Abstract
Clinically, in patients who sustain severe open fractures, there is not only a segmental bone defect needed to be reconstructed but also insufficient healing capacity due to concomitant damages to the periosteum and surrounding soft tissues. For studying the reconstruction of bone defects associated with massive loss of periosteum and surrounding soft tissues, there are no well-established preclinical models in large animals in the literature. The purpose of the study was to generate a large animal model of bone defect with massive periosteum loss and to adopt a tissue engineering approach to achieve rapid bony union with stem cells and biomaterials. In this study, a bone defect with massive periosteum stripping was generated in pigs, which was followed by emptying nearby canal marrow including fat and cancellous bone. The stripped periosteum was a mimic to the situation in the Gustilo type 3 open fractures. Bone defects were then reconstructed by impacting the biocompatible ceramic scaffold, morselized tricalcium phosphate (TCP) loaded with human adipose tissue-derived mesenchymal stem cells (hMSCs). Radiological and pathological assessments indicated that TCP and hMSCs synergistically promoted bone healing with increased lamination and ingrowth of vessels. Both bridging periosteum formation and gap filling were induced rapidly. In conclusion, a porcine model of segmental bone loss with damage of surrounding periosteum was created. Reconstruction of such defects with hMSCs and TCP achieved rapid union of bone defects associated with massive periosteal stripping.
Highlights
IntroductionChronic defect or delayed union of long bones after fractures leads to subsequent complications such as muscle atrophy, joint stiffness, compromised limb function, and poor quality of life
During the formation of the bone callus, the vascular system plays an important role in promoting bone regeneration by supplying oxygen, nutrients, and ions necessary for mineralization through the formation of new vessels
Fixation of tibial bone defects was achieved by metallic plates and screws (Synthes, Inc.)
Summary
Chronic defect or delayed union of long bones after fractures leads to subsequent complications such as muscle atrophy, joint stiffness, compromised limb function, and poor quality of life. In the patients who sustain Gustilo type 3 open fractures, there is a segmental bone defect needed to be reconstructed and insufficient healing capacity due to vascular insufficiency to overcome. Regarding bone defects with massive loss of periosteum, there are no well-established preclinical models in large animals in the literature. Angiogenesis is critical for bone fracture healing. During the formation of the bone callus, the vascular system plays an important role in promoting bone regeneration by supplying oxygen, nutrients, and ions necessary for mineralization through the formation of new vessels. The importance of blood vessels in delivering osteoprogenitors
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