Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds

Abstract

Native extracellular matrix (ECM) is a complex fibrous structure loaded with bioactive cues that affects the surrounding cells. A promising strategy to mimicking native tissue architecture for tissue engineering applications is to engineer fibrous scaffolds using electrospinning. By loading appropriate bioactive cues within these fibrous scaffolds, various cellular functions such as cell adhesion, proliferation and differentiation can be regulated. Here, we report on the encapsulation and sustained release of model hydrophobic drug (dexamethasone (Dex)) within beaded fibrillar scaffold of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT), a polyether-ester multiblock copolymer to direct differentiation of human mesenchymal stem cells (hMSCs). The amphiphilic beads act as depots for sustained drug release that is integrated into the fibrillar scaffolds. The entrapment of Dex within the beaded structure results in sustained release of drug over the period of 28 days. This is mainly attributed to the diffusion driven release of Dex from the amphiphilic electrospun scaffolds. In vitro results indicate that hMSCs cultured on Dex containing beaded fibrillar scaffolds exhibit an increase in osteogenic differentiation potential, as evidenced by increased alkaline phosphatase (ALP) activity, compared to the direct infusion of Dex in culture medium. The formation of mineralized matrix is also significantly enhanced due to the controlled Dex release from the fibrous scaffolds. This approach can be used to engineer scaffolds with appropriate chemical cues to direct tissue regeneration.

Nanoengineered biomaterials for repair and regeneration of orthopedic tissue interfaces

“…[28][29][30] These nanofabricated scaffolds can control the release of therapeutics to guide cellular behavior. [31,32] Complex geometries such as fibers, spheres, sheets, hollow tubes and nets can be fabricated to mimic some of the biological structures. In this review, we only focus on nanomaterials with one of their dimensions less than 500 nm.…”

Sustained Release of Protein Particle Encapsulated in Bead-on-String Electrospun Nanofibers

“…There have been a number of studies in the literature to embed the micron-sized drug particles in elsctrospun nanofibers [19,20] . However, the problem remains in alleviating the initial burst release and maintaining a sustainable release of drugs.…”

Nanosized sustained-release drug depots fabricated using modified tri-axial electrospinning

“…For instance: 1) in the shell, soluble porogenic additives (such poly(ethylene glycol) or poly(vinylpyrrolidone)) could be used to regulate the drug release behavior, as is currently the case in some particle-based drug depots [59]; 2) the approach could be extended to achieve the sustained release of soluble drugs (a major challenge in pharmaceutics); 3) drug delivery systems with more complicated drug release profiles could be achieved, e.g. multiple-phase release of a drug using a pure drug exterior compartment; 4) combined therapies with temporally sequential drug release characteristics could be explored; 5) an extremely wide range of un-spinnable fluids including dilute polymer solutions [60], surfactant or electrolyte solutions could be explored as the outer fluid in modified tri-axial processes, in order to create numerous nanoscale biomaterials with complicated nanostructures.…”

“…Nanosized drug depots, in which a drug reservoir is surrounded by pharmaceutical excipients, have attracted much attention in the biomedical field recently [1][2][3][4][5][6]. They have been explored for drug delivery through a variety of administration routes (such as oral, injected, inhaled, and implanted) and also as stents in tissue engineering [7][8][9][10][11].…”