Model Introduction
Large segmental bone defects refer to the loss of bone tissue caused by severe trauma, bone infection, tumors, and other factors, representing a major challenge in clinical orthopedic treatment. Since large segmental bone defects often cannot heal spontaneously, establishing stable and reproducible animal models is of great significance for studying the mechanisms of bone repair and evaluating osteogenic materials.
Currently, common species used for bone defect animal models include rats (38%), rabbits (19%), mice (13%), sheep (11%), dogs (9%), goats (4%), and other animals (4%). Among them, the rabbit segmental femoral defect model and the rat critical-sized cranial defect model are widely utilized for research into long bone and calvarial defect repair, respectively.
Research Applications
Bone defect models are primarily used to:
- Study the mechanisms of bone regeneration and repair.
- Evaluate the efficacy of osteogenic materials and tissue engineering scaffolds.
- Analyze the role of the periosteum in bone repair.
- Observe the natural healing capacity of critical-sized defects (CSD).
- Evaluate the bone healing process through imaging and histological means. Segmental bone defect models can simulate severe clinical bone loss; critical-sized cranial defect models are suitable for evaluating the osteogenic capacity of bone tissue engineering materials.
Experimental Design Key Points
I. Rabbit Segmental Femoral Defect Model
Experimental Animals
- 6 healthy New Zealand White rabbits, 6 months of age.
- Establishment of a 1.5 cm segmental bone and periosteal defect in the mid-shaft of the left femur.
Surgical Method
- Enter the femur via an anterolateral longitudinal incision.
- Place a 4-hole steel plate pre-bent at 5°–8°.
- Drill holes and secure with 4 screws; use fine steel wire cerclage if necessary.
- Saw through the femur between the 2nd and 3rd holes of the plate.
- Resect a 1.5 cm bone segment and the corresponding periosteum.
- Rinse with saline, suture, and dress the wound.
- Postoperative intramuscular injection of 400,000 U penicillin sodium to prevent infection.
Postoperative Observation and Time Points
- Closely observe mental status, diet, activity, and wound healing.
- Euthanize 2 rabbits each at 6, 12, and 18 weeks post-surgery.
- Perform gross observation and X-ray examination.
II. Rat Cranial Critical-Sized Defect (CSD) Model
Experimental Animals
- 12-week-old male SD rats.
- Body weight: 250–300g.
- Intraperitoneal anesthesia with 3% pentobarbital (30 mg/kg).
Modeling Method
- Median incision on the calvarium.
- Expose the parietal bone.
- Create a full-thickness cranial defect using a circular bone burr with an 8 mm diameter.
- Maintain the integrity of the dura mater.
- Rinse with saline for cooling.
Osteogenic Material Implantation
- Fill with osteogenic material and record the weight.
- Suture the periosteum with 4-0 sutures and the skin with 3-0 sutures.
- Intramuscular injection of 400,000 U penicillin for 3 consecutive days post-surgery.
Imaging Evaluation Time Points
- Day of surgery.
- 4 weeks post-surgery.
- 8 weeks post-surgery.
- 12 weeks post-surgery.
Key Detection Indicators
I. General Condition Observation
- Mental status.
- Dietary intake.
- Locomotor activity.
- Wound redness, swelling, or exudation. In the rabbit model, mental status and activity are slightly poor on the first day post-surgery and gradually recover after 2 days; all rats survived, with some showing swelling that recovered after treatment.
II. Gross and Imaging Observation
Rabbit Femoral Model
- Soft granulation tissue appears in the defect area at 6 weeks.
- No significant callus formation.
- X-ray observation of bone defect healing.
Rat Cranial Model
- CT on the day of surgery shows neat defect margins.
- Only wedge-shaped bone growth is seen at 12 weeks.
- Minimal bridging.
- Defect diameter shows no significant difference compared to the day of surgery.
III. Repair Status Evaluation
- Changes in bone defect area (CT tomographic measurement).
- Internal callus formation.
- Changes at the two osteotomy ends.
- Whether bridging has formed.

