Jaime R. Denning, MD, MS - CORTICES Board of Directors

Denning serves on the board of directors for the Children’s Orthopedic Trauma and Infection Consortium for Evidence Based Studies (CORTICES). CORTICES is a collaboration of pediatric orthopaedic surgeons from nineteen pediatric trauma centers dedicated to improve the quality, safety and value in the management of emergent orthopedic conditions through education, research and optimal care guideline development.

Most recently, Denning co-wrote a study and grant application that received funding from the Pediatric Society of North America (POSNA) to support the research of venous thromboembolism in pediatric orthopaedic surgery. The results were subsequently presented as the ‘Descriptive Epidemiology of Venous Thromboembolism after Pediatric Orthopaedic Surgery’ at POSNA’s annual meeting.

Further accomplishments of the CORTICES study group in the past year include three peer-reviewed articles:

• Current Variation in Joint Aspiration Practice for the Evaluation of Pediatric Septic Arthritis – Journal of the American Academy of Orthopaedic Surgeons
• Pediatric Floating Elbow Injuries Are Not as Problematic as They Were Once Thought to Be: A Systematic Review – Journal of Pediatric Orthopaedics
• Defining the volume of consultations for musculoskeletal infection encountered by pediatric orthopaedic services in the United States - PLOS ONE (Public of Library Science)

The study group had numerous presentations on topics including ‘Isolated Septic Arthritis’ (selected for presentation at POSNA’s award ceremony), ‘Practice Variation in the Surgical Management of Children with Non-Abscess Forming Acute Osteomyelitis,’ ‘Management of Syndesmotic Injuries in Children and Adolescents’ and the ‘Descriptive Epidemiology of Upper Extremity Septic Arthritis (UESA) in Children.’

Current research studies investigating pediatric pelvic / acetabular trauma, non-accidental trauma and distal tibia physical fractures are underway.

Shital N. Parikh, MD, FACS - JUPITER Continued Success

The goal of the ‘Justifying Patellar Instability Treatment by Early Results’ (JUPITER) project is to compare the safety and efficacy of non-operative treatment, isolated medial patellofemoral ligament (MPFL) reconstruction, and an “à la carte” surgical approach to treat patellar instability. Using patient reported outcomes and clinical data, the study compares different surgical treatments with non-surgical treatments in patients who are skeletally mature versus those who are not.

The JUPITER project, led by Parikh in the Division of Pediatric Orthopedics, and Beth Shubin Stein, MD, from the Hospital for Special Surgery, incorporated the help of 12 institutions and 21 surgeons to enroll over 1700 patients in this prospective research study. The JUPITER study focuses on examining the long-term outcomes and care of patellofemoral instability patients with a follow-up time of 10 years for each patient enrolled. The information gained from this study will give insights into arthritis development after patella dislocations, long-term function and the need for recurrent surgeries as these patients grow.

The JUPITER project produced several papers from early data sets that are in the publication process. A descriptive epidemiology paper (American Journal of Sports Medicine) described the patient group, analyzing demographic data, injury history and clinical findings. About 2/3 of the patients received operative treatment and slightly over half of the patients reported multiple patella dislocations. A reliability study comparing the growth plate assessment between surgeons (Orthopaedic Journal of Sports Medicine) found that prior to any discrete training or establishment of criteria the interrater reliability was unacceptably low. However, after the establishment of criteria and training, the interrater reliability was nearly perfect. Another reliability manuscript is currently in the write-up stage that examines the reliability between two trained skeletomuscular radiologists. Similar to the other reliability study, research found that interrater reliability of many clinically relevant patellofemoral instability parameters was unacceptably low. Some measurements were initially unreliable but improved with training and consensus building around measurement definitions.

Future studies using the data collected will look at patient-reported outcomes and how they compare to injury type, treatment decisions, surgical techniques and radiographic measurements.

Patrick W. Whitlock - Musculoskeletal Regenerative Medicine Research Laboratory

The Musculoskeletal Regenerative Medicine Research Laboratory (MRMRL) continues to progress on the treatment of large osteochondral defects during year two of our prior three-year funding award from the Musculoskeletal Transplant Foundation with Dr. James Lin. This work led to two recent abstract acceptances for podium presentations at the upcoming TERMIS and BMES international meetings. We previously presented our prior years' findings virtually at meetings of the ORS, TERMIS, and the BMES.

We continued expansion of our lab and shared lab capabilities with the capital purchase of an Instron mechanical testing machine with the capability of testing materials from hydrogels to bones and metallic implants, a first at Cincinnati Children's. Thus, in cooperation with Cincinnati Children's core facilities, make us a fully equipped and functional Bio-printing laboratory and testing facility. We continue to seek a better solution to large osteochondral defects, avascular necrosis, and other injuries that we may translate clinically to our young patients.

Our latest initiative, for which we are currently actively seeking NIH funding, focuses on developing “An injectable/ 3D printable bioink system for the prevention of osteochondral collapse secondary to avascular necrosis (AVN)” using inductive, composite bioinks utilizing our experience in decellularized scaffolds, 3D additive manufacturing, and the development of hydrogel, polymeric systems. We successfully formulated a chemical strategy for chemically re-mineralizing decellularized extracellular matrix that imparts it bio-physical and bi-chemical cues for guiding mesenchymal stem cell differentiation towards bone cells, without compromising on the mechanical properties. The bioink system is both injectable and bio-printable while retaining excellent mechanical properties due to the formation of a bone-like hydroxyapatite-matrix nano-composite structure. We recently submitted our initial work on this effort for publication as well as presentation at national meetings. We also submitted a grant proposal to the Musculoskeletal Transplant Foundation on the same work by Sumit Murab, PhD, as the principal investigator and Whitlock as the co-principal investigator. We formed a collaboration with Ming Xia’s lab to incorporate vascular organoids into our approach to treating avascular necrosis and plan to include this preliminary data into our NIH R01 proposal in one of the next two grant cycles with Xia as co-principal investigator. Initial results show we are able to combine the vascular organoids into our bioinks in model systems successfully.

We recently published our collaborative work with Joseph Palumbo’s group, titled “Fibrinogen activates focal adhesion kinase (FAK) promoting colorectal adenocarcinoma growth” in the Journal of Thrombosis and Haemostasis. By leveraging our current facilities, recently acquired equipment and the expertise of our newly appointed faculty instructor, Murab, we developed a 3D bioprinted model of colon cancer for studying the effect of fibrinogen in colon cancer proliferation in vitro. Lastly, we collaborate with the Pelling Lab from the University of Ottawa on the development of nanocellulose based mineralized bioinks for orthopaedic tissue engineering applications. We will be submitting this work to the upcoming meeting of the Orthopaedic Research Society.