Bone Formation In Implants Research Articles

Inhibition of BMP9 Induced Bone Formation by Salicylic-acid Polymer Capping.

This work focuses on the development of a system to control the formation of bone to complement developments that have enabled potent regeneration of bony tissue. Scaffolds were fabricated with chemically modified RNA encoding for bone morphogenetic protein-9 (cmBMP9) and capped with salicylic acid (SA)-containing polymer (SAPAE). The goal was to determine if SAPAE could inhibit the formation of bone in a pilot animal study since cmBMP9 has been demonstrated to be highly effective in regenerating bone in a rat calvarial defect model. The results indicated that cmBMP9 increased bone formation (30% increase in area covered compared to control) and that SAPAE trended toward reducing the bone formation. These results suggest SAPAE could be useful as a chemical agent in reducing unwanted bone formation in implants loaded with cmBMP9.

Direct Radial LMHF Microvibration Induced Bone Formation and Promoted Implant Osseointegration

Mechanical loading is known to play an important role in bone remodeling. This study aimed to evaluate the effect of direct low-magnitude high-frequency (LMHF) microvibration on dental implant bone formation and osseointegration. Titanium implants were installed in rabbit tibiae. The implants in the left legs were loaded with mechanical vibration (15 μm) at 10, 20, 30, and 40 Hz (10, 20, 30, and 40 Hz groups, respectively) for 30 minutes every day. The implants on the right legs were used as a sham control and did not receive a vibration load. After 20 days, the 10, 20, and 30 Hz groups showed significantly greater newly formed bone volume, density, ratio of the bone surface area to the trabecular bone surface area, and ratio of the bone surface area in direct contact with osteoclasts versus the total bone surface area in the region of interest compared with the sham control group, especially the 20 Hz group. However, the 40 Hz group did not. In conclusion, the application of direct LMHF (10, 20, or 30 Hz) vibration on the implants promoted bone formation and osseointegration, especially at 20 Hz; however, the use of 40 Hz did not result in any significant improvement.

Osteogenic potential of the human bone morphogenetic protein 2 gene activated nanobone putty

Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2 (hBMP2) gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putty on repairing bone defects. Twenty four Kunming mice were randomly divided into two groups. The nanobone putty + hBMP2 plasmid was injected into the right thigh muscle pouches of the mice (experiment side). The nanobone putty + blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1 (control side 1) or group 2 (control side 2), respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups: Group A, nanobone putty + hBMP2 plasmid; Group B, putty + blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level. The new bone formation rate and antibending strength of group A was significantly higher than those of group B and C. The defects in blank control were not healed. The hBMP2 gene activated nanobone putty exhibited osteoinductive ability, and had a better bone defect repair capability than that of nanobone putty only.

Comparative Study of Bone Cell Culture Methods for Tissue Engineering Applications

Abstract Cells are used in bone tissue engineering applications to facilitate new bone formation in implants. Enzymatic digestion and marrow removal by either centrifugal force or syringe are three methods used to isolate the cells for culture, but each technique has benefits and drawbacks. This comparative study evaluated the effects of the three cell isolation techniques on the attachment, proliferation, and mineralization of rat bone cells. Cells were isolated, seeded, and cultured following standard protocols for each isolation method. Quantitative assays to determine metabolic activity, lactic acid production, glucose consumption, and amounts of intracellular protein, alkaline phosphatase activity, and extracellular calcium were performed. In addition, cell morphology and viability were examined qualitatively. The results indicate that the cell isolation method affects the attachment, proliferation, and type of tissue formed by cells cultured under identical conditions.

Amelogenin gene splice products: potential signaling molecules.

The amelogenins, the major proteins of the developing tooth enamel matrix, are highly conserved throughout most species studied. The gene structure is similar, with a set of seven exons and intervening introns, and remarkable conservation of particular exon sizes over divergent species. Studies of exon skipping and consequent alternative gene splicing suggest that, in vertebrates, exon definition is crucial. In this mechanism, exon size is important. If too small, an exon can be readily skipped, if too large, internal cryptic splice sites may be utilized. Other factors, such as intron length and specific nucleotide sequences at the splice boundaries also modulate splicing efficiency, but amelogenin gene splicing conforms well to the generalized exon length model. Exons 1, 2 and 7 are not subject to splicing that affects the secreted protein product, but exons 3, 4 and 5 are at the lower boundary of exon size, rendering them, 4 and 5 especially, subject to skipping. On the other hand, exon 6 is very long and has cryptic splicing sites that can be used. In the mouse, nine distinct splice product proteins have been detected. The question now is the functions of these products. The larger forms, those that contain the intact proline-rich, hydrophobic exon 6 domains, are important for enamel mineralization. Recent work suggests that the small proteins resulting from deletion of a major part of amelogenin gene exon 6 via utilization of a cryptic site may have signal transduction functions during tooth development. Furthermore, new work also suggests that odontoblasts transiently express the small amelogenins during the period that epithelial-mesenchymal signaling between preodontoblasts and preameloblasts determines the course of tooth development. The same peptides have been demonstrated to act on non-odontogenic cells and effect their phenotypic expression patterns in vitro, and to induce bone formation in implants in vivo.

Effects of bisphosphonates on the incorporation of calcium-45 and 3H-proline in orthotopic and in demineralized matrix-induced bone in rats

The influence of the two bisphosphonates, 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) and dichloromethylene bisphosphonate (Cl 2MBP), on bone formation was studied in demineralized matrix-induced bone in young rats. Cl 2MBP was given in doses of 0.3 and 3 mg P/kg per day and HEBP 2,4 and 8 mg P/kg per day starting immediately after implantation of the bone matrix and continued until sacrifice at 3 weeks. Rates of collagen synthesis and mineralization of implants, femurs and incisor teeth were quantified by assay of 3H-proline and 45Ca injected 24 h before death. New bone formation in implants was also evaluated by histologic examinations. Implants from Cl 2MBP-treated animals had wider bone trabeculae than controls but were colonized by normal appearing hematopoietic tissue. Implants and femurs from both Cl 2MBP groups had a higher ash content than controls, but uptake of the two isotopes was not affected. These results indicate that Cl 2MBP, at these dose levels, inhibits bone resorption without affecting bone formation in rats. The uptake of 45Ca in implants decreased with increasing doses of HEBP; almost no ash or 45Ca activity was encountered with the highest dose. The bone in implants from this group appeared less mature, and only scanty areas of bone marrow were seen. The uptake of 3H-proline was not affected by HEBP. It appears that, in rats, HEBP primarily inhibits mineralization and resorption, whereas matrix formation remains largely unaffected.

29 Bone Formation in Implants of Partially and Wholly Demineralized Bone Matrix

From the Bone Research Laboratory, Division of Orthopedic Surgery, Department of Surgery, U.C.L.A. School of Medicine, Los Angeles, Calif. 90024.