28 research outputs found

    Evaluation of a co-culture of rapidly isolated chondrocytes and stem cells seeded on tri-layered collagen-based scaffolds in a caprine osteochondral defect model

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    Cartilage has poor regenerative capacity and thus damage to the joint surfaces presents a major clinical challenge. Recent research has focussed on the development of tissue-engineered and cell-based approaches for the treatment of cartilage and osteochondral injuries, with current clinically available cell-based approaches including autologous chondrocyte implantation and matrix-assisted autologous chondrocyte implantation. However, these approaches have significant disadvantages due to the requirement for a two-stage surgical procedure and an in vitro chondrocyte expansion phase which increases logistical challenges, hospital times and costs. In this study, we hypothesized that seeding biomimetic tri-layered scaffolds, with proven regenerative potential, with chondrocyte/infrapatellar fat pad stromal cell co-cultures would improve their regenerative capacity compared to scaffolds implanted cell-free. Rapid cell isolation techniques, without the requirement for long term in vitro culture, were utilised to achieve co-cultures of chondrocytes and stromal cells and thus overcome the limitations of existing cell-based techniques. Cell-free and cell-seeded scaffolds were implanted in osteochondral defects, created within the femoral condyle and trochlear ridge, in a translational large animal goat model. While analysis showed trends towards delayed subchondral bone healing in the cell-seeded scaffold group, by the 12 month timepoint the cell-free and cell-seeded groups yield cartilage and bone tissue with comparable quality and quantity. The results of the study reinforce the potential of the biomimetic tri-layered scaffold to repair joint defects but failed to demonstrate a clear benefit from the addition of the CC/FPMSC co-culture to this scaffold. Taking into consideration the additional cost and complexity associated with the cell-seeded scaffold approach, this study demonstrates that the treatment of osteochondral defects using cell-free tri-layered scaffolds may represent a more prudent clinical approach

    Troublesome Heterotopic Ossification after Central Nervous System Damage: A Survey of 570 Surgeries

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    BACKGROUND: Heterotopic ossification (HO) is a frequent complication after central nervous system (CNS) damage but has seldom been studied. We aimed to investigate features of HO for the first time in a large sample and the rate of early recurrence of HO in terms of the time of surgery. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyzed data from an anonymous prospective survey of patients undergoing surgery between May 1993 and November 2009 in our institution for troublesome HO related to acquired neurological disease. Demographic and HO characteristics and neurological etiologies were recorded. For 357 consecutive patients, we collected data on 539 first surgeries for HO (129 surgeries for multiple sites). During the follow-up, recurrences requiring another surgery appeared in 31 cases (5.8% [31/539]; 95% confidence interval [CI]: 3.8%-7.8%; 27 patients). Most HO requiring surgery occurred after traumatic brain injury (199 patients [55.7%]), then spinal cord injury (86 [24.0%]), stroke (42 [11.8%]) and cerebral anoxia (30 [8.6%]). The hip was the primary site of HO (328 [60.9%]), then the elbow (115 [21.3%]), knee (77 [14.3%]) and shoulder (19 [3.5%]). For all patients, 181 of the surgeries were performed within the first year after the CNS damage, without recurrence of HO. Recurrence was not associated with etiology (p = 0.46), sex (p = 1.00), age at CNS damage (p = 0.2), multisite localization (p = 0.34), or delay to surgery (p = 0.7). CONCLUSIONS/SIGNIFICANCE: In patients with CNS damage, troublesome HO and recurrence occurs most frequently after traumatic brain injury and appears frequently in the hip and elbow. Early surgery for HO is not a factor of recurrence

    El índice de Coherencia de Políticas para el Desarrollo: midiendo la Agenda 2030 desde la Coherencia de Políticas para el Desarrollo

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    The article presents the Policy Coherence for Development Index (PCDI) which is, as a whole, a new framework for understanding and interpreting the challenges of the Agenda 2030 and the public policies its approach requires. It provides also an ambitious monitoring system to assess countries’ compliance with the agreed commitments from the policy coherence for development perspective. Previously, the article exposes how the 2030 Agenda requires a new conceptual and instrumental framework in order to consolidate a new narrative about the development challenges based on the universality, integrality and multidimensionality, including also the global interdependencies and interconnections that characterize today’s world. This framework must also provide a solid measurement of progress and setbacks regarding the Sustainable Development Goals and targets internationally agreed

    Titulos uniformes de leyes

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    Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLE2. ed.ESSpai

    Titulos uniformes de leyes

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    Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai

    Emergent collective organization of bone cells in complex curvature fields

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    Individual cells and multicellular systems respond to cell-scale curvatures in their environments, guiding migration, orientation, and tissue formation. However, it remains largely unclear how cells collectively explore and pattern complex landscapes with curvature gradients across the Euclidean and non-Euclidean spectra. Here, we show that mathematically designed substrates with controlled curvature variations induce multicellular spatiotemporal organization of preosteoblasts. We quantify curvature-induced patterning and find that cells generally prefer regions with at least one negative principal curvature. However, we also show that the developing tissue can eventually cover unfavorably curved territories, can bridge large portions of the substrates, and is often characterized by collectively aligned stress fibers. We demonstrate that this is partly regulated by cellular contractility and extracellular matrix development, underscoring the mechanical nature of curvature guidance. Our findings offer a geometric perspective on cell-environment interactions that could be harnessed in tissue engineering and regenerative medicine applications.</p

    Bioprinting of a zonal‐specific cell density scaffold: A biomimetic approach for cartilage tissue engineering

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    The treatment of articular cartilage defects remains a significant clinical challenge. This is partially due to current tissue engineering strategies failing to recapitulate native organization. Articular cartilage is a graded tissue with three layers exhibiting different cell densities: the superficial zone having the highest density and the deep zone having the lowest density. However, the introduction of cell gradients for cartilage tissue engineering, which could promote a more biomimetic environment, has not been widely explored. Here, we aimed to bioprint a scaffold with different zonal cell densities to mimic the organization of articular cartilage. The scaffold was bioprinted using an alginate‐based bioink containing human articular chondrocytes. The scaffold design included three cell densities, one per zone: 20 × 106 (superficial), 10 × 106 (middle), and 5 × 106 (deep) cells/mL. The scaffold was cultured in a chondrogenic medium for 25 days and analyzed by live/dead assay and histology. The live/dead analysis showed the ability to generate a zonal cell density with high viability. Histological analysis revealed a smooth transition between the zones in terms of cell distribution and a higher sulphated glycosaminoglycan deposition in the highest cell density zone. These findings pave the way toward bioprinting complex zonal cartilage scaffolds as single units, thereby advancing the translation of cartilage tissue engineering into clinical practice

    Mechanotransduction in high aspect ratio nanostructured meta-biomaterials: The role of cell adhesion, contractility, and transcriptional factors

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    Black Ti (bTi) surfaces comprising high aspect ratio nanopillars exhibit a rare combination of bactericidal and osteogenic properties, framing them as cell-instructive meta-biomaterials. Despite the existing data indicating that bTi surfaces induce osteogenic differentiation in cells, the mechanisms by which this response is regulated are not fully understood. Here, we hypothesized that high aspect ratio bTi nanopillars regulate cell adhesion, contractility, and nuclear translocation of transcriptional factors, thereby inducing an osteogenic response in the cells. Upon the observation of significant changes in the morphological characteristics, nuclear localization of Yes-associated protein (YAP), and Runt-related transcription factor 2 (Runx2) expression in the human bone marrow-derived mesenchymal stem cells (hMSCs), we inhibited focal adhesion kinase (FAK), Rho-associated protein kinase (ROCK), and YAP in separate experiments to elucidate their effects on the subsequent expression of Runx2. Our findings indicated that the increased expression of Runx2 in the cells residing on the bTi nanopillars compared to the flat Ti is highly dependent on the activity of FAK and ROCK. A mechanotransduction pathway is then postulated in which the FAK-dependent adhesion of cells to the extreme topography of the surface is in close relation with ROCK to increase the endogenous forces within the cells, eventually determining the cell shape and area. The nuclear translocation of YAP may also enhance in response to the changes in cell shape and area, resulting in the translation of mechanical stimuli to biochemical factors such as Runx2.Biomaterials & Tissue Biomechanic

    Emergent collective organization of bone cells in complex curvature fields

    No full text
    Individual cells and multicellular systems respond to cell-scale curvatures in their environments, guiding migration, orientation, and tissue formation. However, it remains largely unclear how cells collectively explore and pattern complex landscapes with curvature gradients across the Euclidean and non-Euclidean spectra. Here, we show that mathematically designed substrates with controlled curvature variations induce multicellular spatiotemporal organization of preosteoblasts. We quantify curvature-induced patterning and find that cells generally prefer regions with at least one negative principal curvature. However, we also show that the developing tissue can eventually cover unfavorably curved territories, can bridge large portions of the substrates, and is often characterized by collectively aligned stress fibers. We demonstrate that this is partly regulated by cellular contractility and extracellular matrix development, underscoring the mechanical nature of curvature guidance. Our findings offer a geometric perspective on cell-environment interactions that could be harnessed in tissue engineering and regenerative medicine applications
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