Evaluation of the clinical effectiveness of bioactive glass (S53P4) in the treatment of non-unions of the tibia and femur: study protocol of a randomized controlled non-inferiority trial

Abstract

BackgroundTreatment of non-union remains challenging and often necessitates augmentation of the resulting defect with an autologous bone graft (ABG). ABG is limited in quantity and its harvesting incurs an additional surgical intervention leaving the risk for associated complications and morbidities. Therefore, artificial bone graft substitutes that might replace autologous bone are needed. S53P4-type bioactive glass (BaG) is a promising material which might be used as bone graft substitute due to its osteostimulative, conductive and antimicrobial properties. In this study, we plan to examine the clinical effectiveness of BaG as a bone graft substitute in Masquelet therapy in comparison with present standard Masquelet therapy using an ABG with tricalciumphosphate to fill the bone defect.Methods/designThis randomized controlled, clinical non-inferiority trial will be carried out at the Department of Orthopedics and Traumatology at Heidelberg University. Patients who suffer from tibial or femoral non-unions with a segmental bone defect of 2–5 cm and who are receiving Masquelet treatment will be included in the study. The resulting bone defect will either be filled with autologous bone and tricalciumphosphate (control group, N = 25) or BaG (S53P4) (study group, N = 25). Subsequent to operative therapy, all patients will receive the same standardized follow-up procedures. The primary endpoint of the study is union achieved 1year after surgery.DiscussionThe results from the current study will help evaluate the clinical effectiveness of this promising biomaterial in non-union therapy. In addition, this randomized trial will help to identify potential benefits and limitations regarding the use of BaG in Masquelet therapy. Data from the study will increase the knowledge about BaG as a bone graft substitute as well as identify patients possibly benefiting from Masquelet therapy using BaG and those who are more likely to fail, thereby improving the quality of non-union treatment.Trial registrationGerman Clinical Trials Register (DRKS), ID: DRKS00013882. Registered on 22 January 2018.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2681-9) contains supplementary material, which is available to authorized users.

Optimized Bioactive Glass: the Quest for the Bony Graft

“…This discovery paved the way to the development of many bioactive materials in the field of bioactive ceramics including variants of the original 45S5 Bioglass, glass‐ceramics, and other ceramics such as HaP and CaP . As evidence of the current interest for bioactive glasses, a clinical trial involving S53P4 BAG in the treatment of nonunion of the tibia and femur in comparison with autologous/tricalciumphosphate graft have been approved and recruitment is in progress …”

“…Finding the right balance between bridging and nonbridging oxygen atoms in BAG is crucial in order to maintain the adequate mechanical properties and obtain the desired degradation behavior while maintaining satisfying biological properties. By varying the composition and the amount of network modifiers, many synthesis parameters can be set, including transition temperature, softening point and solubility . The role of P 2 O 5 in silicate BAG has been a much‐debated subject.…”

“…However, this hypothesis was no longer supported by nuclear magnetic resonance (NMR) and optical data, and the absence of SiOP bridges in 45S5 Bioglass was also confirmed by a 31 P NMR and 17 O multiquantum magic‐angle spinning (MQMAS) experiment . Indeed, in silicate BAG, P 2 O 5 appears to be present as orthophosphate units (PO 4 3− ) that attract cations such as Ca 2+ and Na + to form independent clusters . Calcium and sodium act as charge balancers and are prevented from their network‐modifying role.…”

Sintered S53P4 bioactive glass scaffolds have anti-inflammatory properties and stimulate osteogenesis in vitro

“…The unique properties of the BAG, such as its osteoconductive, osteostimulative, and anti-microbial properties, would make the material ideal for the development of a 1-staged IMT. Indeed, an ongoing clinical trial (Tanner et al, 2018) is investigating the use of BAG-S53P4 granules as the sole substitute in filling of segmental defects using the IMT.…”

Bioactive Glass and Silicate-Based Ceramic Coatings on Metallic Implants: Open Challenge or Outdated Topic?

“…They contain SiO 2 , Na 2 O, CaO, and P 2 O 5 in different ratio (Table 2). In Finland a bioactive glass known as S53P4, containing a higher percentage of silica as compared to 45S5 Bioglass was successfully developed, with encouraging results in the treatment of bone defects [88,89,90]. Glass compounds containing other elements as well have been developed, such as 13-93 glass.…”