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Development of Tripolymeric Triaxial Electrospun Fibrous Matrices for Dual Drug Delivery Applications.

ABSTRACT: Since the first work by Laurencin and colleagues on the development of polymeric electrospinning for biomedical purposes, the use of electrospinning technology has found broad applications in such areas of tissue regeneration and drug delivery. More recently, coaxial electrospinning has emerged as an important technique to develop scaffolds for regenerative engineering incorporated with drug(s). However, the addition of a softer core layer leads to a reduction in mechanical properties. Here, novel robust tripolymeric triaxially electrospun fibrous scaffolds were developed with a polycaprolactone (PCL) (core layer), a 50:50 poly (lactic-co-glycolic acid) (PLGA) (sheath layer) and a gelatin (intermediate layer) with a dual drug delivery capability was developed through modified electrospinning. A sharp increase in elastic modulus after the incorporation of PCL in the core of the triaxial fibers in comparison with uniaxial PLGA (50:50) and coaxial PLGA (50:50) (sheath)-gelatin (core) fibers was observed. Thermal analysis of the fibrous scaffolds revealed an interaction between the core-intermediate and sheath-intermediate layers of the triaxial fibers contributing to the higher tensile modulus. A simultaneous dual release of model small molecule Rhodamine B (RhB) and model protein Fluorescein isothiocynate (FITC) Bovine Serum Albumin (BSA) conjugate incorporated in the sheath and intermediate layers of triaxial fibers was achieved. The tripolymeric, triaxial electrospun systems were seen to be ideal for the support of mesenchymal stem cell growth, as shrinkage of fibers normally found with conventional electrospun systems was minimized. These tripolymeric triaxial electrospun fibers that are biomechanically competent, biocompatible, and capable of dual drug release are designed for regenerative engineering and drug delivery applications.

SUBMITTER: Nagiah N

PROVIDER: S-EPMC6969175 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Development of Tripolymeric Triaxial Electrospun Fibrous Matrices for Dual Drug Delivery Applications.

Nagiah Naveen N Murdock Christopher J CJ Bhattacharjee Maumita M Nair Lakshmi L Laurencin Cato T CT

Scientific reports 20200117 1

Since the first work by Laurencin and colleagues on the development of polymeric electrospinning for biomedical purposes, the use of electrospinning technology has found broad applications in such areas of tissue regeneration and drug delivery. More recently, coaxial electrospinning has emerged as an important technique to develop scaffolds for regenerative engineering incorporated with drug(s). However, the addition of a softer core layer leads to a reduction in mechanical properties. Here, nov ...[more]

PMID: 31953439

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Project description:The novel controlled and localized delivery of drug molecules to target tissues using an external electric stimulus makes electro-responsive drug delivery systems both feasible and desirable, as well as entailing a reduction in the side effects. Novel micro-scaffold matrices were designed based on poly(lactic acid) (PLA) and graphene oxide (GO) via electrospinning. Quercetin (Q), a natural flavonoid, was loaded into the fiber matrices in order to investigate the potential as a model drug for wound dressing applications. The physico-chemical properties, electrical triggering capacity, antimicrobial assay and biocompatibility were also investigated. The newly fabricated PLA/GO/Q scaffolds showed uniform and smooth surface morphologies, without any beads, and with diameters ranging from 1107 nm (10%PLA/0.1GO/Q) to 1243 nm (10%PLA). The in vitro release tests of Q from the scaffolds showed that Q can be released much faster (up to 8640 times) when an appropriate electric field is applied compared to traditional drug-release approaches. For instance, 10 s of electric stimulation is enough to ensure the full delivery of the loaded Q from the 10%PLA/1%GO/Q microfiber scaffold at both 10 Hz and at 50 Hz. The antimicrobial tests showed the inhibition of bacterial film growth. Certainly, these materials could be loaded with more potent agents for anti-cancer, anti-infection, and anti-osteoporotic therapies. The L929 fibroblast cells cultured on these scaffolds were distributed homogeneously on the scaffolds, and the highest viability value of 82.3% was obtained for the 10%PLA/0.5%GO/Q microfiber scaffold. Moreover, the addition of Q in the PLA/GO matrix stimulated the production of IL-6 at 24 h, which could be linked to an acute inflammatory response in the exposed fibroblast cells, as a potential effect of wound healing. As a general conclusion, these results demonstrate the possibility of developing graphene oxide-based supports for the electrically triggered delivery of biological active agents, with the delivery rate being externally controlled in order to ensure personalized release.

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.

Project description:Herpetic infections caused by Herpes simplex virus (HSV) are among the most common human infections, affecting more than two quarters of the world's population. The standard treatment for orofacial herpes is the administration of antiviral drugs, mainly acyclovir (ACV). However, current products are mostly based on semisolid formulations that have limited ability to promote drug skin penetration and tend to leak from the application site, thus showing reduced ability to sustain local drug residence. This work reports on the production of poly (ε-caprolactone) (PCL) fibrous matrices with ACV and omega-3 fatty acids (ω3) for application as dressings to the topical treatment of orofacial herpes. PCL fibrous matrices with the co-incorporated bioactive compounds were obtained by electrospinning and characterized regarding their morphology, chemical, physical, and mechanical properties. The potential use of the developed polymeric fibrous matrices for topical applications was evaluated by: (i) the release kinetics of the bioactive compounds; (ii) the occlusive factor of the fibrous mat; (iii) ACV skin permeation capacity; and (iv) the cytotoxicity in a keratinocyte cell line. PCL fibrous matrices loaded with the bioactive compounds presented a smooth morphology and a good balance between flexibility and hardness essential to be durable for handling, while having a desirable texture to be used comfortably. The fibrous mat also provided a sustained release of ACV during 96 h and improved the skin permeability of this drug (Kp = 0.00928 ± 0.000867 cm/h) presenting also high porosity (74%) and a water vapor transmission rate (WVTR) of 881 ± 91 g/m2day, essential to maintain moist and oxygen for faster healing of herpes lesions. Furthermore, cytotoxicity studies suggest that the fibrous mat are safe for topical application. Overall, the PCL based electrospun fibrous matrices with ACV and ω3 hereby described have the potential to be used as therapeutic bandage systems for the treatment of orofacial herpes.

Dataset Information

Development of Tripolymeric Triaxial Electrospun Fibrous Matrices for Dual Drug Delivery Applications.

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Development of Tripolymeric Triaxial Electrospun Fibrous Matrices for Dual Drug Delivery Applications.

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