Rapid developments in Regenerative Medicine and Tissue Engineering has witnessed an increasing drive toward clinical translation of breakthrough technologies. However, the progression of promising preclinical data to achieve successful clinical market authorisation remains a bottleneck. One hurdle for progress to the clinic is the transition from small animal research to advanced preclinical studies in large animals to test safety and efficacy of products. Notwithstanding this, to draw meaningful and reliable conclusions from animal experiments it is critical that the species and disease model of choice is relevant to answer the research question as well as the clinical problem. Selecting the most appropriate animal model requires in-depth knowledge of specific species and breeds to ascertain the adequacy of the model and outcome measures that closely mirror the clinical situation. Traditional reductionist approaches in animal experiments, which often do not sufficiently reflect the studied disease, are still the norm and can result in a disconnect in outcomes observed between animal studies and clinical trials. To address these concerns a reconsideration in approach will be required. This should include a stepwise approach using in vitro and ex vivo experiments as well as in silico modeling to minimize the need for in vivo studies for screening and early development studies, followed by large animal models which more closely resemble human disease. Naturally occurring, or spontaneous diseases in large animals remain a largely untapped resource, and given the similarities in pathophysiology to humans they not only allow for studying new treatment strategies but also disease etiology and prevention. Naturally occurring disease models, particularly for longer lived large animal species, allow for studying disorders at an age when the disease is most prevalent. As these diseases are usually also a concern in the chosen veterinary species they would be beneficiaries of newly developed therapies. Improved awareness of the progress in animal models is mutually beneficial for animals, researchers, human and veterinary patients. In this overview we describe advantages and disadvantages of various animal models including domesticated and companion animals used in regenerative medicine and tissue engineering to provide an informed choice of disease-relevant animal models.

Gait analysis has been extensively performed in dogs and horses; however, very little is known about feline biomechanics. It was, therefore, the aim of this study to determine the coefficient of variation (CV) among three ground reaction force (GRF) measurements taken for 15 client-owned European shorthaired cats without a training period and a short acclimatisation time. Gait was measured as each cat walked across a pressure-sensitive walkway, and measurements were made three times over a multi-week period (range: 2 to 17 weeks). The parameters evaluated were peak vertical force (PFz), vertical impulse (IFz), stance phase duration (SPD), step length (SL), paw contact area (PCA) and symmetry index (SI%) of the front and hind limbs. After averaging each of the values from the three measurements, the CV and 95% confidence interval (CI) were calculated for all parameters. PFz showed the lowest CV (~ 3%), while IFz showed the highest CV (~11%) when normalised to body mass. When the GRFs were normalised to total force, the CV of PFz dropped to ~2% and that of IFz dropped to ~3%. The CV of SL and PCA were lower (~6% respectively ~5%) compared to the CV for SPD (~10%). The SI% for both PFz and IFz were comparable to the values reported in the gait analysis literature for dogs. Results of the current study indicate that gait analysis of cats using pressure-sensitive walkways produces reliable data and is a promising approach for evaluation of lameness. The results also suggest that PFz may be a more reliable parameter than IFz and that normalisation to percent of total force may aid in interpretation of the evaluated data.

Objectives To evaluate the intra- and inter-observer measurement variability of an existing osteoarthritis (OA) stifle scoring system. Methods Paired caudocranial and mediolateral canine stifle radiographs were selected randomly. A total of 15 assessment points were evaluated independently andgradedtwice (integer numericscale:1–4) at an interval of 2 weeks by three observers with different levels of experience. The grades for each of the 15 factors were summed to obtain the OA score for each patient. Results The 15 independent assessment points measured by the three observers showed high reproducibility and low intra-observer variability. Inter-observer variability was also low (mean: 1.09 4.99, 95% CI [confidence interval]: –0.35 to 2.55). The most discordant ratings among the three observers involved sesamoid bones of gastrocnemius muscle (assessment point 11 of 15) and popliteal surface of femur (assessment point 10 of 15). Clinical Significance A validated and feasible OA scoring method is prerequisite for reliable radiographic assessment of OA progression. The low overall inter- and intra-observer variabilities among the 15 independent measures of the OA scoring system presented herein support its feasibility for application in clinical practice as an objective tool for radiographic scoring of stifle OA.

Objective: The optimal surgical technique for treatment of cranial cruciate ligament rupture in canine has been scientifically discussed for decades. Despite the continuous debate, proximal tibial osteotomies such as tibial plateau leveling osteotomy (TPLO) and tibial tuberosity advancement (TTA) are increasingly common. The objective of this review was to systematically evaluate the literature reporting outcome and complications associated with TPLO and TTA. Materials and methods: A systematic search of literature databases identified articles published from August 2004 to February 2016 describing evaluations of short- or longterm outcomes as well as complications following TPLO or TTA. Results: Ninety-one studies were included in this review and assigned to one out of four evidence levels. Of those, 89 studies provided the lowest evidence level and only two were assigned to the third-best evidence level. A comparison of subjective gait analyses could not detect differences in the decrease of lameness between TPLO and TTA, while objective gait analysis supports the superiority of TPLO. Fewer patients treated with TPLO were diagnosed with postoperative joint instability and TPLO had a lower percent increase of osteoarthritis (OA) after surgery. Owner satisfaction was high for both techniques. For TPLO and TTA the average total, minor, major and catastrophic complication rates were 15.9 % and 20.8 %, 7.9 % and 11.6 %, 5.2 % and 13.2 % as well as 0.8 % and 5.6 %, respectively. Conclusion and clinical significance: The assessed literature supports the hypothesis that TPLO is associated with lower complication rates, an improved clinical-functional outcome and less increase of OA compared to TTA. The results are indicative for a long-term restoration of normal limb function after TPLO. However, the strength of available evidence and the comparability of each study’s results were poor and more comparative studies are needed to draw strong conclusions towards the superiority of the TPLO over the TTA. Gegenstand und Ziel: Die optimale chirurgische Technik zur Behandlung der Ruptur des vorderen Kreuzbands beim Hund ist seit Jahrzehnten ein viel diskutiertes Thema in der Kleintierorthopädie. Trotz anhaltender Diskussionen werden Osteotomietechniken der Tibia, die Tibial Plateau Leveling Osteotomy (TPLO) und das Tibial Tuberosity Advance ment (TTA), immer häufiger angewendet. In diesem Artikel werden die in der Literatur beschriebenen Ergebnisse und Komplikationen nach einer TPLO und TTA systematisch zusammengefasst und verglichen. Material und Methoden: Nach systematischer Literaturrecherche zu klinischen Studien über TPLO oder TTA wurden zwischen August 2004 und Februar 2016 publizierte Studien inkludiert, die über Kurz- oder Langzeitergebnisse und Komplikationen berichteten. Ergebnisse: Die 91 analysierten Studien wurden einer von vier Evidenzklassen zugeteilt. Zwei Studien entsprachen der drittbesten Evidenzklasse, 89 der niedrigsten Evidenzklasse. Ein Vergleich der Ergebnisse subjektiver Lahmheitsuntersuchungen zeigte keine eindeutigen Unterschiede zwischen den Techniken. Objektive Ganganalysen wiesen auf bessere Resultate nach TPLO hin. Die TPLO war mit einer geringeren postoperativen Zunahme der Osteoarthritis (OA) verbunden und bei weniger Patienten wurde postoperativ eine Gelenkinstabilität diagnostiziert. Die durchschnittlichen Gesamtkomplikationsraten betrugen für die TPLO und TTA 15,9 % bzw. 20,8 %, die gering-, mittel- und hochgradigen Komplikationsraten 7,9 % bzw. 11,6 %, 5,2 % bzw. 13,2 % sowie 0,8 % bzw. 5,6 %. Schlussfolgerung und klinische Rele vanz: Aktuelle Publikationen stützen die Hypothese, dass die TPLO mit besseren klinisch-funktionellen und radiologischen Ergebnissen, einer geringeren Zunahme der OA sowie geringeren Komplikationsraten einhergeht. Die Resultate der Studie lassen auf eine Lang-zeitwiederherstellung der normalen Giedmaßenfunktion nach einer TPLO schließen. Zu beachten sind jedoch das niedrige Evidenzniveau und die limitierte Vergleichbarkeit der Resultate verschiedener Studien. Um eindeutige Aussagen bezüglich der Überlegenheit der TPLO gegenüber der TTA ziehen zu können, bedarf es weiterer Vergleichsstudien.

Summary: The objective of the present study was to determine the tibial plateau angle (TPA) in cats without stifle pathology and to compare it with cats suffering from an isolated cranial cruciate ligament rupture. Mediolateral radiographs of the stifle were taken and the tibial plateau angle was measured based on the method previously described by Slocum and Devine (1983) for dogs. Three observers with different levels of experience evaluated the radiographs of all of the cats in this study. The mean tibial plateau angle measured by all three observers in the cats with a rupture of the cranial cruciate ligament (CCL) was 3.1° greater than in cats without stifle pathology. Neither gender, age, body weight nor degenerative joint disease had an influence on measurement results. The authors found an inter-observer variability of ± 5.3°. Hence it can be concluded that cats with cranial cruciate ligament rupture have a greater TPA, and this at least lends some credence to the possibility of higher TPA being a predis-posing factor for cruciate injury in this species.