Tissue engineering methods and compositions

Inventors

Guilak, Farshid • Estes, Bradley T. • Moutos, Franklin Thomas

Assignees

Cytex Therapeutics Inc

Abstract

The presently disclosed subject matter generally relates to methods and systems for facilitating the growth and differentiation of adipose-derived stem cells for laboratory and therapeutic applications. The cells can be employed alone or in conjunction with unique biologically-compatible scaffold structures to generate differentiated tissues and structures, both in vitro and in vivo. The presently disclosed subject matter further relates to methods of forming and using improved tissue engineered scaffolds that can be used as substrates to facilitate the growth and differentiation of cells.

Core Innovation

The disclosed invention relates to a method of resurfacing a predetermined articular joint in a subject, where the joint has a number of focal defects. The method provides an implant having a scaffold of woven fibrous biocompatible material sized to replace substantially all of the articulating surface of the predetermined joint and shaped substantially like the articulating surface. The implant further includes one or more adipocyte stem cells, and the method includes infiltrating or encouraging infiltration of the cells throughout the scaffold and implanting the implant at the joint site to resurface the articulating surface encompassing the focal defects.

In particular embodiments, the approach uses adipose-derived stem cells, including human adipose-derived stem cells, together with BMP-6 as a biologically active factor to differentiate in vitro toward cartilage-relevant phenotypes. BMP-6 is described as strongly inducing chondrogenic marker expression while reducing a hypertrophic marker, with differentiation assessed by DNA content, radiolabeled biosynthesis incorporation assays, qRT-PCR and immunohistochemistry. The differentiation is described as being evaluated under multiple growth factor/cytokine conditions.

The document also describes broad implant concepts combining the woven fibrous scaffold with additional scaffold and material features, including defined interstices/pore sizes and multi-fiber-system architectures, as well as optional biomaterial coatings or gel layers and cell-seeded hydrogel composites. It further describes options for genetic manipulation and selection/validation of differentiated cell subpopulations based on marker expression, and the use of a bioreactor for culture with mechanical/chemical control prior to implantation.

Claims Coverage

The partial content provides two independent claims. Across them, the inventive features center on an implant using a woven fibrous scaffold sized and shaped to cover substantially all of a predetermined articular joint’s articulating surface, seeded with one or more adipocyte stem cells, with cell infiltration and implantation to resurface focal defects; the second independent claim additionally requires devitalizing a fraction of the cells before implantation.

Overall, the claim coverage is centered on resurfacing a predetermined articular joint with an implant that uses a woven fibrous biocompatible scaffold sized and shaped to substantially replace the articulating surface, together with adipocyte stem cells, followed by cell infiltration and implantation to encompass the focal defects; a further independent inventive element requires devitalizing a fraction of the cells before implantation.

Stated Advantages

Documented Applications