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Physicochemical Properties, In Vitro Degradation, and Biocompatibility of Calcium Phosphate Cement Incorporating Poly(lactic-co-glycolic acid) Particles with Different Morphologies: A Comparative Study.

ABSTRACT: Calcium phosphate cement (CPC) is one of the most promising synthetic biomaterials for bone defect repair, but its low degradation rate and the lack of macropores restrict its repair effect. Poly(lactic-co-glycolic acid) (PLGA) is commonly used as an in situ pore forming agent in CPC, and the morphology of PLGA would affect the properties of CPC. In this study, three kinds of PLGA particles with different morphologies, including dense PLGA microspheres, dense milled PLGA particles with an irregular shape, and porous PLGA microspheres, were respectively incorporated into CPC matrix. The influences of the morphology of PLGA particles on the setting time, porosity, mechanical properties, in vitro degradation, and cytocompatibility of CPC were comparatively investigated. The results showed that the CPC composites containing dense spherical and irregularly shaped PLGA particles showed proper setting time and better compressive strength, but the CPC composite incorporating porous PLGA microspheres significantly prolonged the final setting time and dramatically decreased the compressive strength of CPC. The CPC composite containing irregularly shaped PLGA particles has shown a slightly faster in vitro degradation rate than that containing dense PLGA microspheres. In addition, the CPC composites containing dense PLGA particles were beneficial for cell proliferation. Taken together, the dense PLGA particles are suitable for use as in situ pore forming agents in the CPC matrix, and meanwhile, the dense irregularly shaped PLGA particles are more easily prepared with low cost.

SUBMITTER: Lu T

PROVIDER: S-EPMC8015133 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:This study investigated the effects of incorporating glucose microparticles (GMPs) and poly(lactic-co-glycolic acid) microparticles (PLGA MPs) within a calcium phosphate cement on the cement's handling, physicochemical properties, and the respective pore formation. Composites were fabricated with two different weight fractions of GMPs (10 and 20 wt%) and two different weight fractions of PLGA MPs (10 and 20 wt%). Samples were assayed for porosity, pore morphology, and compressive mechanical properties. An in vitro degradation study was also conducted. Samples were exposed to a physiological solution for 3 days, 4 wks, and 8 wks in order to understand how the inclusion of GMPs and PLGA MPs affects the composite's porosity and mass loss over time. GMPs and PLGA MPs were both successfully incorporated within the composites and all formulations showed an initial setting time that is appropriate for clinical applications. Through a main effects analysis, we observed that the incorporation of GMPs had a significant effect on the overall porosity, mean pore size, mode pore size, and in vitro degradation rate of PLGA MPs as early as after 3 days (p < 0.05). After 4 wks and 8 wks, these same properties were affected by the inclusion of both types of MPs (p < 0.05). Advanced polymer chromatography confirmed that the degradation of PLGA MPs coincided with an increase in composite porosity, mean pore size, and mode pore size. Finally, it was observed that the inclusion of GMPs slowed the degradation of PLGA MPs in vitro and reduced the solution acidity due to PLGA degradation products. Our results suggest that the dual inclusion of GMPs and PLGA MPs is a valuable approach for the generation of early macropores, while also mitigating the effect of acidic degradation products from PLGA MPs on their degradation kinetics.Statement of significanceA multitude of strategies and techniques have been investigated for the introduction of macropores with calcium phosphate cements (CPC). However, many of these strategies take several weeks to months to generate a maximal porosity or the degradation products of the porogen can trigger a localized inflammatory response in vivo. As such, it was hypothesized that the fast dissolution of glucose microparticles (GMPs) in a CPC composite also incorporating poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) will create an initial macroporosity and increase the surface area within the CPC, thus enhancing the diffusion of PLGA degradation products and preventing a significant decrease in pH. Furthermore, as PLGA degradation occurs over several weeks to months, additional macroporosity will be generated at later time points within CPCs. The results offer a new method for generating macroporosity in a multimodal fashion that also mitigates the effects of acidic degradation products.

Dataset Information

Physicochemical Properties, In Vitro Degradation, and Biocompatibility of Calcium Phosphate Cement Incorporating Poly(lactic-co-glycolic acid) Particles with Different Morphologies: A Comparative Study.

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