Apples have a long history of inspiring scientific progress. When Sir Isaac Newton watched an apple fall from a tree in 1666, he had a brilliant insight that led to his discovery of gravity.1,2 Little did Newton know that more than three centuries after his epiphany, Canadian researchers would serendipitously conceive of using apples to regenerate bone and that his discovery of gravitational force would shape their understanding of how to do so.
Gravity is essential for maintaining and regrowing bone, which undergoes a natural process of deterioration and restoration.3 The force of gravity and the physical exertion of movement and exercise stimulate the production of osteoblasts—cells that create new bone. Despite this innate regenerative activity, injury, disease, age, and the weightlessness of space travel create bone deficits. As a result, researchers seek ways to bioengineer bone tissue using osteoblasts grown in cell culture.
In a recent study published in the Journal of Biomechanics, Andrew Pelling, a professor of physics and biology at the University of Ottawa, and his multidisciplinary team of engineers, scientists, and artists tested the ability of apples to support osteoblasts in a culture dish and withstand the simulated mechanical forces needed to trigger bone production.4 “Science is this intrinsically creative pursuit. Sitting in the space between the disciplines is a great place to be for capturing these new ideas,” said Pelling.
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The idea of using the “forbidden fruit” to regenerate human tissue first came to Pelling’s student as he watched his labmate eat an apple. Apples are rich in cellulose—a complex carbohydrate that gives plant tissue its structural form. Pelling’s team cut up an apple and stripped away its tissue using detergents, leaving a 3D cellulose scaffold—an apple skeleton—that is remarkably hospitable to bone-synthesizing cells grown in a culture dish. The scaffold mimics the 3-D environment of natural tissue and provides structural support, which makes it a favorable option for bioengineering replacement bone that may one day be used in patients.
Pelling’s team grew osteoblast precursor cells on
5 mm-diameter disks of apple cellulose. They exposed the cells to cycles of mechanical force using a specially designed pressure chamber. In response to the mechanical force, the precursor cells produced functional osteoblasts that mineralized the scaffold, while the scaffold itself retained its elastic properties. “The sensitivity of these bone precursor cells to mechanical stimuli is maintained on these unusual scaffolds, which is a good thing for taking the next steps towards potential therapies,” Pelling said.
“This idea of using plant-derived materials as scaffolding is quite exciting. Cellulose doesn't cause a substantial immune or inflammatory reaction, can reduce the likelihood of infection, [and] can improve blood vessel formation,” said William Murphy, a biomedical engineer and director of the Forward BIO Institute at the University of Wisconsin-Madison, who was not involved in this study. He explained that the biomaterial must withstand applied mechanical forces that simulate those exerted on bone during human locomotion and are necessary for bone cell production and function. “Biophysical forces are pivotal to direct the bone remodeling process,” added Gianluca Fontana, a biomedical engineer and research scientist in Murphy’s lab, who was not involved in this study.
In a poignant celebration of science and serendipity, The Royal Society—of which Newton was once president—sent a 10 cm long archived piece of Newton’s apple tree on a NASA space mission in 2010.5 Orbiting the earth, the tree bark experienced zero gravity alongside astronauts who sustain bone loss under weightlessness. If Pelling’s experimental therapy makes its way out of the culture dish and into humans, these parallel yet interwoven stories will have come full circle.
- W. Stukeley, A.H. White, “Memoirs of Sir Isaac Newton's life, 1752: Being some account of his family and chiefly of the junior part of his life,” Edited by A. Hastings White, London: Taylor and Francis, 1936.
- R. G. Keesing, “The history of Newton's apple tree,” Contemporary Physics, 39(5):377-91, 1998.
- A. Ruggiu, R. Cancedda, “Bone mechanobiology, gravity and tissue engineering: effects and insights,” J Tissue Eng Regen Med, 9(12):1339-51, 2015.
- M. Leblanc Latour, A.E. Pelling, “Mechanosensitive osteogenesis on native cellulose scaffolds for bone tissue engineering,” J Biomech, 2022 Epub ahead of print.
- Royal Society, “Newton's Apple Tree returns from space,” Royal Society, February 12, 2012, Retrieved April 25, 2022, from https://royalsociety.org/news/2010/newton-apple-tree/