New ways to grow human ‘mini-bones’

New ways to grow human ‘mini-bones’
New ways to grow human 'mini-bones'

Purple is bone resorption by osteoclasts and orange is new bone formed by osteoblasts. Credit: Bregje de Wildt

Human bones can recover from small fractures, but if the fractures are too large or the regeneration process is not balanced, as is the case with osteoporosis, treatment is required. Animal experiments are often used to develop treatments, but some treatments developed in this way do not work in humans. So, Bregje de Wildt for his Ph.D. Research has explored ways to grow human “mini-bones” in the lab that could be used to test drugs for treatments and, perhaps in the future, eliminate the need for any animal testing when it comes to testing these drugs.

The human body relies on bones for support, organ protection, movement, and the absorption and breakdown of minerals. “Bones may appear rigid and static, but in reality, bones are always changing and evolving,” says Bregje de Wildt, Ph.D. researcher at the Department of Biomedical Engineering of the TU/e. “Cells come and go. In particular, cells known as osteoclasts break down and resorb bone, while osteoblasts form an equal amount of new bone.”

It sounds a bit strange that a bone cell with “blast” in the name it is involved in bone growth, but this part of its name comes from the Greek word blastano, which means to sprout or germinate. “Together, osteoclasts and osteoblasts contribute to our bones’ ability to remodel or regenerate. Small fractures for the most part are a no-brainer, but for large fractures, or imbalanced osteoclast and osteoblast activity in conditions like osteoporosis, needs treatment,” notes de Wildt.

Treatment Development

Treatments for bone disorders are often developed through animal experiments. Every year around 500,000 animals are used for experiments in the Netherlands. Globally, this number is estimated to be around 100 million. “Unfortunately, less than 1 in 10 treatments developed using animal testing they are also effective in humans, which is probably because the animals used and humans are too genetically different,” says de Wildt.

So, to help evaluate treatments for human bone tissue, de Wildt and his collaborators in the Orthopedic Biomechanics and Bone Bioengineering research groups decided that the best course of action was to use human bone tissue in the first place. “Instead of using a person to test treatments, which would be unethical and risky on many levels, we explored a way to grow living human ‘mini-bones’ in the lab,” says de Wildt.

Key ingredients for tissue engineering

To grow the “mini-bones”, de Wildt needed four main parts. First, she needed specialists Mother cells known as stem cells. Unlike pluripotent stem cells, which are cells that can become any type of cell in the body, stem cells can only become osteoblasts or osteoclasts. De Wildt says, “These stem cells need to receive the correct biochemical signals to help them develop into osteoclasts and osteoblasts.”

Second, de Wildt needed a structure in which bone cells could fuse into the “mini-bone”. “For this we use silk from silkworms since it is a material with favorable mechanical properties, it is biocompatible and human cells can grow in three dimensions in the material,” says de Wildt.

New ways to grow human 'mini-bones'

Parts of the figure drawn with images from Servier Medical Art. Credit: Servier Medical Art, Creative Commons Attribution 3.0 Unported License. (

Third, the cells need an environment in which the bone can grow and thrive. “The cells are placed in an incubator that is kept at a temperature of 37 degrees Celsius and controls oxygen, COtwo and humidity levels,” says de Wildt.

Finally, to mimic bone as much as possible, the bone cells are placed in a bioreactor, which is then placed inside the incubator. De Wildt: “The bioreactor circulates a nutritional fluid and replicates the mechanical loads experienced by bone in the human body. For a ‘mini-bone’ to be representative of real bone, the cells must be challenged to resist these forces.”

“Together, these are the essential elements for tissue engineeringwhich since the 1990s has been used in regenerative medicine to develop implants for the body,” says de Wildt. “Recently, however, tissue engineering has been used to create in vitro versions of human bone, which are versions of bone grown outside the human body.”

Exploring tissue engineering

For their research, de Wildt and colleagues explored a number of different aspects related to the growth of “mini-bones” in vitro. In A study, sought an alternative to fetal bovine serum (which is derived from an unborn cow fetus) as a source of nutrients for cells. “We identified a human-derived replacement for bovine serum that leads to even better growth of ‘mini-bones,'” says de Wildt.

And in another studio, de Wildt and colleagues developed a method to mineralize silk scaffolds. Mineralization in the human body is the process by which soft tissue becomes hard tissue. “We were inspired by the way bone gets its strength, which is associated with the way collagen and minerals (such as calcium and phosphate) are organized in bone. The mineralized silk scaffolds supported the resorption of osteoclasts and osteoblast formation. This miniature approach to growing bone allowed us to study how human cells outside the body remodel bone.”

In addition to looking at nutritional supplementation and scaffolding material, de Wildt also studied how changes in the biochemical and biomechanical culture environment affected bone resorption and bone formation. “We varied the cultural environment to more closely match the in vivo environment within the bodyand we studied the effect of these environments on the balance between bone resorption and formation as a hallmark for healthy bone growth,” says de Wildt.

hopes for the future

And de Wildt has high hopes for his research, particularly given the prevalence of bone disease. “Osteoporosis is the most common bone remodeling disease and affects approximately 1 in 5 people. Although it is not fatal, it affects quality of life and fractures in certain cases can be fatal. I hope that this research can contribute to better treatments.” for bone disorders These are certainly needed as our population lives longer and more and more people develop bone problems in old age.”

In addition, de Wildt is interested in her research helping to change the way we test treatments for people in the future. “I understand that animal models are needed to answer some research questions. However, I have difficulties with how easily they are used for research purposes. In the Netherlands, the rules are relatively strict, but there are also countries with limited regulations. I hope my research contributes to a shift towards more ‘mini-bones’ to replace animal experiments in bone research.”

More information:
Advances in in vitro human bone tissue engineering. … ro-human-bone-models

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