Engineering 3D and Free Standing Tissue Structures

Summary Background: Efforts to build biosynthetic materials or engineered tissues that recapitulate the structure-function relationships of natural processes often fail because of an inability to replicate the proper in vivo conditions. For example, engineering a functional muscle tissue requires that the sarcomere and myofibrillogenesis be controlled at the micron length scale, while cellular alignment and formation of contiguous tissue requires organizational cues over the millimeter to centimeter length scale. Thus, to build functional biosynthetic material, the natural-artificial interface must contain the necessary chemical and mechanical properties to support multiscale operation.

Invention: A novel and robust engineering technique that utilizes free-standing polydimethylsiloxane (PDMS) elastomer films to generate 2D and 3D tissue structures. The fabrication steps used to make free-standing films are as follows: A rigid base material is coated with a sacrificial polymer layer on top of which a flexible polymer layer (PDMS) is temporarily bonded to the rigid base material. An engineered surface chemistry is provided on the flexible polymer layer to enhance or inhibit cell and/or protein adhesion. Cells are seeded onto the flexible polymer layer and cultured in an incubator under physiologic conditions until the cells form a 2D tissue, the shape of which is determined by the engineered surface chemistry. A desired shape of the flexible polymer layer can then be cut out and the sacrificial layer dissolved or actuated to release the flexible polymer from the rigid base. The free-standing flexible film of desired shape can be modified further by adopting/forming a 3D conformation and then integrated into a multi-construct device or prepared for use as a tissue engineering/regeneration scaffold for, e.g., the manufacture and use of biologically actuated control devices, bench-top drug analysis, wound dressings, artificial organs, and grafts for repairing soft and hard tissue.

Examples of cell types that are attached include myocytes (e.g., cardiac myocytes) for muscle-based motion; neurons for electrical-signal propagation; fibroblasts for extra-cellular-matrix deposition; endothelial cells for blood contact; and skin cells. By way of example, the technique can be used to generate so-called muscular thin films (MTF) from cardiac myocytes. The PDMS thin film provides restorative elasticity and improved handling characteristics, while the myocytes provide contractile function. The resulting MTF can be utilized for a number of desired functionalities, such as soft robotics, tissue engineering and the study of cardiac biomechanics. The desired performance characteristics of the MTF can be obtained by engineering the size, shape, thickness, tissue microarchitecture and pacing of actuation. In this example, myocytes were exploited as linear actuators to drive MTFs that bend, twist, rotate, grasp, pump, walk and swim.

Applications Advantages: The bending stiffness of the thin films increases with the elastic modulus, thickness and width while decreasing with length. Using this system, a variety of 2D shapes can be generated that will fold into intricate 3D shapes. The engineered surface chemistry is able to enhance or inhibit cell and/or protein adhesion. The surface chemistry may also be uniform across the surface or patterned spatially (e.g., with features having dimensions ranging from 5, 10, 20, 50, 100 nanometers to 1-1,000 micrometers to the larger macroscale) using soft lithography, self assembly, vapor deposition and photolithography. The surface chemistry can be selected from the following groups: extracellular matrix proteins, growth factors, lipids, fatty acids, steroids, sugars, carbohydrates, combinations of carbohydrates, lipids and/or proteins, Nucleic acids, hormones, enzymes, cell surface ligands and receptors, cytoskeletal filaments and/or motor proteins.

Applications: The potential applications of the technology are widespread. For example, thin films can be used in wound healing, prosthetics, and tissue engineering. The scaffold can also be seeded with functional elements, such as drugs, coagulants, anti-coagulants, etc., and can be kept, e.g., in a medic’s field pack. In addition to myocytes for muscle based motion, examples of cell types that can be utilized in the system include neurons for electrical-signal propagation, fibroblasts for extra-cellular-matrix propagation, endothelial cells for blood contacts, and skin cells. For Further Information Please Contact the Director of Business Development Michal Preminger Email: michal_preminger@hms.harvard.edu Telephone: (617) 432-0920

Inventor(s): Parker, Kevin Kit

Type of Offer: Licensing



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