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Table 3 Different animal models in orthopaedic research

From: Role of animal models in biomedical research: a review

Animal model

Name of the procedure

Anaesthetic protocol

Procedure

Significance and limitations

References

Rat model

Critical size bone defect

Induction: 4% (vol/vol) isoflurane in oxygen for ~ 2 min. Maintenance of anesthesia with 2% (wt/vol) isoflurane. Administration of intraperitoneal (IP) injections of 0.05 mg/kg buprenorphine with 25 gauge needle for peri-operative analgesia and 5 ml/kg sterile normal saline with 18 gauge needle to account for fluid losses during surgery. Provides 30 min anesthesia

5 mm diameter of bilateral calvarial bone defect

The rat femur has more soft tissue coverage than other bones and the model has the potentiality to replicate the risk factors of non-union as humans. Haversian system is lacking, rotational stability is not achieved with only k-wire/intramedullary pins

[167,168,169,170,171,172,173]

Rabbit model

Critical size bone defect (Fig. 1a)

Intramuscular injection of Xylazine hydrochloride (5 mg/kg BW) and ketamine hydrochloride (50 mg/kg BW)

15 mm critical radial defect at distal diaphysis

Similar bone density with humans, though size and shape are different, as well as different in bone microstructure. Tibia and the less-weight carrying bones are more used

[168, 172,173,174,175,176,177,178,179,180]

Goat and sheep

Segmental bone defect

Intramuscular injection of Xylazine hydrochloride @ 0.1–0.2 mg/kg BW

3 cm defect in femur, tibia, radius, and metatarsus

Similar body weight and bone size like humans. Plexiform bone is predominant; Haversian remodeling can be seen in the later stage of the life cycle. Different bone metabolism as compared to monogastric animals

[171, 181,182,183,184,185,186]

Rabbit model

Osteomyelitis

(Fig. 1d)

Intramuscular injection of Xylazine hydrochloride (5 mg/kg BW) and ketamine hydrochloride (50 mg/kg BW)

A needle is to be introduced into the proximal femur medullary cavity, 1 mL of bone marrow is to be removed and replaced with 0.1 mL 5% sodium morrhuate and 0.1 mL of Staphylococcus suspension (Kanin strain, 3 × 106 cfu/mL). The opening point is to be sealed with bone wax

Rabbit bones are ideal for plate and screw fixation and the medullary canal of the tibia and femur are capable to accommodate internal implants. But, a higher dose of inoculation 103–108 CFU is required for successful infection

[187,188,189,190,191,192,193]

Rat model

Osteomyelitis

Induction: 4% (vol/vol) isoflurane in oxygen for ~ 2 min. Maintenance of anesthesia with 2% (wt/vol) isoflurane. Administration of intraperitoneal injections of 0.05 mg/kg buprenorphine with 25 gauge needle for perioperative analgesia and 5 ml/kg sterile normal saline with 18 gauge needle to account for fluid losses during surgery. Provides 30 min anesthesia

K wire is to be inserted into the medullary cavity of tibia and then 5% sodium morrhuate injection followed by a S. aureus suspension (102 cfu/10 μL) is to be injected into the tibial metaphysic. To prevent bacterial leakage fibrin glue and sealant is to be used

Bones in the rat are suitable for a different pattern of fracture and intramedullary implants. But rats require 103–106 CFU inoculation dose

[191, 193, 194]

Goat model

Osteomyelitis

Intramuscular injection of Xylazine hydrochloride @ 0.1–0.2 mg/kg BW

3-mm drill hole is to be made in distal tibia and injection of 1 mL 5% sodium morrhuate, afterwards an injection 10 min later with S. aureus (7.05 × 104 cfu). To prevent bacterial leakage fibrin glue and sealant is to be used

They are larger than other species under study hence implants and prostheses that are used in humans can be used in goats successfully. But they are expensive as well as the raring cost is more. Inoculation dose is 103–105 CFU in goat models

[191, 193, 195]

Rabbit model

Osteoporosis

Intramuscular injection of Xylazine hydrochloride (5 mg/kg BW) and ketamine hydrochloride (50 mg/kg BW)

Bilateral ovariectomy afterwards IM injection of 1 mg/kg BW/day of methylprednisolone for 4 weeks

They achieve early skeletal maturity than other mammals

[196,197,198,199,200]

Sheep model

Osteoporosis

General anesthesia with intramuscular injection of Xylazine hydrochloride @ 0.1–0.2 mg/kg BW

Bilateral ovariectomy, low calcium diet, weekly IM administration of dexamethasone for 6 weeks

They are docile, easy to handle, and house. Bone size similar to human. But, as they are ruminant, hence, oral drug administration does not yield the desired result. Surgical intervention is required to create an abomasal fistula

[201,202,203,204]

Mouse model

Osteosarcoma

Isoflurane/oxygen-based anesthesia for induction then maintenance by IM administration of Xylazine @10 mg/kg BW and ketamine @100 mg/kg BW

After the preparation of osteosarcoma cells as described by Uluçkan et al., a 0.5 cm skin incision is made just below the knee to expose tibial tuberosity, then cells are injected into the medullary cavity with 26–28 G syringe and skin is sutured

Cheap availability, easy to handle, genetic similarity with humans. Hence, become important for oncological research

[205,206,207]