ThrombosisHypertensionWound HealingDuchenne Muscular Dystrophy 
Cardiovascular and Additional ModelsBioModels offers customized solutions for clients working in disease areas that may lack readily standardized models, as well as disease areas that are a bit less mainstream, representing niche areas of inquiry. This work has resulted in the establishment of preclinical rodent models for thrombosis, blood pressure monitoring, wound healing, and more.
Assess your novel therapeutics for efficacy and mechanism of action in BioModels’ established thrombosis models. Thrombosis, the formation of a clot inside a blood vessel, can have devastating consequences, including death. BioModels’ thrombosis models allow you to evaluate blood clot formation in blood vessels.
The BioModels team is experienced with venous and arterial thrombosis models which are available with diverse experimental endpoints, such as:
Assess your novel therapeutics for efficacy and mechanism of action in BioModels’ established hypertension models. Hypertension, or high blood pressure, affects approximately 25% of the adult population in the United States. Left untreated, hypertension can lead to a number of health problems, such as heart disease, heart attack, and stroke. BioModels’ hypertension models allow you to evaluate high blood pressure by monitoring systolic and diastolic pressures.
The BioModels team is experienced with spontaneous and diet-induced hypertension models which are available with diverse experimental endpoints, such as:
Assess your novel therapeutics for efficacy in BioModels’ established wound healing models. Chronic nonhealing wounds are correlated with diseases such as diabetes, hypertension, chronic kidney disease and can have huge quality of life effects on patients. BioModels’ wound healing models allow you to evaluate the complex biological processes associated with healing and repair.
The BioModels team is experienced with splinted wound healing model which is available with diverse experimental endpoints, such as:
Muscular dystrophies are a class of genetic disorders, generally characterized by loss of muscle tissue and function. Duchenne muscular dystrophy (DMD) is an x-linked, recessive disorder caused by mutations in the DMD gene, which result in disruption of dystrophin production.
The BioModels team is experienced with DMD modeling, assessing disease severity through a variety of endpoints such as:
Study Models
The venous thrombosis model can be used to evaluate the impact of anti-coagulants and has been used to evaluate the potential for compounds to increase the propensity for clot formation. In rodents, thrombus is induced by the direct application of a solution of ferric chloride (FeCl3) to the adventitial surface of the femoral vein. Thrombus formation is measured using intravital video microscopy alone or in combination with a laser Doppler flow probe to monitor vessel occlusion. In addition to the primary endpoint of time to complete occlusion, other flow parameters, including a visual evaluation of blood flow using the Thrombolysis in Myocardial Infarction (TIMI) scoring scale, are assessed. In mice, test article responses can be compared to the effects of Lovenox (Enoxaparin sodium).
Laser Doppler flow monitor which utilizes non-invasive surface probes is used to measure femoral vein blood flow in thrombosis-induced animals.
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The arterial thrombosis model can be used to compare the anti-thrombogenic activities of novel therapeutics to provide a pre-clinical means of assessing the potential benefits of new drugs and drug combinations in reducing the risk of arterial thrombosis. In rodents, thrombus is induced by the direct application of a solution of ferric chloride (FeCl3) to the adventitial surface of the carotid artery. Thrombus formation is measured using intravital video microscopy alone or in combination with a laser Doppler flow probe to monitor vessel occlusion. In addition to the primary endpoint of time to complete occlusion, other flow parameters, including a visual evaluation of blood flow using the Thrombolysis in Myocardial Infarction (TIMI) scoring scale, are assessed.
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Study Models
The spontaneous hypertension model can be used to evaluate the potential benefits of novel therapeutics, and drug combinations in reducing high blood pressure. Spontaneous hypertension is modeled using rodents that have a genetic predisposition to developing hypertension. Non-invasive blood pressure monitoring is employed to evaluate systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate.
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The diet-induced hypertension model can also be used to evaluate the potential benefits of novel therapeutics, and drug combinations in reducing high blood pressure. Hypertension is induced in Dahl-Salt Sensitive rats by a high salt diet. High blood pressure is observed from approximately 1 week on high salt diet. Non-invasive blood pressure monitoring is employed to evaluate systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate.
Blood pressure is monitored twice a week in Dahl-Salt sensitive rats using a non-invasive blood pressure system to measure mean arterial blood pressure (top), systolic blood pressure (middle) and diastolic blood pressure (bottom).
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Study Models
Wound healing can be modeled using normal animals or diabetic animals that have a predisposition for impaired wound healing. After being anesthetized, animals have a full-thickness area of skin removed from the center of the back. Animals are evaluated daily for weight change and three times a week for wound healing progression. Wounds can either be splinted, which prevents wound closure by skin contraction and thus allowing wounds to heal through granulation and re-epithelialization, a process similar to that in humans, or be left to heal with contraction allowed to contribute to the wound healing process.
Animals are weighed daily, and body weight change as compared to Day 0 is calculated. The AUC is calculated to compare treatment groups and is shown in the inset. (**** p<0.0001; compared to db/db group)
Wound length and width is measured 3x/week from Day 0 until end of the study. The AUC is calculated to compare treatment groups and is shown in the inset. (*** p<0.001; compared to db/db group)
Blood glucose levels are measured on Day -1 and at sacrifice on Day 28. (**** p<0.0001; compared to db/db group)
Splinted Excisional Wound Healing Progression in Diabetic db/db Mice
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Study Models
The mdx mouse model is a well-defined, translational model that can be utilized to assess efficacy of novel therapeutics for DMD. There are several variations of the mdx model, one of which being DBA/2-mdx mice. DBA/2-mdx mice are often considered a superior variation of the DMD model because they present with increased levels of fibrosis with limited regeneration, thus more closely recapitulating the human characteristics of DMD myopathology. DBA/2-mdx mice show significant signs of progressive skeletal muscle degeneration starting as early as 3 weeks of age. The muscle degeneration can be assessed through functional readouts and histopathology analyses.
D2.B10-Dmdmdx/J
Percent weight change
Functional assessments (RotaRod and Grip strength)
Terminal histopathology and/or IHC analyses
Wire hang
Behavioral testing (Open field, Maze testing)
Clinical scoring
Serum chemistries
Body composition analysis (DEXA)
IHC
Custom assays
Animals were weighed 3x weekly, and percent body weight change relative to Day 0 was calculated. AUCs were calculated to compare groups and are shown in the figure inset (*p<0.05).
Animals were subject to RotaRod testing on a bi-weekly basis, and the average time to fall was recorded for each session. AUCs were calculated to compare groups and are shown in the figure inset (****p<0.0001).
Animals were subject to grip strength testing on a bi-weekly basis, and the average grip strength was recorded for each session. AUCs were calculated to compare groups and are shown in the figure inset (****p<0.0001).
Animals were subject to wire hang testing on a bi-weekly basis, and the average time to fall was recorded for each session. AUCs were calculated to compare groups and are shown in the figure inset.
Animals were subject to open field assessments on a bi-weekly basis, and the time spent in the outer zone was recorded for each session. AUCs were calculated to compare groups and are shown in the figure inset.
Animals were subject to open field assessments on a bi-weekly basis, and the time spent in the inner zone was recorded for each session. AUCs were calculated to compare groups and are shown in the figure inset.
Animals were subject to open field assessments on a bi-weekly basis, and the number of fecal boli left in the field was recorded for each session. AUCs were calculated to compare groups and are shown in the figure inset.
Animals were subject to open field assessments on a bi-weekly basis, and the number of urine spots left in the field was recorded for each session. AUCs were calculated to compare groups and are shown in the figure inset (*p<0.05).
Animals were subject to open field assessments on a bi-weekly basis, and the total distance travelled was recorded for each session. AUCs were calculated to compare groups and are shown in the figure inset.
Combined scores for necrosis, inflammation, mineralization, and regeneration in the diaphragm are shown (A) along with representative micrographs of naïve (B) and diseased (C) animals. Areas of necrosis (open area), mineralization (closed arrow), inflammation (arrowhead) and active regeneration (R) are indicated.
Combined scores for necrosis, inflammation, mineralization, and regeneration in the quadriceps are shown (A) along with representative micrographs of naïve (B) and diseased (C) animals. Areas of necrosis (open area), mineralization (closed arrow), inflammation (arrowhead) and active regeneration (R) are indicated.
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