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PURPOSE: Multiple techniques are described for repair of zone I flexor tendon injuries, many of which are fraught with complications. This study evaluated the clinical complications after a transosseous repair technique. METHODS: A retrospective review of a single institutional database identified all zone I flexor digitorum profundus (FDP) injuries repaired using a transosseous technique. In this technique, 2 nonabsorbable sutures were passed from volar to dorsal through transosseous tunnels and tied dorsally over the distal phalanx proximal to the germinal matrix. Demographics, injury characteristics, operative details, and complications were reviewed. RESULTS: Eight patients met the inclusion criteria. Average age was 31 years (range, 15-66 years) and all patients were male. Eight fingers were included: ring (4), small (3), and middle (1). Seven injuries were closed and one was open. Average time between injury and surgery was 13 days (range, 4-34 days). Five patients experienced complications, including osteomyelitis, chronic draining granuloma, and abnormal nail growth. Three patients required an additional operative procedure for management of complications. CONCLUSIONS: Transosseous repair of zone I flexor digitorum profundus injuries with a buried dorsal suture is associated with a high rate of clinical complications. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.
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Traumatismos dos Dedos , Falanges dos Dedos da Mão , Traumatismos dos Tendões , Adulto , Traumatismos dos Dedos/cirurgia , Falanges dos Dedos da Mão/cirurgia , Humanos , Masculino , Estudos Retrospectivos , Técnicas de Sutura , Traumatismos dos Tendões/cirurgia , TendõesRESUMO
BACKGROUND: Utilization of revision total knee arthroplasty (TKA) has been increasing, and reasons for failure are less understood than those of primary TKA. The purpose of this study is to identify the rates and mechanisms of failure of revision TKA, and compare those between a historic (1986-2005) and modern (2006-2015) cohort. METHODS: All revision TKAs performed at a single institution between 1986 and 2015 were reviewed, with minimum 2-year follow-up. Failure was defined as a second revision surgery in which any component was exchanged. Diagnosis at the time of index and any re-revision procedure was determined. RESULTS: In total, 1632 revision TKAs in 1560 patients were reviewed. The average age was 65.1 and the average follow-up was 61.4 months. Overall failure rate was 22.8%, with no significant differences between the historic and modern cohort (25.1% vs 22.0%, P = .19). The leading cause for failure was infection in 38.5% of failures. The next most common causes for failure were aseptic loosening (20.9%) and instability (14.2%). Failure rate among revision TKAs for infection was 33%, with 67.2% failing due to repeat infection. Multivariate analysis found that septic index revision (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.47-2.48), male gender (OR 1.41, 95% CI 1.11-1.78), and age less than 65 (OR 1.56, 95% CI 1.23-1.97) were independent risk factors for failure. CONCLUSION: There remains a high rate of failure in revision TKA, with infection being the most common reason for failure. Rates and primary reasons for failure have not changed significantly in the past decade.
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Artroplastia do Joelho , Prótese do Joelho , Infecções Relacionadas à Prótese , Idoso , Artroplastia do Joelho/efeitos adversos , Humanos , Articulação do Joelho/cirurgia , Prótese do Joelho/efeitos adversos , Masculino , Falha de Prótese , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/cirurgia , Reoperação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Erythropoietin (EPO) has been identified as a neuroregenerative agent. We hypothesize that it may accelerate recovery after crush injury and may vary with crush severity. METHODS: Mice were randomized to mild, moderate, or severe crush of the sciatic nerve and were treated with EPO or vehicle control after injury. The sciatic function index (SFI) was monitored over the first week. Microstructural changes were analyzed by immunofluorescence for neurofilament (NF) and myelin (P0 ), and electron microscopy was used to assess ultrastructural changes. RESULTS: In moderate crush injuries, EPO significantly improved SFI at 7 days post-injury, an effect not observed with other severity levels. Increases in the ratio of P0 to NF were observed after EPO treatment in moderate crush injuries. Electron microscopy demonstrated endothelial cell hypertrophy in the EPO group. CONCLUSIONS: EPO accelerates recovery in moderately crushed nerves, which may be through effects on myelination and vascularization. Injury severity may influence the efficacy of EPO. Muscle Nerve 56: 143-151, 2017.
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Eritropoetina/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/fisiopatologia , Análise de Variância , Animais , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Filamentos Intermediários/metabolismo , Filamentos Intermediários/patologia , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica , Proteína P0 da Mielina/metabolismo , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/ultraestrutura , Índice de Gravidade de DoençaRESUMO
PURPOSE: To evaluate the changes in maximum flexion angle, gliding coefficient, and bowstringing after a combined repair of both flexor tendons with the flexor digitorum superficialis (FDS) rerouted outside the A2 pulley in cadaveric hands. METHODS: We performed 4 different repairs on cadaveric hands, with each repair tested on 9 unique digits. In total, 12 cadaveric hands and 36 digits were used. The thumb and little finger were removed from each hand and excluded from testing. Group 1 was sham surgery. Group 2 combined flexor digitorum profundus (FDP) and FDS laceration and repair with both slips of the FDS repaired inside the A2 pulley. Group 3 was FDP repair with one slip of the FDS repaired inside A2 and the other slip left unrepaired. Group 4 was FDP repair with both slips of the FDS rerouted and repaired outside the A2 pulley. Maximum flexion angle, gliding coefficient, and bowstringing were measured in simulated active digital motion for each group. RESULTS: Rerouting and repairing the FDS outside the A2 pulley (group 4) significantly lowered gliding coefficient compared with repairs with both slips inside A2, with values similar to sham surgery. We observed no significant differences in maximum flexion angle among the 4 groups. Increased bowstringing was observed with both slips of the FDS repaired and rerouted outside the A2 pulley. CONCLUSIONS: In this cadaveric model, repair of both slips of the FDS outside the A2 pulley improved the gliding coefficient relative to repair within the A2 pulley, which suggests decreased resistance to finger flexion. Repair of the FDS outside the A2 pulley led to a slight increase in bowstringing of the FDS tendon. CLINICAL RELEVANCE: We describe a technique for managing combined laceration of the FDP and FDS tendons that improves gliding function and merits consideration.
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Traumatismos dos Dedos/cirurgia , Lacerações/cirurgia , Procedimentos Ortopédicos/métodos , Traumatismos dos Tendões/cirurgia , Tendões/cirurgia , Traumatismos dos Dedos/fisiopatologia , Humanos , Recuperação de Função Fisiológica , Técnicas de Sutura , Traumatismos dos Tendões/fisiopatologia , Tendões/fisiopatologiaRESUMO
Osteoarthritis (OA) of the hip is a common and debilitating painful joint disease. However, there is paucity of surgically induced hip OA models in small animals that allow scientists to study the onset and progression of the disease. A growing body of evidence indicates a positive association between periarticular myotendinous pathology and the development of hip OA. Thus, in the current study, we aimed to establish a novel mouse instability-associated hip OA model via selective injury of the abductor complex around the hip joint. C57BL6/J mice were randomized to sham surgery or abductor injury, in which the myotendinous insertion at the third trochanter and greater trochanter were surgically detached. Mice were allowed free active movement until they were sacrificed at either 3 weeks or 20 weeks post-injury. Histologic analyses and immunohistochemical staining of the femoral head articular cartilage were performed, along with microCT (µCT) analysis to assess subchondral bone remodeling. We observed that mice receiving abductor injury exhibited significantly increased instability-associated OA severity with loss of proteoglycan and type II collagen staining compared to sham control mice at 20 weeks post-surgery, while comparable matrix metalloproteinase 13 expression was observed between injury and sham groups. No significant differences in subchondral bone remodeling were found after 3 or 20 weeks following injury. Our study further supports the link between abductor dysfunction and the development of instability-associated hip OA. Importantly, this novel surgically induced hip OA mouse model may provide a valuable tool for future investigations into the pathogenesis and treatment of hip OA.
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BACKGROUND: Extraction of implants because of periprosthetic infection (PJI) following complex revision total knee arthroplasty (rTKA) with extensive instrumentation is a daunting undertaking for surgeon and patient alike. The purpose of the present study was to evaluate whether infections following complex rTKA are better treated with 2-stage exchange or irrigation and debridement (I&D) with modular component exchange and antibiotic suppression in terms of infection control, reoperation, and function. METHODS: We reviewed rTKAs that had been performed for the treatment of PJI from 2005 to 2016. Extensive instrumentation was defined as the presence ≥1 of the following: metaphyseal cones/sleeves, distal femoral replacement, periprosthetic fracture instrumentation, or fully cemented stems measuring >75 mm. Cases were categorized according to the initial treatment (I&D with antibiotic suppression or initiation of 2-stage exchange). RESULTS: Eighty-seven patients with PJI and extensive instrumentation were identified: 56 patients who were managed with I&D with suppression and 31 who were managed with the initiation of 2-stage exchange. The rate of success (defined as no reoperation for infection) was similar for the 2 groups (62.5% the I&D group compared with 67.7% for the 2-stage group; p = 0.62). The rate of mortality was also similar (39.3% for the I&D group compared with 38.7% for the 2-stage group; p = 0.96). Of the 31 patients in the 2-stage group, 18 (58.1%) underwent reimplantation with a revision replacement. Of those 18 patients, 13 were still infection-free at the time of the most recent follow-up; however, when the analysis was expanded to all 31 patients in the 2-stage group, only 13 (41.9%) both had a successful reimplantation and did not require additional surgery for infection. Nine (29.0%) of the 31 patients in the 2-stage group never underwent the second stage, and 4 (12.9%) of the 31 required arthrodesis at the second stage. In contrast, 35 (62.5%) of the 56 patients in the I&D group were successfully managed, without additional surgery for the treatment of infection. At the time of the latest follow-up (mean, 3.2 years; range, 2 to 13 years), more patients in the I&D group were ambulatory (76.8% in the I&D group compared with 54.8% in the 2-stage group; p = 0.05) and maintained a functional bending knee joint (85.7% in the I&D group compared with 45.2% in the 2-stage group; p < 0.001). CONCLUSIONS: In the treatment of periprosthetic infection of rTKA with extensive instrumentation, I&D with chronic antibiotic suppression was as effective as 2-stage exchange in terms of preventing reoperation for infection and was more effective in terms of maintaining function. These data apply to rTKA with extensive periarticular instrumentation and should not be extrapolated to primary or simple revision implants. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Artroplastia do Joelho/efeitos adversos , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/cirurgia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Artroplastia do Joelho/instrumentação , Desbridamento , Remoção de Dispositivo , Feminino , Humanos , Articulação do Joelho/cirurgia , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/etiologia , Recuperação de Função Fisiológica , Reoperação , Estudos Retrospectivos , Irrigação Terapêutica , Resultado do TratamentoRESUMO
AIMS: Aseptic loosening of the tibial component is a frequent cause of failure in primary total knee arthroplasty (TKA). Management options include an isolated tibial revision or full component revision. A full component revision is frequently selected by surgeons unfamiliar with the existing implant or who simply wish to "start again". This option adds morbidity compared with an isolated tibial revision. While isolated tibial revision has a lower morbidity, it is technically more challenging due to difficulties with exposure and maintaining prosthetic stability. This study was designed to compare these two reconstructive options. METHODS: Patients undergoing revision TKA for isolated aseptic tibial loosening between 2012 and 2017 were identified. Those with revision implants or revised for infection, instability, osteolysis, or femoral component loosening were excluded. A total of 164 patients were included; 88 had an isolated tibial revision and 76 had revision of both components despite only having a loose tibial component. The demographics and clinical and radiological outcomes were recorded. RESULTS: The patient demographics were statistically similar in the two cohorts. The median follow-up was 3.5 years (interquartile range (IQR) 1 to 12.5). Supplementary femoral metaphyseal fixation was required in five patients in the full revision cohort. There was a higher incidence of radiological tibial loosening in the full component revision cohort at the final follow-up (8 (10.5%) vs 5 (5.7%); p = 0.269). Three patients in the full component revision cohort developed instability while only one in the isolated tibial cohort did. Three patients in the full revision cohort developed a flexion contracture greater than 5° while none in the isolated tibial cohort did. CONCLUSION: Isolated tibial revision for aseptic tibial loosening has statistically similar clinical and radiological outcomes at a median follow-up of 3.5 years, when compared with full component revision. Substantial bone loss can occur when removing a well-fixed femoral component necessitating a cone or sleeve. Femoral component revision for isolated tibial loosening can frequently be avoided provided adequate ligamentous stability can be obtained. Cite this article: Bone Joint J 2020;102-B(6 Supple A):123-128.
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Artroplastia do Joelho , Prótese do Joelho , Complicações Pós-Operatórias/diagnóstico , Falha de Prótese , Reoperação/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , TíbiaRESUMO
AIMS: Two-stage exchange arthroplasty is the most common definitive treatment for prosthetic joint infection (PJI) in the USA. Complications that occur during treatment are often not considered. The purpose of this study was to analyze complications in patients undergoing two-stage exchange for infected total knee arthroplasty (TKA) and determine when they occur. METHODS: We analyzed all patients that underwent two-stage exchange arthroplasty for treatment of PJI of the knee from January 2010 to December 2018 at a single institution. We categorized complications as medical versus surgical. The intervals for complications were divided into: interstage; early post-reimplantation (three months); and late post-reimplantation (three months to minimum one year). Minimum follow-up was one year. In total, 134 patients underwent a first stage of a two-stage exchange. There were 69 males and 65 females with an mean age at first stage surgery of 67 years (37 to 89). Success was based on the new Musculoskeletal Infection Society (MSIS) definition of success reporting. RESULTS: Overall, 70 (52%) patients experienced a complication during the planned two-stage treatment, 36 patients (27%) experienced a medical complication and 47 (41%) patients experienced a surgical complication. There was an 18% mortality rate (24/134) at a mean of 3.7 years (0.09 to 8.3). During the inter-stage period, 28% (37/134) of patients experienced a total of 50 complications at a median of 47 days (interquartile range (IQR) 18 to 139). Of these 50 complications, 22 were medical and 28 required surgery. During this inter-stage period, four patients died (3%) and an additional five patients (4%) failed to progress to the second stage. While 93% of patients (125/134) were reimplanted, only 56% (77/134) of the patients were successfully treated without antibiotic suppression (36%, 28/77) or with antibiotic suppression (19%, 15/77) at one year. CONCLUSION: Reported rates of success of two stage exchanges for PJI have not traditionally considered complications in the definition of success. In our series, significant numbers of patients experienced complications, more often after reimplantation, highlighting the morbidity of this method of treatment. Cite this article: Bone Joint J 2020;102-B(6 Supple A):145-150.
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Artroplastia do Joelho/métodos , Complicações Intraoperatórias/epidemiologia , Prótese do Joelho/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Reoperação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Type II Diabetes (T2DM) dramatically impairs the tendon healing response, resulting in decreased collagen organization and mechanics relative to non-diabetic tendons. Despite this burden, there remains a paucity of information regarding the mechanisms that govern impaired healing of diabetic tendons. Mice were placed on either a high fat diet (T2DM) or low fat diet (lean) and underwent flexor tendon transection and repair surgery. Healing was assessed via mechanical testing, histology and changes in gene expression associated with collagen synthesis, matrix remodeling, and macrophage polarization. Obese/diabetic tendons healed with increased scar formation and impaired mechanical properties. Consistent with this, prolonged and excess expression of extracellular matrix (ECM) components were observed in obese/T2DM tendons. Macrophages are involved in both inflammatory and matrix deposition processes during healing. Obese/T2DM tendons healed with increased expression of markers of pro-inflammatory M1 macrophages, and elevated and prolonged expression of M2 macrophages markers that are involved in ECM deposition. Here we demonstrate that tendons from obese/diabetic mice heal with increased scar formation and increased M2 polarization, identifying excess M2 macrophage activity and matrix synthesis as a potential mechanism of the fibrotic healing phenotype observed in T2DM tendons, and as such a potential target to improve tendon healing in T2DM.
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Cicatriz/metabolismo , Diabetes Mellitus Experimental/metabolismo , Matriz Extracelular/metabolismo , Macrófagos/metabolismo , Obesidade/metabolismo , Traumatismos dos Tendões/metabolismo , Animais , Biomarcadores/metabolismo , Fenômenos Biomecânicos , Glicemia/metabolismo , Cicatriz/genética , Cicatriz/patologia , Colágeno/genética , Colágeno/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica/efeitos adversos , Matriz Extracelular/patologia , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Fibrose , Expressão Gênica , Macrófagos/classificação , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/genética , Obesidade/patologia , Amplitude de Movimento Articular/fisiologia , Traumatismos dos Tendões/genética , Traumatismos dos Tendões/patologia , Traumatismos dos Tendões/reabilitação , Tendões/metabolismo , Tendões/patologia , CicatrizaçãoRESUMO
BACKGROUND: After flexor tendon injury and repair, adhesion formation is a substantial concern, as it can result in loss of motion and functional disability. Matrix metalloproteinase 9 (Mmp9) is a gelatinase that contributes to degradation of extracellular matrix and is expressed during flexor tendon healing. Mmp9(-/-) mice have accelerated remodeling of adhesions during flexor tendon healing, relative to wild-type mice. The purpose of this study was to investigate whether Ro 32-3555, an Mmp9 inhibitor, can improve flexor tendon healing by limiting adhesion formation or enhancing remodeling of scar tissue during murine flexor tendon healing. METHODS: Flexor digitorum longus laceration and repair was performed in female C57BL/6J mice. Mice were treated with vehicle or the Mmp9 inhibitor Ro 32-3555 for 8 days. Analysis was performed for digit range of motion and gliding function, biomechanics, gene expression, and Mmp9 activity. RESULTS: An Mmp9 activity assay and zymography confirmed suppression of Mmp9 activity in mice treated with Ro 32-3555. There was no significant difference in tendon gliding or range of motion between vehicle and Ro 32-3555-treated mice. There was also no difference in tendon biomechanical properties between the two groups. CONCLUSION: Local inhibition of Mmp9 gelatinolytic activity at the flexor tendon repair site is insufficient to alter adhesion formation, remodeling of adhesions, or mechanical properties of healing murine flexor tendons.
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Imidazóis/administração & dosagem , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Inibidores de Metaloproteinases de Matriz/administração & dosagem , Traumatismos dos Tendões/cirurgia , Cicatrização/efeitos dos fármacos , Análise de Variância , Animais , Fenômenos Biomecânicos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Valores de Referência , Traumatismos dos Tendões/tratamento farmacológico , Resistência à Tração/efeitos dos fármacos , Aderências Teciduais/tratamento farmacológico , Aderências Teciduais/enzimologia , Cicatrização/fisiologiaRESUMO
Rotator cuff tears (RCT) are a common clinical problem in the geriatric population, and debate exists over how to best provide pain relief and restore shoulder function. Treatment options can be broadly divided into nonsurgical and surgical, with the majority of patients initially placed on a trial of conservative therapy. For those with irreparable RCT, low functional demand, or interest in nonoperative management, there are a number of nonsurgical treatments to consider, including rehabilitation and injections of corticosteroids, hyaluronate, and platelet-rich plasma. Surgical treatment is increasingly common, as geriatric patients remain active with high functional demands. Studies in elderly populations have demonstrated satisfactory healing and clinical results following surgical repair. Predictors of poor outcome after repair are large tear size as well as higher stages of fatty infiltration. Decompression is a less invasive surgical option that has been shown to provide short-term pain relief, though the lasting effects may deteriorate over time. A number of factors must be weighed when considering which patients are likely to benefit from surgical intervention.
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Clinical/microbiological records of 194 patients with microbiological/histopathological diagnosis of Acanthamoeba keratitis from 2007-11 without history of contact lens wear were retrospectively studied. Positive results on corneal scraping and culture were analyzed. Patients were divided based on positive first smear report (group 1/2) and time of presentation (group 3/4). Primary and secondary outcome measures were microbiological positivity rate and to find any possible differences at presentation in sub-groups, respectively. Mean age of patients was 38.5 ± 13.7 years, M:F was 1.8:1. Positivity of first smear examination was 82% and was 98% overall in three scrapings. Ten percent potassium hydroxide with calcoflur white was better than Grams stain (87.1 versus 71.1%). Culture was positive in 79.4% cases. Sub-group analysis showed clinically/demographically similar groups 1 and 2 (p > 0.05). Patients who presented within a month of symptoms (group 3) were significantly younger than others (p = 0.012). Microscopic diagnosis of non-contact-lens Acanthamoeba keratitis is reliable.
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Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/parasitologia , Adulto , Estudos de Casos e Controles , Lentes de Contato/parasitologia , Córnea/parasitologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acuidade Visual/fisiologia , Adulto JovemRESUMO
Flexor tendons (FT) in the hand provide near frictionless gliding to facilitate hand function. Upon injury and surgical repair, satisfactory healing is hampered by fibrous adhesions between the tendon and synovial sheath. In the present study we used antisense oligonucleotides (ASOs), specifically targeted to components of Tgf-ß signaling, including Tgf-ß1, Smad3 and Ctgf, to test the hypothesis that local delivery of ASOs and suppression of Tgf-ß1 signaling would enhance murine FT healing by suppressing adhesion formation while maintaining strength. ASOs were injected in to the FT repair site at 2, 6 and 12 days post-surgery. ASO treatment suppressed target gene expression through 21 days. Treatment with Tgf-ß1, Smad3 or Ctgf ASOs resulted in significant improvement in tendon gliding function at 14 and 21 days, relative to control. Consistent with a decrease in adhesions, Col3a1 expression was significantly decreased in Tgf-ß1, Smad3 and Ctgf ASO treated tendons relative to control. Smad3 ASO treatment enhanced the maximum load at failure of healing tendons at 14 days, relative to control. Taken together, these data support the use of ASO treatment to improve FT repair, and suggest that modulation of the Tgf-ß1 signaling pathway can reduce adhesions while maintaining the strength of the repair.
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Fator de Crescimento do Tecido Conjuntivo/antagonistas & inibidores , Oligonucleotídeos Antissenso/uso terapêutico , Proteína Smad3/antagonistas & inibidores , Traumatismos dos Tendões/terapia , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Animais , Cicatriz/prevenção & controle , Avaliação Pré-Clínica de Medicamentos , Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Oligonucleotídeos Antissenso/farmacologia , Distribuição Aleatória , Tendões/efeitos dos fármacos , Tendões/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
Flexor tendon injuries are a common clinical problem, and repairs are frequently complicated by post-operative adhesions forming between the tendon and surrounding soft tissue. Prostaglandin E2 and the EP4 receptor have been implicated in this process following tendon injury; thus, we hypothesized that inhibiting EP4 after tendon injury would attenuate adhesion formation. A model of flexor tendon laceration and repair was utilized in C57BL/6J female mice to evaluate the effects of EP4 inhibition on adhesion formation and matrix deposition during flexor tendon repair. Systemic EP4 antagonist or vehicle control was given by intraperitoneal injection during the late proliferative phase of healing, and outcomes were analyzed for range of motion, biomechanics, histology, and genetic changes. Repairs treated with an EP4 antagonist demonstrated significant decreases in range of motion with increased resistance to gliding within the first three weeks after injury, suggesting greater adhesion formation. Histologic analysis of the repair site revealed a more robust granulation zone in the EP4 antagonist treated repairs, with early polarization for type III collagen by picrosirius red staining, findings consistent with functional outcomes. RT-PCR analysis demonstrated accelerated peaks in F4/80 and type III collagen (Col3a1) expression in the antagonist group, along with decreases in type I collagen (Col1a1). Mmp9 expression was significantly increased after discontinuing the antagonist, consistent with its role in mediating adhesion formation. Mmp2, which contributes to repair site remodeling, increases steadily between 10 and 28 days post-repair in the EP4 antagonist group, consistent with the increased matrix and granulation zones requiring remodeling in these repairs. These findings suggest that systemic EP4 antagonism leads to increased adhesion formation and matrix deposition during flexor tendon healing. Counter to our hypothesis that EP4 antagonism would improve the healing phenotype, these results highlight the complex role of EP4 signaling during tendon repair.