frozen through knee cadaveric leg specimens were subjected to different simulated syndesmotic ligament lesions. In Group 1 (n = 10), the order of ligament sectioning was: anterior tibio-fibular ligament (ATFL), superficial deltoid ligament (SDL), deep deltoid ligament (DDL), posterior tibio-fibular ligament (PTFL), and progressive sectioning at 10, 50 and 100 mm of the distal interosseous membrane (IOM). In Group 2 (n = 10), the sequence was: ATFL, PITFL, 10 and then 50 mm of the distal IOM, SDL, DDL, and 100 mm of the distal IOM. Diastasis of 4 mm in the coronal or sagittal plane and external rotation of the ankle greater than 20° were considered indicative of instability. RESULTS: Both coronal and sagittal diastasis exceeded 4 mm with injury patterns characterized by IOM lesions extending beyond 5 cm. External rotation of the ankle exceeded 20° with injury patterns characterized by a DDL lesion. CONCLUSION: Coronal and sagittal plane diastases of the tibio-fibular syndesmosis are particularly affected by sequential lesions involving the IOM, whereas increased external rotation of the ankle most depends on DDL. The identification of the specific syndesmotic and deltoid ligament injuries is crucial to understanding which lesions need operative management. The knowledge of which pattern of tibio-fibular syndesmotic ligament injury influences the ankle joint stability is crucial in defining which lesions need for surgical management.

Osteoarthritis-related biomarkers profile in chronic anterior cruciate ligament injured knee.

OBJECTIVE: Increasing evidence has shown the involvement of the innate immune system and inflammatory response in osteoarthritis (OA) pathogenesis; however, anterior cruciate ligament (ACL) tears are recognized risk factors for development of post-traumatic OA. We investigated (1) whether inflammatory mediators involved in OA pathogenesis are also present at significant concentrations in the knee joint sometime after ACL complete tear and may be considered as prognostic biomarkers of progression to secondary OA; and (2) whether quantification in serum may surrogate synovial fluid (SF) measurements in both cases. METHODS: Thirty-seven end-stage OA patients and 33 patients with ACL complete tear that were included on the waiting list for knee surgery were consecutively recruited. Serum and SF samples were taken before surgery, and tumor necrosis factor-alpha, (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-1 (MMP1), matrix metalloproteinase-3 (MMP3), tissue inhibitor of metalloproteinase-1 (TIMP1), bone morphogenetic protein-7 (BMP7), regulated upon activation normal t-cell expressed and secreted (RANTES), cytokine interferon-γ-induced protein 10 (IP-10) and heat shock protein family A (Hsp70) member 1A (HSPA1A) were quantified by enzyme-linked immunosorbent assay (ELISA.) Normally distributed data were compared using a one-way analysis of variance (ANOVA) test. Data not normally distributed were analyzed using a nonparametric Mann-Whitney rank sum test. Differences in means were compared using a Student's t-test. Correlations were analyzed using Pearson's coefficient of variation. RESULTS: Eighty-seven percent of patients with OA and 86% of those with ACL tear had quantifiable levels of biomarkers in SF. SF levels of IL-6, IL-8, MMP1, MMP3, RANTES, IP-10, BMP7 and HSPA1A were significantly lower in ACL injury knees compared with those with OA, but much higher than those reported in control subjects. Serum levels of IL-6, IP-10, and MMP1 were also lower in patients with ACL tears, who had, however, significantly higher TNF-α, HSPA1A, and TIMP1 levels when compared with OA patients. Levels of biomarkers tested in serum and SF samples were significantly different. CONCLUSIONS: Our data propose that cytokines IL-6 and IL-8 and the chemokines RANTES, IP-10, MMP1, MMP3, and HSPA1A may be involved in the inflammatory process leading to synovitis, the central lesion in OA onset and development; persistent high levels of these substances sometime after ACL injury suggest that they could play an etiopathogenic role in the maintenance of the inflammatory environment leading to post-traumatic OA. Serum biomarker levels do not appear to faithfully reflect what occurs inside the joint. Thus, most biomarkers cannot yet be considered as useful inflammatory biomarkers of knee joint diseases.

Does Orientation of the Femoral Head Affect Acetabular Development? An Experimental Study in Lamb.

BACKGROUND: Derotational osteotomy of the proximal femur has proved to be effective in the treatment of residual acetabular dysplasia. However, the reason why this osteotomy is effective remains debatable. The purpose of this study is to investigate if an alteration of femoral head orientation affects acetabular growth. METHODS: A proximal femoral osteotomy was performed in 21 lambs aged 3 months: 5 varus osteotomies (110 degrees), 4 valgus osteotomies (150 degrees), and 12 derotation osteotomies. Results were compared with a control group (5 animals). Osteotomy was fixed with a screw-plate device. Version was controlled intraoperatively with K-wires. Animals were killed 3 months after surgical procedure. A morphometric study of both proximal femur and acetabulum was performed, including deepness, volume and diameters of the acetabulum, neck-shaft angle and femoral version. RESULTS: The average neck-shaft angle for the normal, anteversion, and retroversion groups was 129 degrees, whereas it was 110 degrees for the varus group and 149 degrees for the valgus group. The average femoral version for the normal, valgus, and varus groups was 21 degrees of anteversion, whereas it was 38 degrees of anteversion for the so-called anteversion group and 17 degrees of retroversion for the retroversion group. Nor the neck-shaft angle, nor the femoral version correlated with the acetabular anteroposterior diameter (P=0.698, 0.6, respectively), the acetabular inferosuperior diameter (P=0.083, 0.451, respectively) or the acetabular deepness (P=0.14, 0.371, respectively). The neck-shaft angle correlated significantly with acetabular volume (P=0.023), so that the lower the neck-shaft angle, the higher the acetabular volume (r=-0.453). The femoral version did not correlated with acetabular volume (P=0.381). CONCLUSIONS: Decreasing the neck-shaft angle provokes an increase in acetabular volume, whereas changes in femoral version do not affect the acetabular growth. Extra-articular osteotomies that alter femoral orientation affect intra-articular gross morphology. LEVEL OF EVIDENCE: Level II-therapeutic study.

Gene expression, protein profiling, and chemotactic activity of infrapatellar fat pad mesenchymal stem cells in pathologies of the knee joint.

The infrapatellar fat pad (IPFP) is a periarticular adipose knee tissue. This tissue contains a large number of mesenchymal stem cells (MSCs). In the present work, we wanted to study the IPFP MSCs and their relationship and differences in two groups, anterior cruciate ligament (ACL) ruptures knees and ostheoarthrosis (OA). The IPFP of 42 patients with OA or ACL rupture were analyzed. Isolation, primary culture, and a genetic and proteomic study of MSCs from IPFP were performed. Gene expression of IL-6, tumor necrosis factor (TNF), IL-8, HSPA1A (Hsp70), CXCL10, RANTES, MMP1, MMP3, TIMP1, and BMP7 was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). We analyzed MSCs from from 12 diferents patients in two cellular pools (6 from AO disease and 6 from ALC rupture to form two cell pool), for the iTRAQ Proteomic Assay. The conditional media were used in quantitative analysis of MSC soluble factors by Luminex and for de migration assay. A higher gene expression of IL-6, TNF, CXCL10, RANTES, and MMP1 and OPG in MSCs from OA versus ACL (p < 0.05) was observed. Conversely HSPA1A, TIMP1, and RANKL showed a significant lower expression in OA-MSCs (p < 0.05). In the secretome analysis, adipsin and visfantin levels in the supernatants from OA-MSCs were lower (p < 0.05) respect to ACL-MSCs. Also, the monocytic cells migrated two-folds in the presence of conditioned media from OA-MSCs patients versus patients with ACL-MSC. The infrapatellar pad should be considered as an adipose tissue capable of producing and excreting inflammatory mediators directly in the knee joint, influencing the development and progression of knee joint pathologies.

Cell Therapies in Tendon, Ligament, and Musculoskeletal System Repair.

In the last few decades, several techniques have been used to optimize tendon, ligament, and musculoskeletal healing. The evidence in favor of these techniques is still not proven, and level I studies are lacking. We performed an analysis of the therapeutic strategies and tissue engineering projects recently published in this field. Here, we try to give an insight into the current status of cell therapies and the latest techniques of bioengineering applied to the field of orthopedic surgery. The future areas for research in the management of musculoskeletal injuries are outlined. There are emerging technologies developing into substantial clinical treatment options that need to be critically evaluated. Mechanical stimulation of the constructs reproduces a more propitious environment for effective healing.

Long-term results of total knee arthroplasty after failed high tibial osteotomy.

PURPOSE: Sometimes, total knee replacement (TKR) is performed after a tibial osteotomy. It is not known if the osteotomy influences the clinical process of a TKR. The aim of this study was to look at the clinical outcome of a TKR after high tibial osteotomy (HTO) compared to a TKR with no HTO. METHODS: Between 1995 and 2005, 41 post-HTO TKRs (group A) with a minimum follow-up of ten years were selected. In parallel, it was selected a control group undergoing simple TKR, consisting of 41 patients (group B) matched with group A. The Knee Society Knee Score (KS), Knee Score Functional Score (FS), the Oxford Knee Score (OKS), and the range of motion (ROM) were used for evaluation at one, five and ten years after surgery. The Insall-Salvatti ratio (ISR), the posterior tibial slope (PTS), and the joint height line (JHL) were also measured both pre-operatively and post-operatively. RESULTS: No differences were found between both groups in KS, FS, OKS, and ROM at the pre-operative stage or at any of the post-operative controls. Higher patellar height was found in group A, both pre-operatively and post-operatively (p < 0.005), and the same for PTS pre-operative (p < 0.001) and post-operative (p < 0.05). No differences were found regarding the JHL. Post-operative differences were found among the post-HTO subgroups at the FS (p < 0.02), the OKS (p < 0.05), and the ROM (p < 0.01) as a function of whether there was a varus or a valgus deformity before the TKR. CONCLUSION: A HTO was not determinant for having a worse outcome at the TKR, even when there were radiographic differences. The coronal alignment with valgus deformity pre-TKR after a HTO showed better functional results than in the case of varus deformity. Level of evidence III.

Modulation of Gene Expression in Infrapatellar Fat Pad-Derived Mesenchymal Stem Cells in Osteoarthritis.

Aim In the osteoarthritis (OA) disease, all structures of the joint are involved. The infrapatellar Hoffa fat pad is rich in macrophages and granulocytes, which also represents a source of adipose mesenchymal progenitor cells (ASC) cells. In our study, we analyze how OA affects the ability of ASC-derived from Hoffa's fat pad to differentiate into chondrocytes. Material and methodology We took knee Hoffa's pad samples and adipose tissue from the proximal thigh from 6 patients diagnosed with severe OA and from another 6 patients with an anterior cruciate ligament (ACL) rupture without OA. From all the patients, we took subcutaneous adipose tissue from the thigh, as the control group. Samples of synovial fluid (SF) were also extracted. The gene expression was analyzed by real-time quantitative polymerase chain reaction. Results PTH1R and MMP13 expression during chondrogenic differentiation were similar between OA and ACL groups, while the expression of OPG, FGF2, TGFß, MMP3 were significantly lower in the OA group. Exposure of differentiated ASC to OA SF induced an increase in the expression of OPG, PTH1R, and MMP13 and a decrease in the expression of FGF2 in cell culture of the ACL group. However, expression of none of these factors was altered by the OA synovial fluid in ASC cells of the OA group. Conclusion OA of the knee also affects the mesenchymal stem cells of Hoffa fat, suggesting that Hoffa fat is a new actor in the OA degenerative process that can contribute to the origin, onset, and progression of the disease.

Biostable scaffolds of polyacrylate polymers implanted in the articular cartilage induce hyaline-like cartilage regeneration in rabbits.

PURPOSE: To study the influence of scaffold properties on the organization of in vivo cartilage regeneration. Our hypothesis was that stress transmission to the cells seeded inside the pores of the scaffold or surrounding it, which is highly dependent on the scaffold properties, determines the differentiation of both mesenchymal cells and dedifferentiated autologous chondrocytes. METHODS: 4 series of porous scaffolds made of different polyacrylate polymers, previously seeded with cultured rabbit chondrocytes or without cells, were implanted in cartilage defects in rabbits. Subchondral bone was injured during the surgery to allow blood to reach the implantation site and fill the scaffold pores. RESULTS: At 3 months after implantation, excellent tissue regeneration was obtained, with a well-organized layer of hyaline-like cartilage at the condylar surface in most cases of the hydrophobic or slightly hydrophilic series. The most hydrophilic material induced the poorest regeneration. However, no statistically significant difference was observed between preseeded and non-preseeded scaffolds. All of the materials used were biocompatible, biostable polymers, so, in contrast to some other studies, our results were not perturbed by possible effects attributable to material degradation products or to the loss of scaffold mechanical properties over time due to degradation. CONCLUSIONS: Cartilage regeneration depends mainly on the properties of the scaffold, such as stiffness and hydrophilicity, whereas little difference was observed between preseeded and non-preseeded scaffolds.

Evaluation of lower limb kinetics during gait, sprint and hop tests before and after anterior cruciate ligament reconstruction.

BACKGROUND: The purpose of this study was to evaluate the functional status prior to and at different times after anterior cruciate ligament reconstruction (ACLR), and to analyze the changes in the kinetic patterns of the involved and uninvolved lower limb during gait, sprint and three hop tests. MATERIALS AND METHODS: Seventy-four male patients with an ACL injury were included in the study. All patients performed a standardized kinetic protocol including gait, sprint and three hop tests (single-leg hop, drop vertical jump and vertical jump tests), preoperatively and at 3, 6, and 12 months after ACLR with a semitendinosus gracilis tendon autograft. Measurements were performed with two force plates. The lower limb symmetry index (LSI) was calculated to determine whether a side-to-side leg difference was classified as normal (LSI >90%) or abnormal (LSI <90%). RESULTS: The LSI presented high values (>90%) at almost all times before and after ACLR in gait, sprint and single-leg hop tests (p < 0.005), with a tendency to increase postoperatively. A lower LSI was observed (<90%) in tests where both extremities were tested simultaneously, such as the drop vertical jump and vertical hop tests (p < 0.05). CONCLUSION: We observed a tendency to increase symmetry restoration in the kinetics of the involved and uninvolved limb up to twelve months after ACLR, especially in those tests, in which, both limbs were tested individually (gait analysis, sprint and single-leg hop tests). Therefore, the isolation of the involved and uninvolved limb seems to be a critical component in the functional rehabilitation and evaluation of patients before and after ACLR. LEVEL OF EVIDENCE: level III.