An anisotropic nanofiber/microsphere composite with controlled release of biomolecules for fibrous tissue engineering

Abstract

Aligned nanofibrous scaffolds can recapitulate the structural hierarchy of fiber-reinforced tissues of the musculoskeletal system. While these electrospun fibrous scaffolds provide physical cues that can direct tissue formation when seeded with cells, the ability to chemically guide a population of cells, without disrupting scaffold mechanical properties, would improve the maturation of such constructs and add additional functionality to the system both in vitro and in vivo. In this study, we developed a fabrication technique to entrap drug-delivering microspheres within nanofibrous scaffolds. We hypothesized that entrapping microspheres between fibers would have a less adverse impact on mechanical properties than placing microspheres within the fibers themselves, and that the composite would exhibit sustained release of multiple model compounds. Our results show that microspheres ranging from 10~20 microns in diameter could be electrospun in a dose-dependent manner to form nanofibrous composites. When delivered in a sacrificial PEO fiber population, microspheres remained securely entrapped between slow-degrading PCL fibers after removal of the sacrificial delivery component. Stiffness and modulus of the composite decreased with increasing microsphere density for composites in which microspheres were entrapped within each fiber, while stiffness did not change when microspheres were entrapped between fibers. The release profiles of the composite structures were similar to free microspheres, with an initial burst release followed by a sustained release of the model molecules over 4 weeks. Further, multiple model molecules were released from a single scaffold composite, demonstrating the capacity for multi-factor controlled release ideal for complex growth factor delivery from these structures.

PLLA-PEG-TCH-labeled bioactive molecule nanofibers for tissue engineering

“…26 Recently, a technology was developed to deliver multiple growth factors by sacrificing microsphere-loaded nanofibers (phase I), resulting in the microspheres being entrapped within the nanofiber (phase II) scaffolds. 27 However, most existing scaffolds for implantation carry no more than two types of therapeutic agents, which may hinder the efficacy of scaffold transplantation.…”

Fabrication of Plga/Hap and Plga/Phb/Hap Fibrous Nanocomposite Materials for Osseous Tissue Regeneration

“…Scientific advances have also contributed to considerable interest in nanofibres obtained by electrospinning and their medical applications. In most cases, fibrous nanostructures used for osseous tissue regeneration, obtained by electrospinning, are fabricated to develop both passive and active materials, with the latter including a system that enables the controlled release of drugs or other active biomolecules [24,[26][27][28]. The application of nanofibres in research aiming to obtain new materials for medicine has been reflected in numerous publications [27,29,30].…”

“…In most cases, fibrous nanostructures used for osseous tissue regeneration, obtained by electrospinning, are fabricated to develop both passive and active materials, with the latter including a system that enables the controlled release of drugs or other active biomolecules [24,[26][27][28]. The application of nanofibres in research aiming to obtain new materials for medicine has been reflected in numerous publications [27,29,30]. The relevant literature includes many papers devoted to the use of nanofibres in the treatment of osseous tissue [31,32], articular cartilages [33,34], muscles [35], ligaments [36], skin [12,37] and use in cardiosurgery [9].…”

A review of electrospinning manipulation techniques to direct fiber deposition and maximize pore size

“…Similar to porogen leaching, a soluble polymer and an insoluble polymer can be co-electrospun onto a central mandrel, followed by a rinse in dissolution media to dissolve the soluble fibers. This leaves the insoluble fibers and causes a higher porosity within the scaffold [133][134][135]. For example, poly(ethylene oxide) (PEO) is a polymer that can be used as either electrosprayed beads or as secondary fibers in combination with silk fibroin (SF), a protein usually extracted from silkworm cocoons, to create a composite scaffold.…”