Bone Healing In Rabbits Research Articles

The mechanism of shock wave treatment in bone healing

The purpose of this study was to investigate the biological mechanism of shock wave treatment in bone healing in rabbits. A closed fracture of the right femur was created with a three-point bend method and the fracture was stabilized with an intra-medullary pin. Shock waves were applied one week after the fracture. Twenty-four New Zealand white rabbits were randomly divided into 3 groups. Group 1 (the control) received no shock waves; group 2 received low-energy; and group 3 high-energy shock waves. The animals were sacrificed at 24 weeks, and a 5-cm segment of the femur bone including the callus was harvested. The specimens were studied with histomorphological examination, biomechanical analysis and immunohistochemical stains. The results showed that high-energy shock waves improved bone healing with significant increases in cortical bone formation and the number neovascularization in histomorphology, better bone strength and bone mass in biomechanics, and increased expressions of angiogenic growth markers including BMP-2, eNOS, VEGF and PCNA than the control and low-energy shock wave groups. The effect of shock wave treatment appears to be dose-dependent. In conclusion, high-energy shock waves promote bone healing associated with ingrowth of neovascularization and increased expressions of angiogenic growth factors.

SUBSTITUTES FOR AUTOLOGOUS BONE GRAFT IN ORTHOPAEDIC TRAUMA

SUBSTITUTES FOR AUTOLOGOUS BONE GRAFT IN ORTHOPAEDIC TRAUMA

Parathyroid hormone-related protein analog RS-66271 is an effective therapy for impaired bone healing in rabbits on corticosteroid therapy

A new class of parathyroid hormone-related protein (PTHrP) analogs has been developed that causes a rapid gain in both trabecular and cortical bone in models of osteopenia. This study investigates the efficacy of the PTHrP analog, RS-66271 ([MAP 1–10] 22–31 hPTHrP(1-34)–NH 2), as systemic therapy for impaired bone healing in corticosteroid-treated rabbits. A 1 mm defect was created bilaterally in the ulnae of 30 rabbits. Delayed healing was induced by daily injections of prednisone (0.15 mg/kg) beginning 2 months prior to surgery and continuing until killing. Rabbits in the experimental group received daily subcutaneous injections of PTHrP analog RS-66271 (0.01 mg/kg) starting 1 day after surgery. Control animals received subcutaneous normal saline. At the 6 week timepoint, nine of ten ulnae from PTHrP-treated rabbits achieved radiographic union, whereas only two of ten limbs achieved union in control rabbits ( p < 0.01). In a separate part of the study, 20 animals (10 control, 10 RS-66271-treated) were killed when radiographic union was achieved bilaterally. In this portion of the study, all limbs in animals treated with PTHrP achieved union by 6 weeks. In the control animals that were allowed to heal for 10 weeks, only 20% of the limbs achieved radiographic union. In addition, ulnae in the PTHrP-analog-treated rabbits showed greater radiographic intensity (20%–40%), larger callus area (209% anteroposterior view, 417% lateral view) (mean area on AP radiographs: control, = 387 ± 276 mm 2; PTHrP analog, 1195 ± 408 mm 2), and greater stiffness (64%) and torque (87%) when compared with controls. RS-66271 was shown to be an effective therapy for preventing impaired bone healing caused by prednisone in a rabbit model.

Fibrin Sealant in Orthopedic Surgery

The use of clotting substances from blood for hemostasis dates back to 1909. In 1972, modern fibrin sealing (FS) was developed in Vienna. For application, the two components, i.e., a sealer protein solution (mainly fibrinogen) and a thrombin solution, are mixed to produce the fibrin clot. The sealant may be applied with a needle, as a spray, or by premixing (e.g., with antibiotics, bone chips) for subsequent sealant application in cavities. While the positive effect of FS in normal wound healing has been conclusively demonstrated, its influence on bone healing remains controversial. The positive experimental results mostly refer to the early phase of bone healing in rabbits (cortical drill hole, autologous and heterologous (Kiel) cancellous transplants, osteotomies, osteochondral fractures) and dogs (cortical bone and spongiosa defects). Some authors observed no effects (in dogs, osteotomy) or delayed healing in artificial bone growth chambers with the use of heterologous sealant. FS was also applied in combination with implantation material (tricalcium phosphate and bone gelatin) to facilitate application. Clinical results are especially convincing as to osteochondral fractures, repair of the Achilles tendon, and in hemophiliacs. Fibrin sealant facilitates hemostasis, permits tissue fixation, enhances plasticity of granular implant material, and stimulates fibroblast growth. Although its direct osteogenic effect remains questionable, fibrin sealant is known to be an excellent tool in orthopedic and trauma surgery.

Bone healing in rabbits after compression osteosynthesis: a comparative study between the radiological and histological findings

The relationship between the radiological and histological findings was studied in a series of rabbit osteotomies and fractures stabilized with plates with and without longitudinal compression. When compression was employed, the gap varied between 10 and 200 μm and no radiologically visible callus was seen. After 4 weeks the smallest gaps of 10–30 μm were filled histologically with structureless material, while the larger gaps contained ‘cortical’ bone derived from periosteal and endosteal proliferation. The degree of union could not be assessed from X-ray examination, as there was no correlation between the histological and radiological appearances. When no compression was employed, the gap varied between 200–1200 μm; radiologically visible periosteal callus and filling of the gap indicated that consolidation had appeared in four weeks. Gaps of 200–500 μm were filled with bone derived from the periosteum and endosteum of lamellar structure which had invaded the original cortical bone (‘plugging’). When the gaps were more than 500 μm, islands of cartilage and connective tissue were found. In all cases studied, many ‘anchoring osteons’ passed from the endosteal and periosteal callus into the original cortical bone. It is concluded that a ‘compression internal fixation’ of cortical bone will not necessarily secure union, as histologically confirmed, even when the formation of radiologically visible callus is suppressed. The lack of periosteal callus appears to be the result of a small gap and rigid fixation, rather than related to strains induced in the bone.

An experimental study on the effect of local hemostatics on bone healing in rabbits

Local hemostatics, Surgicel ® and Hémofibrine ®, were implanted in mandibular and tibial bone cavities of adult rabbits. The effects on bone healing were studied by microradiography after 2 and 4 weeks. Initial bone formation was retarded by the implanted hemostatics. After 4 weeks the difference from the controls was small. The hemostatics are of no value in stimulating bone formation. To arrest bleeding in bone cavities, Surgicel seems to be preferable as it inhibited bone formation less than did Hémofibrine.