Porous HA ceramic for bone replacement: role of the pores and interconnections - experimental study in the rabbit.

Hydroxyapatite (HA) porous ceramics are increasingly used in biomedical applications. Their physical characteristics, such as porous volume, require perfect control of the pore shape, as well as the number and the size of their interconnections. The aim of our study was to evaluate a new HA ceramic using polymethylmethacrylate microbeads (PMMA) as the porous agent. Four interconnection sizes (30, 60, 100 and 130 microm) with a 175-260 microm pore size and three pore sizes (175-260, 260-350 and 350-435 microm) for a 130 microm interconnection size were tested. Various HA implants were appraised by microscopic evaluation in a 4.6 x 10 mm rabbit femur cancellous bone defect 12 weeks after implantation. The best osteoconduction result was obtained in the center of the ceramic by means of a 130 microm interconnection size and a 175-260 microm mean pore size. Bone formation obtained within the pores was double that obtained in our previous study where naphtalen microbeads were used as the porous agents.

Volume effect on biological properties of a calcium phosphate hydraulic cement: experimental study in sheep.

Injectable calcium phosphate hydraulic cements (CPHC) are a new family of bone substitutes within the class of bone reconstruction biomaterials. In this work, CPHC were tested in two consistencies (preset blocks or liquid paste) in an experimental model of cancellous bone defect in sheep. The defects were eight times larger than those investigated previously in rabbits. Three delays (12, 24, and 52 weeks) were used. Before death, a double label of oxytetracycline and alizarine was made intravenously. The distribution of implants was randomized, histomorphometric evaluation was performed and compared with micrographic observation, and optical microscopy of stained sections was performed either under visible, ultraviolet, or polarized light. The results were compared with spontaneous healing of empty defects and with a control group of normal cancellous bone from sheeps of the same age. No significant difference has been observed between premolded and injected implants. In the sheep model, the degradation and new bone formation rates are three times slower, compared with those observed previously in rabbits. New bone formation increased from 5.9% (12 weeks) up to 11.0% (24 weeks) in the empty defect group. In the cement groups, 28.3% new bone was obtained at 12 weeks, which seemed then to level off (27.8% new bone at 24 weeks). Cement residues appear as radio-opaque cylinders on microradiographs. In all cases, a radiolucent layer was observed at the cement/bone interface at 24 weeks. Stained sections showed the formation of a fibroconnective capsule around the residual cement, which presumably slows down new bone formation. Nevertheless, quantitative bone remodeling was accelerated in the cement group; mineral apposition as well as adjusted apposition rates were higher, and the formation period as well as the mineralization of osteoid tissue were faster compared with empty cavities and controls. These results point to higher osteoblast activity and better exchange with surrounding tissues in the defects filled with cement.

Association of porous hydroxyapatite and bone marrow cells for bone regeneration.

The preparation of hybrid material with osteoinductive capacity may be achieved by association of cultured autologous bone cells with a porous ceramic vehicle. We optimized culture conditions for rabbit marrow stromal stem cells (MSCs), notably by selection from batches of fetal calf serum. Rabbit MSCs formed colony-forming unit-ribroblastic (CFU-Fs) in vitro. Their alkaline phosphatase (ALP) activity was doubled in the presence of dexamethasone. Autologous rabbit serum allowed the formation of ALP-positive CFU-Fs, but results were highly variable depending on the rabbit. We tested the osteogenic potential of autologous cultured (with or without dexamethasone addition in the culture medium) and noncultured rabbit MSCs associated with a porous hydroxyapatite ceramic after a dorsal intramuscular implantation. Nucleated cells (10(7) or 10(8)/mL) were used for the preparation of autologous hybrid material. A significantly higher number of implants containing bone was obtained with a suspension of 10(7) cells/mL cultured in the presence of 10(-8) M dexamethasone. Some positive implants were also obtained with a suspension of 10(8) noncultured cells/mL. We demonstrated the feasibility of preparing rabbit autologous hybrid materials following a process for controlling culture conditions, cell characterization and cell/material association.

Experimental model of posterolateral spinal arthrodesis in sheep. Part 1. Experimental procedures and results with autologous bone graft.

OBJECTIVES: The authors evaluated the reliability in obtaining a posterolateral spinal arthrodesis (PSA) with autologous bone graft. SUMMARY OF BACKGROUND DATA: Posterolateral spinal arthrodesis using autogenous cancellous bone graft is the most simple and efficient technique to get a spinal graft. No extensive biomechanical study of PSA is available. Thus, an experimental model of PSA is needed. METHODS: Eleven sheep underwent lumbar autologous bone grafts and Cotrel-Dubousset instrumentations, and four sheep were used as controls. Sacrifice and biomechanical evaluation of the lumbar spines were performed after 1 year. RESULTS: All grafts appeared continuous. A large decrease of flexibility (in rotation and in translation) was found in grafted spines in every direction. Failure in extension occurred at a mean value of 35.26 +/- 3.71 Nm. CONCLUSION: A constant and homogenous PSA appears to be obtained in sheep under conditions close to the human surgery.

Experimental model of posterolateral spinal arthrodesis in sheep. Part 2. Application of the model: evaluation of vertebral fusion obtained with coral (Porites) or with a biphasic ceramic (Triosite).

OBJECTIVES: The authors evaluated two bone substitutes in a posterolateral spinal arthrodesis (PSA) model in sheep: coral porites (99% calcium carbonate, Biocoral, Inoteb, France) and a biphasic ceramic (BCP) (65% hydroxyapatite and 35% B tricalcium phosphate, Triosite, Zimmer International). SUMMARY OF BACKGROUND DATA: Bone substitutes would be of great interest for PSA. Previous trials began with two kinds of biomaterials: natural coralline calcium carbonate, and phosphate calcium ceramic. METHODS: A lumbar PSA was performed in 11 sheep (coral group) and in 9 sheep (BCP group). Sacrifice and biomechanical tests were performed after 1 year. RESULTS: A large decrease of flexibility in all directions was obtained with both coral PSA and BCP PSA similarly to autologous graft. No nonfusion case was observed. CONCLUSION: In conditions close to the human surgery, a PSA can be obtained using either coral porites or BCP as bone substitutes.

Effects of the calcium channel blocker nifedipine on epiphyseal growth plate and bone turnover: a study in rabbit.

The potential effects of a calcium channel blocker (nifedipine) on epiphyseal growth plate and bone remodeling have been investigated in growing rabbits. The treated group received 6 mg/kg/day nifedipine twice daily by gavage for 10 weeks. An untreated group was used as control; with this dose, neither toxic effects nor decrease in the body weight have been observed. No modifications of blood phosphocalcic parameters have been found. In the treated group there is a significant lower cancellous bone volume, lower osteogenesis, shorter labeled perimeters, and lower mineral apposition rate than in the control group. Epiphyseal growth plate thickness is lower than in the untreated animals and considerable morphological changes are observed in the growth zone compared with the control group. A decrease in the growth of humerus length was found. In conclusion, nifedipine affects bone physiology, especially with consequences on bone growth. These effects appear to be quantitatively important, and there is the possibility of bone side effects on therapeutic use in humans, especially in young subjects.

[Effect of a calcium inhibitor, verapamil, on the development of heterotopic ossifications. An experimental study in rats]. / Effet d'un inhibiteur calcique, le vérapamil, sur le développement des ossifications hétérotopiques. Etude expérimentale chez le rat.

After division of the tendo achilles in rats heterotopic bone forms in the muscle and in the tendon stumps. Tenotomy was performed in 26 male rats. Thirteen received Verapamil (36 mm/Kg) for six days per week for five months, and the remainder were not given this drug. The onset of heterotopic ossification was monitored by monthly x-rays. After five months the animals were killed and the sectioned tendons examined microscopically. The radiographs had shown that the amount of ossification was less in rats treated with Verapamil. This was confirmed at microscopy, but examination of the sections under polarised light showed that the ratio of lamellar to woven bone was the same in the two groups. Verapamil appeared to reduce the amount of heterotopic bone formation but did not influence the substitution of woven by lamellar bone.