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1.
Brain Spine ; 4: 102749, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38510636

RESUMEN

Introduction: Deformity of the spinal column after trauma could lead to pain, impaired function, and may sometimes necessitate extensive and high-risk surgery. This 'condition' has multiple terms and definitions that are used in research and clinics. A specific term and definition of this condition however is still lacking. A uniform and internationally accepted term and definition are necessary to compare cases and treatments in the future. Research question: Reach consensus on the term and definition of this deformity after spine trauma using a Delphi approach. Material and methods: An 'all-rounds invitation' Delphi process was used in this study among a group of international experts. The first round consisted of an online survey using input from preparatory studies, a typical clinical case and ICD-11 codes. The second round showed the results in-person and discussion was encouraged. Participants voted for rejection of certain terms. In the third round the final vote took place. When >80 % of the votes was for or against a term the term was rejected or accepted. Results: Response rate was high (≥84 %). The 3 Delphi rounds were completed. Unanimous voting led to the acceptance of the term and abbreviation as PSD. Deformity in any plane, pain, impaired function, and neurological deficit, were deemed important to include in the definition of PSD. Discussion and conclusion: Unanimous consensus was reached on 'Posttraumatic spinal deformity: Condition where a trauma to the spine results in a deformity in any plane and results in pain and an impaired function with or without a neurological deficit.'

2.
Eur Spine J ; 29(12): 3194-3202, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32468192

RESUMEN

PURPOSE: To evaluate whether a new PEEK vertebral body replacement can maintain the sagittal alignment as an anterior column reconstruction device in thoracic and lumbar spinal defects due to trauma or tumor. METHODS: Retrospective review of 48 patients who underwent a corpectomy between T5 and L5 due to trauma or tumor and were stabilized with the new PEEK vertebral body replacement, between 2013 and 2017. We excluded patients who underwent a corpectomy for infection or degenerative disease and patients without complete follow-up in our institution. The primary outcome was the bi-segmental kyphotic angle (BKA). Secondary outcomes were the assessment of pedicle screw loosening, cage height, and subsidence or tilting of the cage. The clinical outcomes were assessed through the COMI-Score, EuroQol-5D, and Karnofsky indexes. Bony fusion and complications were registered. RESULTS: After the surgery BKA decreased by 12.1° (p < 0.001). At the end of the follow-up, we observed a mean loss of reduction of 1.6° (p = 0.002). This was accompanied by an increase in subsidence of 2.1 mm (p < 0.001) and mean tilting of the cage of 1.4° (p = 0.003). The height of the cage and other parameters did not experience any changes. Clinically, the COMI-Score (p = 0.02) and the EuroQol-5D Index (p = 0.012) showed significant improvement, same as Karnofsky-Index (p = 0.015) at final follow-up. The fusion rate according to Bridwell was 92.1%. The 2% late complications were related to implant malpositioning. CONCLUSION: The new PEEK expandable vertebral body replacement is effective and safe in thoracic and lumbar anterior column reconstruction in tumor and trauma diseases.


Asunto(s)
Fusión Vertebral , Cuerpo Vertebral , Benzofenonas , Estudios de Seguimiento , Humanos , Cetonas , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Polietilenglicoles , Polímeros , Estudios Retrospectivos , Resultado del Tratamiento
3.
Eur Cell Mater ; 39: 1-17, 2020 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-31899537

RESUMEN

Appropriate cell sources, bioactive factors and biomaterials for generation of functional and integrated annulus fibrosus (AF) tissue analogues are still an unmet need. In the present study, the AF cell markers, collagen type I, cluster of differentiation 146 (CD146), mohawk (MKX) and smooth muscle protein 22α (SM22α) were found to be suitable indicators of functional AF cell induction. In vitro 2D culture of human AF cells showed that transforming growth factor ß1 (TGF-ß1) upregulated the expression of the functional AF markers and increased cell contractility, indicating that TGF-ß1-pre-treated AF cells were an appropriate cell source for AF tissue regeneration. Furthermore, a tissue engineered construct, composed of polyurethane (PU) scaffold with a TGF-ß1-supplemented collagen type I hydrogel and human AF cells, was evaluated with in vitro 3D culture and ex vivo preclinical bioreactor-loaded organ culture models. The collagen type I hydrogel helped maintaining the AF functional phenotype. TGF-ß1 supplement within the collagen I hydrogel further promoted cell proliferation and matrix production of AF cells within in vitro 3D culture. In the ex vivo IVD organ culture model with physiologically relevant mechanical loading, TGF-ß1 supplement in the transplanted constructs induced the functional AF cell phenotype and enhanced collagen matrix synthesis. In conclusion, TGF-ß1-containing collagen-PU constructs can induce the functional cell phenotype of human AF cells in vitro and in situ. This combined cellular, biomaterial and bioactive agent therapy has a great potential for AF tissue regeneration and rupture repair.


Asunto(s)
Anillo Fibroso/patología , Colágeno/farmacología , Poliuretanos/farmacología , Andamios del Tejido/química , Factor de Crecimiento Transformador beta1/farmacología , Cicatrización de Heridas/efectos de los fármacos , Adulto , Animales , Anillo Fibroso/efectos de los fármacos , Biomarcadores/metabolismo , Bovinos , Células Cultivadas , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Técnicas de Cultivo de Órganos , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Rotura , Cicatrización de Heridas/genética
4.
Osteoarthritis Cartilage ; 27(7): 1094-1105, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31002939

RESUMEN

OBJECTIVE: This study aimed to characterize the mesenchymal stem cell (MSC) subpopulation migrating towards a degenerated intervertebral disc (IVD) and to assess its regenerative potential. DESIGN: Based on initial screening for migration towards C-C motif chemokine ligand 5 (CCL5), the migration potential of CD146+ and CD146- mesenchymal stem cells (MSCs) was evaluated in vitro and in a degenerated organ culture model (degeneration by high-frequency loading in a bioreactor). Discogenic differentiation potential of CD146+ and CD146- MSCs was investigated by in vitro pellet culture assay with supplementation of growth and differentiation factor-6 (GDF6). Furthermore, trypsin degenerated IVDs were treated by either homing or injection of CD146+ or CD146- MSCs and glycosaminoglycan synthesis was evaluated by Sulphur 35 incorporation after 35 days of culture. RESULTS: Surface expression of CD146 led to a higher number of migrated MSCs both in vitro and in organ culture. CD146+ and CD146- pellets responded with a similar up-regulation of anabolic markers. A higher production of sulfated glycosaminoglycans (sGAG)/DNA was observed for CD146+ pellets, while in organ cultures, sGAG synthesis rate was higher for IVDs treated with CD146- MSCs by either homing or injection. CONCLUSIONS: The CD146+ MSC subpopulation held greater migration potential towards degenerative IVDs, while the CD146- cells induced a stronger regenerative response in the resident IVD cells. These findings were independent of the application route (injection vs migration). From a translational point of view, our data suggests that CD146+ MSCs may be suitable for re-population, while CD146- MSCs may represent the primary choice for stimulation of endogenous IVD cells.


Asunto(s)
Antígeno CD146/genética , Movimiento Celular/genética , Regulación de la Expresión Génica , Degeneración del Disco Intervertebral/genética , Anciano , Animales , Biopsia con Aguja , Bovinos , Diferenciación Celular/genética , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunohistoquímica , Degeneración del Disco Intervertebral/patología , Masculino , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Persona de Mediana Edad , Distribución Aleatoria , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Regeneración/genética , Factores de Riesgo
5.
Eur Cell Mater ; 34: 271-290, 2017 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-29064532

RESUMEN

The degeneration of the intervertebral disc (IVD) within the spinal column represents a major pain source for many patients. Biological restoration or repair of the IVD using "compressive-force-resistant" and at the same time "cytocompatible" materials would be desirable over current purely mechanical solutions, such as spinal fusion or IVD implants. This review provides an overview of recent research on the repair of the inner (nucleus pulposus = NP) and the outer (annulus fibrous = AF) parts of the IVD tissue. Many studies have addressed NP repair using hydrogel-like materials. However, only a few studies have so far focused on AF repair. As the AF possesses an extremely low self-healing capacity and special attention to shear-force resistance is essential, special repair designs are required. In our review, we stated the challenges in IVD repair and highlighted the use of composite materials such as silk biomaterials and fibrin cross-linked reinforced hydrogels. We elaborated on the origin of silk and its many in tissue engineering. Furthermore, techniques such as electrospinning and 3D printing technologies allow the fabrication of versatile and functionalised 3D scaffolds. We summarised the research that has been conducted in the field of regenerative medicine over the recent years, with a special focus on the potential application and the potential of combining silk and reinforced - and thus mechanically tailored - hydrogels for IVD repair.


Asunto(s)
Materiales Biocompatibles/farmacología , Hidrogeles/farmacología , Degeneración del Disco Intervertebral/tratamiento farmacológico , Disco Intervertebral/efectos de los fármacos , Seda/farmacología , Animales , Humanos , Disco Intervertebral/patología , Disco Intervertebral/fisiopatología , Degeneración del Disco Intervertebral/fisiopatología , Regeneración/efectos de los fármacos
6.
Injury ; 48(8): 1825-1830, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28687363

RESUMEN

INTRODUCTION: A preoperative planning approach for percutaneous screw fixation of the iliosacral joint provides specific entry points (EPs) and aiming points (APs) of intraosseous screw pathways (as defined by CT scans) for lateral fluoroscopic projections used intraoperatively. The potential to achieve the recommended EPs and APs, to obtain an ideal screw position (perpendicular to the iliosacral joint), to avoid occurrence of extraosseous screw misplacement, to reduce the operating time and the radiation exposure by utilizing this planning approach have not been described yet. METHODS: On preoperative CT scans of eight human cadaveric specimen individual EPs and APs were identified and transferred to the lateral fluoroscopic projection using a coordinate system with the zero-point in the center of the posterior cortex of the S1 vertebral body (x-axis parallel to upper S1 endplate). Distances were expressed in relation to the anteroposterior distance of the S1 upper endplate (in%). In each specimen on one side a screw was placed with provided EP and AP (New Technique) whereas at the contralateral side a screw was placed without given EP and AP (Conventional Technique). Both techniques were compared using postoperative CT scans to assess distances between predefined EPs and APs and the actually obtained EPs and APs, screw angulations in relation to the iliosacral joint in coronal and axial planes and the occurrence of any extraosseous screw misplacement. The "operating time (OT)" and the "time under fluoroscopy (TUF)" were recorded. Statistical analysis was performed by the Wilcoxon signed-rank test. RESULTS: EPs were realized significantly more accurate using the new technique in vertical direction. The screw positions in relation to the iliosacral joint showed no significant difference between both techniques. Both techniques had one aberrantly placed screw outside the safe corridor. The (mean±SD) "OT" and the (mean±SD) "TUF" were significantly decreased using the new technique compared to the conventional technique (OT: 7.6±2min versus 13.1±5.8min, p=0.012; TUF: 1.5±0.8min versus 2.2±1.1min). CONCLUSION: The presented preoperative planning approach increases the accuracy in percutaneous screw fixation of the iliosacral joint, reduces operating time and minimizes radiation exposure to patient and staff.


Asunto(s)
Fluoroscopía , Fijación Interna de Fracturas , Fracturas Óseas/cirugía , Ilion/cirugía , Cuidados Preoperatorios/métodos , Exposición a la Radiación/prevención & control , Sacro/cirugía , Tornillos Óseos , Cadáver , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Fracturas Óseas/diagnóstico por imagen , Humanos , Ilion/anatomía & histología , Ilion/diagnóstico por imagen , Tempo Operativo , Guías de Práctica Clínica como Asunto , Exposición a la Radiación/efectos adversos , Reproducibilidad de los Resultados , Sacro/anatomía & histología , Sacro/diagnóstico por imagen
7.
Eur Cell Mater ; 33: 197-210, 2017 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-28266688

RESUMEN

Spinal fusion is hampered by the presence of remaining intervertebral disc (IVD) tissue and leads to spinal non-union. While the exact mechanism remains unknown, we hypothesise that factors preventing disc ossification, such as antagonists of the bone morphogenetic proteins (BMP), could be responsible for this process. The objective of this study was to investigate spinal non-union using an in vitro human model with a focus on the BMP signalling components and to identify factors contributing to the incomplete and delayed ossification. Human bone marrow-derived mesenchymal stromal cells (MSC) were cocultured with IVD cells in the presence of L51P, a BMP2 variant with osteoinductive potential. The ossification of MSC was evaluated by quantitative reverse transcription polymerase chain reaction (qPCR), alkaline phosphatase (ALP) activity and alizarin red staining. Endogenous expression of major BMP antagonists, namely Gremlin (GREM1), Noggin (NOG) and Chordin (CHRD) was detected in IVD-derived cells, with abundance in nucleus pulposus cells. Osteogenesis of MSC was hindered by IVD cells as shown by reduced alizarin red staining, ALP activity and qPCR. L51P, added to the cocultures, restored mineralisation, blocking the activity of the BMP antagonists secreted by IVD cells. It is possible that the BMP antagonists secreted by IVD cells are responsible for spinal non-unions. The inhibition of BMP antagonists with L51P may result in an efficient and more physiological osteoinduction rather than delivery of exogenous osteogenic factors. Therefore, L51P might represent an attractive therapeutic candidate for bone healing.


Asunto(s)
Proteína Morfogenética Ósea 2/farmacología , Diferenciación Celular , Disco Intervertebral/citología , Células Madre Mesenquimatosas/citología , Osteogénesis , Adolescente , Adulto , Fosfatasa Alcalina/metabolismo , Biomarcadores/metabolismo , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Matriz Ósea/efectos de los fármacos , Matriz Ósea/metabolismo , Calcificación Fisiológica/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Células Madre Mesenquimatosas/enzimología , Persona de Mediana Edad , Osteogénesis/efectos de los fármacos , Donantes de Tejidos , Adulto Joven
8.
Eur J Trauma Emerg Surg ; 42(5): 645-650, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26459473

RESUMEN

PURPOSE: Open surgical management of unstable pelvic ring injuries has been discussed controversially compared to percutaneous techniques in terms of surgical site morbidity especially in older patients. Thus, we assessed the impact of age on the outcome following fixation of unstable pelvic ring injuries through the modified Stoppa approach. METHODS: Out of a consecutive series of 92 patients eligible for the study, 63 patients (mean age 50 years, range 19-78) were evaluated [accuracy of reduction, complications, failures, Majeed-Score, Oswestry Disability Questionnaire (ODI), Mainz Pain Staging System (MPSS)] at a mean follow-up of 3.3 years (range 1.0-7.9). Logistic multivariate regression analysis was performed to assess the outcome in relation to increasing patient age and/or Injury Severity Score (ISS). RESULTS: Out of 63 patients, in 36 an "anatomic" reduction was achieved. Ten postoperative complications occurred in eight patients. In five patients, failure of fixation was noted at the anterior and/or posterior pelvic ring. In 49 patients, an "excellent" or "good" Majeed-Score was obtained; the mean ODI was 14 % (range 0-76 %); 50 patients reported either no or only minor chronic pelvic pain (MPSS). Only an increasing ISS conferred an increased likelihood of the occurrence of a non-anatomical reduction, a "poor" or "fair" Majeed-Score, or an ODI >20 %. CONCLUSIONS: Increasing age did not impact the analysed parameters. Open reduction and internal fixation of the anterior pelvic ring through a modified Stoppa approach in unstable pelvic ring injuries did not result in an unfavourable outcome with increasing age of patients.


Asunto(s)
Acetábulo/cirugía , Fijación Interna de Fracturas/métodos , Fracturas Óseas/cirugía , Huesos Pélvicos/cirugía , Acetábulo/diagnóstico por imagen , Acetábulo/lesiones , Adulto , Anciano , Femenino , Estudios de Seguimiento , Fijación Interna de Fracturas/instrumentación , Fracturas Óseas/diagnóstico por imagen , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/lesiones , Radiografía , Estudios Retrospectivos , Resultado del Tratamiento
9.
Injury ; 46(10): 2003-9, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26190629

RESUMEN

INTRODUCTION: In iliosacral screw fixation, the dimensions of solely intraosseous (secure) pathways, perpendicular to the ilio-sacral articulation (optimal) with corresponding entry (EP) and aiming points (AP) on lateral fluoroscopic projections, and the factors (demographic, anatomic) influencing these have not yet been described. METHODS: In 100 CTs of normal pelvises, the height and width of the secure and optimal pathways were measured on axial and coronal views bilaterally (total measurements: n=200). Corresponding EP and AP were defined as either the location of the screw head or tip at the crossing of lateral innominate bones' cortices (EP) and sacral midlines (AP) within the centre of the pathway, respectively. EP and AP were transferred to the sagittal pelvic view using a coordinate system with the zero-point in the centre of the posterior cortex of the S1 vertebral body (x-axis parallel to upper S1 endplate). Distances are expressed in relation to the anteroposterior distance of the S1 upper endplate (in %). The influence of demographic (age, gender, side) and/or anatomic (PIA=pelvic incidence angle; TCA=transversal curvature angle, PID-Index=pelvic incidence distance-index; USW=unilateral sacral width-index) parameters on pathway dimensions and positions of EP and AP were assessed (multivariate analysis). RESULTS: The width, height or both factors of the pathways were at least 7mm or more in 32% and 53% or 20%, respectively. The EP was on average 14±24% behind the centre of the posterior S1 cortex and 41±14% below it. The AP was on average 53±7% in the front of the centre of the posterior S1 cortex and 11±7% above it. PIA influenced the width, TCA, PID-Index the height of the pathways. PIA, PID-Index, and USW-Index significantly influenced EP and AP. Age, gender, and TCA significantly influenced EP. CONCLUSION: Secure and optimal placement of screws of at least 7mm in diameter will be unfeasible in the majority of patients. Thoughtful preoperative planning of screw placement on CT scans is advisable to identify secure pathways with an optimal direction. For this purpose, the presented methodology of determining and transferring EPs and APs of corresponding pathways to the sagittal pelvic view using a coordinate system may be useful.


Asunto(s)
Fijación Interna de Fracturas , Fracturas Óseas/cirugía , Ilion/cirugía , Huesos Pélvicos/cirugía , Sacro/cirugía , Tomografía Computarizada por Rayos X , Adulto , Tornillos Óseos , Hilos Ortopédicos , Fluoroscopía , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/fisiopatología , Humanos , Ilion/anatomía & histología , Ilion/diagnóstico por imagen , Huesos Pélvicos/anatomía & histología , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/lesiones , Guías de Práctica Clínica como Asunto , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sacro/anatomía & histología , Sacro/diagnóstico por imagen
10.
J Tissue Eng Regen Med ; 9(12): E167-76, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23303720

RESUMEN

Nucleus pulposus (NP) regeneration by the application of injectable cell-embedded hydrogels is an appealing approach for tissue engineering. We investigated a thermo-reversible hydrogel (TR-HG), based on a modified polysaccharide with a thermo-reversible polyamide [poly(N-isopropylacrylamide), pNIPAM], which is made to behave as a liquid at room temperature and hardens at > 32 °C. In order to test the hydrogel, a papain-induced bovine caudal disc degeneration model (PDDM), creating a cavity in the NP, was employed. Human mesenchymal stem cells (hMSCs) or autologous bovine NP cells (bNPCs) were seeded in TR-HG; hMSCs were additionally preconditioned with rhGDF-5 for 7 days. Then, TR-HG was reversed to a fluid and the cell suspension injected into the PDDM and kept under static loading for 7 days. Experimental design was: (D1) fresh disc control + PBS injection; (D2) PDDM + PBS injection; (D3) PDDM + TR-HG (material control); (D4) PDDM + TR-HG + bNPCs; (D5) PDDM + TR-HG + hMSCs. Magnetic resonance imaging performed before and after loading, on days 9 and 16, allowed imaging of the hydrogel-filled PDDM and assessment of disc height and volume changes. In gel-injected discs the NP region showed a major drop in volume and disc height during culture under static load. The RT-PCR results of injected hMSCs showed significant upregulation of ACAN, COL2A1, VCAN and SOX9 during culture in the disc cavity, whereas the gene expression profile of NP cells remained unchanged. The cell viability of injected cells (NPCs or hMSCs) was maintained at over 86% in 3D culture and dropped to ~72% after organ culture. Our results underline the need for load-bearing hydrogels that are also cyto-compatible.


Asunto(s)
Resinas Acrílicas , Hidrogeles , Degeneración del Disco Intervertebral , Células Madre Mesenquimatosas , Modelos Biológicos , Papaína/toxicidad , Resinas Acrílicas/química , Resinas Acrílicas/farmacología , Animales , Antígenos de Diferenciación/biosíntesis , Bovinos , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Degeneración del Disco Intervertebral/inducido químicamente , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/patología , Degeneración del Disco Intervertebral/terapia , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Técnicas de Cultivo de Órganos
11.
Global Spine J ; 4(2): 109-14, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25061549

RESUMEN

Study Design Case report. Objectives With only two previously reported cases, localized amyloidosis of the sacrum is extremely rare. Here we report a 64-year-old woman with a large osteolytic lesion accompanied by weakness and paresthesia of the right leg and difficulties in bladder control. Methods Fine needle biopsy and standard staging procedures revealed a primary solitary amyloidoma that was treated with intralesional resection, lumbopelvic stabilization, and consolidation radiotherapy. Results Clinical follow-up revealed the diagnosis of multiple myeloma 9 months after initial treatment. At 12 months, no local recurrence has occurred, the neurologic symptoms have resolved, and the systemic disease is in remission. Conclusions Intralesional resection with adjuvant radiotherapy of the amyloidoma achieved good local tumor control with limited morbidity.

12.
Eur Cell Mater ; 27: 5-11, 2014 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-24802611

RESUMEN

Intervertebral disc (IVD) degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encouraging results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium "Where Science meets Clinics", sponsored by the AO Foundation and held in Davos, Switzerland, from September 5-7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imaging methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neuro-genesis. Discogenic pain, originating from "black discs" or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.


Asunto(s)
Degeneración del Disco Intervertebral/cirugía , Trasplante de Células Madre/métodos , Investigación Biomédica Traslacional , Animales , Ensayos Clínicos como Asunto , Humanos , Trasplante de Células Madre/efectos adversos
13.
Eur Cell Mater ; 27: 124-36; discussion 136, 2014 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-24500793

RESUMEN

Release of chemotactic factors in response to tissue damage has been described for different musculoskeletal tissues, including the intervertebral disc (IVD). This study investigated the chemoattractants that are released by induced degenerative IVDs and may be involved in recruiting mesenchymal stem cells (MSCs). Bovine caudal discs were cultured within a bioreactor and loaded under conditions that mimicked physiological or degenerative settings. Between days 4-6, medium was replaced by PBS, which was subsequently used for proteomic, ELISA and immunoprecipitation analyses of secreted chemokines and cytokines. A Boyden chamber assay was used to observe human MSC migration towards native and chemokine depleted media. Gene expression levels of chemokine receptors in human MSCs were analysed, and CCL5 was localised in bovine and human IVD by immunohistochemistry. Proteomic analysis revealed the presence of CCL5 and CXCL6 within conditioned media. Higher concentrations of CCL5 were found in the degenerative media, and a relationship was found between interleukin-1ß and CCL5 concentration. Chemokine immunoprecipitation showed that MSCs had a significantly reduced chemotactic migration towards CCL5-immunoprecipitated and CCL5/CXCL6 co-immunoprecipitated media, whilst CXCL6 depletion did not change MSC chemotaxis. MSCs showed a significant increase in mRNA expression of the CCL5 receptors, CCR1 and CCR4, upon culture in degenerative media. Furthermore, CCL5 was identified in bovine and human disc tissue by immunohistochemistry. Hence, CCL5 may be a key chemoattractant that is produced and released by the intervertebral disc cells. Therefore, these factors could be used to enhance stem/progenitor cell mobilisation in regenerative therapies for early stages of disc degeneration.


Asunto(s)
Quimiocina CCL5/metabolismo , Degeneración del Disco Intervertebral/metabolismo , Disco Intervertebral/metabolismo , Animales , Reactores Biológicos , Bovinos , Células Cultivadas , Quimiocina CCL5/farmacología , Quimiotaxis , Medios de Cultivo Condicionados/farmacología , Humanos , Disco Intervertebral/crecimiento & desarrollo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Proteoma/genética , Proteoma/metabolismo
14.
Eur Cell Mater ; 26: 49-64; discussion 64-5, 2013 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-23986333

RESUMEN

Blood supply is a critical issue in most tissue engineering approaches for large defect healing. As vessel ingrowth from surrounding tissues is proven to be insufficient, current strategies are focusing on the neo-vascularisation process. In the present study, we developed an in vitro pre-vascularised construct using 3D polyurethane (PU) scaffolds, based on the association of human Endothelial Progenitor Cells (EPC, CD34+ and CD133+) with human Mesenchymal Stem Cells (MSC). We showed the formation of luminal tubular structures in the co-seeded scaffolds as early as day 7 in culture. These tubular structures were proven positive for endothelial markers von Willebrand Factor and PECAM-1. Of special significance in our constructs is the presence of CD146-positive cells, as a part of the neovasculature scaffolding. These cells, coming from the mesenchymal stem cells population (MSC or EPC-depleted MSC), also expressed other markers of pericyte cells (NG2 and αSMA) that are known to play a pivotal function in the stabilisation of newly formed pre-vascular networks. In parallel, in co-cultures, osteogenic differentiation of MSCs occurred earlier when compared to MSCs monocultures, suggesting the close cooperation between the two cell populations. The presence of angiogenic factors (from autologous platelet lysates) in association with osteogenic factors seems to be crucial for both cell populations' cooperation. These results are promising for future clinical applications, as all components (cells, growth factors) can be prepared in an autologous way.


Asunto(s)
Células Madre Mesenquimatosas/citología , Pericitos/citología , Andamios del Tejido , Antígeno CD146/genética , Antígeno CD146/metabolismo , Diferenciación Celular , Células Endoteliales/citología , Humanos , Células Madre Mesenquimatosas/metabolismo , Neovascularización Fisiológica , Pericitos/metabolismo , Poliuretanos
15.
Eur Cell Mater ; 25: 1-21, 2013 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-23283636

RESUMEN

Lumbar discectomy is the surgical procedure most frequently performed for patients suffering from low back pain and sciatica. Disc herniation as a consequence of degenerative or traumatic processes is commonly encountered as the underlying cause for the painful condition. While discectomy provides favourable outcome in a majority of cases, there are conditions where unmet requirements exist in terms of treatment, such as large disc protrusions with minimal disc degeneration; in these cases, the high rate of recurrent disc herniation after discectomy is a prevalent problem. An effective biological annular repair could improve the surgical outcome in patients with contained disc herniations but otherwise minor degenerative changes. An attractive approach is a tissue-engineered implant that will enable/stimulate the repair of the ruptured annulus. The strategy is to develop three-dimensional scaffolds and activate them by seeding cells or by incorporating molecular signals that enable new matrix synthesis at the defect site, while the biomaterial provides immediate closure of the defect and maintains the mechanical properties of the disc. This review is structured into (1) introduction, (2) clinical problems, current treatment options and needs, (3) biomechanical demands, (4) cellular and extracellular components, (5) biomaterials for delivery, scaffolding and support, (6) pre-clinical models for evaluation of newly developed cell- and material-based therapies, and (7) conclusions. This article highlights that an interdisciplinary approach is necessary for successful development of new clinical methods for annulus fibrosus repair. This will benefit from a close collaboration between research groups with expertise in all areas addressed in this review.


Asunto(s)
Desplazamiento del Disco Intervertebral/cirugía , Implantes Absorbibles , Animales , Artroplastia de Reemplazo , Fenómenos Biomecánicos , Trasplante de Células/métodos , Modelos Animales de Enfermedad , Humanos , Disco Intervertebral/metabolismo , Disco Intervertebral/patología , Disco Intervertebral/fisiopatología , Degeneración del Disco Intervertebral/patología , Degeneración del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/patología , Técnicas de Cultivo de Órganos , Regeneración , Medicina Regenerativa , Andamios del Tejido
16.
Eur J Trauma Emerg Surg ; 39(5): 445-53, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26815439

RESUMEN

Minimally invasive vertebral augmentation-based techniques have been used for the treatment of spinal fractures (osteoporotic and malignant) for approximately 25 years. In this review, we try to give an overview of the current spectrum of percutaneous augmentation techniques, safety aspects and indications. Crucial factors for success are careful patient selection, proper technique and choice of the ideal cement augmentation option. Most compression fractures present a favourable natural course, with reduction of pain and regainment of mobility after a few days to several weeks, whereas other patients experience a progressive collapse and persisting pain. In this situation, percutaneous cement augmentation is an effective treatment option with regards to pain and disability reduction, improvement of quality of life and ambulatory and pulmonary function.

17.
Vet Comp Orthop Traumatol ; 25(3): 173-7, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22451010

RESUMEN

INTRODUCTION: Several studies have described 'open' approach techniques for cementation of sheep and goat vertebrae; however, no percutaneous technique has been developed so far for use in non-primates. The aim of this study was to develop an animal model for percutaneous vertebroplasty under clinical conditions. METHODS: In a pilot study with dissected cadaveric ovine vertebrae, the technique and instruments as well as the optimal needle position were determined. In an in vivo animal study using 33 lumbar vertebrae of 11 sheep, a percutaneous vertebroplasty was performed under general anaesthesia. Needle position and cement volume were evaluated from high resolution, quantitative computed tomography imaging. RESULTS: The percutaneous technique for vertebroplasty was applicable to the vertebral bodies (L1 to L5) of the ovine lumbar spine without any related adverse effects for the animals. The procedure showed a steep learning curve represented by the reduction of the distance between the actual and planned needle positioning (7.2 mm to 3.7 mm; median value) and shorter surgery times (21.3 min to 15.0 min, average) with progression of the study. CONCLUSION: The described technique is feasible and repeatable under clinical conditions. This is the first percutaneous vertebroplasty technique for non-primates and we conclude that the sheep is a valid animal model to investigate the effects of cement augmentation in vivo.


Asunto(s)
Vértebras Lumbares/cirugía , Ovinos , Vértebras Torácicas/cirugía , Vertebroplastia/veterinaria , Animales , Cadáver , Proyectos Piloto , Vertebroplastia/métodos
18.
Injury ; 41(8): 818-22, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20430386

RESUMEN

INTRODUCTION: As part of the primary survey, polytrauma patients in our emergency department are examined using the new 'Lodox Statscan' (LS) digital low-radiation imaging device. The LS provides full-body anterior and lateral views based on enhanced linear slot-scanning technology, in accordance with the recommended Advanced Trauma Life Support (ATLS) Guidelines. This study's objectives were to establish whether LS appropriately rules out peripheral bone injuries and to examine whether LS imaging provides adequate information for the preoperative planning of such lesions. METHODS: A total of 245 consecutive polytrauma patients aged 16 years or more undergoing LS imaging were included in this retrospective chart analysis. The results of the LS scans were reviewed and compared to additional plain radiographs or computed tomography scans, whenever further radiological imaging was required to determine consecutive therapy. RESULTS: The sensitivity and specificity of the LS scans were 73% and 100%, respectively, for peripheral skeletal injuries. Additional plain radiographs were performed in 50% of cases for (1) superior focussing and more precise resolution of the affected part of the body, (2) additional second or third plane, (3) additional information about fracture type and planning of the surgical approach and (4) for preoperative planning of implant size and positioning on calibrated digitised films, <1% because of the low quality of the LS scan and <1% because the fracture zone had not been fully captured. CONCLUSION: The study demonstrates that despite LS's high sensitivity and specificity in the detection of peripheral skeletal injuries, additional radiological imaging for diagnostic or preoperative reasons was required. Our results imply that LS, although efficient for patient screening in the emergency room, cannot always rule out peripheral skeletal injuries.


Asunto(s)
Fracturas Óseas/diagnóstico por imagen , Traumatismo Múltiple/diagnóstico por imagen , Tecnología Radiológica/instrumentación , Tomografía Computarizada por Rayos X/instrumentación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Cuidados Preoperatorios , Estudios Retrospectivos , Sensibilidad y Especificidad , Tecnología Radiológica/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto Joven
19.
Knee Surg Sports Traumatol Arthrosc ; 18(7): 911-5, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20012938

RESUMEN

The management of insufficiency fractures of the tibial plateau in osteoporotic patients can be very challenging, since it is difficult to achieve a stable fixation, an essential condition for the patients' early mobilization. We present a minimally invasive technique for the treatment of proximal tibial plateau fractures, "tibiaplasty", using percutaneous polymethylmethacrylate augmentation. Five osteoporotic patients (7 fractures) with a non-traumatic insufficiency tibial plateau fracture were treated with this technique at the authors' institution from 2006 to 2008. The patients' median age was 79 (range 62-88) years. The intervention was performed percutaneously under general or spinal anesthesia; after the intervention, immediate full weight bearing was allowed. The technique was feasible in all patients and no complications related to the intervention were observed. All patients reported a relevant reduction in pain, were able to mobilize with full weight bearing and would undergo the operation again. No secondary loss of reduction or progression of arthrosis was observed in radiological controls; no revision surgery was required. Our initial results indicate that tibiaplasty is a good treatment option for the management of insufficiency in tibial plateau fractures in osteoporotic patients. The technique is minimally invasive, safe and allows immediate mobilization without restrictions. In our group of patients, we found excellent early to mid-term results.


Asunto(s)
Cementos para Huesos/uso terapéutico , Fijación Interna de Fracturas/métodos , Fracturas por Estrés/cirugía , Polimetil Metacrilato/uso terapéutico , Fracturas de la Tibia/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente
20.
Br J Sports Med ; 43(13): 1020-5, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19846420

RESUMEN

OBJECTIVE: To analyse risk factors in alpine skiing. DESIGN: A controlled multicentre survey of injured and non-injured alpine skiers. SETTING: One tertiary and two secondary trauma centres in Bern, Switzerland. PATIENTS AND METHODS: All injured skiers admitted from November 2007 to April 2008 were analysed using a completed questionnaire incorporating 15 parameters. The same questionnaire was distributed to non-injured controls. Multiple logistic regression was performed. Patterns of combined risk factors were calculated by inference trees. A total of 782 patients and 496 controls were interviewed. RESULTS: Parameters that were significant for the patients were: high readiness for risk (p = 0.0365, OR 1.84, 95% CI 1.04 to 3.27); low readiness for speed (p = 0.0008, OR 0.29, 95% CI 0.14 to 0.60); no aggressive behaviour on slopes (p<0.0001, OR 0.19, 95% CI 0.09 to 0.37); new skiing equipment (p = 0.0228, OR 59, 95% CI 0.37 to 0.93); warm-up performed (p = 0.0015, OR 1.79, 95% CI 1.25 to 2.57); old snow compared with fresh snow (p = 0.0155, OR 0.31, 95% CI 0.12 to 0.80); old snow compared with artificial snow (p = 0.0037, OR 0.21, 95% CI 0.07 to 0.60); powder snow compared with slushy snow (p = 0.0035, OR 0.25, 95% CI 0.10 to 0.63); drug consumption (p = 0.0044, OR 5.92, 95% CI 1.74 to 20.11); and alcohol abstinence (p<0.0001, OR 0.14, 95% CI 0.05 to 0.34). Three groups at risk were detected: (1) warm-up 3-12 min, visual analogue scale (VAS)(speed) >4 and bad weather/visibility; (2) VAS(speed) 4-7, icy slopes and not wearing a helmet; (3) warm-up >12 min and new skiing equipment. CONCLUSIONS: Low speed, high readiness for risk, new skiing equipment, old and powder snow, and drug consumption are significant risk factors when skiing. Future work should aim to identify more precisely specific groups at risk and develop recommendations--for example, a snow weather index at valley stations.


Asunto(s)
Esquí/lesiones , Adulto , Traumatismos en Atletas/etiología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Equipos de Seguridad/estadística & datos numéricos , Factores de Riesgo , Suiza , Tiempo (Meteorología) , Adulto Joven
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