Background. Calcium sulfate and phosphate have a long clinical history of use as bone-void fillers (BVF) with established biocompatibility and resorption profiles. It has been widely reported that the addition of ‘impurity’ elements such as Silicon, Strontium and Zinc to calcium phosphate is advantageous, resulting in an improved bone healing response. Methods. This study examined the in vivo response of two formulations of calcium sulfate, as 3mm diameter hemispherical beads, in critical sized defects created in cancellous bone of distal femur and proximal tibia (10mm diameter × 13mm depth) in adult sheep; beads prepared from recrystallised pharmaceutical grade calcium sulfate (RPCS, Stimulan, Biocomposites Ltd, UK) and a lower purity medical grade material containing 1% strontium (SrCS). The animals were sacrificed at 3, 6 and 12 weeks post implantation and the surgical sites analysed using microCT and decalcified histology. Results. Radiographic analysis showed a slower resorption for SrCS compared to RPCS. Radiographic analysis for both materials confirmed little residual beads at three weeks post implantation. Radiographs at sacrifice confirmed no adverse reactions at any sites at 3, 6 and 12 weeks. Radiographic data alone was not adequate to determine the status of the bone formation and the implant resorption at the implant site. Histological analysis confirmed little or no adverse tissue reactions to either material. However, RPCS outperformed the modified material in terms of new bone formation at all time points post implantation. At 3 weeks histology for RPCS confirmed that residual beads were still visible with active new bone growth appearing to penetrate centripetally into the defect with some resorption of the implant material. By 6 weeks significant new bone was present throughout the defect. In comparison, absorption of the modified material was slower, and penetration of new bone into the defect was less progressed. Conclusions. The rapid bone regenerative ability of the recrystallised pharmaceutical grade calcium sulfate was demonstrated. The presence of 1% Strontium impurity acted to delay implant absorption and bone healing in this model

Although bone morphogenetic protein 2 (BMP-2) has been FDA-approved for spinal fusion for decades, its disadvantages of promoting osteoclast-based bone resorption and suboptimal carrier (absorbable collagen sponge) leading to premature release of the protein limit its clinical applications. Our recent study showed an excellent effect on bone regeneration when BMP-2 and zoledronic acid (ZA) were co-delivered based on a calcium sulphate/hydroxyapatite (CaS/HA) scaffold in a rat critical-size femoral defect model. Therefore, the aim of this study was to evaluate whether local application of BMP-2 and ZA released from a CaS/HA scaffold is favorable for spinal fusion. We hypothesized that CaS/HA mediated controlled co-delivery of rhBMP-2 and ZA could show an improved effect in spinal fusion over BMP-2 alone. 120, 8-week-old male Wistar rats (protocol no. 25-5131/474/38) were randomly divided into six groups in this study (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, CaS/HA + BMP-2 + local ZA). A posterolateral spinal fusion at L4 to L5 was performed bilaterally by implanting group-dependent scaffolds. At 3 weeks and 6 weeks, 10 animals per group were euthanized for µCT, histological staining, or mechanical testing. µCT and histological results showed that the CaS/HA + BMP-2 + local ZA group significantly promoted bone regeneration than other treated groups. Biomechanical testing showed breaking force in CaS/HA + BMP + local ZA group was significantly higher than other groups at 6 weeks. In conclusion, the CaS/HA-based biomaterial functionalized with bioactive molecules rhBMP-2 and ZA enhanced bone formation and concomitant spinal fusion outcome

Acknowledgements: Many thanks to Ulrike Heide, Anna-Maria Placht (assistance with surgeries) as well as Suzanne Manthey & Annett Wenke (histology).

The combination of natural polymers with calcium phosphate cements (CPCs) by mimicking the highly mineralized collagen-based matrix of native bone is crucial in order to obtain mechanically compatible injectable bone substitute (IBS) formulations. This combination overcomes the drawbacks of CPCs like high resorbability, poor mechanical properties, and degradability. In this study, methylcellulose (MC) was combined with CPCs because of MC's thermoresponsive behavior which makes MC suitable for IBS application. In addition, gelatin (GEL) was also incorporated to adjust the gelation temperature and to enhance cell adhesion. These polymers combination makes the liquid (L) phase. The powder (P) phase comprised of tetra calcium phosphate (TTCP), dicalcium phosphate dehydrates (DCPD), and calcium sulfate dehydrates (CSD). TTCP and DCPD are commonly studied for the development of bone cements and they lead to high-density products. CSD was added to the powder phase to increase the porosity as well as to enhance mechanical properties of the IBS. TTCP was synthesized using a solid state method. Test tube inversion method was used to adjust the gelation temperature. GEL concentration was kept constant at 5 wt% and MC concentration varied between 1.5 and 12 wt%. The weight fraction of P/L phase was used as 1.8:1 (wt/wt). Synthesized IBS was characterized by using X-Ray Diffraction (XRD), Fourier Transform Infrared Analysis (FTIR), Zeta Particle Size Analysis, rheometry, and thermogravimetric analysis. XRD and FTIR analysis proved that TTCP was successfully synthesized with a particle size of 430.1 nm. The particle size of P phase mixture was measured as 581.1 nm. Based on the test tube inversion tests, weight fraction of MC was chosen as 10 and 12 while the weight fraction of GEL was fixed as 5. FTIR spectra of the liquid phase was showed that there was a hydrophilic interaction between MC and GEL since both Amide I at 1633 cm. −1. and β-gylcosides bonds among saccharide units at 900–1230 cm. −1. were clearly seen. MC10GEL5/P and MC12GEL5/P were analyzed by the XRD. According to this analysis, only the peaks of TTCP, DCPD, and CSD were observed. From the rheological data obtained from the rheometer, it is evident that all the prepared formulations exhibited Newtonian flow. The measured viscosity of all the investigated formula remained constant with the applied force over time. The MC12GEL5/P had the highest viscosity value due to its high concentration of MC (12% w/v). Results of TG of the synthesized IBS showed two main decomposition steps for the L phase because of the hydrophilic interaction between MC and GEL. The synthesized self-crosslinkable IBS represent promising platforms for future studies in bone tissue engineering. Overall, the presented study identified a novel IBS with suitable viscoelastic properties for non-invasive treatment of bone defects which may ultimately be a substitute for surgery for a wide variety of therapeutic applications

Objectives

This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling.