Research grants

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.

Investigators: Alex Hawkins / Roger Smith / Andrew Fiske-Jackson / Andew Carr
ARI Principal Coinvestigator: Caroline Constant

Intra-synovial tendon tears are common in both humans (rotator cuff tears of the shoulder) and horses (deep digital flexor tendon tears within the digital flexor tendon sheath). These injuries, although in different anatomical locations, show remarkable similarities in the two species because of the common synovial environment (Lui, Maffulli et al. 2011). This synovial environment exerts significant adverse effects on the tendon tissue exposed to the synovial fluid, where it kills resident tenocytes (Garvican, Salavati et al. 2017). This significantly hampers tendon healing and clinically both injuries of the rotator cuff and the deep digital flexor tendon in the horse show ‘failed’ healing and lesions persist within the synovial environment, in some cases indefinitely. However, lesions which are open to the synovial environment also contribute in the other direction into the tendon sheath or bursa. Recurrent bleeding from the tear, as well as the release of fragmented matrix proteins (‘matrikines’), cause persistent inflammation and drive permanent restrictive fibrosis in the tendon sheath or bursal capsule. There has been significant interest in the use of stem cells to treat tendinopathy over the past 20 years. Our group was the first to implant bone marrow-derived mesenchymal stem cells into injured extra-synovial equine tendons (Smith, Korda et al. 2003) which has shown promise in reducing the clinical consequences (e.g. re-injury) of this injury in horses (Godwin, Young et al. 2012) through improvement in the tissue repair (Smith, Werling et al. 2013). However, subsequent studies which have evaluated the benefit of intra-synovial administration of these cells for tendon tears within a synovial environment has shown no benefit in a large animal model based on the naturally occurring injury in the horse (Khan, Dudhia et al. 2018), at least in part because of their failure to attach to the injured tendon matrix (Khan, Smith et al. 2013). This was also the case for synovially derived MSCs (Khan, Smith et al. 2019).

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.

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.

Fracture of long bones is one of the major common orthopedic conditions encountered in ruminants and accounts for up to 10% of the caseload at referral centers. Tibial fractures account for 15-41% of long bone fractures in cattle, regardless of age. The majority of neonatal calves sustain a tibial fracture during assisted delivery or trauma from the dam resulting in typical configurations. In older calves, tibial fractures can occur during transport, while in pasture or in cattle sheds.18 The resulting fracture is typically affecting the diaphysis. Proximal and distal physeal tibial fractures are very unstable and result in a significant economic loss when the bone fails to heal or if the fracture develops into an open fracture, both of which can result from the employment of inadequate fixation methods.

While conservative treatment involving stall confinement and/or use of external coaptation has been reported, severe and potentially life-threatening complications and not acceptable bone healing have been frequently described even in newborn calves less than 80kg. Severe angular limb deformity of the fractured limb with persistent lameness despite bone healing is reported. While open reduction and internal fixation using bone plates and screws can be successful in adults, the thin cortices of calves juvenile bone do not provide sufficient physical strength to hold bone screws. Reports detailing other treatments for juvenile bovine tibial fractures include bone intramedullary rods and external skeletal fixator and describe high complication rates and overall poor clinical outcomes. Intramedullary interlocking nail (IIN) fixation has been used in small animals and resulted in successful outcomes in a large number of cases with similar fractures. Recently, a tibial fracture repair technique using an 8-mm angle-stable interlocking nailing system was reported in 2 calves with encouraging results. While such a small diameter INN system may provide an effective alternative for osteosynthesis of tibial fractures in young calves, biomechanical evaluation of such repair is needed before wide implementation of the system in clinical patients. In current recommendations regarding INN in humans, the largest possible nail diameter should be chosen to tailor the narrowest region of the inside of the medullary cavity as it offers the best biomechanical outcomes. While 8-mm diameter INN are available to veterinary surgeons, choosing a larger nail diameter may make more biomechanical sense, since it allows the superior stiffness offered by a larger-diameter, as compared with smaller-diameter, nail to be exploited. The identification of a IIN system already commercially available from the veterinary or human market to optimally exploit the mechanical potential of the implant within the constraint of what is feasible in farm animal clinical practice would facilitate and accelerate its implementation in surgery.

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.

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.