Bicomponent nanofibrous tissue engineering scaffolds for the dual release of biomacromolecules and anti-cancer drug

Abstract

Cancer is a major cause for human deaths. At present, surgical removal is a primary treatment for solid and isolated tumors for cancer patients. However, functional disorders are common after tissue removal. Scaffold-based tissue engineering promotes tissue regeneration at the surgical site. Biomacromolecules such as growth factors can influence cell attachment, proliferation, differentiation and migration. Growth factors can be encapsulated in electrospun nanofibrous scaffolds and subsequently released to enhance tissue regeneration. The recurrence of cancer after surgery is another major issue. Anti-cancer drug may also be contained in electrospun scaffolds for treating cancer recurrence. In this study, different types of delivery vehicles were investigated for the dual delivery of biomacromolecules and anti-cancer drug for both regenerating body tissue and treating cancer recurrence. Bovine serum albumin (BSA) and doxorubicin hydrochloride (DOX) were used as model biomacromolecules and drug. Using dual-source-dual-power (DSDP) electrospinning, novel bicomponent fibrous scaffolds were made as dual delivery vehicles. BSA and DOX were encapsulated in PLGA50/50 nanofibers and PLGA75/25 nanofibers, respectively. The bicomponent scaffolds were made by either DSDP blend electrospinning or DSDP emulsion electrospinning. The morphology and structure of these scaffolds were studied using SEM and TEM. The encapsulation efficiency and in vitro release behavior of BSA and DOX were investigated. BSA and DOX encapsulated in scaffolds by different electrospinning techniques exhibited different encapsulation efficiencies and release behaviors. BSA and DOX in emulsion electrospun scaffolds showed higher encapsulation efficiency. Severe burst release of BSA and DOX from scaffolds made by blend electrospinning was observed. BSA and DOX from emulsion electrospun scaffolds showed slight burst release in the initial 24 hours. More sustained and controlled release of BSA and DOX from emulsion electrospun scaffolds was subsequently observed. Another type of bicomponent scaffolds were also made for the dual release investigations: BSA was encapsulated in PLGA50/50 nanofibers and DOX was encapsulated in PLGA75/25 microspheres. These bicomponent scaffolds were made by either DSDP blend electrospinning and electrospray or DSDP emulsion electrospinning and electrospray. Burst release was observed for blend electrospun fibers and blend electrosprayed microspheres. Both BSA and DOX release from bicomponent scaffolds made by DSDP emulsion electrospinning and electrospray exhibited limited initial burst release which was followed by sustained release. This study demonstrates that controlled dual release of biomacromolecules and anti-cancer drug could be achieved using electrospun fibrous scaffolds. It also shows that the release behaviours could be influenced by the scaffold fabrication method and design of delivery vehicles.