ORTHOPEDICS • CONTINUED FROM PREVIOUS PAGE
Engineering the right
environment
The problem has to do with the mechanism of
healing. Inflammatory cells invade the area and lay
down the fibrous tissue necessary to stitch it back
together, along, some studies have suggested, with
an influx of mesenchymal stem cells. In the second
week, blood vessels begin to form, which cues the
stem cells to become bone.
“But if you can create an environment that
promotes cartilage,” says Dr. Payne, “it’s possible to
make those stem cells become cartilage instead.”
cement currently used to prevent bony bars, it’s a
personalized, 3D printed implant that blocks bony
bar reformation and stabilizes the growth plate,
ideally while the tissue regenerates.
For that, her lab collaborates with mechanical
engineer and bone mechanics expert Virginia
Ferguson, PhD, and materials science and 3D
printing expert Stephanie Bryant, PhD, both of the
University of Colorado Boulder. Together, they’re
working to match the mechanical properties of the
implant to each of the growth plate’s five zones
— an aspect of the growth plate that, so far, no
research team has ever tried to deduce.
If you can create an environment that promotes
cartilage, it’s possible to make those stem cells become
cartilage instead.”
K A R I N PAY N E , P h D
Director, Payne Regenerative Orthopedics Lab
Her lab is currently testing that idea on animal
models of bony bars using a number of delivery
mechanisms, in collaboration with bioengineers,
biochemists and computing experts from all over
the state. They’re testing factors and combinations
of factors that block angiogenesis, that attract
stem cells, that mimic the chemical conditions
under which cartilage develops and grows.
In the lab, a cadre of grad students, research
assistants and fellows resect tibia and humeri
the length of thumbtacks, dry them, pack them in
paraffin and chop them five microns thick. Stained,
the slides provide the proof: bright blue eruptions
of cartilage where, compared to samples left
untreated, the bar reformed.
These projects show promise, but the project
Dr. Payne is most excited about — the one she
thinks is closest to clinical practice, maybe
even just a few years out — is more tangible
still. Conceived to replace the fat grafts or bone
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Fabricated as an interlocking system of pillars,
the implants can then be infilled with cartilage-
promoting hydrogels. Animal models have shown
they’re able not only to prevent bony bars from
reforming after resection, but to encourage
cartilage formation as well.
“It’s fascinating,” says Dr. Hadley-Miller, who
contributes both bench and clinical work to the
project. “What keeps these cells from spreading
out instead of sticking together? How do the cells
progress downward? What are the signals that
turn them on and off? They’re communicating, like
a little city. There’s a whole circle of life in there we
know almost nothing about.”
Getting the pieces in place
The clinical picture of growth plate injury isn’t
much clearer. On that side, Dr. Hadley-Miller and
her team at Children’s Colorado’s Musculoskeletal
Research Center, or MRC, are assembling a
comprehensive study — another first for the field.
Epidemiologist Patrick Carry, MS, can get a good
idea of the incidence of fractures that affect the
growth plate by pulling from a number of national
trauma databases. But what those databases can’t
offer is longitude. tend toward growth plate injury. When the
charts are pulled, he and his team will comb
through thousands of X-rays and diagnostic codes,
a huge, time-intensive effort requiring many, many
man hours. Co-Chief of
“As a Level 1 Trauma Center, we get a lot of kids
referred with existing growth plate injuries, but
we don’t know how many started with a fracture
that developed into a growth plate injury, or how
many of those injuries resulted in these growth
plate disturbances,” he says. “So we’re developing
a strategy to answer that question.” That kind of effort is largely possible through the
unique funding model of the MRC, which pools
clinical dollars earned from surgery toward an
infrastructure of 14 research assistants and
two statisticians who power dozens of surgeon-
directed research efforts. As the MRC’s first such
research assistant, Carry has been working with
Dr. Hadley-Miller, the MRC’s medical director, for
more than ten years. PhD, Director of the
But their growth plate work started with a joint
research grant opportunity between Children’s
Colorado and the School of Mines. At the time,
Dr. Payne was working in adult cartilage
regeneration, mostly focused on degenerative
joint disease. She hadn’t done growth plate
research before. Neither, for that matter, had promising so far.
As one of the first pediatric institutions in the
U.S. to adopt an electronic medical record system,
Children’s Colorado has comprehensive data
stretching back well more than a decade. The
question is how to access and sort it.
Carry, an expert in study design, is currently
working out the inclusion criteria with a targeted
chart review of bones and trauma types that
Pediatric
Orthopedics Nancy
Hadley-Miller, MD,
and Karin Payne,
Payne Regenerative
Orthopedics Lab,
examine a stain
from an animal
model that aims to
regenerate injured
growth plate tissue.
The results are
NEW CONSTELLATIONS
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