Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Surgery

Background:

• Autologous bone transfer, the current standard for large bone defects, has limitations in availability and donor site morbidity.
• Developing functional tissue-engineered bone grafts requires effective orthotopic engraftment and suitable pre-clinical models.
• Prevascularization is crucial for engineered tissue survival and integration.

Purpose of the Study:

• To evaluate the engraftment of tissue-engineered bone with different prevascularization strategies in a novel rabbit humerus segmental defect model.
• To assess the impact of immediate (1-step) versus delayed (2-step) vascularization on graft integration and bone formation.
• To characterize the host response and graft remodeling within the defect model.

Main Methods:

• Utilized decellularized bone matrix (Tutobone) seeded with bone marrow mesenchymal stromal cells.
• Implemented two prevascularization strategies: immediate (1-step) and delayed (2-step) insertion with a vascular component.
• Assessed graft outcomes at 12 weeks using histological and radiological evaluations in a rabbit segmental bone defect model.

Main Results:

• Significant necrotic tissue formation was observed in all engineered grafts.
• While the 2-step strategy showed more vascularization, neither strategy reduced necrotic tissue significantly.
• No evidence of new bone formation or graft remodeling by osteoclasts was detected.

Conclusions:

• The developed rabbit humerus segmental defect model presents a significant challenge for bone tissue engineering.
• Current prevascularization strategies are inadequate for promoting survival and integration of engineered bone grafts.
• Further advancements in engineered bone grafts are needed, focusing on enhanced prevascularization, resorbability, and osteogenicity.