Incorporation of bioactive glass in calcium phosphate cement: An evaluation.

Bioactive glasses (BGs) are known for their unique ability to bond to living bone. Consequently, the incorporation of BGs into calcium phosphate cement (CPC) was hypothesized to be a feasible approach to improve the biological performance of CPC. Previously, it has been demonstrated that BGs can successfully be introduced into CPC, with or without poly(d,l-lactic-co-glycolic) acid (PLGA) microparticles. Although an in vitro physicochemical study on the introduction of BG into CPC was encouraging, the biocompatibility and in vivo bone response to these formulations are still unknown. Therefore, the present study aimed to evaluate the in vivo performance of BG supplemented CPC, either pure or supplemented with PLGA microparticles, via both ectopic and orthotopic implantation models in rats. Pre-set scaffolds in four different formulations (1: CPC; 2: CPC/BG; 3: CPC/PLGA; and 4: CPC/PLGA/BG) were implanted subcutaneously and into femoral condyle defects of rats for 2 and 6 weeks. Upon ectopic implantation, incorporation of BG into CPC improved the soft tissue response by improving capsule and interface quality. Additionally, the incorporation of BG into CPC and CPC/PLGA showed 1.8- and 4.7-fold higher degradation and 2.2- and 1.3-fold higher bone formation in a femoral condyle defect in rats compared to pure CPC and CPC/PLGA, respectively. Consequently, these results highlight the potential of BG to be used as an additive to CPC to improve the biological performance for bone regeneration applications. Nevertheless, further confirmation is necessary regarding long-term in vivo studies, which also have to be performed under compromised wound-healing conditions.

Incorporation of bioactive glass in calcium phosphate cement: material characterization and in vitro degradation.

Calcium phosphate cements (CPCs) have been widely used as an alternative to biological grafts due to their excellent osteoconductive properties. Although degradation has been improved by using poly(D,L-lactic-co-glycolic) acid (PLGA) microspheres as porogens, the biological performance of CPC/PLGA composites is insufficient to stimulate bone healing in large bone defects. In this context, the aim of this study was to investigate the effect of incorporating osteopromotive bioactive glass (BG; up to 50 wt %) on setting properties, in vitro degradation behavior and morphological characteristics of CPC/BG and CPC/PLGA/BG. The results revealed that the initial and final setting time of the composites increased with increasing amounts of incorporated BG. The degradation test showed a BG-dependent increasing effect on pH of CPC/BG and CPC/PLGA/BG pre-set scaffolds immersed in PBS compared to CPC and CPC/PLGA equivalents. Whereas no effects on mass loss were observed for CPC and CPC/BG pre-set scaffolds, CPC/PLGA/BG pre-set scaffolds showed an accelerated mass loss compared with CPC/PLGA equivalents. Morphologically, no changes were observed for CPC and CPC/BG pre-set scaffolds. In contrast, CPC/PLGA and CPC/PLGA/BG showed apparent degradation of PLGA microspheres and faster loss of integrity for CPC/PLGA/BG pre-set scaffolds compared with CPC/PLGA equivalents. Based on the present in vitro results, it can be concluded that BG can be successfully introduced into CPC and CPC/PLGA without exceeding the setting time beyond clinically acceptable values. All injectable composites containing BG had suitable handling properties and specifically CPC/PLGA/BG showed an increased rate of mass loss. Future investigations should focus on translating these findings to in vivo applications.

Non-glycosylated BMP-2 can induce ectopic bone formation at lower concentrations compared to glycosylated BMP-2.

Bone morphogenic protein-2 (BMP-2) is a well-known growth factor that can improve the biological performance of bone substitute materials. BMP-2 produced via bacterial expression systems are non-glycosylated (ng) whereas native and recombinant equivalents produced in mammalian cell expression systems are glycosylated (g) proteins. ngBMP-2 is less soluble, resulting in lower BMP-2 release from carriers as used as bone substitute materials. This seems promising for reducing the amount of included growth factor in bone substitute materials. Hence, it was hypothesized that ngBMP-2 would induce formation of the same amount of bone at an ectopic site at lower dosage as gBMP-2. To that end, gBMP-2 and ngBMP-2 were firstly in vitro comparatively evaluated for biological activity and release from a calcium phosphate (CaP) based bone substitute material. Thereafter, an ectopic implantation model in rats was used, in which gBMP-2 and ngBMP2 were loaded in various dosages (2-20 µg/implant) on the CaP-based bone substitute material and implanted for 4 and 12 weeks. The results revealed that both the in vitro biological activity of and the in vitro release of ngBMP-2 are lower compared to gBMP2. Upon ectopic implantation, however, ngBMP-2 loaded implants induced more bone formation at lower concentrations from 4-weeks onward compared to gBMP-2 equivalents, indicating the value of ngBMP-2 as a potential alternative for mammalian produced recombinant BMP-2 for bone regenerative therapies.