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Matt Oetgen talks about an x-ray

Nicotine-like anti-inflammatories may protect limbs, testicles from inflammatory damage after injury

Matt Oetgen talks about an x-ray

Dr. Matt Oetgen is teaming up with pediatric urologist Dan Casella for a POSNA-funded pre-clinical study of the anti-inflammatories varenicline and cytisine.

A new pre-clinical study will explore the use of anti-inflammatory medications to prevent the body’s inflammatory response from further damaging limbs after an injury restricts blood flow. Varenicline and cytisine, anti-inflammatories with similarities to nicotine, have shown early promise in similar pre-clinical laboratory studies of the testicles and will now be tested in arms and legs.

Matthew Oetgen, M.D., MBA, chief of Orthopaedic Surgery and Sports Medicine at Children’s National and Children’s pediatric urologist Daniel Casella, M.D., will jointly lead the new study entitled, “Modulation of the Injury Associated with Acute Compartment Syndrome,” which builds on Dr. Casella’s previous work with the two anti-inflammatory agents. Drs. Oetgen and Casella recently were awarded the Angela S.M. Kuo Memorial Award Research Grant to fund this research during the Pediatric Orthopaedic Society of North America’s (POSNA) Annual Meeting.

“We are honored that this important research was selected by POSNA for support,” says Dr. Oetgen. “An arm or leg injury can trigger the body’s natural inflammatory response, causing severe swelling that restricts blood flow. Even after blood flow is restored, the inflammatory response can lead to permanent muscle or nerve damage or even loss of limb. This grant will give us the opportunity to truly explore the application of anti-inflammatories after injury and see if this approach can modulate the immune response to protect the limbs.”

If successful in the laboratory, the team hopes to expand this work to human clinical trials.

The Angela S.M. Kuo Memorial Award Research Grant is given each year to an outstanding investigator aged 45 or younger based on criteria including the study’s potential significance, impact, originality/innovation, the investigator’s track record and study feasibility. The award totals $30,000.

While at POSNA’s 2019 Annual Meeting, Dr. Oetgen and Children’s pediatric orthopaedic surgery colleagues also participated in podium presentations and poster sessions, including:

  • “Achieving Consensus on the Treatment of Pediatric Femoral Shaft Fractures,” Matthew Oetgen, M.D., MBA
  • “A Prospective, Multi-centered Comparative Study of Non-operative and Operative Containment Treatments in Children Presenting with Late-stage Legg-Calve-Perthes Disease,” Benjamin Martin, M.D.

The Pediatric Orthopaedic Society of North America is an organization of 1,400 surgeons, physicians, and allied health members dedicated to advancing musculoskeletal care for children and adolescents. The annual meeting presents the latest research and expert clinical opinion in pediatric orthopaedics through presentations, posters, and symposia. It was held May 15-18, 2019, in Charlotte, North Carolina.

young girl sitting on a bed with a cast

Creating better casts

young girl sitting on a bed with a cast

Each year, millions of children in the U.S. come to hospital emergency departments with fractures. While broken bones are commonplace, the expertise to stabilize these injuries and cast them is not, says Children’s National Health System orthopedic surgeon Shannon Kelly, M.D.

Most fractures are casted by an on-call resident without the assistance of an orthopedist, she explains. Whether that resident applies a cast successfully depends largely on how well he or she learned this skill as an intern. While most current training models have interns take calls with residents, picking up casting skills through hands-on experience from their more senior peers, they can also pick up mistakes – which get repeated once they’re caring for patients independently as residents themselves, Kelly says.

Casting mistakes aren’t trivial, she adds. They can have serious consequences for patients. For example, a cast that’s not tight enough in the right places can leave bones vulnerable to shifting, a scenario that doctors call a loss in reduction, Kelly explains. If bones aren’t in the right position to heal, doctors must reposition them either in the operating room, often exposing patients to general anesthesia, or through painful, in-office procedures.

Conversely, casts that are too tight – particularly on a fresh fracture that’s prone to swelling – can damage tissues from loss of circulation. To avoid this latter problem, doctors often create a “bivalve” cast in which the two halves are split like a clamshell, leaving room for tissues to expand. But they must use extreme care when they cut open the cast with a saw to avoid cutting patients with the rotating blade or burning them with heat generated from its friction.

“Each year, thousands of children are harmed from improper casting and must go through additional procedures to fix the damage done,” Kelly says.

That’s why she and her colleagues are developing a better way to train interns before they start their orthopedics rotation. Starting this spring, the team will be directing a series of casting workshops to train interns on the proper casting technique.

The workshops will take advantage of models that allow interns to practice without harming patients. Some of these models have simulated bones that show up on an X-ray, allowing participants to evaluate whether they achieved a good reduction once they’re finished. Other models are made of wax that melts if the heat of a cast saw becomes too intense and show nicks if the blade makes contact. Learning proper technique using this tool can help spare human patients painful burns and cuts, Kelly says.

To broaden this effort beyond Children’s National, Kelly and her colleagues received a $1,000 microgrant from the Pediatric Orthopaedic Society of North America to create videos based on material from these workshops. These videos will help trainees at medical institutions across the country learn the same pivotal casting skills.

“A broken bone is difficult enough,” Kelly says. “We’re hoping to decrease the number of times that a child has to have an unnecessary procedure on top of that from a casting mistake that could have been avoided.”

Matthew Oetgen

3D printed implant used to repair knee cartilage

Matthew Oetgen

“Our preliminary study shows this novel 3D printed material is able to allow ingrowth from the bone, so the body started to grow into the material to help fix it in place,” says Matthew Oetgen, M.D., M.B.A. “These are the first step requirements for an implant like this to be acceptable for treating lesions.”

Every year, an estimated 1 million children tear the articulate cartilage that lines their knees. Unfortunately, these types of injuries are extremely hard to repair because of the cartilage’s poor healing qualities and unique physiochemical properties.

Now, a new study by Children’s National Health System researchers has found that a three dimensional (3D) printed synthetic implant can be successfully used as a scaffold to encourage the healing and repair of articulate cartilage lesions.

Three bones meet in the knee joint: the femur, the tibia and the patella. The surface of these bones is covered with articulate cartilage, which can be damaged by injury or by normal wear and tear. Because articulate cartilage has poor healing qualities, these injuries will rarely heal or regenerate on their own, especially in younger and more active patients.

“These are active 12 to 19 year olds, so it can really affect relatively normal kids,” says Matthew Oetgen, M.D., M.B.A., Division Chief of Orthopaedic Surgery and Sports Medicine at Children’s National. “While there are many ways to repair these lesions — from implanting autogenous cells to using grafts to fill the defect — none of these options are perfect, and they all have some down sides.”

To facilitate repair of these injuries, a team of researchers led by Dr. Oetgen received a grant from the Pediatric Orthopaedic Society of North America (POSNA) to design a 3D printed implant that promotes bone and cartilage growth.

To make the implant, the team used nanoporous thermoplastic polyurethane (TPU), a biodegradable material that is highly elastic and yet strong, very much like the native cartilage in the osteochondral region. TPU is also porous, which allows blood and nutrient flow through the implant.

“The implant is designed to allow native cells to repair the lesions with normal articular cartilage and not scar tissues like some repairs,” says Dr. Oetgen.

The implant itself has a stratified structure: an upper region that contains micro channels to allow for increased perfusion; a middle zone with a nanoporous structure that mimics porous cartilage and encourages stem cell recruitment, growth and differentiation; and a lower region, or articular surface, that allows for smooth transition from the articulating surface to the implant surface and minimizes adverse interactions between the articulate cartilage and the meniscus.

When tested in vitro, the implant was able to support the growth of stem cells and vascular cells, and structurally mature vascularized bone was formed around the implant after 10 days. In animal models with full thickness osteochondral lesions the implant did just as well: The scaffold was able to promote bone, soft tissue and vascular growth without eliciting an immune response.

“Our preliminary study shows this novel 3D printed material is able to allow ingrowth from the bone, so the body started to grow into the material to help fix it in place,” says Dr. Oetgen. “These are the first step requirements for an implant like this to be acceptable for treating lesions.”

Because of the ease with which 3D printing can be scaled up, Dr. Oetgen is hopeful that the implant will one day become a viable option for repairing articulate cartilage injuries. He plans on trying the implants in a larger animal model and on larger lesions, and is also looking at custom printing for the implants to match natural lesion shapes and sizes.

Femoral fracture

POSNA grant addresses variations in femoral fracture treatment

Femoral fracture

While there are plenty of options for treating pediatric femoral diaphyseal fractures, doctors don’t have a lot of specific guidance on the optimal regimen for each patient age, fracture location and fracture pattern.

Pediatric femoral diaphyseal fractures are some of the most common types of long bone fractures. There are many effective ways to treat these injuries, but unfortunately this assortment of options also leads to variations in cost and clinical outcome for patients and makes it difficult to develop clinical trials exploring the treatment of pediatric femur fractures.

To address this issue, a Children’s National research team led by Matthew Oetgen, M.D., M.B.A., Division Chief of Orthopaedic Surgery and Sports Medicine, received a $30,000 grant from the Pediatric Orthopaedic Society of North America (POSNA) to design a multi-centered, randomized, controlled clinical trial for the treatment of pediatric diaphyseal femur fractures. The team’s ultimate goal is to submit the resulting trial design to an extramural agency for study funding.

While there are plenty of options for treating pediatric femoral diaphyseal fractures, doctors don’t have a lot of specific guidance on the optimal regimen for each patient age, fracture location and fracture pattern. As a result, many treatment decisions are based on surgeon preference, regional variation in care and previous training or experience.

Another issue that arises in the treatment of diaphyseal femur fractures is the impact on the patient’s family. In general, femur fractures are caused by significant trauma that affects both the patient and the family members. On top of this, families are faced with issues such as extended hospitalization, the need for wheelchairs and walkers, pain control, missed school and secondary surgeries for removal of implants. Often, families are left to their own devices to resolve these issues, many of which are more impactful than the injury itself.

Dr. Oetgen believes that a well-planned and well-structured randomized clinical trial guided by patient and family concerns as well as expert surgical opinion has the potential to improve both treatment and care of femoral diaphyseal fracture patients.

“It is no longer good enough to design studies that only look at healing time for femur fractures,” explains Dr. Oetgen. “These injuries have such significant secondary impacts for the families of these patients, we need to determine which treatment is optimal for both fracture healing and is easiest for the families to tolerate. This grant will allow us to consider all of these outcomes in designing a study to find the best treatment for these injuries.”

To aid in the design of their clinical trial, Dr. Oetgen and his team will:

  1. Conduct an extensive literature review on the impact and treatment of pediatric femur fractures.
  2. Survey a diverse group of pediatric orthopaedic surgeons to establish areas of agreement, opposition and equipoise on the surgical treatment of pediatric femur fractures, and use that information to form a consensus opinion on the optimal design of the clinical trial.
  3. Solicit input from non-physician stakeholders (families, parents, payers, state Medicaid representatives, patient advocacy groups, professional organizations) on the important aspects of care in pediatric femur fracture treatment.

The team expects to have the study design competed by February 2019.