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Fast dissolving glucose porogens for early calcium phosphate cement degradation and bone regeneration.

ABSTRACT: Here, we demonstrate the in vivo efficacy of glucose microparticles (GMPs) to serve as porogens within calcium phosphate cements (CPCs) to obtain a fast-degrading bone substitute material. Composites were fabricated incorporating 20 wt% GMPs at two different GMP size ranges (100-150 ?m (GMP-S) and 150-300 ?m (GMP-L)), while CPC containing 20 wt% poly(lactic-co-glycolic acid) microparticles (PLGA) and plain CPC served as controls. After 2 and 8 weeks implantation in a rat femoral condyle defect model, specimens were retrieved and analyzed for material degradation and bone formation. Histologically, no adverse tissue response to any of the CPC-formulations was observed. All CPC-porogen formulations showed faster degradation compared to plain CPC control, but only GMP-containing formulations showed higher amounts of new bone formation compared to plain CPC controls. After 8 weeks, only CPC-porogen formulations with GMP-S or PLGA porogens showed higher degradation compared to plain CPC controls. Overall, the inclusion of GMPs into CPCs resulted in a macroporous structure that initially accelerated the generation of new bone. These findings highlight the efficacy of a novel approach that leverages simple porogen properties to generate porous CPCs with distinct degradation and bone regeneration profiles.

SUBMITTER: Grosfeld EC

PROVIDER: S-EPMC7683932 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Fast dissolving glucose porogens for early calcium phosphate cement degradation and bone regeneration.

Grosfeld Eline-Claire EC Smith Brandon T BT Santoro Marco M Lodoso-Torrecilla Irene I Jansen John A JA Ulrich Dietmar Jo DJ Melchiorri Anthony J AJ Scott David W DW Mikos Antonios G AG van den Beucken Jeroen J J P JJJP

Biomedical materials (Bristol, England) 20200217 2

Here, we demonstrate the in vivo efficacy of glucose microparticles (GMPs) to serve as porogens within calcium phosphate cements (CPCs) to obtain a fast-degrading bone substitute material. Composites were fabricated incorporating 20 wt% GMPs at two different GMP size ranges (100-150 μm (GMP-S) and 150-300 μm (GMP-L)), while CPC containing 20 wt% poly(lactic-co-glycolic acid) microparticles (PLGA) and plain CPC served as controls. After 2 and 8 weeks implantation in a rat femoral condyle defect m ...[more]

PMID: 31810074

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Project description:Calcium phosphate cements (CPCs) have been extensively investigated as scaffolds in bone tissue engineering in light of their chemical composition closely resembling the mineral component of bone extracellular matrix. Yet, the degradation kinetics of many CPCs is slow compared to de novo bone formation. In order to overcome this shortcoming, the use of porogens within CPCs has been suggested as a potential strategy to increase scaffold porosity and promote surface degradation. This study explored the usage of glucose microparticles (GMPs) as porogens for the introduction of macroporosity within CPCs, and characterized the handling properties and physicochemical characteristics of CPCs containing GMPs. Samples were fabricated with four different weight fractions of GMPs (10, 20, 30, and 40%) and two different size ranges (100-150μm and 150-300μm), and were assayed for porosity, pore size distribution, morphology, and compressive mechanical properties. Samples were further tested for their handling properties - specifically, setting time and cohesiveness. Additionally, these same analyses were conducted on samples exposed to a physiological solution in order to estimate the dissolution kinetics of GMPs and its effect on the properties of the composite. GMPs were efficiently encapsulated and homogeneously dispersed in the resulting composite. Although setting times increased for GMP/CPC formulations compared to control CPC material, increasing the Na2HPO4 concentration in the liquid phase decreased the initial setting time to clinically acceptable values (i.e. <15min). Incorporation of GMPs led to the formation of instant macroporosity upon cement setting, and encapsulated GMPs completely dissolved in three days, resulting in a further increase in scaffold porosity. However, the dissolution of GMPs decreased scaffold compressive strength. Overall, the introduction of GMPs into CPC resulted in macroporous scaffolds with good handling properties, as well as designer porosity and pore size distribution via selection of the appropriate size/weight fraction of GMPs. The data demonstrate that GMPs are promising porogens for the production of highly tunable porous CPC scaffolds.Statement of significanceCalcium phosphate cements have shown great promise for the regeneration of bone. However, macropores (>100μm) are required for promoting bone ingrowth. Several studies have investigated methods to generate macroporosity within calcium phosphate cements but many of these methods either affect the cement setting or take weeks or months to generate the maximum porosity. This work offers a new method for generating macroporosity within calcium phosphate cements by utilizing glucose microparticles. The microparticles dissolve in less then 72h, thereby generating scaffolds with maximum porosity in short period of time. The results will offer a new method for generating macroporosity within calcium phosphate cements.

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

Fast dissolving glucose porogens for early calcium phosphate cement degradation and bone regeneration.

Publications

Fast dissolving glucose porogens for early calcium phosphate cement degradation and bone regeneration.

Similar Datasets

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