Preclinical models
What animal models can and cannot tell you about human regeneration.
Regenerative strategies are tested in animals before humans, and the models form a ladder: rodents for mechanism and screening, then larger species — rabbit, sheep, dog, pig — for load-bearing and scale. The calvarial defect and the segmental femoral defect are standard critical-size models in bone.
The limits are structural rather than incidental. Rodents heal far more readily than humans, are usually young and healthy where patients are old and comorbid, and differ in remodeling biology — rodent long bones lack the Haversian remodeling of human cortical bone. Loading is different, defect scale is different, and follow-up is months where a human implant must last decades.
None of this makes models useless; it makes them specific. A rodent study is evidence a mechanism operates, not evidence a therapy works. Over-reading them is a major contributor to the attrition described in Translation in regenerative medicine and to the Reproducibility in biomedical research problem.
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