A Dynamic Interbody Cage Improves Bone Formation in Anterior Cervical Surgery: A Porcine Biomechanical Study.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) with a rigid interbody spacer is commonly used in the treatment of cervical degenerative disc disease. Although ACDF relieves clinical symptoms, it is associated with several complications such as pseudoarthrosis and adjacent segment degeneration. The concept of dynamic fusion has been proposed to enhance fusion and reduce implant subsidence rate and post-fusion stiffness; this pilot preclinical animal study was conducted to begin to compare rigid and dynamic fusion in ACDF. QUESTIONS/PURPOSES: Using a pig model, we asked, is there (1) decreased subsidence, (2) reduced axial stiffness in compression, and (3) improved likelihood of bone growth with a dynamic interbody cage compared with a rigid interbody cage in ACDF? METHODS: ACDF was performed at two levels, C3/4 and C5/6, in 10 pigs weighing 48 to 55 kg at the age of 14 to 18 months (the pigs were skeletally mature). One level was implanted with a conventional rigid interbody cage, and the other level was implanted with a dynamic interbody cage. The conventional rigid interbody cage was implanted in the upper level in the first five pigs and in the lower level in the next five pigs. Both types of interbody cages were implanted with artificial hydroxyapatite and tricalcium phosphate bone grafts. To assess subsidence, we took radiographs at 0, 7, and 14 weeks postoperatively. Subsidence less than 10% of the disc height was considered as no radiologic abnormality. The animals were euthanized at 14 weeks, and each operated-on motion segment was harvested. Five specimens from each group were biomechanically tested under axial compression loading to determine stiffness. The other five specimens from each group were used for microCT evaluation of bone ingrowth and ongrowth and histologic investigation of bone formation. Sample size was determined based on 80% power and an α of 0.05 to detect a between-group difference of successful bone formation of 15%. RESULTS: With the numbers available, there was no difference in subsidence between the two groups. Seven of 10 operated-on levels with rigid cages had subsidence on a follow-up radiograph at 14 weeks, and subsidence occurred in two of 10 operated-on levels with dynamic cages (Fisher exact test; p = 0.07). The stiffness of the unimplanted rigid interbody cages was higher than the unimplanted dynamic interbody cages. After harvesting, the median (range) stiffness of the motion segments fused with dynamic interbody cages (531 N/mm [372 to 802]) was less than that of motion segments fused with rigid interbody cages (1042 N/mm [905 to 1249]; p = 0.002). Via microCT, we observed bone trabecular formation in both groups. The median (range) proportions of specimens showing bone ongrowth (88% [85% to 92%]) and bone volume fraction (87% [72% to 100%]) were higher in the dynamic interbody cage group than bone ongrowth (79% [71% to 81%]; p < 0.001) and bone volume fraction (66% [51% to 78%]; p < 0.001) in the rigid interbody cage group. The percentage of the cage with bone ingrowth was higher in the dynamic interbody cage group (74% [64% to 90%]) than in the rigid interbody cage group (56% [32% to 63%]; p < 0.001), and the residual bone graft percentage was lower (6% [5% to 8%] versus 13% [10% to 20%]; p < 0.001). In the dynamic interbody cage group, more bone formation was qualitatively observed inside the cages than in the rigid interbody cage group, with a smaller area of fibrotic tissue under histologic investigation. CONCLUSION: The dynamic interbody cage provided satisfactory stabilization and percentage of bone ongrowth in this in vivo model of ACDF in pigs, with lower stiffness after bone ongrowth and no difference in subsidence. CLINICAL RELEVANCE: The dynamic interbody cage appears to be worthy of further investigation. An animal study with larger numbers, with longer observation time, with multilevel surgery, and perhaps in the lumbar spine should be considered.

Dual-functional bone implants with antibacterial ability and osteogenic activity.

A growing number of biomaterial-associated infections cause bone implant failures in early and long-term applications. In this regard, a calcium silicate-gelatine composite bone implant with high strength and superior osteogenic activity was coated with a layer of Ag, chitosan polysaccharide (CS) or water-soluble chitosan oligosaccharide (COS) as a bactericidal agent. The influences of surface modifications to the bone implants on phase composition, microstructure, antibacterial effectiveness, and osteogenic activity in vitro were evaluated. Experimental results revealed the presence of the coating on the implant surface using a simple deposition technique. The in vitro antibacterial evaluation indicated that the antimicrobial effectiveness of the Ag coating against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) was inferior to the 0.4% CS coating, but comparable to those of 0.2% CS and 0.4% COS coatings after 48 h of culture. CS presented a greater bactericidal effect than COS, which was bacteria-independent. CS and COS coatings had no significant cytotoxicity towards L929 cells at coating concentrations of 0.1%, 0.2%, and 0.4%, except for the cells exposed to the 0.4% CS coating, while the 0.004% Ag coating remarkably produced cytotoxicity. The assays of cell functions consistently showed significantly higher osteogenic activity of MG63 cells grown on CS and COS-coated surfaces by increased attachment, proliferation, alkaline phosphatase, osteocalcin, and calcium deposits production, except for the 0.4% CS coating, in comparison with those on the Ag coated surface. It was concluded that, taking antibacterial ability and osteogenic activity into account, 0.2% CS-coated and 0.4% COS-coated calcium silicate-gelatine composite bone implants had a large potential to be used in bone grafts and fracture fixation devices.

Acid-resistant calcium silicate-based composite implants with high-strength as load-bearing bone graft substitutes and fracture fixation devices.

To achieve the excellent mechanical properties of biodegradable materials used for cortical bone graft substitutes and fracture fixation devices remains a challenge. To this end, the biomimetic calcium silicate/gelatin/chitosan oligosaccharide composite implants were developed, with an aim of achieving high strength, controlled degradation, and superior osteogenic activity. The work focused on the effect of gelatin on mechanical properties of the composites under four different kinds of mechanical stresses including compression, tensile, bending, and impact. The evaluation of in vitro degradability and fatigue at two simulated body fluid (SBF) of pH 7.4 and 5.0 was also performed, in which the pH 5.0 condition simulated clinical conditions caused by bacterial induced local metabolic acidosis or tissue inflammation. In addition, human mesenchymal stem cells (hMSCs) were sued to examine osteogenic activity. Experimental results showed that the appropriate amount of gelatin positively contributed to failure enhancement in compressive and impact modes. The 10wt% gelatin-containing composite exhibits the maximum value of the compressive strength (166.1MPa), which is within the reported compressive strength for cortical bone. The stability of the bone implants was apparently affected by the in vitro fatigue, but not by the initial pH environments (7.4 or 5.0). The gelatin not only greatly enhanced the degradation of the composite when soaked in the dynamic SBF solution, but effectively promoted attachment, proliferation, differentiation, and formation of mineralization of hMSCs. The 10wt%-gelatin composite with high initial strength may be a potential implant candidate for cortical bone repair and fracture fixation applications.

In vitro degradation and angiogenesis of the porous calcium silicate-gelatin composite scaffold.

Calcium silicate-based materials have attracted a great deal of interest due to their osteogenesis and have been used as implant materials for bone repair and regeneration. The purpose of this study was to use gelatin with and without genipin cross-linking for controlling degradation, improving mechanical properties, and enhancing angiogenesis of calcium silicate bioceramics. The in vitro degradation of gelatin-containing scaffolds was analysed in a simulated body fluid (SBF) solution. Human mesenchymal stem cells (hMSCs) were used to examine angiogenesis. The results indicated that the gelatin-containing scaffolds showed a diametral tensile strength of about 2 MPa and a porosity of about 60% falling within the range of values reported for the cancellous bone. Apatite precipitation occurred on all scaffold surfaces after soaking in SBF for 1 week. The gelatin-containing scaffold without cross-linking exhibited a greater weight loss and porosity than the control without gelatin. The cross-linking agent, genipin, significantly improved the mechanical stability of the composite scaffold. The gelatin enhanced the viable cell populations. More importantly, gelatin actively promoted the secretion of angiogenic factors such as von Willebrand factor and angiopoietin-1 in hMSCs. It is concluded that combination of calcium silicate and gelatin may synergistically enhance clinically desirable functions in terms of controlled degradation, improved mechanical properties, and enhanced angiogenesis.

Enhanced Hydrophilicity and Biocompatibility of Dental Zirconia Ceramics by Oxygen Plasma Treatment.

Surface properties play a critical role in influencing cell responses to a biomaterial. The objectives of this study were (1) to characterize changes in surface properties of zirconia (ZrO2) ceramic after oxygen plasma treatment; and (2) to determine the effect of such changes on biological responses of human osteoblast-like cells (MG63). The results indicated that the surface morphology was not changed by oxygen plasma treatment. In contrast, oxygen plasma treatment to ZrO2 not only resulted in an increase in hydrophilicity, but also it retained surface hydrophilicity after 5-min treatment time. More importantly, surface properties of ZrO2 modified by oxygen plasma treatment were beneficial for cell growth, whereas the surface roughness of the materials did not have a significant efficacy. It is concluded that oxygen plasma treatment was certified to be effective in modifying the surface state of ZrO2 and has the potential in the creation and maintenance of hydrophilic surfaces and the enhancement of cell proliferation and differentiation.

Impact Behavior of Three Notched All-Ceramic Restorations after Soaking in Artificial Saliva.

Biomechanics play a critical role in influencing the clinical applications of all-ceramic dental restorations. The restorative biomaterials have to demonstrate mechanical durability in the oral environment because they are always exposed to a variety of oral environments. This study was designed to evaluate the effect of soaking time, notch and saliva pH values on the impact energy of three commonly used all-ceramic materials for CAD/CAM. The leucite-reinforced glass ceramic (ProCAD), lithium disilicate glass ceramic (IPS e.max CAD) and zirconia-based ceramic materials (IPS e.max ZirCAD) were used. The experimental results indicated that the impact energy of ProCAD decreased with an increase in soaking time, but not for IPS e.max CAD and IPS e.max ZirCAD. The impact energy of the zirconia system was higher than leucite-reinforced and lithium disilicate-based ceramic systems. When subjected to preformed 0.5 mm U-shape notch on the bar specimen of 3 mm thick, the impact energy of the all-ceramic restorations revealed a markedly reduction of about 80%-90%, almost irrespective of dental compositions, which indicated the effect of flaw to a great degree. No statistically significant influence (p > 0.05) of pH values (4, 7 and 9) on impact energy was found for each group. It is concluded that the no matter which all-ceramic materials were used, it was appreciably sensitive to the presence of notches. The ceramic composition and microstructure have been shown to affect mechanical durability.

In vitro physicochemical properties, osteogenic activity, and immunocompatibility of calcium silicate-gelatin bone grafts for load-bearing applications.

The use of a composite made of natural polymer gelatin and bioactive calcium silicate resembling the morphology and properties of natural bone may provide a solution to the problem of ceramic brittleness for load-bearing applications. The in vitro bioactivity, degradability, osteogenic activity, and immunocompatibility of three types of calcium silicate-gelatin composite bone grafts were characterized. The osteogenic activity and immunocompatibility were evaluated by incubating the bone grafts with human dental pulp cells. After soaking in a simulated body fluid (SBF) for 1 day, all materials were covered with clusters of "bone-like" apatite spherulites. The control material without gelatin exhibited an insignificant change in strength, degradability, and porosity and a small weight loss of 6% after 180 days of soaking in the SBF solution. In contrast, the soaking time imposed in this study did have a statistically significant effect on compressive strength, porosity, and weight loss of the gelatin-containing composites. After 180 days of soaking, the composite with 10 wt % gelatin lost 47% and 10% in compressive strength and weight, respectively, with a porosity of 23%. However, the presence of gelatin promoted greater cell attachment and proliferation on the composite bone grafts. Pulp cells on the calcium silicate-gelatin bone grafts expressed higher levels of osteocalcin, osteopontin, and bone sialoprotein. The inhibition of inducible nitric oxide synthase and interleukin-1 expression and the activation of interleukin-10 were increased with increasing gelatin content. Overall, these findings provide evidence that composite bone grafts containing 10 wt % gelatin with a high initial strength were bioactive, nontoxic, and osteogenic and may be able to promote bone healing for load-bearing applications.