Microcapillary mesh oxygen transporter for cell transplantations

Inventors

Tai, Yu-ChongShang, Kuang-MingKomatsu, Hirotake

Assignees

Cite Of HopeCalifornia Institute of TechnologyCity of Hope

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Publication Number

US-12415018-B2

Patent

Publication Date

2025-09-16

Expiration Date


Abstract

A two-dimensional lattice or mesh scaffold for therapeutic cell implants is disclosed as well as methods for manufacture and use. The lattice is constructed of crisscrossing capillaries of hydrophobic parylene, such as parylene AF4, that may be coated with a hydrophilic polymer, such as parylene C, for cell adhesion. At each intersection of the crisscross, the intersecting capillaries are internally connected so as to allow oxygen to flow freely within. The walls of the capillaries are thin enough to be permeable to oxygen, on the scale of a micron thick, so that oxygen can flow through the lattice and permeate through the capillary walls. For some implants, cells are sandwiched between two or more lattices, the cells being slightly held apart from aggregation with each other by the lattice holes. The implants may then be surgically implanted within a subject.

Core Innovation

The invention relates to a 2D therapeutic cell scaffold/oxygen transporter that includes a two-dimensional lattice of interconnected hollow microcapillaries of hydrophobic parylene. The hydrophobic parylene is parylene AF4, and the microcapillaries intersect to form an array of lattice holes between the capillaries.

The capillary walls have micron-scale thickness so as to be permeable to diatomic oxygen, and the lattice holes and oxygen-permeable capillary walls are configured to support oxygen transport through the lattice. Intersections are internally connected to enable oxygen shunting through the lattice, providing low diffusion resistance across the scaffold.

The hydrophobic interior resists water condensation while permitting oxygen and vapor transport, and the lattice holes are spaced to reduce cell aggregation. Therapeutic cells are incorporated in the scaffold, including pancreatic islet β-cells that secrete insulin, and the cells can be sandwiched between multiple 2D lattices with hydrogel support.

Claims Coverage

Two independent claims are present. The inventive features are based on a two-dimensional lattice of hydrophobic parylene AF4 interconnected capillaries with oxygen-permeable walls and defined lattice-hole spacing, and on incorporating therapeutic cells in a sandwich arrangement between such lattices.

Two-dimensional lattice of interconnected hydrophobic parylene AF4 capillaries

A two-dimensional lattice of interconnected capillaries of hydrophobic parylene, wherein the hydrophobic parylene is parylene AF4, the capillaries intersecting to form an array of lattice holes therebetween.

Oxygen-permeable capillary walls with defined thickness

Hydrophobic parylene capillaries having walls between 0.1 μm and 10 μm in thickness so as to be permeable to diatomic oxygen.

Defined lattice-hole center-to-center spacing

Lattice holes having a center-to-center spacing between 1 μm and 500 μm.

Therapeutic cells sandwiched between two-dimensional lattices

Therapeutic cells sandwiched between the two-dimensional lattices.

Cell therapy implant with multiple two-dimensional lattices

A plurality of two-dimensional lattices, each lattice comprising interconnected capillaries of hydrophobic parylene, wherein the hydrophobic parylene is parylene AF4, the capillaries intersecting to form an array of lattice holes therebetween.

Overall, the independent claims require a 2D lattice of interconnected hydrophobic parylene AF4 capillaries forming lattice holes, oxygen-permeable capillary walls with specified thickness, lattice-hole spacing within a specified range, and therapeutic cells arranged as a sandwich between such 2D lattices.

Stated Advantages

An increase in cell viability versus a control without an oxygen-transporting mesh (reported as 4–5× increase).

Reduction of hypoxia for subcutaneous or liver implantation.

Documented Applications

Subcutaneous implantation for hypoxia reduction.

Liver implantation for hypoxia reduction.

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