Approaches to Establish an Animal Model With Composite Bone-soft Tissue Defects for Complex Regenerative Strategies

Regenerative strategies of composite tissue defects represent a formidable clinical challenge due to the distinct regeneration pathways of each tissue type and their complex interactions. To address the limitations of single-tissue defect models, the authors firstly established an animal model with simultaneously composite bone-soft tissue defects and then observed the wound healing, body weight, and overall health after the operation. The soft tissue defects exhibited complete macroscopic closure within 21 days. Furthermore, micro-computed tomography and histological assessments at 8 weeks demonstrated that the calvarial defect was unhealed, confirming its characteristics as a critical-size defect. In the authors' model, a 5 mm defect remained unhealed at 8 weeks, suggesting that it also exhibits critical-size defect properties, though a direct comparison with the classical 8 mm model requires further validation. Quantitative evaluations revealed limited new bone formation confined primarily to the defect margins, while the central portion of the defect remained filled with fibrous tissue. This composite model not only advances authors' understanding of multitissue repair processes but also offers a valuable preclinical platform for the development and optimization of next-generation regenerative strategies for complex tissue injuries.