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Preparation and modeling of three-layered PCL/PLGA/PCL fibrous scaffolds for prolonged drug release.

ABSTRACT: The authors present the preparation procedure and a computational model of a three-layered fibrous scaffold for prolonged drug release. The scaffold, produced by emulsion/sequential electrospinning, consists of a poly(D,L-lactic-co-glycolic acid) (PLGA) fiber layer sandwiched between two poly(ε-caprolactone) (PCL) layers. Experimental results of drug release rates from the scaffold are compared with the results of the recently introduced computational finite element (FE) models for diffusive drug release from nanofibers to the three-dimensional (3D) surrounding medium. Two different FE models are used: (1) a 3D discretized continuum and fibers represented by a simple radial one-dimensional (1D) finite elements, and (2) a 3D continuum discretized by composite smeared finite elements (CSFEs) containing the fiber smeared and surrounding domains. Both models include the effects of polymer degradation and hydrophobicity (as partitioning) of the drug at the fiber/surrounding interface. The CSFE model includes a volumetric fraction of fibers and diameter distribution, and is additionally enhanced by using correction function to improve the accuracy of the model. The computational results are validated on Rhodamine B (fluorescent drug l) and other hydrophilic drugs. Agreement with experimental results proves that numerical models can serve as efficient tools for drug release to the surrounding porous medium or biological tissue. It is demonstrated that the introduced three-layered scaffold delays the drug release process and can be used for the time-controlled release of drugs in postoperative therapy.

SUBMITTER: Milosevic M

PROVIDER: S-EPMC7341868 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Polylactide (PLA) electrospun fibers have been reported as a scaffold for bone tissue engineering application, however, the great hydrophobicity limits its broad application. In this study, the hybrid amphiphilic poly(ethylene glycol) (PEG)/hydrophobic PLA fibrous scaffolds exhibited improved morphology with regular and continuous fibers compared to corresponding blank PLA fiber mats. The prepared PEG/PLA fibrous scaffolds favored mesenchymal stem cell (MSC) attachment and proliferation by providing an interconnected porous extracellular environment. Meanwhile, MSCs can penetrate into the fibrous scaffold through the interstitial pores and integrate well with the surrounding fibers, which is very important for favorable application in tissue engineering. More importantly, the electrospun hybrid PEG/PLA fibrous scaffolds can enhance MSCs to differentiate into bone-associated cells by comprehensively evaluating the representative markers of the osteogenic procedure with messenger ribonucleic acid quantitation and protein analysis. MSCs on the PEG/PLA fibrous scaffolds presented better differentiation potential with higher messenger ribonucleic acid expression of the earliest osteogenic marker Cbfa-1 and mid-stage osteogenic marker Col I. The significantly higher alkaline phosphatase activity of the PEG/PLA fibrous scaffolds indicated that these can enhance the differentiation of MSCs into osteoblast-like cells. Furthermore, the higher messenger ribonucleic acid level of the late osteogenic differentiation markers OCN (osteocalcin) and OPN (osteopontin), accompanied by the positive Alizarin red S staining, showed better maturation of osteogenic induction on the PEG/PLA fibrous scaffolds at the mineralization stage of differentiation. After transplantation into the thigh muscle pouches of rats, and evaluating the inflammatory cells surrounding the scaffolds and the physiological characteristics of the surrounding tissues, the PEG/PLA scaffolds presented good biocompatibility. Based on the good cellular response and excellent osteogenic potential in vitro, as well as the biocompatibility with the surrounding tissues in vivo, the electrospun PEG/PLA fibrous scaffolds could be one of the most promising candidates in bone tissue engineering.

Project description:BackgroundDecellularized xenogenic scaffolds represent a promising substrate for tissue-engineered vascular prostheses, particularly those with smaller diameters (<6 mm). Despite their benefits, a notable limitation presents itself during decellularization, namely, the diminished mechanical strength that introduces the risk of aneurysmal dilations in the early post-implantation period. This study introduces a strategy for modification the mechanical properties of these biological scaffolds through the forming of an external polymeric reinforcement via thermal extrusion.MethodsThe study utilized scaffolds fabricated from bovine internal mammary arteries through decellularization and preservation. The scaffolds were divided into subgroups and reinforced with polymeric helices made of Polyvinylidene fluoride (PVDF) and Polycaprolactone (PCL), n = 5 for each. An experimental setup for external reinforcement coating was designed. Computed microtomography was employed to obtain accurate 3D models of the scaffolds. Mechanical properties were evaluated through in vitro uniaxial tension tests (Z50, Zwick/Roell, Germany), compliance evaluation and numerical simulations (Abaqus/CAE, Dassault Systemes, France) to investigate the effect of external reinforcement on aneurysm growth.ResultsUsing a double-layer helix for the reinforcement significantly enhanced the radial tensile strength of the scaffolds, increasing it up to 2.26 times. Yet, the comparison of vessel's compliance between two reinforced and the Control scaffolds within the physiological pressures range did not reveal any significant differences. Numerical simulation of aneurysm growth showed that thin-walled regions of the Control scaffold developed aneurysmal-type protrusions, bulging up to 0.7 mm, with a substantial degradation of mechanical properties. In contrast, both PVDF and PCL reinforced scaffolds did not exhibit significant property degradation, with deformations ranging 0.1-0.13 mm depending on the model, and a maximum decrease in the modulus of elasticity of 23%.ConclusionThe results of the study demonstrated that the external polymer helical reinforcement of decellularized scaffolds via thermal extrusion enables a controlled modification of mechanical properties, notably enhancing radial strength while maintaining sufficient compliance within the physiological pressure range. A series of in vitro tests demonstrated the consistency and potential of this approach for decellularized xenogenic scaffolds, a concept that had not been explored before.

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Preparation and modeling of three-layered PCL/PLGA/PCL fibrous scaffolds for prolonged drug release.

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