Large Animal Models of Orthopedic Injury

Large Animal Models of Orthopedic Injury

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Description: Objectives of large animal modeling: A. Assessment of the predictive value of preclinical models for clinical efficacy. B.

Mimic wound healing environment in a challenging clinical settings: large bone and soft tissue defects, sites of prior surgery. C. Macroscopic similarities to people: Weight bearing and biomechanics closer to human subjects.

D. Microscopic similarities are in question: Canine possibly the closest. Where and how: Contract laboratories- Protocol driven, Efficient, Expensive.

Institutional laboratories- Intellectual contribution to model and study development, Vested interest from local PI, Ancillary expertise, Time consuming, Excessive overhead costs.

 
Author: John Peroni (Fellow) | Visits: 813 | Page Views: 991
Domain:  Medicine Category: Veterinary 
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Contents:
Large animal models of orthopedic
injury
JOHN PERONI

Introduction
• Why large animal models
• Where and How
• Bone

– Osteotomy and non-osteotomy models

• Tendon/ligment

– Mechanical injury
– Chemical injury

• Naturally occurring models
• Cartilage

– Intact joint cartilage defects
– Osteoarthritis modeling

Translation from rodent model

Translation from rodent model
BMP-2

2 weeks

Control

2 weeks

BMP-2

3 weeks

Control

3 weeks

Objectives of large animal modeling
A. Assessment of the predictive value of preclinical
models for clinical efficacy.
B. Mimic wound healing environment in a challenging
clinical settings.



large bone and soft tissue defects
sites of prior surgery

C. Macroscopic similarities to people.


Weight bearing and biomechanics closer to human subjects

D. Microscopic similarities are in question


Canine possibly the closest

Guidelines are still missing

Where and how
• Contract laboratories
– Protocol driven
– Efficient
– Expensive

• Institutional laboratories






Intellectual contribution to model and study development
Vested interest from local PI
Ancillary expertise
Time consuming
Excessive overhead costs

Bone defect types
• Osteotomy
• Non-osteotomy
• Void defect

Decker S, et al Non-Osteotomy and Osteotomy Large Animal Fracture Models in Orthopedic
Trauma Research. Orthopedic Reviews. 6(4).2014

Osteotomy fracture models

Decker S, et al Non-Osteotomy and Osteotomy Large Animal Fracture Models in Orthopedic
Trauma Research. Orthopedic Reviews. 6(4).2014

Ovine Metacarpal
defect

Empty Defect

14 days

28 days

Cancellous
Bone graft

14 days

28 days

Periosteum
Stripped

14 days

28 days

Defect only

Bone graft

Periosteal stripping

505L

644L

644R

Defect only

Bone graft

Periosteal stripping

505L

644L

644R

Ulna osteotomy
• Point of insertion of the triceps apparatus.
– Tensile stress

• Surrounded in part by muscle
– Flexor unit

Day 14

Day 28

Tibia defect model
• External Fixation
• Bone plating

Tibia defect model
• High morbidity
• Taxing postoperative care

• Critical size
• Internal fixation an
option

Naturally occurring bone models

Tibial Tuberosity Advancement
Tibial Plateau Leveling Osteotomy

Tendonitis
• Mechanical fiber disruption
– Controlled injury
– Reproducible

Tendonitis
• Chemical fiber disruption (collagenase)
– Widespread injury
– Variability of injury
– Inflammation relative to enzyme

Tendonitis
• Equine tendinopathy as a naturally occurring model

30 days

120 days

Thank you