Multimodal pore formation in calcium phosphate cements

Abstract

Calcium phosphate cements (CPCs) are commonly used as bone substitute materials. However, their slow degradation rate and lack of macroporosity hinders new bone formation. Poly(dl-lactic-co-glycolic acid) (PLGA) incorporation is of great interest as, upon degradation, produces acidic by-products that enhance CPC degradation. Yet, new bone formation is delayed until PLGA degradation occurs a few weeks after implantation. Therefore, the aim of this study was to accelerate the early stage pore formation within CPCs in vitro. With that purpose, we incorporated the water-soluble porogen sucrose at different weight percentages (10 or 20 wt %) to CPC and CPC/PLGA composites. The results revealed that incorporation of sucrose porogens increased mass loss within the first week of in vitro degradation in groups containing sucrose compared to control groups. After week 1, a further mass loss was observed related to PLGA and CPC degradation. Macroporosity analysis confirmed that macroporosity formation is influenced by the dissolution of sucrose at an early stage and by the degradation of PLGA and CPC at a later stage. We concluded that the combination of sucrose and PLGA porogens in CPC is a promising approach to promote early stage bone tissue ingrowth and complete replacement of CPC through multimodal pore formation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 500-509, 2018.

Incorporation of fast dissolving glucose porogens and poly(lactic-co-glycolic acid) microparticles within calcium phosphate cements for bone tissue regeneration

“…In addition, the mass of composites that only contained GMPs (G10P0 and G20P0) remained constant over the duration of the study. These observations support the conclusion that this change in mass loss can be attributed to the dissolution of GMPs, which is consistent with other studies that have leveraged water-soluble porogens within CPCs [16,24]. On the contrary, composites that contained only PLGA MPs (G0P10 and G0P20) did not show a decrease in mass loss after 3 days compared to the CPC controls.…”

“…In addition, these results corroborate with other studies that have introduced polysaccharides for the generation of macroporosity with CPCs [16,24,37]. However, groups that also incorporated PLGA MPs saw an additional increase in porosity.…”

“…Analyses of the initial setting times of the GMP/PLGA/CPC composites emphasized that the inclusion of GMPs and PLGA MPs increased the initial setting time compared to the control. However, all groups had an initial setting time that was within the upper limit for clinical use, in agreement with previous investigations that have used water-soluble porogens or polymer based porogens [16,24,31,33]. Bohner et al states that one can observe a three- to fourfold reduction in the setting time of apatite CPCs when the temperature increases from 20 to 37 °C [34].…”

“…Composites that included both GMPs and PLGA MPs saw an initial mass loss after 3 days, as a result of the dissolution of the GMPs, followed by a gradual mass loss that was proportional to the amount of PLGA MPs for the duration of the study. Since it has been shown that the acidic PLGA degradation products accelerate the degradation of the CPC matrix, the addition of PLGA MPs presents another benefit of this system compared to relying on only GMPs [24]. These observations are further corroborated with the SEM micrographs.…”

“…The resulting paste was injected into Teflon molds (6 mm diameter, 12 mm height). As previously described, the samples were left to set at room temperature for 24 h, removed from the molds, and stored in a vacuum dryer with Drierite (Drierite Co LTD, Xenia, Ohio) until further testing [6,24]. …”