Three-dimensional fibrous scaffolds for cell culture
Inventors
Mohapatra, Subhra • Mohapatra, Shyam S. • Davis, Yvonne Kathleen • Wang, Chunyan
Assignees
Publication Number
US-9624473-B2
Publication Date
2017-04-18
Expiration Date
2033-02-25
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Abstract
Provided herein is a three-dimensional scaffold composition comprising randomly oriented fibers, wherein the fibers comprise a polyethylene glycol-polylactic acid block copolymer (PEG-PLA) and a poly(lactic-co-glycolic acid) (PLGA). Also provided are methods for using the three-dimensional scaffolds described herein.
Core Innovation
The invention provides a three-dimensional scaffold composition consisting of randomly oriented fibers, where each fiber is made of a polyethylene glycol-polylactic acid block copolymer (PEG-PLA) and poly(lactic-co-glycolic acid) (PLGA). The resulting three-dimensional scaffold mimics aspects of the native extracellular matrix and is formed by electrospinning the PEG-PLA and PLGA components to create a fibrous mesh with defined pore sizes and fiber diameters. In some embodiments, a chitosan coating may be applied to the scaffold surface.
A key problem addressed by this invention is the lack of realistic tumor models for studying tumorigenesis and for effective anticancer drug screening. Traditional two-dimensional cell culture systems do not represent the natural three-dimensional microenvironment of tumors, resulting in limitations regarding mechanical, biochemical, and physical cues experienced by cancer cells. While some three-dimensional models, like spheroids, exist, they are typically entirely cell-based and do not replicate the mechanical context provided by extracellular matrix (ECM) structures.
The disclosed scaffold composition enables cancer cells to form spheroids when cultured on the fibers, a process not observed on unmodified PLGA fibers or traditional monolayer cultures. The scaffold’s combination of topography and chemical composition directs spheroid formation and allows for the study of processes such as epithelial-mesenchymal transition (EMT), drug response, and gene expression changes in a context that closely resembles in vivo tumor biology. The scaffold provides a platform for cultivating cancer cell spheroids, evaluating pharmacological efficacy, and investigating mechanisms of tumor progression and drug resistance.
Claims Coverage
The independent claim covers one primary inventive feature as detailed by the claim text.
Three-dimensional scaffold with PEG-PLA and PLGA nanofibers supporting cancer cell spheroid formation
A three-dimensional scaffold composition consisting of randomly oriented nanofibers, where the fibers consist of polyethylene glycol-polylactic acid block copolymer (PEG-PLA) and poly(lactic-co-glycolic acid) (PLGA), with the following characteristics: - The ratio of PEG-PLA to PLGA in the fibers is approximately 1:4. - Fiber diameters range from approximately 0.69 to 4.18 micrometers. - The scaffold has pores with diameters of less than approximately 10 micrometers. - The composition includes a spheroid comprising a homogeneous population of cancer cells generated from an isolated cancer cell from a tumor or a cultured cancer cell line. These elements are present in claim 1, and the dependent claims specify preferred molecular weights, PLGA ratios, optional chitosan coating, and identified cancer cell lines.
The claim coverage centers on the specific composition and structure of a three-dimensional scaffold made of PEG-PLA and PLGA nanofibers in a defined ratio and dimension, capable of supporting cancer cell spheroid formation.
Stated Advantages
The scaffold provides a more realistic three-dimensional tumor model for studying tumorigenesis and for effective screening of anticancer drugs.
The three-dimensional fibrous structure offers good spatial interconnectivity, a high surface-to-volume ratio, and porosity suitable for fluid transport and cell organization.
Spheroid formation on the scaffold facilitates induction and study of epithelial-mesenchymal transition (EMT), which is relevant for investigating tumor invasion and metastasis.
The scaffold enables monitoring of pharmacological efficacy and can be used in high throughput screening of drugs to treat cancer, serving as an intermediate decision-making step.
The scaffold composition allows for easy detachment and transfer of spheroids for long-term culture and further experimental manipulation.
The scaffold chemistry and topography direct spheroid formation not observed on unmodified PLGA scaffolds or two-dimensional monolayer cultures, highlighting its unique effect on cell behavior.
PEG is used to enhance hydrophilicity, biocompatibility, and minimize protein adsorption, thereby contributing to the scaffold’s functionality.
Documented Applications
Use as a platform to study processes in tumorigenesis, including EMT and gene expression changes associated with cancer progression.
Screening pharmaceuticals for cancer treatment efficacy using the scaffold seeded with cancer cells and quantitating drug effects on live and dead cells.
Methods for growing cancer cell spheroids in a three-dimensional environment.
Methods for tissue culture and tissue regeneration using the fibrous scaffold.
Methods for treating arthritis with the three-dimensional scaffold.
Methods for wound therapy employing the scaffold composition.
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