Brief Review of Models of Ectopic Bone Formation

Abstract

Ectopic bone formation is a unique biologic entity--distinct from other areas of skeletal biology. Animal research models of ectopic bone formation most often employ rodent models and have unique advantages over orthotopic (bone) environments, including a relative lack of bone cytokine stimulation and cell-to-cell interaction with endogenous (host) bone-forming cells. This allows for relatively controlled in vivo experimental bone formation. A wide variety of ectopic locations have been used for experimentation, including subcutaneous, intramuscular, and kidney capsule transplantation. The method, benefits and detractions of each method are summarized in the following review. Briefly, subcutaneous implantation is the simplest method. However, the most pertinent concern is the relative paucity of bone formation in comparison to other models. Intramuscular implantation is also widely used and relatively simple, however intramuscular implants are exposed to skeletal muscle satellite progenitor cells. Thus, distinguishing host from donor osteogenesis becomes challenging without cell-tracking studies. The kidney capsule (perirenal or renal capsule) method is less widely used and more technically challenging. It allows for supraphysiologic blood and nutrient resource, promoting robust bone growth. In summary, ectopic bone models are extremely useful in the evaluation of bone-forming stem cells, new osteoinductive biomaterials, and growth factors; an appropriate choice of model, however, will greatly increase experimental success.

Human Perivascular Stem Cell-Based Bone Graft Substitute Induces Rat Spinal Fusion

“…Prior to this study, evaluation of bone regeneration of hPSC were limited to nonfunctional bone regeneration models, including ectopic bone formation in a muscle pouch implant model [32] and reossification of calvarial bone defects [34]. Ectopic bone formation models are limited to validating in vivo osteogenic potential, and calvarial bone defects simply assess ossification and do not assess the functional properties of newly formed bone [44,45]. In contrast, spinal fusion models provide a more clinically relevant assessment of the newly formed bone, including bone quantity and biomechanical strength.…”

Effects of Aging on Osteogenic Response and Heterotopic Ossification Following Burn Injury in Mice

“…While several models exist to study HO formation in vivo, the advantage of our Achilles tenotomy model is its physiologic basis that mirrors causes of HO seen clinically [38]. The resulting formation of ectopic bone is caused solely by musculoskeletal and burn trauma rather than by the introduction of foreign scaffolds, cells, osteoinductive substances, or genetic mutations.…”

Influence of Implants Surface Properties on Bone Tissue Formation in the Ectopic Osteogenesis Test

“…Ectopic osteogenesis was studied in vivo [3,10]. Eight Wistar rats received syngeneic red bone marrow.…”