Faculty Bibliography

Advances in the understanding of the complexities of the Wnt signaling pathway during development and tissue homeostasis have made the Wnt pathway one of the prime candidates for translational applications during tissue regeneration. Wnts are key components of the stem cell niche and are short range signaling molecules responsible for cellular decisions such as proliferation and differentiation. Systemic treatment using biologics targeting the Wnt signaling pathway have shown promising early results and will likely enter the clinical arena in the near future. This comprehensive review summarizes the intricacies how Wnts function in the context of the bone regeneration.

The next frontier of orthopedic implants are resorbable devices. Tissue engineering advances have created a demand for scaffolds that can facilitate biologic regeneration. Scaffolds that will degrade over time with the infiltration of host cells are of particular interest. Several principles have been identified as desirable design features for such scaffolds. Furthermore, the era of 3D printing has ushered new possibilities for scaffold production that brings this technology closer to market use. This article explores the future of the design and manufacture of resorbable scaffolds.

Orthobiologics are organic and synthetic materials that are used in and outside of the operating room to augment both bone and soft tissue healing. The orthobiologics portfolio has vastly expanded over the years, and it has become imperative for orthopedic surgeons to understand the role and function of this new class of biologic adjuvants. This review will highlight key components and product groups that may be relevant for the practicing orthopedic surgeon in any subspecialty. This by no means is an extensive list of the available products but provides an important overview of the most highlighted products available in the market today. Those discussed include, bone void fillers, extracelluar matrix (ECM) products, platelet-rich plasma (PRP), bone morphogenetic protein-2 (BMP-2), bone marrow aspirate (BMA), bone marrow aspirate concentrate (BMAC), and mesenchymal stem cells (MSCs). These are further categorized into their uses in several subspecialties including, traumatology, sports medicine, sports surgery, and spine surgery.

Fractures of the talus are challenging to manage, with historically poor outcomes and a high rate of complications. The rare nature of this injury limits the number of studies available to guide treatment. Fortunately, a number of advancements have been made in the last decade. There is increased recognition regarding the importance of anatomic reconstruction of the osseous injury. Advanced imaging is used to assess the subtalar joint, where even slight displacement may predispose to arthritis. Increasing use of dual anteromedial and anterolateral approaches, along with plate fixation, has improved our ability to accurately restore the anatomy of the talus. Modification of the original Hawkins classification can both guide treatment and allow us to better predict which patients will develop avascular necrosis. Lastly, improved reconstructive techniques help address the most common complications after talus fracture, including arthritis, avascular necrosis, and malunion.

OBJECTIVES/OBJECTIVE:To investigate how muscle and fasciocutaneous flaps influence the progression of bone healing in acute Gustilo IIIB tibia fractures. DESIGN/METHODS:Retrospective Chart Review. SETTING/METHODS:Urban Academic Level I Trauma Center. PATIENTS/PARTICIPANTS/METHODS:Between 2006 and 2016, 39 patients from a database of operatively treated long bone fractures met the inclusion criteria, which consisted of adults with acute Gustilo IIIB tibia shaft fracture requiring flap coverage and having at least 6 months of radiographic follow-up. INTERVENTION/METHODS:Soft tissue coverage for patients with Gustilo IIIB open tibia fractures was performed with either a muscle flap or fasciocutaneous flap. MAIN OUTCOME MEASUREMENTS/METHODS:A radiographic union score for tibia (RUST) fractures, used to evaluate fracture healing, was assigned to patients' radiographs postoperatively, at 3, 6, and 12 months from the initial fracture date. Mean RUST scores at these time points were compared between those of patients with muscle flaps and fasciocutaneous flaps. Union was defined as a RUST score of 10 or higher. RESULTS:There was a significant difference (P = 0.026) in the mean RUST score at 6 months between the muscle group (8.54 ± 1.81) and the fasciocutaneous group (6.92 ± 2.46). There was no significant difference in the mean RUST score at 3 months (P = 0.056) and at 12 months (P = 0.947) between the 2 groups. There was also significance in the number of fractures reaching union, favoring muscle flaps, at 6 months (P = 0.020). CONCLUSIONS:Patients with acute Gustilo IIIB tibia fractures who received muscle flaps have significantly faster radiographic progression of bone healing in the first 6 months than do patients who received fasciocutaneous flaps. Furthermore, according to radiographic evaluation, more Gustilo IIIB tibia fractures receiving muscle flaps reach union by 6 months than those flapped with fasciocutaneous tissue. LEVEL OF EVIDENCE/METHODS:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

INTRODUCTION/BACKGROUND:Aminocaproic acid is approved as an anti-fibrinolytic for use in joint replacement and spinal fusion surgeries to limit perioperative blood loss. Previous animal studies have demonstrated a pro-osteogenic effect of aminocaproic acid in spine fusion models. Here, we tested if aminocaproic acid enhances appendicular bone healing and we sought to uncover the effect of aminocaproic acid on osteoprogenitor cells (OPCs) during bone regeneration. METHODS:We employed a well-established murine femur fracture model in adult C57BL/6J mice after receiving two peri-operative injections of aminocaproic acid. Routine histological assays, biomechanical testing and micro-CT analyses were utilized to assess callus volume, and strength, progenitor cell proliferation, differentiation, and remodeling in vivo. Two disparate ectopic transplantation models were used to study the effect of the growth factor milieu within the early fracture hematoma on osteoprogenitor cell fate decisions. RESULTS:Aminocaproic acid treated femur fractures healed with a significantly smaller cartilaginous callus, and this effect was also observed in the ectopic transplantation assays. We hypothesized that aminocaproic acid treatment resulted in a stabilization of the early fracture hematoma, leading to a change in the growth factor milieu created by the early hematoma. Gene and protein expression analysis confirmed that aminocaproic acid treatment resulted in an increase in Wnt and BMP signaling and a decrease in TGF-β-signaling, resulting in a shift from chondrogenic to osteogenic differentiation in this model of endochondral bone formation. CONCLUSION/CONCLUSIONS:These experiments demonstrate for the first time that inhibition of the plasminogen activator during fracture healing using aminocaproic acid leads to a change in cell fate decision of periosteal osteoprogenitor cells, with a predominance of osteogenic differentiation, resulting in a larger and stronger bony callus. These findings may offer a promising new use of aminocaproic acid, which is already FDA-approved and offers a very safe risk profile.

Mechanical loading is an important aspect of post-surgical fracture care. The timing of load application relative to the injury event may differentially regulate repair depending on the stage of healing. Here, we used a novel mechanobiological model of cortical defect repair that offers several advantages including its technical simplicity and spatially confined repair program, making effects of both physical and biological interventions more easily assessed. Using this model, we showed that daily loading (5N peak load, 2Hz, 60 cycles, 4 consecutive days) during hematoma consolidation and inflammation disrupted the injury site and activated cartilage formation on the periosteal surface adjacent to the defect. We also showed that daily loading during the matrix deposition phase enhanced both bone and cartilage formation at the defect site, while loading during the remodeling phase resulted in an enlarged woven bone regenerate. All loading regimens resulted in abundant cellular proliferation throughout the regenerate and fibrous tissue formation directly above the defect demonstrating that all phases of cortical defect healing are sensitive to physical stimulation. Stress was concentrated at the edges of the defect during exogenous loading, and finite element (FE)-modeled longitudinal strain (εzz) values along the anterior and posterior borders of the defect (~2200με) was an order of magnitude larger than strain values on the proximal and distal borders (~50-100με). It is concluded that loading during the early stages of repair may impede stabilization of the injury site important for early bone matrix deposition, whereas loading while matrix deposition and remodeling are ongoing may enhance stabilization through the formation of additional cartilage and bone.

A substantial proportion of fractures can present with nonunion, and the management of nonunion continues to present a challenge for orthopaedic surgeons. A variety of biological, mechanical, patient, and injury factors can contribute to the occurrence of nonunion, and often the cause of nonunion may be multifactorial. Successful management often requires assessment and treatment of more than one of these factors. This article reviews common factors that may contribute to nonunion including infection, impaired biology, and metabolic disorders. In addition, new and evolving strategies for diagnosing the cause and effectively treating nonunion including the diagnosis of infection, metabolic workup, bone grafting, cell-based therapies, and biological adjuvants are reviewed and discussed.

The key stages of fracture healing are proliferation, differentiation, and remodeling. Each stage of fracture healing is regulated by specific growth factors. Orthopaedic surgeons should understand the basic biologic principles of fracture repair and the therapeutic targets that can augment the natural regenerative capacity of the human body. In addition, orthopaedic surgeons should be aware of the key regulators in fracture healing and their potential uses in the field of orthopaedics.