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. 2022 Mar 21;5(3):1151-1158.
doi: 10.1021/acsabm.1c01210. Epub 2022 Feb 24.

Blood Compatibility of Hydrophilic Polyphosphoesters

Chiara Pelosi  1 , Iren Constantinescu  2 , Helena H Son  2 , Maria Rosaria Tinè  1 , Jayachandran N Kizhakkedathu  2   3 , Frederik R Wurm  4
Affiliations

Blood Compatibility of Hydrophilic Polyphosphoesters

Chiara Pelosi et al. ACS Appl Bio Mater. .

Abstract

Polyphosphoesters (PPEs) are a class of versatile degradable polymers. Despite the high potential of this class of polymers in biomedical applications, little is known about their blood interaction and compatibility. We evaluated the hemocompatibility of water-soluble PPEs (with different hydrophilicities and molar masses) and PPE-coated model nanocarriers. Overall, we identified high hemocompatibility of PPEs, comparable to poly(ethylene glycol) (PEG), currently used for many applications in nanomedicine. Hydrophilic PPEs caused no significant changes in blood coagulation, negligible platelet activation, the absence of red blood cells lysis, or aggregation. However, when a more hydrophobic copolymer was studied, some changes in the whole blood clot strength at the highest concentration were detected, but only concentrations above that are typically used for biomedical applications. Also, the PPE-coated model nanocarriers showed high hemocompatibility. These results contribute to defining hydrophilic PPEs as a promising platform for degradable and biocompatible materials in the biomedical field.

Keywords: RBC interaction; biodegradable polymers; blood coagulation; hemocompatibility; platelet activation; poly(ethylene glycol); polyphosphoesters.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Set of samples analyzed in this work.
Figure 2
Figure 2
Effect of PPE polymers on (a) PT and (b) APTT at different concentrations (0.1, 0.5, and 1 mg/mL). The clotting time was normalized for the saline control run for each sample (33.2 ± 2.8 s for APTT and 9.8 ± 1.1 s for PT analysis). Unfractionated heparin (UFH) was used as a control. The data have been obtained by analyzing the blood of three different donors (N = 3).
Figure 3
Figure 3
Whole blood coagulation studied using ROTEM in the presence of PPEs. (a) Reaction time (R), time for the first significant clot formation, K (achievement of certain clot firmness, angle (kinetics of clot development), and MA (maximum amplitude–maximum strength of clot). (b) ROTEM profile of sample #1 at 1 mg/mL (as made (blue), 2 weeks (green), and saline control (pink)).
Figure 4
Figure 4
Platelet activation in the presence of the PPE polymers at different concentrations, observed by measuring the expression of the activation marker CD62P on the surface of platelets using flow cytometry analysis. Saline solution and TRAP have been used as, respectively, negative and positive controls for the experiment.
Figure 5
Figure 5
(a) Lysis of RBC after incubation with the tested PPE polymers at different concentrations (0.1, 0.5, and 1 mg/mL); saline solution and deuterated water (D2O) were used as, respectively, negative and positive controls for the experiment. (b) Representative images obtained by optical microscopy, showing RBC aggregation in the presence of sample #1 (magnification: 40×). The sample does not show any detectable aggregation at all the concentrations tested (0.1, 0.5, and 1 mg/mL), in comparison to the saline control shown on the left. The optical micrographs recorded for the other samples are reported in the Supporting Information, Figure S3.
Figure 6
Figure 6
(a) Lysis of RBCs after incubation with sample #6. Effect of sample #6 on (b) APTT and (c) PT. The clotting time was normalized for the saline control run for each sample. The data have been obtained by analyzing the blood of three different donors (N = 3).
See this image and copyright information in PMC

References

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