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Topic:Clinical Study

Clinical studies in equine research involve the systematic investigation of health and disease in horses through structured scientific methods. These studies aim to evaluate the safety and efficacy of treatments, understand disease mechanisms, and improve veterinary care practices. Clinical studies can include randomized controlled trials, observational studies, and case-control studies. They may focus on various aspects such as pharmacokinetics, therapeutic interventions, and diagnostic techniques. This page compiles peer-reviewed research studies and scholarly articles that explore the design, implementation, and findings of clinical studies in equine medicine, providing insights into their impact on horse health and veterinary practices.
Assessment of quantitative polymerase chain reaction for equine herpesvirus-5 in blood, nasal secretions and bronchoalveolar lavage fluid for the laboratory diagnosis of equine multinodular pulmonary fibrosis.
Equine veterinary journal    January 18, 2016   Volume 49, Issue 1 34-38 doi: 10.1111/evj.12545
Pusterla N, Magdesian KG, Mapes SM, Zavodovskaya R, Kass PH.The ante mortem diagnosis of equine multinodular pulmonary fibrosis (EMPF) relies on histopathological results and polymerase chain reaction (PCR)-positive equine herpesvirus (EHV)-5 testing of lung tissue. Polymerase chain reaction detection of EHV-5 in bronchoalveolar lavage fluid (BALF) is commonly used to support a diagnosis of EMPF. However, the diagnostic power of EHV-5 testing on BALF and other biological samples such as blood and nasal secretions has yet to be shown to support a diagnosis of EMPF. Objective: To determine the frequency of detection and the viral loads of EHV-5 by quanti...
Delivery and evaluation of recombinant adeno-associated viral vectors in the equine distal extremity for the treatment of laminitis.
Equine veterinary journal    January 16, 2016   Volume 49, Issue 1 79-86 doi: 10.1111/evj.12547
Mason JB, Gurda BL, Van Wettere A, Engiles JB, Wilson JM, Richardson DW.Our long-term aim is to develop a gene therapy approach for the prevention of laminitis in the contralateral foot of horses with major musculoskeletal injuries and non-weightbearing lameness. Objective: The goal of this study was to develop a practical method to efficiently deliver therapeutic proteins deep within the equine foot. Methods: Randomised in vivo experiment. Methods: We used recombinant adeno-associated viral vectors (rAAVs) to deliver marker genes using regional limb perfusion through the palmar digital artery of the horse. Results: Vector serotypes rAAV2/1, 2/8 and 2/9 all succes...
Effect of Arthroscopic Lavage on Systemic and Synovial Fluid Serum Amyloid A in Healthy Horses.
Veterinary surgery : VS    January 15, 2016   Volume 45, Issue 2 223-230 doi: 10.1111/vsu.12439
Sanchez-Teran AF, Bracamonte JL, Hendrick S, Burguess HJ, Duke-Novakovski T, Schott M, Hoff B, Rubio-Martínez LM.To evaluate the effect of arthroscopic lavage on systemic serum amyloid A (SAA) and SAA, total protein, nucleated cell count, and percentage of neutrophils in synovial fluid in healthy horses. Methods: Prospective experimental study. Methods: Healthy adult horses (n = 6). Methods: Middle carpal joints were randomly assigned to 1 of 2 treatments: arthrocentesis (controls) or arthroscopic lavage, with 30 day washout period between treatments. Synovial fluid and blood samples were collected at 0, 24, 48, 72, 96, and 120 hours. Measurements included systemic and synovial fluid SAA, as well as ...
The Effects of a Crosslinked, Modified Hyaluronic Acid (xCMHA-S) Gel on Equine Tendon Healing.
Veterinary surgery : VS    January 15, 2016   Volume 45, Issue 2 231-239 doi: 10.1111/vsu.12440
Jann HW, Hart JC, Stein LE, Ritchey J, Blaik M, Payton M, Fackelman GE, Rezabek GB, Mann BK.To assess the effects of a crosslinked, modified hyaluronic acid (xCMHA-S) gel on equine tendon healing using an in vivo surgical model. Methods: In vivo experimental study. Methods: Adult horses (n = 5). Methods: Full thickness bilateral forelimb window tenectomies were surgically created in both forelimb superficial digital flexor tendons and xCMHA-S gel was implanted intraoperatively into the right forelimb lesion of each horse whereas the left forelimb served as the untreated control. Healing was monitored by serial ultrasound examinations every 14 days over the course of the 84 day st...
Prosthetic Mesh for Obliteration of the Nephrosplenic Space in Horses: 26 Clinical Cases.
Veterinary surgery : VS    January 15, 2016   Volume 45, Issue 2 201-207 doi: 10.1111/vsu.12434
Burke MJ, Parente EJ.To report surgical complications, occurrence of post-obliteration colic, long term outcome, and return to previous function for horses treated with prosthetic mesh obliteration of the nephrosplenic space. Methods: Retrospective study. Methods: Horses (n = 26) having nephrosplenic space obliteration using prosthetic mesh. Methods: Horses undergoing mesh obliteration between January 2006 and May 2013 were included. A Proxplast™ mesh was secured to the nephrosplenic space with titanium helical coils in standing horses using laparoscopic technique. Perioperative data were obtained from the m...
Comparison of corneal degeneration and calcific band keratopathy from 2000 to 2013 in 69 horses.
Veterinary ophthalmology    January 15, 2016   Volume 20, Issue 1 16-26 doi: 10.1111/vop.12338
Berryhill EH, Thomasy SM, Kass PH, Reilly CM, Good KL, Hollingsworth SR, Maggs DJ, Magdesian KG, Pusterla N.To compare signalment, presentation, treatment, and outcome in horses diagnosed with corneal degeneration (CD) or calcific band keratopathy (CBK) at a referral hospital. Methods: Sixty-nine horses (87 eyes) diagnosed with either CD or CBK. Methods: Medical records of horses diagnosed with CD or CBK at the University of California-Davis Veterinary Medical Teaching Hospital (UCD-VMTH) between 2000 and 2013 were reviewed. Signalment, concurrent ophthalmic diagnoses, previous therapies, diagnostic tests, systemic diagnoses, treatment, follow-up, and outcomes were compared between horses diagnosed ...
Computed Tomographic Appearance of the Temporomandibular Joint in 1018 Asymptomatic Horses: A Multi-Institution Study. Carmalt JL, Kneissl S, Rawlinson JE, Zwick T, Zekas L, Ohlerth S, Bienert-Zeit A.Published descriptions of nonseptic arthritis of the equine temporomandibular joint (TMJ) are rare and large studies investigating variations in the TMJ for asymptomatic horses are lacking. The objectives of this cross-sectional, retrospective, multi-institutional study were to describe anatomical variations in the TMJ detected using computed tomography (CT) in an equid population asymptomatic for TMJ disease and determine whether these variations were associated with patient signalment, reason for CT examination, or CT slice width. Medical records at eight hospitals were searched for horses t...
Pharmacokinetics of guaifenesin following administration of multiple doses to exercised Thoroughbred horses.
Journal of veterinary pharmacology and therapeutics    January 14, 2016   Volume 39, Issue 4 416-419 doi: 10.1111/jvp.12287
Knych HK, Stanley SD, Benson D, Arthur RM.Guaifenesin is an expectorant commonly used in performance horses to aid in the clearance of mucus from the airways. Guaifenesin is also a centrally acting skeletal muscle relaxant and as such is a prohibited drug with withdrawal necessary prior to competition. To the authors' knowledge, there are no reports in the literature describing single or multiple oral administrations of guaifenesin in the horse to determine a regulatory threshold and related withdrawal time. Therefore, the objective of the current study was to describe the pharmacokinetics of guaifenesin following oral administration ...
Feasibility and Safety of Contrast-Enhanced Ultrasound in the Distal Limb of Six Horses. Seiler GS, Campbell N, Nixon B, Tsuruta JK, Dayton PA, Jennings S, Redding WR, Lustgarten M.Vascular alterations play important roles in many orthopedic diseases such as osteoarthritis, tendonitis, and synovitis in both human and equine athletes. Understanding these alterations could enhance diagnosis, prognosis, and treatment. Contrast-enhanced ultrasound (CEUS) could be a valuable method for evaluation of blood flow and perfusion of these processes in the equine distal limb, however no reports were found describing feasibility or safety of the technique. The goal of this prospective, experimental study was to describe the feasibility and safety of distal limb CEUS in a sample of si...
The effect of isosorbide dinitrate on uterine and ovarian blood flow in cycling and early pregnant mares: A pilot study.
Theriogenology    January 14, 2016   Volume 85, Issue 9 1562-1567 doi: 10.1016/j.theriogenology.2016.01.009
Zoller D, Lüttgenau J, Steffen S, Bollwein H.Poor uterine perfusion has been proposed as a cause of infertility in mares. The objective of this study was to investigate the effect of isosorbide dinitrate (ISDN), a nitric oxide donor, on uterine and ovarian blood flow resistance during diestrus and early pregnancy in mares. Six Trotter mares, aged 7 to 14 years, were examined daily during the first 11 days of three diestrous periods, and five of those mares were also examined during the first 11 days of two pregnancies. Six mares randomly received a placebo, a low dose (30 mg, ISDN30), or a high dose of ISDN (60 mg, ISDN60) through t...
Regional heterogeneity in the reactivity of equine small pulmonary blood vessels.
Journal of applied physiology (Bethesda, Md. : 1985)    January 14, 2016   Volume 120, Issue 6 599-607 doi: 10.1152/japplphysiol.00975.2015
Stack A, Derksen FJ, Williams KJ, Robinson NE, Jackson WF.Regional differences in large equine pulmonary artery reactivity exist. It is not known if this heterogeneity extends into small vessels. The hypothesis that there is regional heterogeneity in small pulmonary artery and vein reactivity to sympathomimetics (phenylephrine and isoproterenol) and a parasympathomimetic (methacholine) was tested using wire myography on small vessels from caudodorsal (CD) and cranioventral (CV) lung of 12 horses [9 mares, 3 geldings, 8.67 ± 0.81 (age ± SE) yr, of various breeds that had never raced]. To study relaxation, vessels were precontracted with U46619 (10(-...
Abnormal coagulation factor VIII transcript in a Tennessee Walking Horse colt with hemophilia A.
Veterinary clinical pathology    January 14, 2016   Volume 45, Issue 1 96-102 doi: 10.1111/vcp.12315
Norton EM, Wooldridge AA, Stewart AJ, Cusimano L, Schwartz DD, Johnson CM, Boudreaux MK, Christopherson PW.Hemophilia A is an X-chromosome-linked disorder caused by a deficiency in factor VIII (FVIII). Although foals have been diagnosed with hemophilia A based on deficiency in FVIII activity, causative gene mutations have not been identified. The genomic DNA and cDNA encoding FVIII of a Tennesee Walking Horse colt affected with hemophilia A and the genomic DNA of his dam and a normal unrelated horse were analyzed with no splice site or coding sequence abnormalities identified in any of the horses. Polymerase chain reactions (PCR) were then performed on hepatic cDNA from the affected colt and an unr...
[New causes of animal poisoning in Switzerland].
Schweizer Archiv fur Tierheilkunde    January 13, 2016   Volume 157, Issue 3 147-152 doi: 10.17236/sat00011
Schediwy M, Mevissen M, Demuth D, Kupper J, Naegeli H.This retrospective study evaluated the frequency, etiology, therapy and prognosis of animal poisoning registered from 2003 to 2012. The relevant cases reported to the Swiss Toxicological Information Center (STIC) were compared with those from previously examined periods. Human medicines not approved for animals and pesticides represented the most common causes of poisoning in dogs. Novel cases occurred as a consequence of the exposure of dogs to ricinus fertilizers, grape residues from wineries, pepper lachrymatory spray and dry bouillon. Cats are still freequently poisoned by pyrethroid drugs...
Relationship between uterine biopsy score, endometrial infection and inflammation in the mare.
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    January 13, 2016   Volume 44, Issue 3 158-163 doi: 10.15653/TPG-150581
Buczkowska J, Kozdrowski R, Nowak M, Sikora M.Endometrial biopsy score is an accepted marker of uterine health and predicted fertility, and it has been suggested that endometrial alternations are correlated with susceptibility to persistent infectious endometritis. The objective of this study was to investigate associations of endometrial biopsy score with: 1) presence of polymorphonuclear cells (PMNs) in the epithelium and stratum compactum in histopathology; 2) presence of PMNs in cytology and 3) presence of infection in microbiology. Methods: The material for examination was collected from 69 mares suspected for subclinical endometriti...
Initial analytic quality assessment and method comparison of an immunoassay for adrenocorticotropic hormone measurement in equine samples.
Veterinary clinical pathology    January 12, 2016   Volume 45, Issue 1 154-163 doi: 10.1111/vcp.12326
Irvine KL, Burt K, Hill AJ, Shaw S, Papasouliotis K.Equine pituitary pars intermedia dysfunction (PPID) may be diagnosed by measuring baseline plasma adrenocorticotrophic hormone (ACTH). The Immulite 1000 analyzer uses an automated chemiluminescence enzyme assay, previously validated for measuring equine ACTH. Recently, an automated bench-top immunoassay analyzer (AIA-360), designed for analytes in people, became available for veterinary use. Objective: Objectives were to evaluate analytic performance of the AIA immunoassay for measuring equine ACTH, and compare the results with those obtained by the Immulite. Methods: Adrenocorticotrophic horm...
Combined albumin and bicarbonate induces head-to-head sperm agglutination which physically prevents equine sperm-oviduct binding.
Reproduction (Cambridge, England)    January 11, 2016   Volume 151, Issue 4 313-330 doi: 10.1530/REP-15-0471
Leemans B, Gadella BM, Stout TA, Sostaric E, De Schauwer C, Nelis H, Hoogewijs M, Van Soom A.In many species, sperm binding to oviduct epithelium is believed to be an essential step in generating a highly fertile capacitated sperm population primed for fertilization. In several mammalian species, this interaction is based on carbohydrate-lectin recognition. D-galactose has previously been characterized as a key molecule that facilitates sperm-oviduct binding in the horse. We used oviduct explant and oviduct apical plasma membrane (APM) assays to investigate the effects of various carbohydrates; glycosaminoglycans; lectins; S-S reductants; and the capacitating factors albumin, Ca(2+) a...
Effect of repeated through-and-through joint lavage on serum amyloid A in synovial fluid from healthy horses.
Veterinary journal (London, England : 1997)    January 11, 2016   Volume 210 30-33 doi: 10.1016/j.tvjl.2016.01.001
Sanchez-Teran AF, Bracamonte JL, Hendrick S, Riddell L, Musil K, Hoff B, Rubio-Martínez LM.The objective of this study was to evaluate the effect of through-and-through joint lavage on systemic and synovial serum amyloid A (SAA), total protein, nucleated cell count and percentage of neutrophils in the synovial fluid of six healthy horses. A prospective experimental study was performed where one healthy tarsocrural joint of each horse was randomly assigned to receive repeated through-and-through joint lavage at 0, 48 and 96 h. Synovial fluid and blood samples were collected at 0 (baseline), 24, 48, 72, 96 and 120 h. Systemic and synovial SAA, total protein, nucleated cell count a...
Longitudinal Cell Tracking and Simultaneous Monitoring of Tissue Regeneration after Cell Treatment of Natural Tendon Disease by Low-Field Magnetic Resonance Imaging.
Stem cells international    January 10, 2016   Volume 2016 1207190 doi: 10.1155/2016/1207190
Berner D, Brehm W, Gerlach K, Gittel C, Offhaus J, Paebst F, Scharner D, Burk J.Treatment of tendon disease with multipotent mesenchymal stromal cells (MSC) is a promising option to improve tissue regeneration. To elucidate the mechanisms by which MSC support regeneration, longitudinal tracking of MSC labelled with superparamagnetic iron oxide (SPIO) by magnetic resonance imaging (MRI) could provide important insight. Nine equine patients suffering from tendon disease were treated with SPIO-labelled or nonlabelled allogeneic umbilical cord-derived MSC by local injection. Labelling of MSC was confirmed by microscopy and MRI. All animals were subjected to clinical, ultrason...
Horseback Riding-Related Vertebral Compression Fracture from Walking in Women with Low Bone Mineral Density: Reports of Two Cases.
Current sports medicine reports    January 9, 2016   Volume 15, Issue 1 38-40 doi: 10.1249/JSR.0000000000000221
Oh J, Oh HM, Lee JI.No abstract available
Ultrasound-Guided Injections in Horses with Cranioventral Distension of the Coxofemoral Joint Capsule: Feasibility for a Cranioventral Approach. Whitcomb MB, Vaughan B, Katzman S, Hersman J.Intrasynovial access to the equine coxofemoral joint (CFJ) is inherently challenging. Blind injection techniques rely upon inconsistently palpable landmarks, and ultrasound guidance requires expertise for needle placement into the coxofemoral articulation. Aspiration is recommended to confirm intrasynovial placement and avoid sciatic nerve anesthesia. The aim of this observational, descriptive, retrospective study was to evaluate the feasibility for an alternative ultrasound-guided approach in horses with cranioventral distention of the CFJ identified during pelvic ultrasound. Thirteen horses ...
Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects: Does It Enhance Repair?
The Journal of bone and joint surgery. American volume    January 8, 2016   Volume 98, Issue 1 23-34 doi: 10.2106/JBJS.O.00407
Goodrich LR, Chen AC, Werpy NM, Williams AA, Kisiday JD, Su AW, Cory E, Morley PS, McIlwraith CW, Sah RL, Chu CR.The chondrogenic potential of culture-expanded bone-marrow-derived mesenchymal stem cells (BMDMSCs) is well described. Numerous studies have also shown enhanced repair when BMDMSCs, scaffolds, and growth factors are placed into chondral defects. Platelets provide a rich milieu of growth factors and, along with fibrin, are readily available for clinical use. The objective of this study was to determine if the addition of BMDMSCs to an autologous platelet-enriched fibrin (APEF) scaffold enhances chondral repair compared with APEF alone. Methods: A 15-mm-diameter full-thickness chondral defect wa...
P2Y(1) receptors mediate purinergic relaxation in the equine pelvic flexure.
Veterinary journal (London, England : 1997)    January 8, 2016   Volume 209 74-81 doi: 10.1016/j.tvjl.2016.01.002
Mas M, Mañé N, Fernández F, Gallego D, Pumarola M, Jiménez M.In the equine large intestine, the knowledge of the basic mechanisms underlying motility function is crucial to properly treat motility disorders. P2Y1 receptors are responsible for mediating purinergic colonic relaxation in several species. In vitro experimental studies of the circular muscle from the equine pelvic flexure (n = 6) were performed to characterize inhibitory and excitatory neuromuscular transmission. Electrophysiological studies showed that electrical field stimulation (EFS) evoked biphasic inhibitory junction potentials (IJPs) in smooth muscle cells: a fast IJP (IJPf) follo...
Orthodontic correction of overjet/overbite (‘parrot mouth’) in 73 foals (1999-2013).
Equine veterinary journal    January 8, 2016   Volume 48, Issue 5 565-572 doi: 10.1111/evj.12540
Easley J, Dixon PM, Reardon RJ.There are limited reports on the efficacy of functional orthodontic correction of overjet or overbite in foals. Objective: To report the outcome of using orthodontic tension bands in combination with an inclined plane biteplate in the treatment of overjet, with or without concurrent overbite, rates of correction of these 2 malocclusions and associated complications. And to examine factors associated with outcomes. Methods: Retrospective case series. Methods: Clinical records for 73 foals treated at a single clinic, by the same surgeon were analysed. Overall change and rates of change in overje...
The use of dexmedetomidine continuous rate infusion for horses undergoing transvenous electrical cardioversion–A case series.
The Canadian veterinary journal = La revue veterinaire canadienne    January 8, 2016   Volume 57, Issue 1 70-75 
Marly-Voquer C, Schwarzwald CC, Bettschart-Wolfensberger R.Five horses were presented for treatment of atrial fibrillation by transvenous electrical cardioversion (TVEC). A dexmedetomidine infusion was administered for sedation during positioning of the cardioversion catheters, and continued during general anesthesia. Shocks were applied until return to sinus rhythm. Dexmedetomidine infusion provided excellent conditions for TVEC catheter placement and procedure. Utilisation d’une perfusion continue de dexmedetomidine lors de cardioversion électrique transveineuse chez le cheval: une série de cas. Cinq chevaux présentant une fibrillation atriale ...
Cytokine, catabolic enzyme and structural matrix gene expression in synovial fluid following intra-articular administration of triamcinolone acetonide in exercised horses.
Equine veterinary journal    January 8, 2016   Volume 49, Issue 1 107-115 doi: 10.1111/evj.12531
Knych HK, Vidal MA, Chouicha N, Mitchell M, Kass PH.The frequent use of intra-articular triamcinolone acetonide (TA) in performance horses warrants further study of the duration of as well as the beneficial and detrimental effects on gene expression associated with administration. Objective: To assess the effects of intra-articular administration of TA on the expression of selected anti- and proinflammatory and structural matrix genes following its administration into joints of exercised Thoroughbred horses and to correlate these effects with plasma and synovial fluid drug concentrations. Methods: Block design experiment. Methods: Eight exercis...
High-throughput analysis of horse sperms’ 3D swimming patterns using computational on-chip imaging.
Animal reproduction science    January 7, 2016   Volume 169 45-55 doi: 10.1016/j.anireprosci.2015.12.012
Su TW, Choi I, Feng J, Huang K, Ozcan A.Using a high-throughput optical tracking technique that is based on partially-coherent digital in-line holography, here we report a detailed analysis of the statistical behavior of horse sperms' three-dimensional (3D) swimming dynamics. This dual-color and dual-angle lensfree imaging platform enables us to track individual 3D trajectories of ∼1000 horse sperms at sub-micron level within a sample volume of ∼9μL at a frame rate of 143 frames per second (FPS) and collect thousands of sperm trajectories within a few hours for statistical analysis of their 3D dynamics. Using this high-throughp...
Removing movement artifacts from equine ECG recordings acquired with textile electrodes. Lanata A, Guidi A, Baragli P, Paradiso R, Valenza G, Scilingo EP.This study reports on the implementation of a novel system to detect and reduce movement artifact (MA) contribution in electrocardiogram (ECG) recordings acquired from horses in free movement conditions. The system comprises both integrated textile electrodes for ECG acquisition and one triaxial accelerometer for movement monitoring. Here, ECG and physical activity are continuously acquired from seven horses through the wearable system and a model that integrates cardiovascular and movement information to estimate the MA contribution is implemented. Moreover, in this study we propose a new alg...
In vitro anticancer activity of Betulinic acid and derivatives thereof on equine melanoma cell lines from grey horses and in vivo safety assessment of the compound NVX-207 in two horses.
Chemico-biological interactions    January 7, 2016   Volume 246 20-29 doi: 10.1016/j.cbi.2016.01.002
Liebscher G, Vanchangiri K, Mueller T, Feige K, Cavalleri JM, Paschke R.Betulinic acid, a pentacyclic triterpene, and its derivatives are promising compounds for cancer treatment in humans. Melanoma is not only a problem for humans but also for grey horses as they have a high potential of developing melanoma lesions coupled to the mutation causing their phenotype. Current chemotherapeutic treatment carries the risk of adverse health effects for the horse owner or the treating veterinarian by exposure to antineoplastic compounds. Most treatments have low prospects for systemic tumor regression. Thus, a new therapy is needed. In this in vitro study, Betulinic acid a...
Intra-arterial versus intra venous contrast-enhanced computed tomography of the equine head.
BMC veterinary research    January 7, 2016   Volume 12 6 doi: 10.1186/s12917-016-0632-9
Crijns CP, Baeumlin Y, De Rycke L, Broeckx BJ, Vlaminck L, Bergman EH, van Bree H, Gielen I.The anatomical complexity of the horse's head limits the abilities of radiography. Computed tomography (CT) in combination with contrast enhanced CT is used more often for diagnosing various head pathology in horses. The objective of this study was to compare intravenous and intra-arterial contrast-enhancement techniques and describe normal and abnormal contrast enhancement in the horse's head. Results: All 24 horses included in the study recovered without complication from the procedures. Compared to the pre-contrast studies, post-contrast studies showed significant contrast enhancement in th...
The benefits and limitations of animal models for translational research in cartilage repair.
Journal of experimental orthopaedics    January 6, 2016   Volume 3, Issue 1 1 doi: 10.1186/s40634-015-0037-x
Moran CJ, Ramesh A, Brama PA, O'Byrne JM, O'Brien FJ, Levingstone TJ.Much research is currently ongoing into new therapies for cartilage defect repair with new biomaterials frequently appearing which purport to have significant regenerative capacity. These biomaterials may be classified as medical devices, and as such must undergo rigorous testing before they are implanted in humans. A large part of this testing involves in vitro trials and biomechanical testing. However, in order to bridge the gap between the lab and the clinic, in vivo preclinical trials are required, and usually demanded by regulatory approval bodies. This review examines the in vivo models ...