Synthesis, Characterization, and Paclitaxel Release from a Biodegradable, Elastomeric, Poly(ester urethane)urea Bearing Phosphorylcholine Groups for Reduced Thrombogenicity

Hong, Yi; Ye, Sang‐Ho; Pelinescu, Anca L.; Wagner, William R.

doi:10.1021/bm301158j

Cited by 57 publications

(70 citation statements)

References 55 publications

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“…Its mechanical properties and degradation can be tuned by altering the chemical components [24,32,33]. Biofunctional and bioactive agents are capable of being incorporated with polyurethane urea through chemistry and engineering approaches [12,34–36]. Its good biocompatibility has been verified from in vitro cell culture and in vivo implantation [24,37–39].…”

Section: Discussionmentioning

confidence: 99%

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Electrospun biodegradable elastic polyurethane scaffolds with dipyridamole release for small diameter vascular grafts

et al. 2014

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Acellular biodegradable small diameter vascular grafts (SDVGs) require antithrombosis, intimal hyperplasia inhibition and rapid endothelialization to improve the graft patency. However, current antithrombosis and antiproliferation approaches often conflict with endothelial cell layer formation on SDVGs. To address this limitation, biodegradable elastic polyurethane urea (BPU) and the drug dipyridamole (DPA) were mixed and then electrospun into a biodegradable fibrous scaffold. The BPU would provide the appropriate mechanical support, while the DPA in the scaffold would offer biofunctions as required above. We found that the resulting scaffolds had tensile strengths and strains comparable with human coronary artery. The DPA in the scaffolds was continuously released up to 91 days in phosphate buffer solution at 37 °C, with a low burst release within the first 3 days. Compared to BPU alone, improved non-thrombogenicity of the DPA-loaded BPU scaffolds was evidenced with extended human blood clotting time, lower TAT complex concentration, lower hemolysis and reduced human platelet deposition. The scaffolds with a higher DPA content (5 and 10%) inhibited proliferation of human aortic smooth muscle cell significantly. Furthermore, the DPA-loaded scaffolds had no adverse effect on human aortic endothelial cell growth, yet it improved their proliferation. The attractive mechanical properties and biofunctions of the DPA-loaded BPU scaffold indicate its potential as an acellular biodegradable SDVG for vascular replacement.

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Section: Discussionmentioning

confidence: 99%

“…Those include surface modification [9–11], polymer composition modification [8,12], nitric oxide release [13–15] and drug release [16–18]. Of these strategies, the drug release approach is an easy way to improve the biofunctions of biodegradable polymers.…”

Section: Introductionmentioning

confidence: 99%

Electrospun biodegradable elastic polyurethane scaffolds with dipyridamole release for small diameter vascular grafts

et al. 2014

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“…29 The chemical tunability that has been employed for rational design of tissue engineering scaffolds can also be used to modulate the release of physicochemically diverse drugs from electrospun fibers. For example, Hong et al observed that grafting aminated phosphorylcholine onto the PLC-based poly(ester urethane) urea backbone slightly enhanced the release of paclitaxel from electrospun fibers.…”

Section: Introductionmentioning

confidence: 99%

“…For example, Hong et al observed that grafting aminated phosphorylcholine onto the PLC-based poly(ester urethane) urea backbone slightly enhanced the release of paclitaxel from electrospun fibers. 29 Changing polymer chemistry may also increase the overall hydrophobicity of the bulk polymer and swelling ratio of the polymer matrix, with generally predictable effects on how the polymer interacts with hydrophilic or hydrophobic drugs encapsulated within the fibers. Similarly, Galperin et al observed more prolonged release of norfloxacin (NFL) from porous polyHEMA hydrogels with increasing fluorostyrene content in the bulk hydrogel.…”

Section: Introductionmentioning

confidence: 99%

Rapidly Biodegrading PLGA-Polyurethane Fibers for Sustained Release of Physicochemically Diverse Drugs

Blakney

Simonovsky

Suydam

et al. 2016

ACS Biomater. Sci. Eng.

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Sustained release of physicochemically diverse drugs from electrospun fibers remains a challenge and precludes the use of fibers in many medical applications. Here, we synthesize a new class of polyurethanes with poly(lactic-co-glycolic acid) (PLGA) moieties that degrade faster than polyurethanes based on polycaprolactone. The new polymers, with varying hard to soft segment ratios and fluorobenzene pendant group content, were electrospun into nanofibers and loaded with four physicochemically diverse small molecule drugs. Polymers were characterized using GPC, XPS, and 19F NMR. The size and morphology of electrospun fibers were visualized using SEM, and drug/polymer compatibility and drug crystallinity were evaluated using DSC. We measured in vitro drug release, polymer degradation and cell-culture cytotoxicity of biodegradation products. We show that these newly synthesized PLGA-based polyurethanes degrade up to 65–80% within 4 weeks and are cytocompatible in vitro. The drug-loaded electrospun fibers were amorphous solid dispersions. We found that increasing the hard to soft segment ratio of the polymer enhances the sustained release of positively charged drugs, whereas increasing the fluorobenzene pendant content caused more rapid release of some drugs. In summary, increasing the hard segment or fluorobenzene pendant content of segmented polyurethanes containing PLGA moieties allows for modulation of physicochemically diverse drug release from electrospun fibers while maintaining a biologically relevant biodegradation rate.

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“…For instance, drug-releasing phosphorylcholine-grafted polyurethane vascular stents have been investigated in vitro for the inhibition of rat smooth muscle proliferation and demonstrated impaired platelet deposition with phosphorylcholine incorporation. [71] The hemocompatibility of MPC has been further utilized in attempting to recreate the luminal side of complex bioartificial organs exposed to blood. For instance, a polysulfone/MPC blend has been used to make asymmetrical membrane surfaces, with one side used to promote renal tubule epithelial cells and the other used to promote hemocompatibility to facilitate surface renal tube generation.…”

Section: In Vitro Studiesmentioning

confidence: 99%

Phosphorous-containing polymers for regenerative medicine

Watson¹,

Kasper²,

Mikos³

2014

Biomed. Mater.

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Disease and injury have resulted in a large, unmet need for functional tissue replacements. Polymeric scaffolds can be used to deliver cells and bioactive signals to address this need for regenerating damaged tissue. Phosphorous-containing polymers have been implemented to improve and accelerate the formation of native tissue both by mimicking the native role of phosphorous groups in the body and by attachment of other bioactive molecules. This manuscript reviews the synthesis, properties, and performance of phosphorous-containing polymers that can be useful in regenerative medicine applications.

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Synthesis, Characterization, and Paclitaxel Release from a Biodegradable, Elastomeric, Poly(ester urethane)urea Bearing Phosphorylcholine Groups for Reduced Thrombogenicity

Cited by 57 publications

References 55 publications

Electrospun biodegradable elastic polyurethane scaffolds with dipyridamole release for small diameter vascular grafts

Electrospun biodegradable elastic polyurethane scaffolds with dipyridamole release for small diameter vascular grafts

Rapidly Biodegrading PLGA-Polyurethane Fibers for Sustained Release of Physicochemically Diverse Drugs

Phosphorous-containing polymers for regenerative medicine

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