Research grants

Funding opportunities for applied research that support clinical issues relevant to the veterinary field 

From traditional research grants to investigator training

AO VET is working on the development of training grants for young investigators, better opportunities for structured research mentoring of young trainees, and the introduction of new, innovative surgical training courses on best practices in preclinical animal research.

AO VET will also act as a resource across the AO group to facilitate the most ethical appropriate use of animals in research.

Research grant calls

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AO VET/ARI Collaborative Research Grant

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AO VET Seed Grants

Funded research projects

AO VET–ARI Collaborative Research Grants

Principal Investigator: Sun Young Kim, Purdue University, United States

Abstract:

Proximal femoral fractures are common in young, growing dogs, with femoral neck fractures accounting for approximately 30% of these injuries, most often due to trauma. In small animals, the standard fixation method involves a lag screw with an anti-rotational pin. However, fractures at the base of the femoral neck carry a high risk of complications, including implant failure, malunion, and nonunion—likely due to axial and rotational shear forces generated during weight-bearing. Recent studies suggest that a positional screw may better resist shear forces than a lag screw while providing comparable interfragmentary compression. Additionally, two small screws placed apart may offer superior rotational stability compared to a single large screw.

This study will biomechanically compare lag versus positional screw fixation and dual small screws versus a single large screw in canine femoral neck fractures, using paired cadaveric femora. Standardized osteotomies and implant placement will be guided by 3D models from CT scans and specimen-specific 3D-printed drill guides. Bone-implant constructs will undergo axial loading tests simulating walking, using a mechanical testing machine to measure strain, load at 2mm displacement, and failure modes.

The aim is to provide evidence-based insights into optimal fixation strategies for basicervical femoral neck fractures in dogs, ultimately guiding surgical decision-making and improving patient outcomes. In the long term, this research seeks to support the development of reliable surgical techniques and innovative implant designs tailored to small animals.

  • Principal Investigator: Ariane Campos, Grosbois Equine Clinic, France

    Abstract:

    Background: Due to the high rate of postoperative complications, none of the current techniques for distal interphalangeal joint arthrodesis in horses are considered satisfactory. The joint’s complex anatomy, its location within the hoof capsule, and its exposure to complex multidirectional forces make the procedure particularly challenging. Distal interphalangeal joint arthrodesis has been used as a salvage procedure for severe osteoarthritis, joint instability, luxations, and chronic fractures. The surgery allows to restore a pain-free and functional use of the affected limb long-term. Recently, two new plates designs have been developed in an attempt to address the main challenges of distal interphalangeal joint arthrodesis, namely the surgical approach and construct stability.   

    Objectives: To compare the ex vivo biomechanical properties of three distinct distal interphalangeal joint arthrodesis constructs: (1) a 6-hole 3D printed titanium DIPJ (6H3DP) plate with two abaxial transarticular (TA) 5.5mm cortex screw inserted in lag fashion through the plate holes, (2) a 4-hole 316 stainless steel L-shaped plate (4HL) combined with two axially directed TA 5.5mm cortex screws inserted in lag-fashion adjacent to the plate, and (3) a 3-hole PIP-LCP (3HLCP) construct with two abaxial transarticular 5.5mm cortex screws inserted in lag-fashion adjacent to the plate. The application of both the 6H3DP and 4HL plates does not involve penetrating the dorsal hoof wall capsule.   

    Materials and methods: Twenty-four pairs of fresh-frozen equine thoracic limbs from adult Warmblood horses will be used for this study. The limbs will be assigned to two groups for cyclic loading: (1) neutral axial compression and (2) asymmetrical axial compression. Each group will be subdivided into four subgroups: six limbs will be used as negative controls, and the remaining limbs subjected to distal interphalangeal joint arthrodesis using either the 6H3DP, the 4HL, or the 3HLCP. Specimens will be tested using bi-axial servo-hydraulic testing system. Asymmetrical loading will be induced by raising the hoof laterally with a 12° wedge, creating a rotational and lateromotion effect on the joint and simulating uneven load distribution observed in vivo. Quasi-static cyclic loading will be followed by destructive cyclic loading. Cycles to failure, yield stiffness, and failure load will be recorded, with failure modes documented via fluoroscopy and radiography.   

    Hypothesis: The authors hypothesize that the 6H3DP construct will demonstrate comparable resistance to axial cyclic fatigue when compared to the 4HL plate and 3-hole LCP constructs but will exhibit superior resistance to lateromotion and rotational cyclic fatigue.   

    Long-term goal: To develop a surgical technique for distal interphalangeal joint arthrodesis that avoids penetrating the hoof wall and can withstand the multiplanar forces exerted on the joint and ultimately improving the success rate of DIPJ arthrodesis in horses.  

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  • Investigator: Matthew Stewart, University of Illinois, USA

    Several murine-based genetic models have demonstrated the primacy of periosteal activity in fracture repair by endochondral ossification. Although the osteogenic potentials of periosteal and other osteoprogenitor cell populations have received a great deal of attention, the regulation of periosteal chondrogenesis has been less well investigated; this despite the fact that the generation of a cartilaginous callus is a mandatory stage of endochondral fracture repair. The experiments in this proposal will utilize a novel periosteal chondrogenesis model based on non-adherent culture conditions maintained in defined serum-free medium to address the impact of hypoxia on periosteal chondrogenic differentiation. Early fracture sites represent local hypoxic environments, due to vascular injury, consequently inadequate oxygen and carbon dioxide exchange, and increased oxygen demands from reparative cells. In this respect, periosteal chondrogenesis develops within a hypoxic milieu. Further, it is well established that hypoxic conditions stimulate stem cell chondrogenesis in vitro. 

    The study will take advantage of the hypoxic cell culture facility developed by ARI's Regenerative Orthopaedics group to test the linked hypotheses that hypoxic conditions will stimulate periosteal chondrogenic differentiation and stimulate periosteal cartilage matrix synthesis. Equine periosteal cells, expanded to passage 3, will be transferred into our non-adherent aggregate culture model and maintained under normoxic (20% O2) or hypoxic (5% O2) conditions for up to 21 days. Samples will be collected for phenotypic and matrix synthesis assays at days 3, 7, 14 and 21.  

    Differential induction of a chondrogenic phenotype will be determined by changes in expression of chondrocyte-specific genes Sox 5, 6, 9 and 11, collagen types II, VI, IX, XI, aggrecan, link protein and HAS 2. Induction of a hypertrophic chondrogenic phenotype will be monitored by expression of collagen type X, alkaline phosphatase, RANKL, VEGF and MMP 13 mRNAs and by aggregate ALP enzymatic activity. The impact of hypoxia on periosteal cartilage matrix synthesis will be assessed by incorporation of collagen type II and sulfated proteoglycan into periosteal aggregate matrices and by overall aggregate mass. Periosteal chondrogenic aggregates will characterized histologically with matrix staining for sulfated proteoglycans and collagen.

    Collectively, these experiments will determine the impact of hypoxia in driving periosteal chondrogenesis and will inform cell-based strategies for improving fracture and nonunion repair


 

  • Investigators: Maria Podsiedlik / Loic Dejardin / Kati Glass / Boyko Gueorguiev / Caroline Constant, Michigan State University, USA

    Drilling is an essential part of many orthopedic surgeries. It should be a crucial and fundamental technical skill required for every orthopedic surgeon. Implementation of improper drilling technique has been associated with drill bit breakage, damage to the surrounding soft tissues, nerves and vessels as well as thermal osteonecrosis. Surgical drilling is causing transient bone and drill bit temperature rise. Multiple studies looked at the bone temperature level threshold above which bone tissue necrosis occurs. Thermal osteonecrosis can have dire post-operative consequences resulting in necrotic tissue resorption leading to loss of bone-screw stability and ultimate implant failure. Finding the most effective drilling technique which is causing the least amount of bone temperature rise is crucial in order to prevent a thermal osteonecrosis during orthopedic implants placement. Continuous quest for improving drilling quality in order to preserve the bone tissue led to multiple evaluations of different drill and drilling parameters. The "gold standard" technique has yet to be determined.

    Pulse a.k.a. peck drilling is a technique that relies on intermittent tool feeding and is frequently used in mechanical industry. It is recommended for tool cooling and chip removal. Furthermore, peck drilling has been shown to improve drilling accuracy, pilot hole quality, decrease tool failure and increase drill bit life. Despite this drilling technique being well known and established in a field of metallurgy, there is still a lack of evidence of its benefits on a drilled bone quality while compared to the traditional, continuous drilling techniques.

    Data generated in this study will help to evaluate, a previously unreported in orthopedics, pulse drilling technique and compare it to the conventional continuous drilling. The results of this research will help surgeons in decision making process while choosing the most effective drilling technique with the lowest risk for causing thermal osteonecrosis. Additionally, in a long-term we are aiming to identify parameters that would improve bone drilling techniques in general. Should this procedure prove effective, it could be easily incorporated into the AO skills-lab exercises and be taught to aspiring orthopedic surgeons worldwide.

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Investigators: Mila Freire / Joachim Lahiani / Dominique Gagnon / Xavier Montasell / Tristan Juette
ARI Principal Coinvestigator: Caroline Constant

External skeletal fixators (ESFs) are widely used in small animal fracture fixation, most frequently for comminuted, non-reconstructible fractures of radius and tibia.3,8,9,11-13 Their stiffness relays, among other factors, on the rigidity of the attachment of the transfixation pins to the connecting bars.5,11,14 Maximal tightening of clamps is recommended for optimal clamp mechanical performance.5,11 Clinical experience shows that nut loosening occurs frequently, and it is common practice to schedule regular patient reassessments to tighten the nuts as part of the postoperative ESFs care. It is assumed that the repetitive loads and external impacts are responsible of the decrease in nut tightening, although frequency and degree of this phenomenon, and how this might affect the biomechanical properties of ESFs is lacking in the literature. Inadvertent nut loosening decreases rigidity of ESFs and stability of the fracture, which might have catastrophic consequences in fracture healing.4,10 Several anti-loosening devices are available, including split lock washers and nylon insert lock nuts, but they are currently not incorporated into ESF frames and their potential benefit in preventing nut loosening has not been investigated. With this project we aim to investigate the impact that cyclic loading has on the degree of loosening of the nuts of ESF clamps and how nut loosening affects biomechanical properties of ESFs. The addition of anti-loosening devices to the nuts of these frames could prevent this phenomenon and protect the long-term rigidity of ESFs in the postoperative period.

The proposed project is the continuation of Dr Lahiani’s research work within his ACVS residency program. The first completed project entitled “Effects of transfixation pin positioning on the biomechanical properties of acrylic external skeletal fixators in a fracture gap model”, to be presented at the ACVS Symposium 2022 Resident’s Forum, evaluated the effects of eccentric pin positioning in the acrylic connecting bars on the biomechanical properties of acrylic ESFs. This grant would allow us to further investigate the influence of different variables on the biomechanical properties of ESFs, focusing this time on anti-loosening devices and their potential long-term benefits. Although this will be a continuation of previous work in ESFs of our research group, this study is not part of a larger project. The experimental part will be completed in its entirety at the ARI, allowing Dr Lahiani to participate actively in the experimental part. This grant would be a unique opportunity for him to visit ARI facilities and train with structured mentoring on best research practices. Dr Mila Freire, principal investigator and currently enrolled in the Faculty Education Program of AO VET, will visit the ARI facilities in 2023 and participate in the experimental part of this work as well.

The main goal of internal fixation is maintaining fracture stability to encourage bone union while maintaining a functional limb during healing. Therefore, successful fracture fixation results when the various loading forces acting on the fracture fragments are resisted by the mechanical stiffness of the bone-implant construct. Given the extreme forces equine patients can apply to fracture fixation devices, surgeons routinely work at mechanical limits of implants during the repair of adult long-bone fractures. Despite improved orthopedic equipment such as the LCP, providing a fixation with adequate strength to protect the fracture from weight-bearing forces throughout the healing period, equine fracture repair remains challenging. Taken together, this explains why open reduction and internal fixation in equine surgery are associated with poor survival rates and a high risk of catastrophic failure of the repair or cyclic fatigue failure of the implants.

Larger and stronger implants for internal fixation can reduce the incidence of catastrophic implant failure. A more robust plate, the 5.5-mm broad LCP, was specially designed with an increased plate thickness for large animal fracture repair. This modification led to superior resistance to static overload and a 31% increase in cyclic fatigue of the 5.5 LCP compared to the 4.5 LCP. A larger cortical screw, the 5.5-mm large animal cortex screw, was also specially created for the large animal veterinary market. This modification in the core diameter led to an increased area moment of inertia (area moment of inertia (I) = π r4/4), leading to an improved bending stiffness of the 5.5-mm cortex screw compared to the 4.5-mm. Nevertheless, screw loosening and breakage remain a frequent complication in the clinical application of LCP in horses and occur in almost 20% of LCP stabilization. The 5.5 LCP and 5.5-mm cortical screw were designed with the same head-related features as the 4.5 LCP and 4.5-mm cortical screw, meaning they have the same Combi hole and screw head diameter, respectively. Hence, the relatively small area of pressure under the screw head in the 5.5 LCP Combi hole and the small head diameter of the 5.5-mm cortex screw could reduce the full potential of this construct by undermining its ability to limit stress rising around the screw heads and to produce plate-to-bone compression. The use of modified LCP to accommodate cortical screws with larger head diameters should improve biomechanical stress distribution around the screw heads and allow better plate-to-bone compression, and therefore have the potential to reduce the incidence of implant failure. Generally, when the stress is better distributed around the implants and bone, more cycles are needed to break the implant due to fatigue. In addition, the ability of a screw to generate a higher insertion torque could increase its ability to obtain a stable construct from decreased micromovements between the LCP and bone in the region of the plate occupied by cortical screws. The increased stability of an LCP construct for hybrid plating would be of significant clinical advantage for long bone fracture repair proximal to the third metacarpus/metatarsus, which currently has a poorer prognosis, partly because of the decreased ability to supplement internal fixation with external coaptation.

Investigators: Andrey Kalinovskiy / Christoph Lischer / Anna Ehrle / Kathrin Mählmann
ARI Principal Coinvestigator: Caroline Constant

The study entitled "Comparison of equine pastern-arthrodesis techniques: 2 vs. 4 trans-articular screws combined with LCP plate" is one part of a larger project evaluating equine pastern-arthrodesis techniques both in vitro and in vivo. Pathological conditions affecting the proximal interphalangeal joint (PIPJ), including osteoarthritis, subluxation and subchondral bone lesions often result in progressive, and ultimately intractable lameness in the horse.1 PIPJ-arthrodesis should be considered when the horse is unable to ambulate or perform as intended due to lameness localized to the PIPJ that is not responsive to medical therapy.1-3 Arthrodesis provides a good prognosis for resolution of lameness and often allows the horse to return to its expected level of performance.1,2,4-8 Currently the PIPJ-arthrodesis using 2 transarticular cortical lag screws (TLS) combined with the proximal interphalangeal locking compression plate (PIP-LCP) provides the best standard of care in equine surgery (Figure 1).1,3,5,8,9 However, there are still several open questions with potential room for improvement concerning PIPJ arthrodesis, which the study parts listed below are intended to address. The following studies are to be performed during the entire project:

  1. Comparison of equine pastern-arthrodesis techniques: 2 vs. 4 trans-articular screws combined with LCP plate. Further description detailed in the present application below.
  2. Correlation of preoperative computed tomography (CT)-findings with intraoperative screw positioning and postoperative outcome following pastern arthrodesis. The prospective study is carried out at the equine hospital of Free University of Berlin. No external funding.
  3. Comparison of standard inverted-T with modified non-inverted-T skin incision for pastern-arthrodesis approach. The amount of cartilage that can be removed from the PIPJ articular surface via the two different approaches is evaluated during a cadaveric study. The correlation of the approach with the occurrence of wound infection is assessed clinically. The study is carried out at the equine hospital of Free University of Berlin. No external funding.
  4. Clinical outcome of PIPJ arthrodesis in a Warmblood horse population. The retrospective study is carried out at the equine hospital of Free University of Berlin. No external funding.

  • The humerus is the most commonly fractured proximal bone in Thoroughbred racehorses, with a prevalence of 50% of all proximal limb and pelvic fractures occurring on race-day and during training. Humeral fractures are also common after a traumatic event such as falling, and is the fourth most commonly fractured long bone in a heterogeneous equine population following kick injuries with a prevalence surpassing that of the third metacarpal/tarsal bones. The characteristic complete fracture of the humerus courses from the caudoproximal cortex in a long oblique or soft spiral configuration to the caudodistal cortex. Complete humeral fractures in mature horses (>300 kg body weight) are difficult to treat by internal fixation and the principal decision has to be between euthanasia or extended stall rest. In the largest published case series, only 23% of horses undergoing internal fixation for humeral fractures had a positive outcome. The grave to guarded prognosis is a consequence of unsuitable surgical implants that do not have sufficient strength to achieve adequate stability. Thus, conservative therapy with stall rest is currently the only viable alternative to surgical fixation and only for minimally or not displaced fracture but complications are frequent and include support limb laminitis, ongoing fracture displacement with associated soft tissue injury and/or radial nerve paralysis, malunion, and nonunion.

    Fracture stabilization in equine orthopedics is usually achieved with double plate fixation, which is technically challenging in the humerus because of the complex surface topographies and difficulty to engage adequate bone stock, particularly distally. More recently, IIN fixation has been used successfully in veterinary orthopedics and has resulted in successful outcomes in foals with diaphyseal humeral fractures. The IIN veterinary systems are designed for small animals and are too weak to be used in mature horses with the size of the largest nail available (8-mm diameter) limiting its usage to neonatal and young foals. A larger custom IIN prototype with a 12.7-mm diameter has be described for large animal humeral and femoral fracture fixation and showed encouraging results in horses up to 377 kg used in combination with a cranial bone plate in heavier animals. However, this prototype never reached the veterinary market and no IIN systems for use in large animal fracture fixation is currently commercially available. The identification of a IIN system already commercially available from the human market would facilitate and accelerate its implementation in large animal surgery and would limit the research and development investments that would be required to market a new nail only for the large animal veterinary market.

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    • The main goal of internal fixation is to maintain fracture stability to encourage bone union while maintaining a functional limb during healing. Therefore, successful fracture fixation results when the various loading forces acting on the fracture fragments are resisted by the mechanical stiffness of the bone-implant construct. Given the extreme forces horse patients can apply to fracture fixation devices, equine surgeons routinely work at mechanical limits of implants during the repair of adult long-bone fractures. Despite improved orthopedic equipment such as the LCP, providing a fixation with adequate strength to protect the fracture from the forces of weight-bearing throughout the healing period in equine fracture repair remains challenging. Taken together, this explains why open reduction and internal fixation in equine surgery is associated with poor survival rates and a high risk of catastrophic failure of the repair or cyclic fatigue failure of the implants.

      Larger and stronger implants for internal fixation can reduce the incidence of catastrophic implant failure. A stronger plate, the 5.5-mm broad LCP, was specially designed with an increased plate thickness for large animal fracture repair. This modification lead to a superior resistance to static overload and a 31% increase in cyclic fatigue of the 5.5 LCP compared to the 4.5 LCP. However, screw loosening and breakage remain a frequent complication in the clinical application of LCP in horses and occur in almost 20% of LCP stabilization. Screw breakage is influenced by the bending stiffness of the screw which can be evaluated by calculation of the area moment of inertia for the screw core diameter (area moment of inertia (I) = π r4/4). A small increase in the core diameter of a screw such as the introduction of a new locking screw with a 1-mm core diameter increase will have a large effect on its bending stiffness and have the potential to reduce the incidence of implant failure. The increased stability of a locking screw with a larger core diameter would be of significant clinical advantage for long bone fracture repair proximal to the third metacarpus/metatarsus which currently have a poorer prognosis, partly because of the decreased ability to supplement internal fixation with external coaptation. Generally, if greater bending loads are applied during a given cycle of loading, fewer cycles are needed to break the implant as a result of fatigue. Another interesting advantage of a screw with an increased bending stiffness worth noting is its expected decreased displacement under an applied load (deflection) improving fatigue resistance. The increased capability of resisting cyclic fatigue of a locking screw with a larger core diameter could improve fracture healing in all fracture repair allowing placement of 6.0-mm locking screws.

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In orthopaedic, spine and maxillofacial surgery there is a growing, unmet need for biomaterials that can support bone regeneration in the millions of patients who suffer from challenging and non-healing bone defects each year. Although autologous bone grafts ("autograft") is considered the standard of care for replacing bone it has several important limitations, including donor site morbidity and a physical limit as to how much bone can be harvested. Allograft bone, which provides an option for replacing larger bone defects, also has limitations, including cost and the potential disease transmission.

In light of the unmet needs of patients with non-healing bone defects and the limitations (described above) of current "natural" bone graft materials, the market for synthetic bone graft substitutes in humans continues to increase and is expected to top $4 billion by year 2025. However, these commercially available, off-the-shelf bone graft substitutes assume that one size fits all, which is not the case when dealing with complex post trauma, post-cancer resection or congenital anomalies bone reconstruction surgeries where surgeons are facing individually unique bone defects (anatomically, mechanically and functionally). There is an urgent need to a cost-efficient, customizable solution for repairing these bone defects in both humans and animals.

3D printing has revolutionized our approach to surgery and to the development of customised, biomimetic scaffolds for tissue engineering. A number of research groups are actively exploring the use of these 3D printed matrices as bone replacement scaffolds or as depot systems for delivering antimicrobial or chemotherapeutic agents to skeletal sites. The material that we have developed is relatively inexpensive and easily sourced. There is a long and successful history of bovine tissues being used in surgery, and the chemical processing used in preparing the decellularised matrix dramatically reduces the immunogenicity of the material. The combination of DECM with PCL, a material with a solid track record as a resorbable polymer, offers real potential as a solution for patients with significant bone loss. In contrast with existing 3D-printable composites made of ceramic and polymer, we expect that the use of a decellularised bovine matrix will provide tangible benefits in terms of early healing response by virtue of the residual bone-derived growth factors in the processed material.

    • The main goal of internal fixation is to maintain fracture stability to encourage bone union while maintaining a functional limb during healing. Therefore, successful fracture fixation results when the various loading forces acting on the fracture fragments are resisted by the mechanical stiffness of the bone-implant construct. Given the extreme forces horse patients can apply to fracture fixation devices, equine surgeons routinely work at mechanical limits of implants during the repair of adult long-bone fractures. Despite improved orthopedic equipment such as the LCP, providing a fixation with adequate strength to protect the fracture from the forces of weight-bearing throughout the healing period in equine fracture repair remains challenging. Taken together, this explains why open reduction and internal fixation in equine surgery is associated with poor survival rates and a high risk of catastrophic failure of the repair or cyclic fatigue failure of the implants.

      Larger and stronger implants for internal fixation can reduce the incidence of catastrophic implant failure. A stronger plate, the 5.5-mm broad LCP, was specially designed with an increased plate thickness for large animal fracture repair. This modification lead to a superior resistance to static overload and a 31% increase in cyclic fatigue of the 5.5 LCP compared to the 4.5 LCP. However, screw loosening and breakage remain a frequent complication in the clinical application of LCP in horses and occur in almost 20% of LCP stabilization. Screw breakage is influenced by the bending stiffness of the screw which can be evaluated by calculation of the area moment of inertia for the screw core diameter (area moment of inertia (I) = π r4/4). A small increase in the core diameter of a screw such as the introduction of a new locking screw with a 1-mm core diameter increase will have a large effect on its bending stiffness and have the potential to reduce the incidence of implant failure. The increased stability of a locking screw with a larger core diameter would be of significant clinical advantage for long bone fracture repair proximal to the third metacarpus/metatarsus which currently have a poorer prognosis, partly because of the decreased ability to supplement internal fixation with external coaptation. Generally, if greater bending loads are applied during a given cycle of loading, fewer cycles are needed to break the implant as a result of fatigue. Another interesting advantage of a screw with an increased bending stiffness worth noting is its expected decreased displacement under an applied load (deflection) improving fatigue resistance. The increased capability of resisting cyclic fatigue of a locking screw with a larger core diameter could improve fracture healing in all fracture repair allowing placement of 6.0-mm locking screws.

  •  


 

The main goal of internal fixation is maintaining fracture stability to encourage bone union while maintaining a functional limb during healing. Therefore, successful fracture fixation results when the various loading forces acting on the fracture fragments are resisted by the mechanical stiffness of the bone-implant construct. Given the extreme forces equine patients can apply to fracture fixation devices, surgeons routinely work at mechanical limits of implants during the repair of adult long-bone fractures. Despite improved orthopedic equipment such as the LCP, providing a fixation with adequate strength to protect the fracture from weight-bearing forces throughout the healing period, equine fracture repair remains challenging. Taken together, this explains why open reduction and internal fixation in equine surgery are associated with poor survival rates and a high risk of catastrophic failure of the repair or cyclic fatigue failure of the implants.

Larger and stronger implants for internal fixation can reduce the incidence of catastrophic implant failure. A more robust plate, the 5.5-mm broad LCP, was specially designed with an increased plate thickness for large animal fracture repair. This modification led to superior resistance to static overload and a 31% increase in cyclic fatigue of the 5.5 LCP compared to the 4.5 LCP. A larger cortical screw, the 5.5-mm large animal cortex screw, was also specially created for the large animal veterinary market. This modification in the core diameter led to an increased area moment of inertia (area moment of inertia (I) = π r4/4), leading to an improved bending stiffness of the 5.5-mm cortex screw compared to the 4.5-mm. Nevertheless, screw loosening and breakage remain a frequent complication in the clinical application of LCP in horses and occur in almost 20% of LCP stabilization. The 5.5 LCP and 5.5-mm cortical screw were designed with the same head-related features as the 4.5 LCP and 4.5-mm cortical screw, meaning they have the same Combi hole and screw head diameter, respectively. Hence, the relatively small area of pressure under the screw head in the 5.5 LCP Combi hole and the small head diameter of the 5.5-mm cortex screw could reduce the full potential of this construct by undermining its ability to limit stress rising around the screw heads and to produce plate-to-bone compression. The use of modified LCP to accommodate cortical screws with larger head diameters should improve biomechanical stress distribution around the screw heads and allow better plate-to-bone compression, and therefore have the potential to reduce the incidence of implant failure. Generally, when the stress is better distributed around the implants and bone, more cycles are needed to break the implant due to fatigue. In addition, the ability of a screw to generate a higher insertion torque could increase its ability to obtain a stable construct from decreased micromovements between the LCP and bone in the region of the plate occupied by cortical screws. The increased stability of an LCP construct for hybrid plating would be of significant clinical advantage for long bone fracture repair proximal to the third metacarpus/metatarsus, which currently has a poorer prognosis, partly because of the decreased ability to supplement internal fixation with external coaptation.

AO VET Seed grants

  • Principal Investigator:  Isabel Cristina Franzolini Silva, Sao Paulo State University (UNESP) - Faculty of Agricultural and Veterinary Sciences (FCAV), Brazil

    Translational research

    Abstract: 

    The humerus is one of the bones that constitute the appendicular skeleton of dogs and plays a primary role in movement of the thoracic limbs. It may undergo angular deformities or growth disturbances derived from genetic factors, malunion of fractures, nutritional deficiencies, or metabolic disorders, even when it is not the primary site affected. Its complex anatomy makes fracture reduction and stabilization, as well as the correction of angular deviations, challenging. For the correction of malalignment, it is necessary to measure it in different planes. In the transverse plane, torsional deviations can be visualized, which represent the axial alignment of the bone and are measured in degrees (°). Data on the magnitude and characteristics of physiological humeral torsion in dogs are scarce in the literature, and there are divergences among authors regarding the mean value of the humeral torsion angle. The present study aims to evaluate the magnitude and characteristics of humeral torsion (overall, proximal, diaphyseal, and distal humerus) in at least 20 normal dogs through the acquisition of computed tomography images, in order to establish anatomical reference parameters. A descriptive statistical analysis will be conducted, followed by linear association analysis, positional correlation analysis, and logistic regression analysis, with the objective of identifying possible correlations between the angles and the effects of controlled factors on the variability of humeral torsion angles. The level of significance adopted in the analyses will be 0.05.

  • Principal Investigator:  Morgan Steiner, Texas A&M Large Animal Hospital, United States

    Principal Investigator:  Morgan Steiner, Texas A&M Large Animal Hospital, United States

    Translational research

    Abstract: 

    Degeneration of the navicular bone (NB) and/or opposing deep digital flexor tendon (DDFT) are leading causes of performance-limiting lameness in the equine athlete without effective clinical treatments. Despite the high prevalence, the etiopathogenesis of navicular complex lesions is unclear and represents a critical gap for developing effective treatments. Knowledge of the development and maturation of the navicular complex is crucial for delineating the etiopathogenesis of navicular disease. Therefore, this research will investigate NB mineralization and establish the timelines of development and maturation of the fibrocartilage at NB-DDFT "functional" enthesis, and DDFT-P3 enthesis during gestational and post-gestational stages, as well as in juvenile and mature horses. Mineralization and modeling of the NB and P3 flexor surface will be determined using quantitative micro-computed tomography. Confocal second harmonic generation (SHG) microscopy and quantitative Toluidine Blue and Safranin-O-Fast-Green histology will evaluate navicular complex fibrocartilage development and maturation. From a clinical standpoint, concurrent lesions at these sites of structural specialization are not only common but are also associated with poor prognosis and validates our approach to investigate the development and maturation of the navicular complex as a whole. This research will lay a strong foundation for our overarching goal to determine the mechanical factors implicated in "functional" enthesis and tendon-to-bone enthesis injuries, and aid in developing targeted strategies to enhance tendon-fibrocartilage-bone interfacial tissue healing, including equine deep digital flexor, human Achilles and rotator cuff tendon complexes.

  • Principal Investigator:  Kati Glass, Texas A&M College of Veterinary Medicine & Biomedical Sciences, United States

    Clinical research

    Abstract: 

    Conventional cortical screws (BTS) have a buttress thread design that withstands unidirectional axial loading with less resistance to multiaxial forces. The bone-screw-fastener (BSF) has an interlocking thread geometry that resists multiaxial loading and provides improves maximum compression. The thin cortex in the region of common equine proximal phalanx (P1) fractures is prone to stripping and failure to radiographically resolve after stabilization with BTS. Improved implants that can withstand the multidirectional loading while allowing improved interfragmentary compression and reduced screw stripping is a clinical priority for equine fracture repair. This project will test the hypothesis that uniarticular P1 fractures repaired with 4.8mm BSF will have improved interfragmentary compression, sustain more cycles to failure, and sustain higher load at failure compared to those repaired with 4.5mm BTS. Sixteen pairs of P1s acquired postmortem from adult horses of any sex aged 5-20 years of age, euthanized for reasons unrelated to pathology of the metacarpo/metatarsophalangeal joint or P1 will be harvested, stripped of soft tissues, and stored frozen in saline-soaked towels until testing. A simulated uniarticular fracture will be repaired using three, 4.8mm BSF or three, 4.5mm BTS in standard triangular fashion to determine: (1) Interfragmentary compression generated during screw tightening (2a) Cyclical axial load, number of cycles to yield, and the fracture gap at yield, and (2b) Load to ultimate failure in axial compression. The BSF group is expected to achieve greater interfragmentary compression, withstand more cycles prior to failure, and achieve higher axial load at failure compared to BTS.

  • Principal Investigator:  Andres Bonilla,  Colorado State University, United States

    Clinical research

    Abstract: 

    Fractures of the distal phalanx (P3) are a common cause of lameness in horses and may require CT-guided internal fixation when articular involvement is present. Current CT-guided techniques rely on iterative radiopaque marker placement and repeated scans, increasing procedure time, radiation exposure, and technical variability. A more structured and reproducible method is needed. This project evaluates a novel grid-based CT trajectory planning system designed to define screw paths using coordinate-based planning after a single CT acquisition. In a randomized cadaveric study, sixteen equine distal limbs with standardized parasagittal P3 fractures will undergo fixation using either conventional marker-based planning or the grid-based technique. Outcomes will include procedure time, number of CT scans, radiation exposure, and screw trajectory accuracy assessed by postoperative CT. We expect the grid-based method to reduce imaging requirements, decrease radiation exposure, and improve precision while remaining compatible with standard instrumentation and widely available CT systems. The long-term goal is to establish a standardized, efficient CT-guided planning workflow that improves safety, reproducibility, and surgical education, with translational relevance for both veterinary and human fracture fixation.

  • Principal Investigator:  Clair Park,  Virginia Maryland College of Veterinary Medicine, United States

    Clinical research

    Abstract: 

    Mini total hip replacement (THR) has expanded hip arthroplasty to small dogs and cats; however, limited morphologic reference data and narrow implant size margins make surgical planning challenging in this population. Most available data are derived from medium- to large-breed dogs and may not be applicable to smaller patients. This prospective clinical study will enroll small dogs undergoing mini THR to characterize computed tomography (CT) “derived femoral morphology and evaluate its relationship to implant positioning, functional recovery, and complication risk. All subjects will undergo preoperative and immediate postoperative CT imaging, with a subset evaluated at 6 months, and outcomes will be assessed through orthopedic examination and validated owner-reported measures over 12 months. Morphologic parameters will be described and compared to existing standard THR data, and exploratory analyses will identify imaging and implant-related factors associated with outcomes. This study is highly relevant to improving surgical precision in mini THR, where small deviations in implant size or positioning may have clinically meaningful consequences. Expected outcomes include establishment of foundational morphologic reference data and identification of candidate risk factors for future studies. The long-term goal is to develop evidence-based, patient-specific planning strategies that improve outcomes and inform standards of care in small animal joint replacement.

  • Principal Investigator:  Shannon Connard,  Cornell University, United States

    Translational research

    Abstract: 

    Adhesion formation within the equine digital flexor tendon sheath (DFTS) is a major complication of septic tenosynovitis and tendon injury, leading to impaired tendon gliding, persistent lameness, and poor performance outcomes. Fibrin deposition and inadequate fibrinolysis are key drivers of adhesion development, yet targeted fibrinolytic therapies for this condition remain limited. Tenecteplase, a modified tissue plasminogen activator with increased fibrin specificity and stability, represents a promising therapeutic candidate but has not been evaluated in equine tendon sheath “relevant systems. The objective of this study is to evaluate the in vitro safety of tenecteplase in equine tendon sheath “derived cells and establish a model to evaluate the fibrinolytic potential in synovial fluid. In Aim 1, primary equine synovial fibroblasts and tenocytes will be exposed to a range of tenecteplase concentrations, with cytotoxicity assessed at multiple timepoints. In Aim 2, a fibrin clot formation and lysis assay in a synovial fluid matrix will be developed using a turbidimetric microplate method, adapted from established plasma fibrinolysis assays. Tenecteplase will be evaluated across a clinically relevant concentration range to confirm measurable fibrinolytic activity. Tenecteplase is expected to demonstrate minimal cytotoxicity and measurable fibrinolytic activity under physiologically relevant conditions. This work will establish a reproducible in vitro platform to support future dose “response and comparative studies of fibrinolytic therapies within a synovial fluid environment. The long-term goal is to optimize safe and effective fibrinolytic therapies to prevent adhesion formation and improve clinical outcomes in horses with DFTS disease. Data generated from this study will support future in vivo investigations and comparative studies evaluating tenecteplase in comparison to other fibrinolytic agents.

  • Principal Investigator:  Marie Llido, University of Montreal, Canada

    Clinical research

    Abstract: 

    "Common calcaneal tendon (CCT) injury is a frustrating condition, with significant existing gap in knowledges available in veterinary medicine for its treatment. Several suturing patterns have been described but with inconsistent results. Failure results in gap formation and inadequate function. Several locations of rupture have been described (1) “ avulsion at the level of the calcaneum, sharp traumatism in the tendinous portion or myotendinous junction rupture. The latter is particularly challenging due to the lack of robust structure proximally to anchor sutures. The aims of this cadaveric study are to: 1. Â Â Â Â Assess the feasibility on canine cadavers of a new surgical technique bridging the myotendinous junction rupture, with a synthetic tendon implant suture at the distal tendon portion and attached proximally at the level of the distal femur with a bone tunnel and interference screw to mimic the insertion of the gastrocnemius muscle and restore functional biomechanic. Each separate component of this surgical technique has been previously validated with rigorous and controlled biomechanical testing in another clinical application.(2) 2. Â Â Â Â Compare this new surgical technique for myotendinous junction rupture of canine CCT to a standard suture augmented with a synthetic implant suture to the muscle and tendon. The same dog will be used with a different repair on each side, therefore being his own control. We aim to test resistance to tensile loading and ultimate load to failure for both repairs. We hypothesized that this new technique will be feasible, and anchorage of the implant at the level of the distal femur will be more resistant to tension than standard repair. The objective of this study is to provide preliminary results and biomechanical data about surgical repair for myotendinous junction repair. This study aims to be the milestone of future development of implants specific to this condition to provide better therapeutic options for canine patients."

  • Principal Investigator:  Laura Arnaldi,  AniCura Tierklinik Thun, Switzerland

    Translational research

    Abstract: 

    Background/Significance.  Surgeons use several methods to create interfragmentary compression in TPLO, and some additionally place a lag screw; yet no head-to-head evidence shows when a lag screw improves the pressure field along the curvilinear osteotomy. This project delivers the first standardized pressure-mapping comparison of three practical lag screw strategies versus a no-lag control using 3D-printed guides and a single TPLO plate.

    Aims and approach.  (1) Test whether adding a lag screw yields a more uniform, centered pressure field than no-lag; (2) identify which application "Perpendicular (90°) lag screw (arc-normal), lag screw via plate, or oblique cranial-biased lag screw (~15°)" performs best; (3) produce a replicable SOP for intra-operative compression targeting. We will use a prospective, randomized bench design with prespecified endpoints and blinded analysis.

    Relevance.  Results are intended to inform everyday TPLO technique without changing implants.

    Materials and methods.  Standardized synthetic tibiae stabilized with a 3.5-mm locking TPLO plate across four arms: A no-lag control; B Perpendicular (90°) lag screw (arc-normal); C lag screw via plate; D oblique cranial-biased lag screw (~15°). Interfragmentary pressure will be recorded with pressure-sensitive film and analyzed centrally. Primary endpoint: Uniformity Index (coefficient of variation across four quadrants). Coprimary: cranial-caudal balance, pressure-centroid offset, global compression integral. Planned sample: n=12 per arm (48 constructs). Duration: 12 months.

    Expected results.  Lag screw via plate and oblique cranial-biased lag screw are expected to reduce the Uniformity Index by ≥10 CV points versus no-lag and improve centering/balance without focal over-compression.

    Long-term goal.  Establish an evidence-based, widely adoptable SOP for uniform, centered TPLO compression and provide the foundation for cadaveric and clinical validation.

  • Principal Investigator: Mana Okudaira, Auburn University, United States

    Clinical research

    Abstract: 

    Proximal sesamoid bone (PSB) fracture is the most common cause of fatal fetlock injury in Thoroughbred racehorses worldwide. Midbody PSB fractures result from chronic repetitive stress that often manifest as acute catastrophic injuries. Understanding the mechanobiology of PSB fractures is inherently complicated given the extensive range of motion of the fetlock joint and the numerous ligamentous attachments that collectively apply forces circumferentially on the PSB. Entheses are a type of specialized tissue that optimize force transmission and dissipation of stress at the junction of two differing materials (i.e. bone and ligament). Therefore, the forces that the PSBs encounter are directly related to their entheses. Morphologic changes to the entheses in response to chronic repetitive stress have been described in the context of enthesopathy.

    The relationship between enthesopathy and PSB fracture has not yet been investigated. The conceptualization of the PSB as part of an enthesis organ has not been previously described and provides a novel context of understanding PSB fracture etiopathogenesis.

    The objective of this study is to characterize equine PSB entheses in non-fractured control and fractured horses using high field (7T) magnetic resonance imaging and histologic analysis. We hypothesize that horses with unilateral biaxial/uniaxial PSB fracture will have bilateral evidence of enthesopathy that is more severe than in control horses, and that fracture limbs (FX-PSBs) will have more severe changes than contralateral limbs (FX-CL PSBs). Knowledge gained from this study is intended to improve our understanding of PSB fracture pathophysiology and enhance PSB fracture risk assessment to mitigate the risk of catastrophic fetlock injury in Thoroughbred racehorses. 

  •  


 

Principal Investigator: Anja Knudsen Ghent University Belgium

Translational research

Abstract:

Background: Osteosynthesis of equine third metacarpal (MCIII) fractures and fetlock arthrodesis are commonly performed using orthopaedic plates and screws inserted into MCIII. During the application of internal fixation, screw re-insertion into the same drill hole may occur. Studies in human bone have found that repeated reinsertion of screws results in a reduction in pull-out strength, but to the authors knowledge equine bone has not yet been investigated. This study aims to determine whether repeated reinsertion of cortical screws leads to a reduction in pull-out strength in adult equine diaphyseal MCIII, with the goal of informing equine surgeons on optimal surgical techniques for the treatment of conditions requiring screw insertion into the MCIII. 

Method: 24 adult equine cadaver MCIII's will be sectioned into three equal pieces, creating 72 bone segments which will be equally divided between three groups (n=24/group). A unicortical hole will then be drilled and tapped transversely across the diaphysis at the midpoint of each bone segment. A 4.5-mm cortical screw will be inserted into each drill hole with a torque of 6Nm. In Group 1, no further manipulation will be performed. In group 2, the screw will be removed and reinserted once. In Group 3, the screw will be removed and reinserted five times. Pull out strengths will then be tested using a load cell and the results compared between groups. 

Expected results and relevance: Preliminary data suggests there could be potential reduction in pull out strength in Group 3 compared to Groups 1 and 2. If the expected results are found, it may suggest increased likelihood of implant failure if screws are reinserted multiple times into the same drill hole. Therefore care should be taken to avoid repeated screw reintroduction during procedures requiring screw insertion into the equine MCIII. However, one screw reinsertion could be performed safely without causing a significant reduction in pull out strength. 

 

Principal Investigator: Sabrina Tan, College of Veterinary Medicine, Murdoch University, Australia

Clinical research

Abstract:

Introduction: A plated construct’s stiffness and strength are affected by the intrinsic properties of the plate material, the structural features of the plate, plate-bone ratio, plate size, plate-bone distance, working length, screw number configuration. If these factors are kept constant in different limb segment lengths, the moment arm and bending moment varies with the same applied force. The biomechanical impact in construct stiffness and strength by larger bending moment in longer limb segment is lacking. The primary aim of this research is to determine the effect of limb segment length on construct stiffness and strength in a diaphyseal fracture gap model stabilized with a 3.5mm locking compression plate with a consistent plate working length and screw number configuration. The second aim is to determine the effect of plate-bone ratio on construct stiffness and strength in long limb segments.

Material and methods: Synthetic fracture gap models made of Delrin tubes sectioned for long and short limb segments with a 10mm fracture gap. Models are stabilized by 16-hole and 8-hole 3.5mm LCP for long and short limb segments respectively, maintaining 80% plate-bone ratio. Long limb segment will be stabilized by 8-hole LCP separately. All constructs assembled using standard AO technique with 3 bicortical locking screws per segment, 3mm plate standoff distance and same working length. All constructs will be tested under non-destructive and destructive axial compression. Each construct will be ramp loaded for three cycles and axial stiffness will be determined from the slope of the linear elastic portion of the load displacement curve in n/mm. Load and actuator placement measurements from the 3rd cycle will be used. Load to failure (N) will be recorded as the maximum load prior to permanent plastic deformation. Six replicates of each limb segment for a total of 18 constructs will be tested.

Expected results: Longer limb segments with larger bending moment will have lower construct stiffness and strength in axial compression. Longer plate-bone ratio increases construct stiffness and strength in long limb segments.

Relevance: Tibial length varies between small animals of the same animal weight. A 30 kg Greyhound will have a significantly longer tibial length as compared to a 30 kg Staffordshire Bull Terrier. The same size plate of different length will be used clinically to achieve 80% plate-bone ratio in a bridging fashion for a comminuted fracture in animals of the same weight and tibial width but different tibial length. Determination of the effect of limb segment length on construct stiffness and strength in a synthetic fracture gap model aim to show that long limb segments have more challenging biomechanics and are more prone to construct failure. This may guide construct selection for the treatment of complex fracture in small animals. 

Principal Investigator: Andres Bonilla, Colorado State University, United States

Translational research

Abstract:

This project aims to evaluate the feasibility of using O-arm imaging combined with surgical navigation for performing cervical foraminotomies in horses with cervical nerve root compression due to intervertebral foramen stenosis. This condition causes pain, stiffness, and lameness, and while conservative treatments offer temporary relief, they don't address the underlying mechanical compression.

The study will assess the accuracy, workflow, and potential complications of this technology in equine cadavers. We hypothesize that O-arm-assisted navigation will enable precise IVF decompression with minimal risk to adjacent neurovascular structures. The expected results will demonstrate improved surgical accuracy, reduced intraoperative complications, and more effective decompression. This approach has the potential to enhance clinical outcomes for affected horses, improve surgical capabilities in equine orthopedics, and make this treatment more accessible to equine surgeons worldwide.

Principal Investigator: Elena Lozano Onrubia, Langford Vets Small Animal Referral Hospital,United Kingdom

Clinical research

Abstract:

The aim of this study is to test two types of commercially available screws used for the stabilisation of humeral intracondylar fissures:

  1. 4.5mm cortical screws
  2. Self-compressing headless screws (Humeral Intracondylar Repair System—HIRS).

We aim to test ultimate load to failure and resistance to cyclical loading for both implant types. We will also compare the compression generated by the two implant types. The cortical screw will be applied as a lag screw.

Investigators: Norihiro Muroi / Po-Yen Chou, University of California, Davis, USA

Objective:

We aim to develop a method to reliably measure the combined version angle in dogs using CT scan images and computer-aided design (CAD) software and to explore the relationship between the standing angle and the combined anteversion angle of the hip joint in dogs.

Study Design:

Aim 1: Methods for measuring combined version angle in dogs
CT scans of dogs presented to our institution between 2019 and 2023 will be retrospectively reviewed. Six mid to large-breed dogs with complete CT scans of the pelvis and pelvic limbs and no radiographic evidence of osteoarthritis and orthopedic disease will be selected. Morphometric measurements of the acetabulum and proximal femoral will be performed. After determining the dorsal, median, and transverse of the pelvis and acetabular orientation planes, the angle of lateral opening (ALO), version angle, and inclination angle will be calculated. The version angle of the femoral neck is measured as the angle between the axis of the femoral neck and the axis of the distal femoral condyle. The inclination angle of the femoral neck is measured as the angle between the femoral neck axis and the proximal femoral anatomical axis. The combined version angle will be calculated using two different methods. The reliability and repeatability of each method will be compared.

Aim 2: Measurement of combined anteversion angle and its correlation with standing hip extension angle
The study will include dogs presented to our institution for reasons unrelated to orthopedic disease. To be eligible for the study, the dogs would be between 2 and 6 years of age and free of clinical symptoms associated with pelvic limbs and joints. We will take CT scans and standing photographs of the 12 dogs. Measurements in CT images will be performed using the same methods as in (Aim 1). The standing hip extending angle will be determined by measuring the lateral view photograph of the dogs, and the correlation between the standing angle and the combined version angle will be determined.

Investigators: Holly Stewart / David Levine / Jose Garcia-Lopez / Kyla Ortved / Kate Bills / Mathieu Spriet, University of Pennsylvania, School of Veterinary Medicine, USA

Orthopedic infections are a serious complication that may result in extensive morbidity and even mortality in the horse. Surgical site infections (SSI) are the most common type of orthopedic infection and have been identified in 32%-80% of equine distal limb fracture repair and arthrodesis with orthopedic plates. Early and precise diagnosis of infection are critical aspects for appropriate case management and therapeutic interventions. Surgical site infections are often diagnosed by a combination of clinical assessment, evaluation of hematologic parameters, and imaging. Radiography is often used as a first-line diagnostic modality but lacks sensitivity.

Positron emission tomography (PET) has recently become available for imaging in the standing horse and has numerous potential applications, including in the identification of sepsis. Commonly utilized radiotracers, including 18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) can be used for the assessment of soft tissue infection, osteomyelitis, and bone remodeling associated with sepsis.

The objective of this exploratory pilot study is to use PET imaging to follow a cohort of horses at high risk of developing infections secondary to orthopedic procedures. A total of 2 client-owned horses will be evaluated in this study. Enrolled horses will undergo dual-radiotracer PET imaging within 5 days of metacarpophalangeal or metatarsophalangeal (fetlock) arthrodesis. Enrolled horses will undergo a second dual-radiotracer PET imaging at 10-14 days post-operatively, around the time when SSIs are most observed.

Fetlock arthrodesis procedures have an extremely high rate of SSIs, in part due to the open surgical approach and catastrophic events preceding injury. Changes in PET imaging can be compared to other imaging modalities and the clinical progress of the patient to assess changes that occur with normal healing and orthopedic infections. The overarching goal of this pilot study is to investigate the clinical utility of PET and its potential role for the early diagnosis of orthopedic infections to help improve patient outcomes.

Investigators: Zuzanna Graczyk / Annette McCoy / Mariana Kersh, University of Illinois Urbana-Champaign, USA

Fractures involving the distal condyles of the third metacarpal bone (MC3) represent a common orthopaedic challenge, and public welfare concern, in equine sports medicine and surgery. There are notable differences between medial and lateral condylar fractures when considering frequency, configuration, and outcome. We hypothesize that in juvenile horses, the medial and lateral condyles of the third metacarpal bone (MC3) exhibit significant differences in their inherent bone properties (e.g., mechanical properties, tissue density, microstructure) and that age-related variations and differential developmental patterns in these locations could impact the bone's load-bearing capacity, which in turn could influence the likelihood and nature of future fractures.

Utilizing 18 cadaveric equine forelimbs from foals <1 year of age euthanized for medical reasons unrelated to infectious orthopedic disease, we will assess bone properties in the medial and lateral condyle of the MC3 and how they change as the animal matures. In Specific Aim 1, we will determine variations in trabecular bone density and microstructure of the medial and lateral MC3 condyles during the first year of life using clinical and micro-computed tomography. In Specific Aim 2, we will correlate bone properties of the medial and lateral MC3 condyles with mechanical characteristics of bone cores from those regions.

By establishing the impact of structural properties on bone strength in juvenile bone, we will be able to advance the understanding of equine bone development and better understand the etiology of condylar fractures, offering insights that could lead to the development of targeted strategies for reducing the incidence of such injuries in racehorses.

Investigators: Sebastian Cardona-Ramirez / Wilson Cardona Galeano / Andres Yepes-Perez, Universidad de Antioquia, Colombia

Osteosarcoma (OS) represents 85% of all skeletal tumors in dogs, making it the most prevalent bone tumor in this species causing aggressive tumors with high grade of metastases (micrometastasis occur in over 90 % of dogs). As a result of this, its treatment is a challenge for the veterinary practitioner. For this reason, it is necessary to increase in a significant way the research on this matter to avoid all the consequences associated to this pathology and the median survival of animals. Considering the current limitations of chemotherapy associated to high grades of toxicity and resistance, the use of chemoprevention has emerged as an important strategy in the search for new therapeutic alternatives against different diseases, including cancer, to reduce morbidity and mortality associated either to the symptoms of the malignancy or the treatment itself.

As an alternative that supports the use of chemoprevention, molecular hybridization (MH) has emerged as a promising strategy. MH chemically fuses two or more structural domains (pharmacophores) that may display a dual biological function, not necessarily acting on the same target, with the idea of finding a better candidate that could be useful to solve the current limitations associated with conventional chemotherapy. Thereon, melatonin, an endogenous neurohormone produced by the pineal gland, has recently received great attention due to its potential against malignant diseases such as cancer, using in vitro and in vivo models. Considering the reported findings about the potential of this compound, we propose this could be an important candidate to design hybrid molecules based on its structure to explore new alternatives for the treatment of osteosarcoma. For that reason, we have previously synthesized and evaluated the potential of different hybrids based on chalcone and melatonin, finding one compound with remarkable cytotoxicity and selectivity over colorectal cancer cells (named CM6f in this proposal).

In this research we propose to evaluate the previous reported hybrid CM6f over OS cells to determine its potential to decrease cell viability and to induce apoptosis. The objective of this proposal is to evaluate the cytotoxic and proapoptotic activity of the CM6f hybrid over OS cell line OSCA-32. Additionally, we aimed to compare the effect of the CM6f hybrid to the effect of Cisplatin on OS cells. We hypothesize that the synthetic hybrid CM6f based on chalcone, and melatonin may significantly decrease cell viability and increase apoptosis of osteosarcoma cells.

Investigators: Pavel Slunsky / Diana Joos, AniCura Kleintierspezialisten Augsburg, Germany

A cornerstone of internal fracture fixation involves the utilization of bone plates and screws. Regarding screw insertion, both non-self-tapping (NSTS) and self-tapping screws (STS) are available options. With NSTS, a thread must be cut into the drilled bone prior to screw insertion, whereas STS features a cutting flute on the tip, enabling screw insertion without the need for thread cutting using a tap. Consequently, STS insertion requires fewer tools and is executed more swiftly. According to Gonzalez et al., using STS could reduce hardware application time by one-third compared to NSTS employment.

Therefore, employing STS leads to decreased operative costs, decreased anesthesia time, and a reduced risk of surgical wound infections. The holding power of a bone screw is defined as the maximum uniaxial tensile force required to cause failure in either the bone or the screw itself. This power is assessed by applying an uniaxial force to a screw inserted into bone or a synthetic substitute and measuring the peak tensile force required for screw pull-out. In STS, the presence of cutting flutes reduces the overall surface area of the bone-screw interface, thereby diminishing pull-out strength by 10-30% if the cutting flutes remain in the far cortex. Presently, it is recommended to advance STS 2 mm beyond the far cortex to achieve screw-holding powers comparable to NSTS. Conversely, protruding cutting flutes could potentially interfere with adjacent tendon gliding, cause damage to neurovascular structures, impinge upon soft tissues, and ultimately result in pain. In conventional bone plating with cortical screws, the screws are axially preloaded to generate compression between bone and plate. This compression should create adequate friction to transfer loads acting orthogonal to the screw axis.

In plate fixation, screws are not meant to endure significant bending loads to avoid shear failure. Thus, the holding power of cortical screws can be evaluated through screw pull-out tests. The objective of this study is to determine whether the depth of insertion through the far cortex of STS cortical screws of varying diameters significantly influences pull-out strength in synthetic bones and feline cadaveric bones. Additionally, it aims to ascertain if inserting STS an additional 2 mm past the far cortex offers biomechanical advantages. To the best of our knowledge, the holding power of these screws in feline bone has not been previously reported.

Investigators: Davide Mancusi / Lisa Adele Piras / Bruno Peirone

Total hip replacement (THR) is a well-established procedure for the treatment of disabling disorders of the coxofemoral joint such as canine hip dysplasia, traumatic coxofemoral luxation, femoral head and neck fractures and failed femoral head and neck ostectomy. THR involves the surgical replacement of the femoral head, neck and acetabulum with implants consisting of a cup, a head and neck unit and a femoral stem. One of the most challenging aspects of THR is accurate positioning of the acetabular component. The Zurich Cementless THR (ZC-THR, Kyon, Zurich, Switzerland) was developed at the University of Zurich in the late 1990s. The Zurich THR uses a locking screw implantation system for application of the femoral component (stem) while the acetabular component (cup) uses an initial press-fit stabilization followed by long-term stabilization via bone ingrowth through a porous design of the cup. In Human Medicine, the orthopaedic surgeon can make use of computer-assisted navigation systems that significantly improve consistency of acetabular cup placement over freehand placement. Unfortunately this advanced technology is not available in Veterinary Medicine due to the excessive costs. As a consequence, the easiness of use and the reliability of the surgical instrumentation (impactors) provided by the companies that produce the implants and the experience of the surgeon are the main factor influencing cup positioning in Veterinary Medicine. The comparison of two different types of impactor could aid the veterinary surgeon in a more accurate cup positioning decreasing the possible complication related to cup incorrect orientation. The objective of this study will be to find the best cup impactor (Impactor 1 Vs Impactor 2) that could allow an easier and more accurate cup positioning also for novice unexperienced THR surgeons. The first part of this project will be a cadaveric study (n=20). Two different impactors will be used by two surgeons with different level of THR surgery experience, for a total of at least 10 cups for each of the four resulting study groups. After implantation two orthogonal radiographic projections of the pelvis (VD, LL) will be obtained. ALO and cup retroversion values will be measured and compared between groups.

Investigators: Angela Gaesser / Renata Linardi / Kyla Ortved

The objective of this proposal is to determine if extracellular vesicles (EVs) isolated from equine bone marrow-derived mesenchymal stem cells (BM-MSCs) have chondroprotective properties, and if those isolated from BM-MSCs expanded in media supplemented with equine serum (ES) have different characteristics and function than those expanded in fetal bovine serum (FBS) supplemented media. Mesenchymal stem cells (MSCs) can modulate the local tissue response and stimulate healing, and equine BM-MSCs have been shown to have immunomodulatory properties. It has been suggested that the robust bioactive properties of MSCs are in large part due to the production of EVs, which are small membrane-enclosed vesicles released by the parent cell into the extracellular environment. EVs contain complex biologic cargo, including proteins, lipids, and nucleic acids, and are extensively involved in cell-to-cell signaling. The potential use of MSC-derived EVs (MSC-EVs) to modulate inflammation in posttraumatic osteoarthritis (PTOA) has garnered significant interest recently. There are currently no effective treatments for PTOA in the horse, despite the disease’s high morbidity and mortality rates. The ability of MSC-derived EVs to regulate inflammation within the joint has been reported in human and murine models. For MSC-EV harvest, MSCs are typically culture expanded in FBS supplemented media until confluent. Then, a 48-hour serum starvation period is instituted to prevent contamination of the sample with bovine EVs, followed by the collection of the cell culture supernatant and isolation of EVs. However, this serum starvation period can cause cell stress, altering the population of EVs released. We propose using commercially available ES for the expansion of BM-MSCs to circumvent the serum starvation period. We hypothesize that MSC-EVs will have chondroprotective properties and that those isolated from BM-MSCs cultured in ES will have superior chondroprotective abilities. These hypotheses will be tested using two specific aims:

Aim 1: To determine if EVs from BM-MSCs cultured in FBS or equine serum are chondroprotective using an ex vivo cartilage explant model.

Aim 2: To determine if EVs from BM-MSCs cultured in equine serum without a serum starvation period have different characteristics than those cultured in FBS with a serum starvation period before EV harvest.

Investigators: Elizabeth Bester / Adriaan Kitshoff

Cranial cruciate ligament (CrCL) disease is the most common orthopaedic condition of the stifle joint in dogs (Pacchiana et al., 2003). Cranial cruciate ligament rupture is considered a major cause of degenerative joint disease of the stifle joint (Paatsama, 1952; Marshall, 1971). Tibial plateau leveling osteotomy (TPLO) is a surgical treatment that dynamically stabilizes the cranial cruciate ligament deficient stifle (Pacchiana et al., 2003; Paatsama, 1952; Marshall, 1971; Priddy et al., 2003; Reif et al., 2002).

Reported complication rates after TPLO range from 18-28%. Patellar ligament thickening has been observed anecdotally following TPLO, however there is limited documentation of the reasons for this thickening (Pacchiana et al., 2003). A radiographic study demonstrated thickening of the distal portion of the patella ligament following TPLO surgery, concluding patella desmitis as a possible complication of TPLO (Mattern et al., 2006).

Stifle arthrotomy versus arthroscopy has also been investigated to explain patellar ligament thickening following TPLO surgery. The study found that arthroscopy was associated with an increased the patellar ligament thickness compared to medial arthrotomy (Owen et al., 2018).
There has been numerous proposed mechanisms for the patellar ligament thickening seen post TPLO surgery some are increase patellar strain, vascular damage, intra-operative trauma to the ligament or altered biomechanics of the stifle (Gallagher et al, 2012; Owen et al., 2018).

Current research has focused on alterations of the biokinematics of the patellofemoral and femorotibial joint of a CrCL deficient stifle as a possible cause for the patellar desmopathies associated with TPLO surgery in dogs (Warzee et al., 2011). An ex vivo cadaveric study reported no significant changes in the stifle extensor mechanism load following a TPLO (Drew et al. 2018). However, some major limitations to this study was that it was performed without transection of the cranial cruciate ligament and that the load in the whole extensor mechanism was tested rather than focusing on the strain in the patella ligament (Drew et al. 2018). To the authors knowledge there has been no investigation into the alterations in strain directly in the patella ligament following TPLO surgery as a possible explanation for the patellar desmopathies often associated with this surgical technique.

Our assumption is that an increase in the strain in the patellar ligament will be associated with an increased in rotation of the tibial plateau (post TPLO) and subsequent reduction in tibial plateau angle.

Investigators: James Crowley / Patrick Kenny

The current veterinary literature supports prophylactic fenestration as a safe way to reduce future disc herniation at fenestrated sites. The efficacy of prophylactic disc fenestration to prevent future herniation at non-affected disc spaces remains controversial. Published studies suggest that fenestration reduces the recurrence rate of IVDE, and surgeons should particularly consider fenestration of calcified discs. Additionally, the reported incidence of side effects from fenestration is 0.2% across the pooled studies (>1100 procedures) (Moore, Tipold et al. 2020). However, high quality evidence in support of this is not available and it is not known how many sites should be fenestrated to achieve the best outcome, nor is it known what the effect of fenestration on development of IVDE in adjacent non-fenestrated sites of substantial consequence is (ex. L4-5 in the patient fenestrated from T11-L4). Further, a common surgical technique employed in practice is to fenestrate the affected and immediately adjacent disc spaces because they are readily accessible from the surgical approach. We do not currently have information on the benefit of this approach vs single site fenestration. This study aims to answer this question.

To the best of the author’s knowledge, this will be the first study to prospectively evaluate the effect of prophylactic fenestration of adjacent disc spaces to a site of extrusion. The findings of this study will benefit veterinary surgeons and neurologists by providing clinically relevant data to better inform clinical decision making.

Previous studies such as Longo et al (2020) have documented the increased risk of recurrence of completely degenerate IVD. No study has prospectively evaluated the prophylactic effect of single site vs adjacent site IVD fenestration on recurrence of IVDE and/or associated clinical signs, the latter based on the degenerate CT/MRI appearance on preoperative imaging. Additionally, the pre-operative appearance of IVDs has been demonstrated to change with time. There is a need to correlate pre-operative IVD appearance on diagnostic imaging modalities with the degree of degeneration/mineralisation/calcification.

Investigators: Daniel Lomas / Nicolas Barthelemy

Total hip replacement (THR) is a salvage procedure that is increasingly being performed in the cat for the management of conditions of the hip joint including osteoarthritis, traumatic fractures, or slipped capital femoral epiphysis. Although femoral head and neck excision (FHNE) is an established treatment in cats with coxofemoral disease, long term outcome can be unpredictable with a small case series demonstrating inferior outcomes after FHNE compared to THR (Liska et al; 2009). As a result, THR is gaining increased popularity in cats. A recent large cohort study of cats undergoing THR demonstrated a low overall complication rate and high owner satisfaction (Rodino Tilve et al; 2022).

Currently cemented and cementless systems are available for small animal patients. Cemented systems use PMMA for fixation and long-term stability, and cementless systems relying on osteointegration. Cementless systems are becoming increasingly popular in canine THR due to reduced surgical time, increased ability to adjust implant positioning and reduced risk of long-term complications such as aseptic loosening. Hybrid THR, which combines cemented and cementless systems, has recently been demonstrated to have lower long-term complication rates in medium and large breed dogs compared to cemented and cementless systems (Allaith et al; 2023). Until recently smaller acetabular and femoral implants, appropriate for patients under approximately 15kg have been exclusively cemented. The aim of this study is to describe the use of hybrid THR in cats with coxofemoral conditions, using a CFX Biomedtrix femoral stem in combination with a micro BFX acetabular cup consisting of a UHMWPE liner and titanium electron beam melting porous outer casing. The study will compare complication rates and owner-reported outcomes to cemented feline THR performed at the same institute. This will represent the first description of the technique and outcomes of hybrid THR in cats with potential implications for improving outcomes and quality of life for feline patients with coxofemoral conditions.

There is a need for improved, non-invasive products that can fixate canine mandibular fractures and promote osteosynthesis. Dogs sustaining facial fractures commonly suffer fractures to the mandible (~90%). These jaw fractures typically (~50%) involve the major chewing tooth (mandibular first molar). The large size of this tooth creates an area of weakness that is prone to fracture. Mandibular fracture repair can be particularly challenging in the caudal mandible of dogs. Muscular attachments and neurovascular structures in the caudal mandible complicate surgical exposure compared to rostral fracture repair.

Repairing these fractures are typically approached by either open reduction and rigid internal fixation, or through non-invasive repair techniques where stabilization is applied in the oral cavity. Anatomic structures such as tooth roots and the inferior alveolar neurovascular bundle severely limit locations where pilot screw holes can be created for conventional plate fixation. Noninvasive fracture repair techniques minimize surgical exposure of the fracture site and minimize risk for damaging or disrupting anatomic structures such as tooth roots or vessels. Intraoral repair techniques that spare the health of neighboring teeth include placing wires around teeth (interdental wiring) and the application of composite splints bonded to the tooth crowns. Whilst this may generate enough stabilization to promote healing, it is not as rigid as bone plating techniques and TN may provide additional stabilization for noninvasive fracture repair. Thus far, TN has demonstrated increased load to failure in transverse, osteotomized mandibles. Characterization and quantification of TN’s contribution to composite splint stabilization in spontaneously created fractures will help guide clinical repair recommendations.

Osteoarthritis (OA), a chronic degenerative joint disease characterized by cartilage breakdown, subchondral bone remodeling and synovial inflammation, is the most common musculoskeletal disorder in humans as well as in horses and among the most important causes of pain, disability and health related economic loss. Secondary to a variety of etiologic factors such as mechanical injury, genetics, ageing, gender and obesity, a common molecular pathway linking biochemical and biomechanical processes leads to the typical pathological progression of OA with an imbalance of cartilage matrix synthesis and degradation and a vicious positive feedback loop involving cartilage breakdown and synovial inflammation. All tissues within a joint (cartilage, synovial membrane, subchondral bone and potential auxiliary structures like meniscus) contribute to and simultaneously are affected by the disease process. They release pro-inflammatory cytokines and proteolytic enzymes that trigger a positive feedback loop leading to further destruction of articular cartilage and articular inflammation. Synovial macrophages were found to be key player in promoting this artcular inflammation during OA. The synovial macrophages can be classified as “classically activated” M1 macrophages that have a pro-inflammatory phenotype and “alternatively activated” M2 macrophages with an anti-inflammatory phenotype and involvement in tissue remodeling.

Unfortunately, to date no disease-modifying treatment is available and therapy is largely limited to relieving the symptoms of OA. Several intra articular medications, including ACS, PRP and PAAG have reportedly achieved clinical improvement with reduction in lameness, but the mechanism by which their administration may result in alleviation of OA symptoms is incompletely understood.

Up to now the readout of most reports, testing new treatment approaches for OA, is based on clinical improvement, single molecular markers or diagnostic imaging. Hence, we still know very little about the exact molecular mechanism, signalling pathways and crosstalk between the different joint tissues and even less how these are modulated by intra articular medications. To date only a very limited number of studies exists that describe treatment effects on specific molecular pathways in a joint in the course of OA. Most of these in vitro cultures focus on only one or two articular tissues involved in the onset and/or progression of OA. However, given the complex pathophysiology of OA, it is paramount to study treatment effects in a model system, which account for the intricate interaction of cartilage, synovium and subchondral bone. Evaluating the effect of currently used intra articular treatments on different components of a joint, their crosstalk and their inflammatory response will help understanding pathophysiologic processes of OA and offer valuable information how to optimize application modalities or their composition. The aim of the proposed study is to unravel the modes of action of these treatments on the molecular level and compare their influence on the pathophysiological pathways active during OA using our recently developed in vitro osteochondral-synovial explant model for OA.

Cranial cruciate ligament rupture (CrCLR) is an orthopedics disease that occurs with high frequency in dogs. While anterior cruciate ligament rupture in humans occurs with trauma, CrCLR in dogs occurs as a result of chronic degenerative changes of the ligament. The chronic progression is called “cruciate disease.” Cruciate disease is characterized by cartilage metaplasia, weakening by microfracture, and partial tearing followed by complete rupture of the cranial cruciate ligament (CrCL). Although the pathological condition has not yet been clarified, excessive tibial plateau angle (eTPA) is known to be one of the factors of cruciate disease. When a vertical compressive force is applied at the tibiofemoral joint as during weight bearing, cranial tibial thrust (CrTT) is generated and displaces the tibia forward under the CrCLR. It is considered that the greater the tibial plateau angle (TPA), the greater the CrTT, and consequently the greater the load on CrCL. Therefore, Macias and colleagues suggested that caudal deformities of the proximal tibia resulting in excessive TPA(eTPA) were thought to be responsible for CrCL failure in dogs. Our group has previously shown by experiments that increasing TPA can induce CrCL degeneration including cartilage metaplasia.

CrCL is composed of cells and extracellular matrix (ECM), and most of the dry weight is collagens. Up to 90% of ligamentous collagens are type I collagen (COL1) which is the most resistant to tensile force among collagens. Vasseur and colleagues reported that histological findings on hematoxylin eosin staining (HE) as cartilage metaplasia showed reduced mechanical property. Then, Ichinohe and colleagues reported ECM of ruptured CrCL has changed such as decreased COL1, increased type 2 (COL2) and 3 (COL3) collagens, and enhanced expression of the sry-type HMG box 9 (SOX9).

The clinical efficacy of tibial plateau leveling osteotomy (TPLO) is widely recognized. TPLO is a functional stabilization method that was first described by Slocum and Slocum. This surgical method involves an osteotomy and rotation of the proximal tibia to correct the TPA. The goal of TPLO is to neutralize CrTT and prevent cranial displacement of the tibia during the stance phase. Krotscheck and colleagues compared the peak vertical force (PVF) as the weight bearing function between normal dogs versus dogs with CrCLR treated by TPLO, and found that the PVF in the TPLO group had recovered to the level of the normal dogs during both walking and trotting by 6 months postoperatively. However, Rayward and colleagues reported a significant increase in the osteoarthritis (OA) score from preoperatively to 6 months postoperatively. We consider that one of the factors of OA progression is instability that cannot be limited by TPLO. We reported TPLO provided affective craniocaudal stabilization during vertical compression in stifle joint with a transected CrCL. However, TPLO promote instability under drawer movement and internal-external movement in stifle joint with transected CrCL. In clinical cases, the instabilities also may be related to the pivot-shift phenomenon postoperatively. Hulse and colleagues reported that the extent of injury of the articular cartilage after TPLO depends on the degree of CrCL damage. They evaluated the articular cartilage by arthroscopy after TPLO and found that when the CrCL function was preserved, the articular cartilage became normal or nearly normal and the further damage of the CrCL was suppressed, whereas when the CrCL function was not preserved, the degree of damage of the articular cartilage was worsened. Against this background, the focus is also on the treatment of partial CrCL tear. An ex vivo study showed that the smaller the TPA created by TPLO, the lesser the CrCL strain during compression in the stifle. The results of these biomechanical studies suggest that TPLO also reduces the mechanical load on CrCL in vivo, and it is expected that such effects may lead to better CrCL macroscopic findings of partial tears.

However, it is unclear whether this degenerative change has been restored or has been slowed down and healed at the organizational level. So, the purpose of this study is to clarify the prophylactic effects of TPLO on CrCL degeneration in the stifle joints with the eTPA.

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