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In a groundbreaking study, scientists from University College London (UCL), in collaboration with the University of Padua and the Veneto Institute of Molecular Medicine (VIMM), have successfully developed a method to create mechanical force sensors directly in the developing brains and spinal cords of chicken embryos. This innovative approach, detailed in the journal Nature Materials, aims to enhance the understanding and prevention of birth malformations such as spina bifida.

A New Approach to Studying Embryonic Development

Congenital spinal cord malformations, such as spina bifida, impact approximately one in 2,000 newborns annually in Europe. Despite extensive research, these conditions cannot be fully elucidated through molecular and genetic studies alone. Consequently, researchers are now exploring the role of physical and mechanical forces in tissue development during embryogenesis. The embryonic spinal cord is minuscule and delicate, necessitating similarly small and soft force-measuring devices to avoid disrupting normal growth.

To address these challenges, the research team employed 3D printing technology to fabricate tiny force sensors, approximately 0.1mm wide, directly within the developing nervous system of chicken embryos. These sensors begin as a liquid applied to the embryos and transform into a spring-like solid upon exposure to a strong laser. This solid then attaches to the growing spinal cord and deforms under the mechanical forces exerted by the embryo’s cells.

Measuring Minute Forces

The newly developed sensors enabled the measurement of extremely small forces, roughly a tenth of the weight of a human eyelash, crucial for the proper formation of the spinal cord. For normal embryonic development, the forces generated by the cells must outweigh opposing negative forces. Accurately quantifying these forces opens the door to potential drug interventions that could either increase positive forces or reduce negative ones, thereby helping to prevent congenital malformations like spina bifida. These drugs could also enhance the preventative benefits of folic acid intake, which is a well-established strategy for reducing developmental issues during pregnancy.

Promising Future Applications

Dr. Eirini Maniou, a Marie Sklodowska-Curie postdoctoral fellow at UCL Great Ormond Street Institute of Child Health and the University of Padua, emphasized the significance of this study. “Thanks to the use of novel biomaterials and advanced microscopy, this study promises a step change in the field of embryonic mechanics and lays the foundation for a unified understanding of development,” she said. “Our work paves the way for identifying new preventative and therapeutic strategies for central nervous system malformations.”

The research team also demonstrated that this technology could be applied to human stem cells as they develop into spinal cord cells. This advancement could facilitate comparisons between the stem cells of healthy individuals and those of patients with spina bifida, potentially uncovering the reasons behind the condition’s development.

Broad Implications for Biomedical Research

Dr. Gabriel Galea, a co-senior author from UCL Great Ormond Street Institute of Child Health, highlighted the versatility of this technology. “This technology is very versatile and widely applicable to many research fields, and we hope it will be quickly adopted and applied by other groups to address fundamental questions,” he stated.

Professor Nicola Elvassore, another co-senior author from the University of Padua and VIMM, added, “This discovery not only allows us to better understand the mechanical forces at play during embryonic development but also offers new perspectives for intervening and preventing conditions like spina bifida. The ability to quantify embryonic forces with such precision represents a significant step forward in biomedical research.”

The innovative approach pioneered by these scientists promises to revolutionize the study of embryonic development and birth malformations, potentially leading to new preventive and therapeutic strategies for conditions like spina bifida.

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