The survival of transplanted embryo bone grafted to chorioallantoic membrane, and subsequent osteogenesis

Hancox, N. M.

doi:10.1113/jphysiol.1947.sp004211

Cited by 37 publications

(25 citation statements)

References 5 publications

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“…Moreover, these cells also co-stained with GFP, confirming their avian origin. Similar cell condensations were shown by Hancox, who implanted chick embryo calvaria fragments on CAM for 10 days37. In accordance with our findings, cell condensations (named by Hancox ‘ectodermal pearls’) were located in proximity to the bone tissue37.…”

Section: Discussionsupporting

confidence: 92%

“…Similar cell condensations were shown by Hancox, who implanted chick embryo calvaria fragments on CAM for 10 days37. In accordance with our findings, cell condensations (named by Hancox ‘ectodermal pearls’) were located in proximity to the bone tissue37. These findings are not surprising given the clinical gold standard biomaterial is bone autograft38, which provides a unique osteogenic microenvironment as a consequence of the plethora of growth factors within the bone matrix ( i.e.…”

Section: Discussionsupporting

confidence: 91%

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The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

Moreno-Jiménez

Hulsart‐Billström

Lanham

et al. 2016

Sci Rep

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Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p < 0.01). This human-avian system offers a simple refinement model for animal research and a step towards a humanized in vivo model for tissue engineering.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

Moreno-Jiménez

Hulsart‐Billström

Lanham

et al. 2016

Sci Rep

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“…The assumption of recirculation in bone grafts is as a rule based on indirect observations of the vasculature during the first week after the transplantation. Some authors report a strikingly early appearance of blood vessels (Hancox 1947, Ray 1972, others a remarkable acceleration of the injectiability of graft vessels from one day to another (Graf 1959, Deleu & Trueta 1965, Forgon & Bornemisza 1970.…”

mentioning

confidence: 99%

In VivoStudies of Bone Grafts: The Possibility of Vascular Anastomoses in Healing Bone

Albrektsson

1980

Acta Orthopaedica Scandinavica

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“…We formerly described the formation of these cell condensations in association with collagen type II deposition from the CAM, again coexpressing with SOX9 and GFP next to the human bone tissue (Moreno‐Jiménez et al, ). Early studies from Hancox, showed formation of similar cell condensations following engraftment of chick embryo calvaria fragments on CAM. Other authors have implanted agarose or gelatin beads carrying BMP7 and shown the formation of comparable clusters of cells as well as significant stratification of the CAM extracellular matrix (Ramoshebi & Ripamonti, ).…”

Section: Discussionmentioning

confidence: 99%

Remodelling of human bone on the chorioallantoic membrane of the chicken egg:De novobone formation and resorption

Moreno-Jiménez

Lanham

Kanczler

et al. 2018

J Tissue Eng Regen Med

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Traditionally used as an angiogenic assay, the chorioallantoic membrane (CAM) assay of the chick embryo offers significant potential as an in vivo model for xenograft organ culture. Viable human bone can be cultivated on the CAM and increases in bone volume are evident; however, it remains unclear by what mechanism this change occurs and whether this reflects the physiological process of bone remodelling. In this study we tested the hypothesis that CAM-induced bone remodelling is a consequence of host and graft mediated processes. Bone cylinders harvested from femoral heads post surgery were placed on the CAM of green fluorescent protein (GFP)-chick embryos for 9 days, followed by micro computed tomography (μCT) and histological analysis. Three-dimensional registration of consecutive μCT-scans showed newly mineralised tissue in CAM-implanted bone cylinders, as well as new osteoid deposition histologically. Immunohistochemistry demonstrated the presence of bone resorption and formation markers (Cathepsin K, SOX9 and RUNX2) co-localising with GFP staining, expressed by avian cells only. To investigate the role of the human cells in the process of bone formation, decellularised bone cylinders were implanted on the CAM and comparable increases in bone volume were observed, indicating that avian cells were responsible for the bone mineralisation process. Finally, CAM-implantation of acellular collagen sponges, containing bone morphogenetic protein 2, resulted in the deposition of extracellular matrix and tissue mineralisation. These studies indicate that the CAM can respond to osteogenic stimuli and support formation or resorption of implanted human bone, providing a humanised CAM model for regenerative medicine research and a novel short-term in vivo model for tissue engineering and biomaterial testing.

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The survival of transplanted embryo bone grafted to chorioallantoic membrane, and subsequent osteogenesis

Abstract: The extent to which bone transplants survive and the source of any new bone subsequently formed are still matters of controversy. Three main hypotheses have been put forward.

Cited by 37 publications

References 5 publications

The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

In VivoStudies of Bone Grafts: The Possibility of Vascular Anastomoses in Healing Bone

Remodelling of human bone on the chorioallantoic membrane of the chicken egg:De novobone formation and resorption

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