Developmental Engineering: A New Paradigm for the Design and Manufacturing of Cell-Based Products. Part I: From Three-Dimensional Cell Growth to Biomimetics of<i>In Vivo</i>Development

Lenas, Petros; Moos, Malcolm; Luyten, Frank P.

doi:10.1089/ten.teb.2008.0575

Cited by 204 publications

(205 citation statements)

References 65 publications

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“…In an attempt to address these challenges, there has been a recent shift away from classical tissue engineering paradigms, towards strategies aimed at recapitulating the natural mechanisms which drive tissue development during skeletogenesis [6]. The long bones of the body form by a process termed endochondral ossification, whereby chondrocytes in a developing cartilaginous rudiment undergo hypertrophy and direct vascularization and remodeling of the cartilaginous template into bone [7].…”

Section: Introductionmentioning

confidence: 99%

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

et al. 2015

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Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) have been shown to generate bone in vivo by executing an endochondral program. This may hinder the use of MSCs for articular cartilage regeneration, but opens the possibility of using engineered cartilaginous tissues for large bone defect repair. Hydrogels may be an attractive tool in the scaling-up of such tissue engineered grafts for endochondral bone regeneration. In this study, we compared the capacity of different naturally derived hydrogels (alginate, chitosan, and fibrin) to support chondrogenesis and hypertrophy of MSCs in vitro and endochondral ossification in vivo. In vitro, alginate and chitosan constructs accumulated the highest levels of sGAG, with chitosan constructs synthesising the highest levels of collagen. Alginate and fibrin constructs supported the greatest degree of calcium accumulation, though only fibrin constructs calcified homogenously. In vivo, chitosan constructs facilitated neither vascularization nor endochondral ossification, and also retained the greatest amount of sGAG, suggesting it to be a more suitable material for the engineering of articular cartilage.Both alginate and fibrin constructs facilitated vascularization and endochondral bone formation as well as the development of a bone marrow environment. Alginate constructs accumulated significantly more mineral and supported greater bone formation in central regions of the engineered tissue. In conclusion, this study demonstrates the capacity of chitosan hydrogels to promote and better maintain a chondrogenic phenotype in MSCs and highlights the potential of utilizing alginate hydrogels for MSC-based endochondral bone tissue engineering applications.

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Section: Introductionmentioning

confidence: 99%

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

et al. 2015

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“…La ingeniería tisular permite desarrollar diferentes tejidos artificiales en el laboratorio mediante el uso de células vivas, la manipulación del entorno celular, la creación de sustitutos biológicos y su consecuente implantación en el cuerpo (8). El injerto de sustitutos artificiales de tejidos se perfila como uno de los mejores tratamientos alternativos (9).…”

Section: Discussionunclassified

Oral mucosa analog allografts in non-consanguineous rats

et al. 2017

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Introducción. A pesar de que existen opciones terapéuticas para el tratamiento de defectos de la mucosa bucal, persiste la necesidad de encontrar sustitutos funcionales, anatómicos y estéticamente similares al tejido que se va a reemplazar, así como soluciones que reduzcan la morbilidad de los injertos autólogos.Objetivo. Determinar la compatibilidad clínica e histológica de aloinjertos equivalentes de mucosa bucal elaborados mediante ingeniería tisular en ratas no consanguíneas.Materiales y métodos. Se utilizó una muestra de mucosa bucal de ratas Sprague Dawley para la obtención de un cultivo de fibroblastos y otro de queratinocitos y fibroblastos. En ambos casos, se usó una membrana de colágeno comercial como soporte. Después de diez semanas de cultivo, las membranas resultantes se injertaron en cuatro ratas Wistar. La primera fase del estudio consistió en la elaboración de los tejidos análogos de mucosa bucal mediante ingeniería tisular, los cuales se implantaron en ratas Wistar inmunocompetentes; posteriormente, se evaluaron las características clínicas e histológicas del aloinjerto.Resultados. La evaluación in vivo de los tejidos análogos demostró que se habían integrado correctamente en los huéspedes inmunocompetentes, y se había logrado el aumento del biotipo periodontal y la creación de una zona con mayor queratinización. Desde el punto de vista histológico, el tejido adquirió características similares a las de la muestra de mucosa bucal de control, sin ningún tipo de reacción inflamatoria ni signos clínicos o histológicos de rechazo.Conclusión. Hubo compatibilidad clínica e histológica de los aloinjertos equivalentes de mucosa bucal obtenidos mediante ingeniería tisular.

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“…However, most of our bones form through the endochondral bone formation process during development. Recapitulating this process as a strategy for bone tissue engineering, known as developmental engineering (Lenas et al, 2009), may circumvent many of the problems that are related to the harmful hypoxia in tissue engineering constructs. In this approach, a cartilaginous template is engineered instead of implanting cell-based constructs that form bone directly (Fig.…”

Section: Endochondral Bone Formation As a Physiological Adaptation Agmentioning

confidence: 99%

Targeting the hypoxic response in bone tissue engineering: A balance between supply and consumption to improve bone regeneration

Stiers

Gastel

Carmeliet

2016

Molecular and Cellular Endocrinology

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a b s t r a c tBone tissue engineering is a promising therapeutic alternative for bone grafting of large skeletal defects. It generally comprises an ex vivo engineered combination of a carrier structure, stem/progenitor cells and growth factors. However, the success of these regenerative implants largely depends on how well implanted cells will adapt to the hostile and hypoxic host environment they encounter after implantation. In this review, we will discuss how hypoxia signalling may be used to improve bone regeneration in a tissue-engineered construct. First, hypoxia signalling induces angiogenesis which increases the survival of the implanted cells as well as stimulates bone formation. Second, hypoxia signalling has also angiogenesis-independent effects on mesenchymal cells in vitro, offering exciting new possibilities to improve tissue-engineered bone regeneration in vivo. In addition, studies in other fields have shown that benefits of modulating hypoxia signalling include enhanced cell survival, proliferation and differentiation, culminating in a more potent regenerative implant. Finally, the stimulation of endochondral bone formation as a physiological pathway to circumvent the harmful effects of hypoxia will be briefly touched upon. Thus, angiogenic dependent and independent processes may counteract the deleterious hypoxic effects and we will discuss several therapeutic strategies that may be combined to withstand the hypoxia upon implantation and improve bone regeneration.

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Developmental Engineering: A New Paradigm for the Design and Manufacturing of Cell-Based Products. Part I: From Three-Dimensional Cell Growth to Biomimetics ofIn VivoDevelopment

Cited by 204 publications

References 65 publications

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

Oral mucosa analog allografts in non-consanguineous rats

Targeting the hypoxic response in bone tissue engineering: A balance between supply and consumption to improve bone regeneration

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