Injectable bone cements:What benefits the combination of calcium phosphates and bioactive glasses could bring?

Out of the wide range of calcium phosphate(CaP)biomaterials,calcium phosphate bone cements(CPCs)have attracted increased attention since their discovery in the 1980s due to their valuable properties such as bioactivity,osteoconductivity,injectability,hardening ability through a low-temperature setting reaction and moldability.Thereafter numerous researches have been performed to enhance the properties of CPCs.Nonetheless,low mechanical performance of CPCs limits their clinical application in load bearing regions of bone.Also,the in vivo resorption and replacement of CPC with new bone tissue is still controversial,thus further improvements of high clinical importance are required.Bioactive glasses(BGs)are biocompatible and able to bond to bone,stimulating new bone growth while dissolving over time.In the last decades extensive research has been performed analyzing the role of BGs in combination with different CaPs.Thus,the focal point of this review paper is to summarize the available research data on how injectable CPC properties could be improved or affected by the addition of BG as a secondary powder phase.It was found that despite the variances of setting time and compressive strength results,desirable injectable properties of bone cements can be achieved by the inclusion of BGs into CPCs.The published data also revealed that the degradation rate of CPCs is significantly improved by BG addition.Moreover,the presence of BG in CPCs improves the in vitro osteogenic differentiation and cell response as well as the tissue-material interaction in vivo.

Injectable bone cement with magnesium-containing microspheres enhances osteogenesis via anti-inflammatory immunoregulation

Injectable bone cement is especially useful in minimally invasive surgeries to repair small and irregular bone defects.Amongst different kinds of injectable bone cements,bioactive calcium phosphate bone cement(CPC)has been widely studied due to its biological activity.However,its dense structure and poor biodegradability prevent the ingrowth of living tissue,which leads to undesirable bone regeneration and clinical translation.To address this issue,we prepared bone cement based on Magnesium-containing microspheres(MMSs)that can not only be cured into a 3D porous scaffold but also have controllable biodegradability that continuously provides space for desired tissue ingrowth.Interestingly,magnesium ions released from MMSs cement(MMSC)trigger positive immunomodulation via upregulation of the anti-inflammatory genes IL-10 and M2 macrophage polarization with increased expression of CD206,which is beneficial to osteogenesis.Moreover,the physicochemical properties of MMSC,including heat release,rheology and setting time,can be tuned to meet the requirements of injectable bone cement for clinical application.Using a rat model,we have demonstrated that MMSC promoted osteogenesis via mediation of tissue ingrowth and anti-inflammatory immunomodulation.The study provides a paradigm for the design and preparation of injectable bone cements with 3D porous structures,biodegradability and anti-inflammatory immunoregulation to efficiently promote osteogenesis.

Use of Cryopreserved Osteogenic Matrix Cell Sheets for Bone Reconstruction

Skeletal diseases, such as nonunion and osteonecrosis, are now treatable with tissue engineering techniques. Single cell sheets called osteogenic matrix cell sheets (OMCSs) grown from cultured bone marrow-derived mesenchymal stem cells show high osteogenic potential;however, long preparation times currently limit their clinical application. Here, we report a cryopreservation OMCS transplantation method that shortens OMCS preparation time. Cryopreserved rat OMCSs were prepared using slow- and rapid-freezing methods, thawed, and subsequently injected scaffold-free into subcutaneous sites. Rapid- and slow-frozen OMCSs were also transplanted directly to the femur bone at sites of injury. Slow-freezing resulted in higher cell viability than rapid freezing, yet all two cryopreservation methods yielded OMCSs that survived and formed bone tissue. In the rapid- and slow-freezing groups, cortical gaps were repaired and bone continuity was observed within 6 weeks of OMCS transplantation. Moreover, while no significant difference was found in osteocalcin expression between the three experimental groups, the biomechanical strength of femurs treated with slow-frozen OMCSs was significantly greater than those of non-transplant at 6 weeks post-injury. Collectively, these data suggest that slow-frozen OMCSs have superior osteogenic potential and are better suited to produce a mineralized matrix and repair sites of bone injury.

Strontium modulates osteogenic activity of bone cement composed of bioactive borosilicate glass particles by activating Wnt/β-catenin signaling pathway

There is a need for synthetic grafts to reconstruct large bone defects using minimal invasive surgery.Our previous study showed that incorporation of Sr into bioactive borate glass cement enhanced the osteogenic capacity in vivo.However,the amount of Sr in the cement to provide an optimal combination of physicochemical properties and capacity to stimulate bone regeneration and the underlying molecular mechanism of this stimulation is yet to be determined.In this study,bone cements composed of bioactive borosilicate glass particles substituted with varying amounts of Sr(0 mol%to 12 mol%SrO)were created and evaluated in vitro and in vivo.The setting time of the cement increased with Sr substitution of the glass.Upon immersion in PBS,the cement degraded and converted more slowly to HA(hydroxyapatite)with increasing Sr substitution.The released Sr2+modulated the proliferation,differentiation,and mineralization of hBMSCs(human bone marrow mesenchymal stem cells)in vitro.Osteogenic characteristics were optimally enhanced with cement(designated BG6Sr)composed of particles substituted with 6mol%SrO.When implanted in rabbit femoral condyle defects,BG6Sr cement supported better peri-implant bone formation and bone-implant contact,comparing to cements substituted with 0mol%or 9mol%SrO.The underlying mechanism is involved in the activation of Wnt/β-catenin signaling pathway in osteogenic differentiation of hBMSCs.These results indicate that BG6Sr cement has a promising combination of physicochemical properties and biological performance for minimally invasive healing of bone defects.