Developing an Organoid Model of the Growth Plate Through Collaboration

From its inception, the growth plate organoid model has been a collaborative venture — between Karin Payne, PhD, and countless clinicians and scientists, between researchers and universities, and between biochemical and mechanical cues. This work began when Nancy Hadley-Miller, MD operated on a child with an abnormal bridge of bone tissue, also known as a bony bar, forming across the growth plate after injury. This sparked a question for Dr. Hadley-Miller: How can we regenerate that growth plate cartilage in kids?

Regenerative medicine and growth plates

Epiphyseal plates, more commonly known as growth plates, are the cartilage regions at the end of long bones in children that facilitate bone growth. When these areas are damaged, the rubbery, flexible tissue can be replaced by bony repair tissue, creating a bony bar and preventing additional growth prematurely. Bony bars typically follow a bone fracture injury. Because they form across the growth plate, they can halt bone growth and cause angular deformities. When clinicians remove these bony bars from an injured limb, they often place an inert material that serves as a space holder but does not regenerate the damaged tissue. If the bar is too large to remove, they perform a procedure to shut down the injured growth plate and repeat the process on the opposite limb to prevent one limb from being longer than the other. By developing a growth plate organoid, the team aims to establish the differentiation of mesenchymal stem cells (MSCs) into cartilage cells so that they can then apply the knowledge to regenerate growth plate cartilage, allowing the injured bone to continue to grow.

Dr. Payne, associate professor in orthopedics, worked alongside her assistant Rachel Rueffert and collaborators at CU Boulder to develop a study to blend organoid models with growth plates, explore them as 3D models with the potential to use them in the future to help prevent skeletal dysplasia and other growth deformities.

What are organoid models?

Organoid models are 3D models designed to closely mimic the structure and function of human tissues in a controlled environment, or in vitro. The growth plate organoid model specifically looks at the active tissue in children's long bones that allows for growth or continued growth after injury. These bones include the femur, humorous, tibia, phalanges and other support bones that are longer than they are wide. While researchers have studied some simple models around the growth plate, Dr. Payne’s offers the first 3D view of the growth plate. It incorporates biochemical cues (molecular signals, including growth factors) and mechanical cues (physical and environmental properties sensed by cells) in an attempt to mimic movements in a dish.

Without intervention after an injury, a child’s healing growth plate cells may make bone instead of cartilage. Dr. Payne’s ultimate goal is to uncover ways to shift that behavior. These ongoing studies will allow her to create an in-vitro organoid model to understand the existing cells. She’ll be able to rigorously study the biophysical and biochemical signals that drive the direction of cell division, differentiation and columnar organization in the growth plate.

Developing orthopedic regenerative medicine approaches for growth plate injuries

Children’s cartilage is different than adult cartilage, so approaches to evaluating and repairing it are different, too. Dr. Payne had previously focused on cartilage injury in adults. In switching to children, she started to look at how to regenerate rather than repair.

“We’ve developed and applied different regenerative medicine approaches that we can study in these animal models. But with the organoid, we can better understand what cells need to develop treatments, and we can possibly one day develop growth plate tissue in a dish that can be placed at the injury site to make cartilage,” Dr. Payne explains.

But first, she needed to take a step back and ask, “What do the cells really need to become growth plate cells, and how do they behave once they’re in that growth plate?”

To develop improved regenerative therapies for kids, providers must have a better understanding of the biological mechanisms, why cells interact and function in certain ways. This approach, using cells, biological cues and biomaterials in the injured area, helps instruct cells to make cartilage rather than bone.

The innovative nature of the growth plate organoid has been well recognized, and was even funded by the National Science Foundation. Growth plates are constantly bearing the pressures of walking and standing, which is hard to replicate in research. But 3D growth plates allow researchers to mimic that load in the dish, showing how the cells react and respond to different pressures.

Making cartilage regenerative research personal

Drs. Hadley-Miller and Payne are hopeful that these models can help improve cartilage regeneration, as well as other areas of medicine.

As a cell culturing tool, the growth plate organoid model could help advance drug discovery for individualized medicine through high volume screening of molecules that regulate growth plate development. This could help uncover one-of-one treatments for more kids.

Our team also expects this work to provide more insights into the mechanobiology of cell-aggregates and how complex feedback mechanisms operate.

A number of skeletal deformities also result from aberrant growth plate development. The differentiation rules shown by these organoid models could lead to a better understanding of skeletal dysplasia.

As development around the organoid continues, the goal is to eventually include patient cells rather than animal cells. “I don’t know if we will get there in the next year, but the goal is to, at some point, make this as personalized as we can to test specific patient cells and see how things are going,” says Dr. Payne.

In the meantime, Dr. Payne and her team have launched an educational event for undergraduates interested in science and technology careers. Held July 16, 2025, at Children’s Hospital Colorado, the event engaged 12 interns from the Children’s Musculoskeletal Research Center Summer Program. Organized by the Graduate Research Assistants from the University of Colorado, Boulder, the program featured three short lectures and interactive workshops on growth plate development, regenerative medicine and computational modeling. The plan is to repeat the event next summer and including the additional learnings between now and then.