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1.
Proc Natl Acad Sci U S A ; 113(47): 13522-13527, 2016 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-27821779

RESUMEN

During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstntm1Sjl/+) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstntm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2oim), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2oim/+ offspring from natural mating of Mstntm1Sjl/+ dams to Col1a2oim/+sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2oim/+ dams to Col1a2oim/+ sires. Finally, increased bone biomechanical strength of Col1a2oim/+ offspring that had been transferred into Mstntm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta.


Asunto(s)
Fémur/fisiopatología , Miostatina/metabolismo , Osteogénesis Imperfecta/fisiopatología , Animales , Biomarcadores/sangre , Fenómenos Biomecánicos , Peso Corporal , Colágeno/metabolismo , Modelos Animales de Enfermedad , Implantación del Embrión , Femenino , Fémur/patología , Masculino , Ratones Endogámicos C57BL , Contracción Muscular , Miostatina/deficiencia , Osteoblastos/metabolismo , Osteogénesis Imperfecta/sangre , Osteogénesis Imperfecta/embriología , Tibia/patología , Tibia/fisiopatología
2.
Arthroscopy ; 35(5): 1473-1483, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30926192

RESUMEN

PURPOSE: To determine whether the deep fibers of the iliotibial band (dITB) or the anterolateral ligament (ALL) provides more control of a simulated pivot shift and whether a minimally invasive anterolateral reconstruction (ALR) designed to functionally restore the ALL and dITB is mechanically equivalent to a modified Lemaire reconstruction (MLR). METHODS: Six matched pairs of cadaveric knees (N = 12) were subjected to a simulated pivot shift to evaluate anteroposterior translation; internal rotation; and valgus laxity at 0°, 30°, and 90° of flexion. The anterior cruciate ligament (ACL) was sectioned in all specimens, and retesting was performed. Within each pair, sequential sectioning of the ALL and dITB was performed, followed by testing; the contralateral knee was sectioned in reverse order. Knees underwent ACL reconstruction (ACLR) and repeat testing. Then, MLR (n = 6) or ALR (n = 6) was performed on matched pairs for final testing. RESULTS: Sectioning of the dITB versus ALL (after ACL sectioning) produced significantly more anterior translation at all flexion angles (P = .004, P = .012, and P = .011 for 0°, 30°, and 90°, respectively). The ACL-plus-dITB sectioned state had significantly more internal rotation at 0° versus ACL plus ALL (P = .03). ACLR plus ALR restored native anterior translation at all flexion angles. ACLR plus MLR restored anterior translation to native values only at 0° (P = .34). We found no statistically significant differences between ACLR plus ALR and ACLR plus MLR at any flexion angle for internal rotation or valgus laxity compared with the native state. CONCLUSIONS: ALR of the knee in conjunction with ACLR can return the knee to its native biomechanical state without causing overconstraint. The dITB plays a more critical role in controlling anterior translation and internal rotation at 0° than the ALL. The minimally invasive ALR was functionally equivalent to MLR for restoration of knee kinematics after ACLR. CLINICAL RELEVANCE: The dITB is more important than the ALL for control of the pivot shift. A minimally invasive extra-articular tendon allograft reconstruction was biomechanically equivalent to a modified Lemaire procedure for control of a simulated pivot shift.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior/métodos , Ligamento Cruzado Anterior/cirugía , Inestabilidad de la Articulación/cirugía , Articulación de la Rodilla/cirugía , Tendones/trasplante , Adulto , Fenómenos Biomecánicos , Cadáver , Humanos , Persona de Mediana Edad , Rango del Movimiento Articular , Rotación , Tendones/cirugía
3.
J Biomech Eng ; 140(8)2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-30003261

RESUMEN

Innovation arises from creativity. "Thinking outside the box" has long been seen as a necessary precursor to innovation and invention in engineering. However, creativity is rarely part of traditional engineering curricula. In 2015, our group began to explore integrating theater-based creativity methods into bioengineering capstone design. Evaluation of student outcomes was encouraging, so we continued to develop the course in 2016 and 2017. As we worked to refine the pedagogical process, we discovered tensions (real or perceived) between providing academic rigor and allowing students to embrace their creativity; for instance, we experienced some resistance from engineering faculty and students toward adopting methods they viewed as "artsy" or lacking academic rigor. Here, we discuss the tensions we observed offer potential ways to mitigate such tensions and begin to consider how to expand on our successes.


Asunto(s)
Creatividad , Curriculum , Ingeniería/educación , Control de Calidad
4.
Toxicol Pathol ; 45(7): 931-938, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-29020891

RESUMEN

Because articular cartilage has very limited healing potential, most symptomatic cartilage injuries eventually result in end-stage osteoarthritis and are treated with artificial joint replacement. Our interdisciplinary, comparative orthopedic research performed by a team of DVMs, MDs, engineers, and basic scientists has yielded marked progress toward effective biologic joint restoration strategies by bringing bench-side ideas to fruition in bedside applications in both canine and human patients. This mini-review summarizes the progress of biologic joint restoration strategies at our center.


Asunto(s)
Artroplastia de Reemplazo , Trasplante Óseo , Cartílago Articular/cirugía , Osteoartritis/cirugía , Animales , Productos Biológicos , Condrocitos/citología , Perros , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
J Biomech Eng ; 139(7)2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28520913

RESUMEN

The creative process is fun, complex, and sometimes frustrating, but it is critical to the future of our nation and progress in science, technology, engineering, mathematics (STEM), as well as other fields. Thus, we set out to see if implementing methods of active learning typical to the theater department could impact the creativity of senior capstone design students in the bioengineering (BE) department. Senior bioengineering capstone design students were allowed to self-select into groups. Prior to the beginning of coursework, all students completed a validated survey measuring engineering design self-efficacy. The control and experimental groups both received standard instruction, but in addition the experimental group received 1 h per week of creativity training developed by a theater professor. Following the semester, the students again completed the self-efficacy survey. The surveys were examined to identify differences in the initial and final self-efficacy in the experimental and control groups over the course of the semester. An analysis of variance was used to compare the experimental and control groups with p < 0.05 considered significant. Students in the experimental group reported more than a twofold (4.8 (C) versus 10.9 (E)) increase of confidence. Additionally, students in the experimental group were more motivated and less anxious when engaging in engineering design following the semester of creativity instruction. The results of this pilot study indicate that there is a significant potential to improve engineering students' creative self-efficacy through the implementation of a "curriculum of creativity" which is developed using theater methods.


Asunto(s)
Creatividad , Ingeniería/educación , Ansiedad , Humanos , Autoinforme , Estudiantes/psicología
6.
Am J Pathol ; 185(7): 2000-11, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25987251

RESUMEN

Null alleles for the COL5A1 gene and missense mutations for COL5A1 or the COL5A2 gene underlie cases of classic Ehlers-Danlos syndrome, characterized by fragile, hyperextensible skin and hypermobile joints. However, no classic Ehlers-Danlos syndrome case has yet been associated with COL5A2 null alleles, and phenotypes that might result from such alleles are unknown. We describe mice with null alleles for the Col5a2. Col5a2(-/-) homozygosity is embryonic lethal at approximately 12 days post conception. Unlike previously described mice null for Col5a1, which die at 10.5 days post conception and virtually lack collagen fibrils, Col5a2(-/-) embryos have readily detectable collagen fibrils, thicker than in wild-type controls. Differences in Col5a2(-/-) and Col5a1(-/-) fibril formation and embryonic survival suggest that α1(V)3 homotrimers, a rare collagen V isoform that occurs in the absence of sufficient levels of α2(V) chains, serve functional roles that partially compensate for loss of the most common collagen V isoform. Col5a2(+/-) adults have skin with marked hyperextensibility and reduced tensile strength at high strain but not at low strain. Col5a2(+/-) adults also have aortas with increased compliance and reduced tensile strength. Results thus suggest that COL5A2(+/-) humans, although unlikely to present with frank classic Ehlers-Danlos syndrome, are likely to have fragile connective tissues with increased susceptibility to trauma and certain chronic pathologic conditions.


Asunto(s)
Colágeno Tipo V/genética , Colágeno/genética , Síndrome de Ehlers-Danlos/genética , Adulto , Alelos , Animales , Colágeno/metabolismo , Colágeno Tipo V/metabolismo , Tejido Conectivo/anomalías , Tejido Conectivo/patología , Síndrome de Ehlers-Danlos/metabolismo , Síndrome de Ehlers-Danlos/patología , Femenino , Heterocigoto , Homocigoto , Humanos , Masculino , Ratones , Ratones Noqueados , Mutación , Fenotipo , Piel/patología
7.
Arthroscopy ; 32(6): 1086-97, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26853947

RESUMEN

PURPOSE: To compare all-inside cortical-button suspensory fixation in sockets versus interference screw fixation in tunnels with respect to clinical, histologic, and biomechanical assessments of all-soft tissue (AST) tendon autografts used for anterior cruciate ligament (ACL) reconstruction in a canine model. METHODS: By use of a validated "hybrid" double-bundle ACL reconstruction technique (reconstruction of the anteromedial bundle with preservation of the native posterolateral bundle), dogs were randomly assigned to undergo either suspensory fixation in sockets (n = 6) or interference screw fixation in tunnels (n = 6). Contralateral knees were used as nonoperated controls (n = 12). Quadrupled extensor tendon autografts were used for both ACL reconstruction groups. Dogs were assessed radiographically and functionally and humanely euthanized at 12 weeks after surgery for arthroscopic, gross, biomechanical, and histologic assessments. RESULTS: Histologic assessments showed significantly (P = .018) better graft incorporation with 4-zone direct healing to bone for the grafts using suspensory fixation in sockets (16.3 ± 1.5) compared with the grafts using interference screw fixation in tunnels (14.2 ± 2.1). Furthermore, graft healing to bone was significantly better at the aperture (P = .05) and mid-socket (P = .01) location for the group that underwent suspensory fixation in sockets (16.1 ± 1.8 and 16.4 ± 1.9, respectively). CONCLUSIONS: Suspensory fixation of AST grafts in sockets was associated with superior tendon-to-bone healing compared with interference screw fixation in tunnels, with 4-zone direct graft healing to bone seen for femoral and tibial sockets only in the suspensory-fixation group. Biomechanical properties were similar between groups. CLINICAL RELEVANCE: These data provide evidence suggesting that an all-inside ACL reconstruction technique using adjustable-loop cortical-button suspensory fixation in bone sockets has potential clinical advantages for ACL reconstruction using AST grafts.


Asunto(s)
Reconstrucción del Ligamento Cruzado Anterior/instrumentación , Reconstrucción del Ligamento Cruzado Anterior/métodos , Tornillos Óseos , Tendones/trasplante , Animales , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/cirugía , Fenómenos Biomecánicos , Modelos Animales de Enfermedad , Perros , Fémur/cirugía , Tendones/diagnóstico por imagen , Tibia/cirugía , Trasplante Autólogo
8.
Arthroscopy ; 32(6): 1117-24, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26895785

RESUMEN

PURPOSE: To evaluate the biomechanical fixation strength of suture anchor and transosseous tunnel repair of the quadriceps tendon in a standardized cadaveric repair model. METHODS: Twelve "patella-only" specimens were used. Dual-energy X-ray absorptiometry measurement was performed to ensure equal bone quality amongst groups. Specimens were randomly assigned to either a suture anchor repair of quadriceps tendon group (n = 6) or a transosseous tunnel repair group (n = 6). Suture type and repair configuration were equivalent. After the respective procedures were performed, each patella was mounted into a gripping jig. Tensile load was applied at a rate of 0.1 mm/s up to 100 N after which cyclic loading was applied at a rate of 1 Hz between magnitudes of 50 to 150 N, 50 to 200 N, 50 to 250 N, and tensile load at a rate of 0.1 mm/s until failure. Outcome measures included load to failure, displacement at 1st 100 N load, and displacement after each 10th cycle of loading. RESULTS: The measured cyclic displacement to the first 100 N, 50 to 150 N, 50 to 200 N, and 50 to 250 N was significantly less for suture anchors than transosseous tunnels. There was no statistically significant difference in ultimate load to failure between the 2 groups (P = .40). Failure mode for all suture anchors except one was through the soft tissue. Failure mode for all transosseous specimens but one was pulling the repair through the transosseous tunnel. CONCLUSIONS: Suture anchor quadriceps tendon repairs had significantly decreased gapping during cyclic loading, but no statistically significant difference in ultimate load to failure when compared with transosseous tunnel repairs. Although suture anchor quadriceps tendon repair appears to be a biomechanically superior construct, a clinical study is needed to confirm this technique as a viable alternative to gold standard transosseous techniques. CLINICAL RELEVANCE: Although in vivo studies are needed, these results support the suture anchor technique as a viable alternative to transosseous repair of the quadriceps tendon.


Asunto(s)
Anclas para Sutura , Técnicas de Sutura , Tendones/fisiología , Tendones/cirugía , Resistencia a la Tracción/fisiología , Absorciometría de Fotón , Fenómenos Biomecánicos , Cadáver , Humanos , Rótula/cirugía , Músculo Cuádriceps/cirugía , Traumatismos de los Tendones/cirugía
9.
Clin Orthop Relat Res ; 472(11): 3404-14, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25030100

RESUMEN

BACKGROUND: Osteochondral allografting is an option for successful treatment of large articular cartilage defects. Use of osteochondral allografting is limited by graft availability, often because of loss of chondrocyte viability during storage. QUESTIONS/PURPOSES: The purpose of this study was to compare osteochondral allografts implanted in canine knees after 28 days or 60 days of storage for (1) initial (1 week) safety and feasibility; (2) integrity and positioning with time (12 weeks and 6 months); and (3) gross, cell viability, histologic, biochemical, and biomechanical characteristics at an endpoint of 6 months. METHODS: With Institutional Animal Care and Use Committee approval, adult dogs (n=16) were implanted with 8-mm cylindrical osteochondral allografts in the lateral and medial femoral condyles of one knee. Osteochondral allografts preserved for 28 or 60 days using either the current tissue bank standard-of-care (SOC) or a novel system (The Missouri Osteochondral Allograft Preservation System, or MOPS) were used, creating four treatment groups: SOC 28-day, MOPS 28-day, SOC 60-day, and MOPS 60-day. Bacteriologic analysis of tissue culture and media were performed. Dogs were assessed by radiographs and arthroscopy at interim times and by gross, cell viability, histology, biochemistry, and biomechanical testing at the 6-month endpoint. RESULTS: With the numbers available, there was no difference in infection frequency during storage (5% for SOC and 3% for MOPS; p=0.5). No infected graft was implanted and no infections occurred in vivo. MOPS grafts had greater chondrocyte viability at Day 60 (90% versus 53%; p=0.002). For 60-day storage, MOPS grafts were as good as or better than SOC grafts with respect to all outcome measures assessed 6 months after implantation. CONCLUSIONS: Donor chondrocyte viability is important for osteochondral allograft success. MOPS allows preservation of chondrocyte viability for up to 60 days at sufficient levels to result in successful outcomes in a canine model of large femoral condylar articular defects. CLINICAL RELEVANCE: These findings provide a promising development in osteochondral allograft technology that can benefit the quantity of grafts available for use and the quality of grafts being implanted.


Asunto(s)
Cartílago Articular/patología , Cartílago Articular/cirugía , Condrocitos/trasplante , Conservación de Tejido/métodos , Conservación de Tejido/normas , Trasplante Homólogo/métodos , Animales , Artroscopía , Fenómenos Biomecánicos , Cartílago Articular/diagnóstico por imagen , Supervivencia Celular , Condrocitos/metabolismo , Perros , Estudios de Factibilidad , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/cirugía , Masculino , Radiografía , Distribución Aleatoria , Bancos de Tejidos/normas , Resultado del Tratamiento , Soporte de Peso
10.
J Shoulder Elbow Surg ; 23(8): 1156-61, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24725901

RESUMEN

BACKGROUND: This study examined histologic characteristics and biomechanical performance of 2 commercially available, small glenoid anchors. METHODS: Adult research dogs (n = 6) were used for histologic analysis. Anchors were inserted into the lateral rim of the glenoid using the manufacturer's protocol. The dogs were humanely euthanatized 8 weeks after anchor implantation, and the glenoids were collected for histologic analysis. Bone socket width data were compared for statistically significant (P < .05) differences. In addition, 4 matched pairs (n = 8) of human cadaveric glenoids were instrumented with 1 BioComposite SutureTak (Arthrex, Naples, FL, USA) and 1 JuggerKnot (Biomet, Warsaw, IN, USA) suture anchor in the anterior-inferior quadrant. Anchor constructs were preloaded to 5 N, cycled from 5 to 25 N for 100 cycles, and then pulled to failure. RESULTS: All JuggerKnot anchor sites were cyst-like cavities with a rim of dense lamellar bone. All BioComposite SutureTak anchor sites contained intact anchors with close approximation of anastomosing trabeculae of lamellar bone. At 8 weeks after implantation, mean socket width of the JuggerKnot anchor sites was 6.3 ± 2.5 mm, which was significantly (P = .013) larger than the mean socket width of 2.7 ± 0.7 mm measured for the BioComposite SutureTak anchor sites. The JuggerKnot anchor demonstrated larger displacements during subfailure cyclic loading (2.9 ± 1.0 mm compared with 1.3 ± 0.4 mm) and load to failure tests (13.7 ± 6.6 mm compared with 3.2 ± 0.5 mm). Statistical differences (P < .01) existed in every category except ultimate load. CONCLUSIONS: Based on the biomechanical in human bone and histologic findings in canine subjects, the all-suture anchor may be at risk for clinical failure.


Asunto(s)
Fibrocartílago/cirugía , Inestabilidad de la Articulación/cirugía , Escápula/cirugía , Articulación del Hombro/cirugía , Anclas para Sutura , Animales , Fenómenos Biomecánicos , Cadáver , Perros , Fibrocartílago/patología , Fibrocartílago/fisiopatología , Humanos , Inestabilidad de la Articulación/patología , Inestabilidad de la Articulación/fisiopatología , Modelos Animales , Escápula/patología , Escápula/fisiopatología , Articulación del Hombro/patología , Articulación del Hombro/fisiopatología , Resistencia a la Tracción , Cicatrización de Heridas
11.
J Biomater Appl ; 38(1): 85-96, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37178228

RESUMEN

Lower back pain is one of the leading causes of disability, affecting 11.9% of the population worldwide and studies have shown that intervertebral disc degeneration is a common cause for chronic lower back pain. We have explored the combination of three components, viscoelastic collagen, genipin, and gold nanoparticles to determine its potential to promote regeneration of the intervertebral disc, specifically for nucleus pulposus regeneration. The goal of this study was to develop, fabricate and characterize different formulations of viscoelastic collagen conjugated with gold nanoparticles and genipin to assess the feasibility as a tissue template. Results demonstrated the successful attachment of gold nanoparticles to the viscoelastic collagen utilizing the genipin crosslinker. For each of the viscoelastic collagen compositions examined, cell biocompatibility was achieved. The results also demonstrated an increase in stiffness of the material with different sizes and concentrations of AuNPs. Results from the TEM and STEM also demonstrated that the viscoelastic collagen that was developed did not display the characteristic D banding pattern of polymerized collagen. The findings from this study could lead to the development of a more efficient and cost-effective treatment for patients with chronic back pain caused by IVD degeneration.


Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Dolor de la Región Lumbar , Nanopartículas del Metal , Humanos , Oro , Dolor de la Región Lumbar/etiología , Colágeno , Degeneración del Disco Intervertebral/terapia
12.
Arthroscopy ; 28(2): 169-77, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22137238

RESUMEN

PURPOSE: This study tested a bone-tendon allograft versus human dermis patch for reconstructing chronic rotator cuff repair by use of a canine model. METHODS: Mature research dogs (N = 15) were used. Radiopaque wire was placed in the infraspinatus tendon (IST) before its transection. Three weeks later, radiographs showed IST retraction. Each dog then underwent 1 IST treatment: debridement (D), direct repair of IST to bone with a suture bridge and human dermis patch augmentation (GJ), or bone-tendon allograft (BT) reconstruction. Outcome measures included lameness grading, radiographs, and ultrasonographic assessment. Dogs were killed 6 months after surgery and both shoulders assessed biomechanically and histologically. RESULTS: BT dogs were significantly (P = .01) less lame than the other groups. BT dogs had superior bone-tendon, tendon, and tendon-muscle integrity compared with D and GJ dogs. Biomechanical testing showed that the D group had significantly (P = .05) more elongation than the other groups whereas BT had stiffness and elongation characteristics that most closely matched normal controls. Radiographically, D and GJ dogs showed significantly more retraction than BT dogs (P = .003 and P = .045, respectively) Histologically, GJ dogs had lymphoplasmacytic infiltrates, tendon degeneration and hypocellularity, and poor tendon-bone integration. BT dogs showed complete incorporation of allograft bone into host bone, normal bone-tendon junctions, and well-integrated allograft tendon. CONCLUSIONS: The bone-tendon allograft technique re-establishes a functional IST bone-tendon-muscle unit and maintains integrity of repair in this model. CLINICAL RELEVANCE: Clinical trials using this bone-tendon allograft technique are warranted.


Asunto(s)
Materiales Biocompatibles , Trasplante Óseo , Dermis/trasplante , Lesiones del Manguito de los Rotadores , Manguito de los Rotadores/cirugía , Tendones/trasplante , Animales , Fenómenos Biomecánicos , Perros , Humanos , Procedimientos Ortopédicos/métodos , Radiografía , Manguito de los Rotadores/diagnóstico por imagen , Anclas para Sutura , Trasplante Homólogo
13.
J Bone Miner Res ; 36(4): 739-756, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33249643

RESUMEN

Osteogenesis imperfecta (OI) is a genetic connective tissue disorder characterized by compromised skeletal integrity, altered microarchitecture, and bone fragility. Current OI treatment strategies focus on bone antiresorptives and surgical intervention with limited effectiveness, and thus identifying alternative therapeutic options remains critical. Muscle is an important stimulus for bone formation. Myostatin, a TGF-ß superfamily myokine, acts through ActRIIB to negatively regulate muscle growth. Recent studies demonstrated the potential benefit of myostatin inhibition with the soluble ActRIIB fusion protein on skeletal properties, although various OI mouse models exhibited variable skeletal responses. The genetic and clinical heterogeneity associated with OI, the lack of specificity of the ActRIIB decoy molecule for myostatin alone, and adverse events in human clinical trials further the need to clarify myostatin's therapeutic potential and role in skeletal integrity. In this study, we determined musculoskeletal outcomes of genetic myostatin deficiency and postnatal pharmacological myostatin inhibition by a monoclonal anti-myostatin antibody (Regn647) in the G610C mouse, a model of mild-moderate type I/IV human OI. In the postnatal study, 5-week-old wild-type and +/G610C male and female littermates were treated with Regn647 or a control antibody for 11 weeks or for 7 weeks followed by a 4-week treatment holiday. Inhibition of myostatin, whether genetically or pharmacologically, increased muscle mass regardless of OI genotype, although to varying degrees. Genetic myostatin deficiency increased hindlimb muscle weights by 6.9% to 34.4%, whereas pharmacological inhibition increased them by 13.5% to 29.6%. Female +/mstn +/G610C (Dbl.Het) mice tended to have similar trabecular and cortical bone parameters as Wt showing reversal of +/G610C characteristics but with minimal effect of +/mstn occurring in male mice. Pharmacologic myostatin inhibition failed to improve skeletal bone properties of male or female +/G610C mice, although skeletal microarchitectural and biomechanical improvements were observed in male wild-type mice. Four-week treatment holiday did not alter skeletal outcomes. © 2020 American Society for Bone and Mineral Research (ASBMR).


Asunto(s)
Osteogénesis Imperfecta , Animales , Huesos , Colágeno Tipo I , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Miostatina/genética , Osteogénesis , Osteogénesis Imperfecta/tratamiento farmacológico , Osteogénesis Imperfecta/genética
14.
J Knee Surg ; 33(4): 365-371, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30727021

RESUMEN

This study compares bioabsorbable nail to metal screw fixation of shell osteochondral allograft (OCAs) for compression and shear strength. Cadaveric distal femurs (n = 5) yielding six 1.5 cm shell grafts (n = 30) were used. Three different fixation methods (2.0 and 2.4 mm headed screws, and copolymer absorbable nail) were compared for statistically significant differences (p < 0.05) in contact area, contact pressure, and shear load-to-failure. No significant differences in contact areas existed among groups (224 ± 33.5 mm2; 233.9 ± 20.8 mm2, 220.6 ± 22.7 mm2; p = 0.509 for 2.4, 2.0 mm screw, and nail, respectively). No significant differences in contact pressures existed (1.7 ± 0.6 MPa/mm2, 1.5 ± 0.8 MPa/mm2, 1.4 ± 0.9 MPa/mm2; p = 0.73 for 2.4, 2.0 mm screw, and nail, respectively). Load-to-failure for each was: 280.7 ± 48.4 N for 2.4 mm screws, 245.1 ± 70.6 N for 2.0 mm screws, and 215.2 ± 39.4 N for nails. There were no statistically significant differences in load-to-failure between 2.4 and 2.0 mm screws (p = 0.29) or between 2.0 mm screws and nails (p = 0.23); however, load-to-failure in shear was significantly higher for 2.4 mm screws compared with nails (p = 0.036). Fixation of shell OCAs using a copolymer headed nail provides initial graft-recipient compression similar to fixation using 2.0 and 2.4 mm headed screws. Nails failed in shear at significantly lower load than 2.4 mm screws but not 2.0 mm screws which have proven adequate for clinical healing. This study has clinical relevance, as a copolymer bioabsorbable headed nail (SmartNail) has graft-recipient compression and shear load-to-failure properties that suggest it is viable for shell OCA fixation.


Asunto(s)
Implantes Absorbibles , Clavos Ortopédicos , Tornillos Óseos , Cartílago/trasplante , Fémur/cirugía , Aloinjertos , Cadáver , Fuerza Compresiva , Humanos , Ensayo de Materiales , Resistencia al Corte , Trasplante Homólogo
15.
Endocrinology ; 161(8)2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32484851

RESUMEN

The prevalence of maternal obesity is increasing at an alarming rate and increases the life-long risk of developing cardiometabolic disease in adult offspring. Leptin, an adipokine, is systemically elevated in the obese milieu. We recently showed that maternal hyperleptinemia without obesity improves offspring insulin sensitivity and glucose tolerance while protecting against weight gain on a high-fat, high-sugar (HFD). Here, we investigate the effect of maternal hyperleptinemia on offspring bone by using 2 independent maternal models. First, we compared wild-type (WT) offspring from severely hyperleptinemic Leprdb/+ (DB/+) dams with those from WT dams. In the second model, WT females were implanted with miniosmotic pumps that released either saline (group SAL) or leptin (group LEP; 650ng/hour) and the WT offspring were compared. At 23 weeks of age, a subset of offspring were challenged with a HFD for 8 weeks. When the offspring were 31 weeks of age, bone geometry, strength, and material properties were investigated. The HFD increased trabecular bone volume but decreased both total breaking strength and material strength of femora from the offspring of WT dams. However, male offspring of DB/+ dams were protected from the detrimental effects of a HFD, while offspring of LEP dams were not. Further material analysis revealed a modest decrease in advanced glycation end product accumulation coupled with increased collagen crosslinking in male offspring from DB/+ dams on a HFD. These data suggest that while maternal leptin may protect bone quality from the effects of a HFD, additional factors of the maternal environment controlled by leptin receptor signaling are likely also involved.


Asunto(s)
Densidad Ósea/genética , Dieta Alta en Grasa/efectos adversos , Efectos Tardíos de la Exposición Prenatal/genética , Receptores de Leptina/genética , Animales , Densidad Ósea/efectos de los fármacos , Desarrollo Óseo/efectos de los fármacos , Desarrollo Óseo/genética , Fuerza Compresiva/efectos de los fármacos , Fuerza Compresiva/fisiología , Grasas de la Dieta/farmacología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Factores Sexuales , Aumento de Peso/efectos de los fármacos , Aumento de Peso/fisiología
16.
J Orthop Surg Res ; 14(1): 246, 2019 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-31382997

RESUMEN

BACKGROUND: While there are several different animal models for use in the characterization of spinal fixation, none have emerged as a definitive model for comparative studies in spinal fixation methods. The purpose of this study is to establish morphometric data of porcine vertebrae and to characterize the feasibility of pedicle screw fixation in porcine spines for potential comparative human study. METHODS: Four spines from 45 to 50 kg Hanford minipigs were cleaned of soft tissue and analyzed by computed tomography and dual-energy x-ray absorptiometry. Two 5 × 30-mm pedicle screws were placed in each vertebra and tested to failure using a combined moment-load protocol. RESULTS: Pedicle widths were measured from L6-T5. Widths ranged from 7.15 mm (T6) to 9.24 mm (T14). Posterior cortex to anterior cortex depth ranged from 25.9 to 32.6 mm. Mean bone mineral density was 1.0665 g/cm2 (range 1.139-1.016). Force-to-failure demonstrated mean 1171.40 N (+ 115.34). CONCLUSION: Our baseline morphometric and compositional data demonstrate that porcine vertebrae can serve as a useful model for comparative studies due to their similar pedicle widths and bone mineral density to the human vertebra. This biomechanical data could provide a baseline comparison for future studies. This study also suggests that the minipig could be a suitable model for comparative studies due to similarities in pedicle width and bone mineral density to the human vertebrae.


Asunto(s)
Densidad Ósea/fisiología , Vértebras Lumbares/fisiología , Vértebras Lumbares/cirugía , Modelos Animales , Tornillos Pediculares , Animales , Fenómenos Biomecánicos/fisiología , Vértebras Lumbares/diagnóstico por imagen , Porcinos , Porcinos Enanos
17.
Hand (N Y) ; 14(4): 547-553, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-29322875

RESUMEN

Background: This study compares the effectiveness of a peripheral capsular repair with a knotless arthroscopic transosseous ulnar tunnel repair (TR) in restoring distal radioulnar joint (DRUJ) stability and stiffness in the setting of a massive triangular fibrocartilage complex (TFCC) tear. Methods: Eight matched pairs of fresh-frozen cadaveric forearms were tested. Each forearm was tested in supination and pronation using 3-dimensional (3D) optical tracking devices prior to any intervention. Each specimen then underwent a diagnostic wrist arthroscopy and sectioning of the TFCC's deep and superficial fibers. All specimens were then retested to assess instability secondary to the tear. The TFCC was repaired with either a peripheral capsular repair (CR) using three 2-0 polydioxanone sutures or a transosseous ulnar TR using a 2-0 FiberWire, and then retested (statistical significance; P < .05). Results: After TFCC arthroscopic sectioning, all specimens were unstable with a significant increase in translation and a significant decrease in stiffness. TFCC repair with TR resulted in displacement and stiffness similar to the native tissue. CR specimens were found to have significantly greater displacement and significantly decreased stiffness compared with the intact state. Conclusions: Arthroscopic sectioning of the TFCC resulted in DRUJ instability, as measured by stiffness and ulnar translation. TR effectively restored DRUJ stability and demonstrated no significant difference in postoperative stiffness or maximal displacement when compared with the intact specimen in pronation and supination. This study provides biomechanical evidence that an arthroscopic ulnar tunnel technique can restore stability to the DRUJ after a massive TFCC tear.


Asunto(s)
Fenómenos Biomecánicos/fisiología , Antebrazo/cirugía , Cápsula Articular/cirugía , Fibrocartílago Triangular/cirugía , Anciano , Artroscopía/métodos , Cadáver , Femenino , Antebrazo/diagnóstico por imagen , Antebrazo/fisiología , Humanos , Inestabilidad de la Articulación/cirugía , Masculino , Complicaciones Posoperatorias/epidemiología , Pronación/fisiología , Supinación/fisiología , Lágrimas , Fibrocartílago Triangular/patología , Cúbito/fisiología , Cúbito/cirugía , Articulación de la Muñeca/cirugía
18.
J Knee Surg ; 32(5): 434-440, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-29702719

RESUMEN

Tendon injury is common in sports. The standard of care (SOC) for tendon repair is surgical treatment. However, restored tendons often lack complete strength and functionality, and surgical repair is often unsuccessful. This controlled laboratory study investigates the healing of an Artelon patch (AP)-augmented tendon versus tendon repair alone in a preclinical canine patellar tendon defect model. Full-thickness proximal and distal flap defects were created in the patella tendons of eight purpose-bred research mongrel dogs. Dogs were randomly allocated into either the AP-augmented repair group or the SOC group (N = 8; four knees per group). Outcomes measures included limb function and pain; range of motion (ROM) and ultrasound assessment at 2, 4, and 8 weeks; and measurements of elongation, biomechanical testing, and histology at 8 weeks. Data were compared for statistically significant differences to preoperative measures and between groups (p < 0.05). The AP group had higher limb function scores compared with the SOC group at 2, 4, and 8 weeks, with statistically significant differences observed at 2 weeks (AP: 7.1 ± 1.4, SOC: 5.5 ± 0.4, p < 0.05) and 8 weeks (AP: 9.5 ± 0.7, SOC: 7.0 ± 0.9, p < 0.05). The ROM was significantly higher for the AP group at 4 weeks (AP: 105 degrees ± 4, SOC: 89 degrees ± 5, p < 0.05). Pain scores were statistically significantly lower in the AP group at 4 (AP: 0.6 ± 0.5, SOC: 2.2 ± 0.5) and 8 weeks (p < 0.05 for both comparisons). All animals in the AP group displayed full bridging tissue at week 4, while most animals of the SOC group displayed full bridging by week 8. Minimal tendon elongation was observed in both groups. Significantly more force was required to elongate tendons in the AP group compared with the SOC group (p < 0.05). Animals with AP-augmented tendon repair show an earlier regain of function, earlier regain of range of movement, less postoperative pain, and improved tendon strength when compared with animals treated with tendon repair alone.


Asunto(s)
Ligamento Rotuliano/cirugía , Poliuretanos/uso terapéutico , Traumatismos de los Tendones/cirugía , Cicatrización de Heridas , Animales , Materiales Biocompatibles , Fenómenos Biomecánicos , Modelos Animales de Enfermedad , Perros , Masculino , Ligamento Rotuliano/diagnóstico por imagen , Rango del Movimiento Articular , Tendones/cirugía
19.
J Orthop Translat ; 16: 102-111, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30723687

RESUMEN

BACKGROUND: Pelvic ring-comminuted transforaminal sacral fracture injuries are rotationally and vertically unstable and have a high rate of failure. OBJECTIVE: Our study purpose was to use three-dimensional (3D) optical tracking to detect onset location of bone-implant interface failure and measure the distances and angles between screws and line of applied force for correlation to strength of pelvic fracture fixation techniques. METHODS: 3D relative motion across sacral-rami fractures and screws relative to bone was measured with an optical tracking system. Synthetic pelves were used. Comminuted transforaminal sacral-rami fractures were modelled. Each pelvis was stabilised by either (1) two iliosacral screws in S1, (2) one transsacral screw in S1 and one iliosacral screw in S1 and (3) one trans-alar screw in S1 and one iliosacral screw in S1; groups 4-6 consisted of fixation groups with addition of anterior inferior iliac pelvic external fixator. Eighteen-instrumented pelvic models with right ilium fixed simulate single-leg stance. Load was applied to centre of S1 superior endplate. Five cycles of torque was initially applied, sequentially increased until permanent deformation occurred. Five cycles of axial load compression was next applied, sequentially increased until permanent deformation occurred, followed by axial loading to catastrophic failure. A Student t test was used to determine significance (p < 0.05). RESULTS: The model, protocol and 3D optical system have the ability to locate how sub-catastrophic failures initiate. Our results indicate failure of all screw-based constructs is due to localised bone failure (screw pull-in push-out at the ipsilateral ilium-screw interface, not in sacrum); thus, no difference was observed when not supplemented with external fixation. CONCLUSION: Inclusion of external fixation improved resistance only to torsional loading. TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Patients with comminuted transforaminal sacral-ipsilateral rami fractures benefit from this fixation.

20.
Int J Biol Macromol ; 130: 88-98, 2019 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-30779988

RESUMEN

Vertebral compression fractures are a very common consequence of osteoporosis for which injection of a non-biodegradable, non-bioactive, mechanically-stiff polymer bone cement into the vertebral body is the most common treatment. Recently, there has been growing interest in using bioactive, degradable, and bone biomechanics-matching products as an alternative approach for treating these fractures. In this research, we focused on creating injectable, chitosan-based hydrogels that can convey mechanical strength similar to vertebral bone as well as possess inherent osteoinductivity. First, we investigated the effects of three different factors - 1) bioactive phosphate ionic crosslinking; 2) genipin covalent crosslinking; 3) mechanically reinforcing cellulose nanocrystal incorporation - on the material properties of chitosan-based hydrogels. Mesenchymal stem cells were then exposed to hydrogels with optimum mechanical properties and stability in order to assess the biological effects of the bioactive phosphate ionic crosslinker. Our results show that hydrogels with higher ionic and covalent crosslinking ratios supplemented with neutral cellulose nanocrystals possessed desirable compressive strength and stability. Also, the significant osteoinductivity of these composite hydrogels demonstrated their potential to function as an injectable system for the future treatment of vertebral compression fractures.


Asunto(s)
Materiales Biocompatibles/farmacología , Celulosa/química , Quitosano/química , Fracturas por Compresión/tratamiento farmacológico , Hidrogeles/química , Nanopartículas/química , Fracturas de la Columna Vertebral/tratamiento farmacológico , Materiales Biocompatibles/química , Materiales Biocompatibles/uso terapéutico , Línea Celular , Fenómenos Mecánicos
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