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Radiopaque scaffolds based on electrospun iodixanol/polycaprolactone fibrous composites.

ABSTRACT: Grafts based on biodegradable polymer scaffolds are increasingly used in tissue-engineering applications as they facilitate natural tissue regeneration. However, monitoring the position and integrity of these scaffolds over time is challenging due to radiolucency. In this study, we used an electrospinning method to fabricate biodegradable scaffolds based on polycaprolactone (PCL) and iodixanol, a clinical contrast agent. Scaffolds were implanted subcutaneously into C57BL/6 mice and monitored in vivo using longitudinal X-ray imaging and micro-computed tomography (CT). The addition of iodixanol altered the physicochemical properties of the PCL scaffold; notably, as the iodixanol concentration increased, the fiber diameter decreased. Radiopacity was achieved with corresponding signal enhancement as iodine concentration increased while exhibiting a steady time-dependent decrease of 0.96% per day in vivo. The electrospun scaffolds had similar performance with tissue culture-treated polystyrene in supporting the attachment, viability, and proliferation of human mesenchymal stem cells. Furthermore, implanted PCL-I scaffolds had more intense acute inflammatory infiltrate and thicker layers of maturing fibrous tissue. In conclusion, we developed radiopaque, biodegradable, biocompatible scaffolds whose position and integrity can be monitored noninvasively. The successful development of other imaging enhancers may further expand the use of biodegradable scaffolds in tissue engineering applications.

SUBMITTER: Perez JVD

PROVIDER: S-EPMC7497787 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:This article reports on a study of the mineralisation behaviour of CaCO3 deposited on electrospun poly(ε-caprolactone) (PCL) scaffolds preliminarily treated with low-temperature plasma. This work was aimed at developing an approach that improves the wettability and permeability of PCL scaffolds in order to obtain a superior composite coated with highly porous CaCO3, which is a prerequisite for biomedical scaffolds used for drug delivery. Since PCL is a synthetic polymer that lacks functional groups, plasma processing of PCL scaffolds in O2, NH3, and Ar atmospheres enables introduction of highly reactive chemical groups, which influence the interaction between organic and inorganic phases and govern the nucleation, crystal growth, particle morphology, and phase composition of the CaCO3 coating. Our studies showed that the plasma treatment induced the formation of O- and N-containing polar functional groups on the scaffold surface, which caused an increase in the PCL surface hydrophilicity. Mineralisation of the PCL scaffolds was performed by inducing precipitation of CaCO3 particles on the surface of polymer fibres from a mixture of CaCl2- and Na2CO3-saturated solutions. The presence of highly porous vaterite and nonporous calcite crystal phases in the obtained coating was established. Our findings confirmed that preferential growth of the vaterite phase occurred in the O2-plasma-treated PCL scaffold and that the coating formed on this scaffold was smoother and more homogenous than those formed on the untreated PCL scaffold and the Ar- and NH3-plasma-treated PCL scaffolds. A more detailed three-dimensional assessment of the penetration depth of CaCO3 into the PCL scaffold was performed by high-resolution micro-computed tomography. The assessment revealed that O2-plasma treatment of the PCL scaffold caused CaCO3 to nucleate and precipitate much deeper inside the porous structure. From our findings, we conclude that O2-plasma treatment is preferable for PCL scaffold surface modification from the viewpoint of use of the PCL/CaCO3 composite as a drug delivery platform for tissue engineering.

Project description:Tissue engineering strategies have emerged in response to the growing prevalence of chronic musculoskeletal conditions, with many of these regenerative methods currently being evaluated in translational animal models. Engineered replacements for fibrous tissues such as the meniscus, annulus fibrosus, tendons, and ligaments are subjected to challenging physiologic loads, and are difficult to track in vivo using standard techniques. The diagnosis and treatment of musculoskeletal conditions depends heavily on radiographic assessment, and a number of currently available implants utilize radiopaque markers to facilitate in vivo imaging. In this study, we developed a nanofibrous scaffold in which individual fibers included radiopaque nanoparticles. Inclusion of radiopaque particles increased the tensile modulus of the scaffold and imparted radiation attenuation within the range of cortical bone. When scaffolds were seeded with bovine mesenchymal stem cells in vitro, there was no change in cell proliferation and no evidence of promiscuous conversion to an osteogenic phenotype. Scaffolds were implanted ex vivo in a model of a meniscal tear in a bovine joint and in vivo in a model of total disc replacement in the rat coccygeal spine (tail), and were visualized via fluoroscopy and microcomputed tomography. In the disc replacement model, histological analysis at 4 weeks showed that the scaffold was biocompatible and supported the deposition of fibrous tissue in vivo. Nanofibrous scaffolds that include radiopaque nanoparticles provide a biocompatible template with sufficient radiopacity for in vivo visualization in both small and large animal models. This radiopacity may facilitate image-guided implantation and non-invasive long-term evaluation of scaffold location and performance.Statement of significanceThe healing capacity of fibrous musculoskeletal tissues is limited, and injury or degeneration of these tissues compromises the standard of living of millions in the US. Tissue engineering repair strategies for the intervertebral disc, meniscus, tendon and ligament have progressed from in vitro to in vivo evaluation using a variety of animal models, and the clinical application of these technologies is imminent. The composition of most scaffold materials however does not allow for visualization by methods available to clinicians (e.g., radiography), and thus it is not possible to assess their performance in situ. In this work, we describe a radiopaque nanofibrous scaffold that can be visualized radiographically in both small and large animal models and serve as a framework for the development of an engineered fibrous tissue.

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Radiopaque scaffolds based on electrospun iodixanol/polycaprolactone fibrous composites.

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