Electrospun nanofibers for 3-D cancer models, diagnostics, and therapy.

As one of the leading causes of global mortality, cancer has prompted extensive research and development to advance efficacious drug discovery, sustained drug delivery and improved sensitivity in diagnosis. Towards these applications, nanofibers synthesized by electrospinning have exhibited great clinical potential as a biomimetic tumor microenvironment model for drug screening, a controllable platform for localized, prolonged drug release for cancer therapy, and a highly sensitive cancer diagnostic tool for capture and isolation of circulating tumor cells in the bloodstream and for detection of cancer-associated biomarkers. This review provides an overview of applied nanofiber design with focus on versatile electrospinning fabrication techniques.

Chitosan-based composite bilayer scaffold as an in vitro osteochondral defect regeneration model.

Prolonged osteochondral tissue damage can result in osteoarthritis and decreased quality of life. Multiphasic scaffolds, where different layers model different microenvironments, are a promising treatment approach, yet stable joining between layers during fabrication remains challenging. Here, a bilayer scaffold for osteochondral tissue regeneration was fabricated using thermally-induced phase separation (TIPS).

Hyaluronic Acid-Coated Aligned Nanofibers for the Promotion of Glioblastoma Migration.

The propensity of glioblastoma multiforme (GBM) cells to migrate along white matter tracts and blood vessels suggests that topographical cues associated with brain parenchyma greatly influence GBM motility and invasion. cell culture platforms that mimic the physical and biochemical characteristics of brain tissue are needed to develop biologically relevant GBM migration models for the development of anticancer therapies. Here, we fabricated highly aligned chitosan-polycaprolactone (C-PCL) polyblend nanofibers coated with hyaluronic acid (HA), a glycosaminoglycan commonly found in the brain, to simulate the structure and biochemistry of native brain tissue.

Fabrication and Characterization of Chitosan-Hyaluronic Acid Scaffolds with Varying Stiffness for Glioblastoma Cell Culture.

The invasive and recurrent nature of glioblastoma multiforme (GBM) is linked to a small subpopulation of cancer cells, which are self-renewing, resistant to standard treatment regimens, and induce formation of new tumors. Matrix stiffness is implicated in the regulation of cell proliferation, drug resistance, and reversion to a more invasive phenotype. Therefore, understanding the relationship between matrix stiffness and tumor cell behavior is vital to develop appropriate in vitro tumor models.

Chitosan-Poly(caprolactone) Nanofibers for Skin Repair.

Dermal wounds, both acute and chronic, represent a significant clinical challenge and therefore the development of novel biomaterial-based skin substitutes to promote skin repair is essential. Nanofibers have garnered attention as materials to promote skin regeneration due to the similarities in morphology and dimensionality between nanofibers and native extracellular matrix proteins, which are critical in guiding cutaneous wound healing. Electrospun chitosan-poly(caprolactone) (CPCL) nanofiber scaffolds, which combine the important intrinsic biological properties of chitosan and the mechanical integrity and stability of PCL, were evaluated as skin tissue engineering scaffolds using a mouse cutaneous excisional skin defect model.

3D Porous Chitosan-Alginate Scaffolds Promote Proliferation and Enrichment of Cancer Stem-Like Cells.

Cancer stem cells are increasingly becoming a primary target for new cancer treatment development. The ability to study their transient behavior in vitro will provide the opportunity for high-throughput testing of more effective therapies. We have previously demonstrated the use of 3D porous chitosan-alginate (CA) scaffolds to promote cancer stem-like cell (CSC) proliferation and enrichment in glioblastoma.

Culture on 3D Chitosan-Hyaluronic Acid Scaffolds Enhances Stem Cell Marker Expression and Drug Resistance in Human Glioblastoma Cancer Stem Cells.

The lack of in vitro models that support the growth of glioblastoma (GBM) stem cells (GSCs) that underlie clinical aggressiveness hinders developing new, effective therapies for GBM. While orthotopic patient-derived xenograft models of GBM best reflect in vivo tumor behavior, establishing xenografts is a time consuming, costly, and frequently unsuccessful endeavor. To address these limitations, a 3D porous scaffold composed of chitosan and hyaluronic acid (CHA) is synthesized.

Modeling the tumor microenvironment using chitosan-alginate scaffolds to control the stem-like state of glioblastoma cells.

Better prediction of in vivo drug efficacy using in vitro models should greatly improve in vivo success. Here we utilize 3D highly porous chitosan-alginate complex scaffolds to probe how various components of the glioblastoma microenvironment including extracellular matrix and stromal cells affect tumor cell stem-like state.

High-throughput and high-yield fabrication of uniaxially-aligned chitosan-based nanofibers by centrifugal electrospinning.

The inability to produce large quantities of nanofibers has been a primary obstacle in advancement and commercialization of electrospinning technologies, especially when aligned nanofibers are desired. Here, we present a high-throughput centrifugal electrospinning (HTP-CES) system capable of producing a large number of highly-aligned nanofiber samples with high-yield and tunable diameters. The versatility of the design was revealed when bead-less nanofibers were produced from copolymer chitosan/polycaprolactone (C-PCL) solutions despite variations in polymer blend composition or spinneret needle gauge.

Thermoreversible poly(ethylene glycol)-g-chitosan hydrogel as a therapeutic T lymphocyte depot for localized glioblastoma immunotherapy.

The outcome for glioblastoma patients remains dismal for its invariably recrudesces within 2 cm of the resection cavity. Local immunotherapy has the potential to eradicate the residual infiltrative component of these tumors. Here, we report the development of a biodegradable hydrogel containing therapeutic T lymphocytes for localized delivery to glioblastoma cells for brain tumor immunotherapy.

Chitosan-based thermoreversible hydrogel as an in vitro tumor microenvironment for testing breast cancer therapies.

Breast cancer is a major health problem for women worldwide. Although in vitro culture of established breast cancer cell lines is the most widely used model for preclinical assessment, it poorly represents the behavior of breast cancers in vivo. Acceleration of the development of effective therapeutic strategies requires a cost-efficient in vitro model that can more accurately resemble the in vivo tumor microenvironment.