Biomechanical and clinical evaluation of minimal invasive plate osteosynthesis for two-part clavicle shaft fractures.

BACKGROUND: Many surgical treatment methods exist for clavicle shaft fractures. A locking compression plate (LCP) fixation with three screws per fracture side is commonly used. For certain fractures a stabilization with 2 screws per side is potentially suitable, offering the advantage of reduced soft tissue approach, while avoiding the disadvantages of minimally-invasive nailing at the same time. This hypothesis was evaluated biomechanically and clinically. METHODS: Four treatment procedures were investigated biomechanically using composite human clavicle specimens. A load-to-failure test was performed using a three-point cantilever test. In group 1, a simple shaft fracture was simulated and stabilized with 2 screws per fracture side (5-hole LCP). In the second group 3 screws per side (7-hole LCP) were used. In group 3, a non-reduced fracture zone was simulated and treated with 3 screws per side (7-hole LCP). In group 4, an anatomically reduced fracture zone was simulated and treated with 3 screws per side (7-hole LCP). Furthermore 27 patients treated with a short plate and 2 screws per side (similar to group 1) were assessed after a minimum follow-up of 12 months (Constant and DASH Score). RESULTS: The maximum load-to-failure of group 1 was 367N. We observed the highest load-to-failure in group 2 with 497N and the lowest in group 3 with 90N. In group 4 a maximum load-to-failure of 298N could be evaluated. There was no significant difference in load-to-failure between the treatment of a simple clavicle fracture using 5- or 7-hole LCP (p = 0.121). However, we found a significant difference of load-to-failure between the simple and anatomically reduced fracture using a 7-hole plate (p = 0.014). The mean constant score of the surgically treated patients was 95 and the DASH score 3.0. Fracture consolidation was observed in 96.3%. CONCLUSIONS: For certain non-fragmented and well interlocking 2-part fractures, a plate osteosynthesis fixed with only 2 screws per fracture side might offer sufficient biomechanical stability, better soft tissue preservation and comparable fusion rates compared to the operative treatment with 3 screws per side. However, the maximum load-to-failure of the 7-hole LCP was higher than of the 5-hole LCP, but this difference was not statistically significant. TRIAL REGISTRATION: Approval from the ethics committee of the Technical University of Dresden was retrospectively obtained (EK 588122019).

Toward Biofabrication of Resorbable Implants Consisting of a Calcium Phosphate Cement and Fibrin-A Characterization In Vitro and In Vivo.

Cleft alveolar bone defects can be treated potentially with tissue engineered bone grafts. Herein, we developed novel biphasic bone constructs consisting of two clinically certified materials, a calcium phosphate cement (CPC) and a fibrin gel that were biofabricated using 3D plotting. The fibrin gel was loaded with mesenchymal stromal cells (MSC) derived from bone marrow. Firstly, the degradation of fibrin as well as the behavior of cells in the biphasic system were evaluated in vitro. Fibrin degraded quickly in presence of MSC. Our results showed that the plotted CPC structure acted slightly stabilizing for the fibrin gel. However, with passing time and fibrin degradation, MSC migrated to the CPC surface. Thus, the fibrin gel could be identified as cell delivery system. A pilot study in vivo was conducted in artificial craniofacial defects in Lewis rats. Ongoing bone formation could be evidenced over 12 weeks but the biphasic constructs were not completely osseous integrated. Nevertheless, our results show that the combination of 3D plotted CPC constructs and fibrin as suitable cell delivery system enables the fabrication of novel regenerative implants for the treatment of alveolar bone defects.

Composites consisting of calcium phosphate cements and mesoporous bioactive glasses as a 3D plottable drug delivery system.

Calcium phosphate cements (CPC) and mesoporous bioactive glasses (MBG) are two well studied biomaterial groups widely under investigation on their applicability to treat bone defects in orthopaedics and maxillofacial surgery. Recently the extrusion properties of CPC-MBG composites using a pasty CPC based on a hydrophobic carrier-liquid were studied in our group demonstrating that such composites are suitable for low temperature 3D plotting. Based on this work, we show in this study that by variation of the MBG content in the composite the degradation of the final scaffolds can be influenced. Furthermore, by modifying the cement phase and/or the MBG with therapeutically active ions like strontium, the released ion concentration can be varied over a wide range. In a second step the MBG was functionalized exploiting the high specific surface area of the glass as a carrier system for proteins like lysozyme or grow factors. We developed a protocol that allows the incorporation of protein-laden MBG in CPC pastes without impairing the extrudability of the CPC-MBG composites. Additionally, we found that released proteins from pure MBG or 3D plotted composite-scaffolds maintained their biological activity. Therefore, the combination of CPC and MBG allows the creation of a highly flexible composite system making it a promising candidate for bone tissue engineering. STATEMENT OF SIGNIFICANCE: Calcium phosphate cements and mesoporous bioactive glasses are two promising degradable biomaterials for the regenerative treatment of bone defects. The combination of both materials to a 3D printable composite enables the creation of implants with patient specific geometry. By varying the composition of the composite, the degradation behaviour can be influenced and especially the release of therapeutically active ions is tailorable over a wide range. We demonstrated this for strontium, as it has been shown to stimulate bone formation. Moreover, the bioactive glass can be used as a carrier system for drugs or growth factors and we show the successful combination of such functionalised glass particles and a cement paste without affecting the printability.

Treatment of critical bone defects using calcium phosphate cement and mesoporous bioactive glass providing spatiotemporal drug delivery.

Calcium phosphate cements (CPC) are currently widely used bone replacement materials with excellent bioactivity, but have considerable disadvantages like slow degradation. For critical-sized defects, however, an improved degradation is essential to match the tissue regeneration, especially in younger patients who are still growing. We demonstrate that a combination of CPC with mesoporous bioactive glass (MBG) particles led to an enhanced degradation in vitro and in a critical alveolar cleft defect in rats. Additionally, to support new bone formation the MBG was functionalized with hypoxia conditioned medium (HCM) derived from rat bone marrow stromal cells. HCM-functionalized scaffolds showed an improved cell proliferation and the highest formation of new bone volume. This highly flexible material system together with the drug delivery capacity is adaptable to patient specific needs and has great potential for clinical translation.

Tailorable Zinc-Substituted Mesoporous Bioactive Glass/Alginate-Methylcellulose Composite Bioinks.

Bioactive glasses have been used for bone regeneration applications thanks to their excellent osteoconductivity, an osteostimulatory effect, and high degradation rate, releasing biologically active ions. Besides these properties, mesoporous bioactive glasses (MBG) are specific for their highly ordered mesoporous channel structure and high specific surface area, making them suitable for drug and growth factor delivery. In the present study, calcium (Ca) (15 mol%) in MBG was partially and fully substituted with zinc (Zn), known for its osteogenic and antimicrobial properties. Different MBG were synthesized, containing 0, 5, 10, or 15 mol% of Zn. Up to 7 wt.% of Zn-containing MBG could be mixed into an alginate-methylcellulose blend (algMC) while maintaining rheological properties suitable for 3D printing of scaffolds with sufficient shape fidelity. The suitability of these composites for bioprinting applications has been demonstrated with immortalized human mesenchymal stem cells. Uptake of Ca and phosphorus (P) (phosphate) ions by composite scaffolds was observed, while the released concentration of Zn2+ corresponded to the initial amount of this ion in prepared glasses, suggesting that it can be controlled at the MBG synthesis step. The study introduces a tailorable bioprintable material system suitable for bone tissue engineering applications.

Development and Characterization of Composites Consisting of Calcium Phosphate Cements and Mesoporous Bioactive Glass for Extrusion-Based Fabrication.

Calcium phosphate cements (CPC) and mesoporous bioactive glasses (MBG) are two degradable biomaterial groups widely under investigation concerning their applicability to treat bone defects. MBG-CPC composites were recently shown to possess enhanced degradation properties in comparison to pure CPC. In addition, modification of MBG allows an easy incorporation of therapeutically effective ions. Additive manufacturing of such composites enables the fabrication of patient-specific geometries with further improved degradation behavior due to control over macroporosity. In this study, we developed composites prepared from a non-aqueous carrier-liquid (cl) based CPC paste and MBG particles suitable for extrusion-based additive manufacturing (3D plotting). CPC with the addition of up to 10 wt % MBG were processible by adjusting the amount of cl. Scaffolds consisting of a 4, 6 and 8%-MBG-CPC composite were successfully manufactured by 3D plotting. While mechanically characterization of the scaffolds showed an influence of the MBG, no changes of microstructure were observed. During degradation of the composite, the release of Ca2+ and Sr2+ ions could be controlled by the MBG composition and plotted scaffolds with macropores showed a significant higher release than bulk samples of comparable mass. These findings demonstrate a high flexibility regarding ion release of the developed composites and suggest utilizing the drug binding capacities of MBG as a prospective delivery system for biologically active proteins.