3D in vitro Models of Lung Tissue
OwnerChelsea M. MAGIN, Tyler J. D'OVIDIO +1inventors
InventorsChelsea M. MAGIN, Tyler J. D'OVIDIO, Nicole Joanne DARLING
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Abstract
The invention relates to the discovery of tissue mimicking constructs and compositions that can be used to study the growth and development of cells in vitro. In certain embodiments, the invention provides methods of culturing cells on the tissue mimicking polymer microspheres. In other embodiments, the invention provides methods of treating a disease or disorder using the compositions and constructs of the invention.
Claims21
-72. (canceled)
A method of culturing cells in an in vitro tissue model, the method comprising:
- incubating cells seeded in a uniformly dispersed polymer microsphere composition;
- aggregating portions of the uniformly dispersed polymer microsphere composition to form alveoli-like clusters;
- and
- encapsulating and incubating the alveoli-like clusters in an encapsulating matrix material;
- wherein the polymer microspheres comprise:
- at least one multifunctional monomer;
- at least one peptide segment;
- and at least one degradable crosslinker;
- wherein the encapsulating matrix material comprises:
- at least one multifunctional monomer;
- at least one crosslinker, wherein the at least one crosslinker is at least one non-degradable crosslinker, at least one degradable crosslinker, or at least one non-degradable crosslinker and at least one degradable crosslinker;
- and at least one peptide segment.
An encapsulating matrix material composition, comprising;
- at least one multifunctional monomer, and optionally further comprising at least one crosslinker, or at least one crosslinker and at least one peptide segment, and when present, the at least one crosslinker is in an off-stoichiometric amount in relation to the amount of the at least one multifunctional monomer;
- wherein the at least one multifunctional monomer is a compound of Formula (IA):
- wherein:
- each instance of L3 independently comprises a linkage selected from the group consisting of a bond,
- wherein the * side of the linkage is bound to the monomer and the opposite side is bound to R1, and wherein q is an integer selected from 0 to 6;
- each instance of R1 independently comprises a functionality selected from the group consisting of acrylate, methacrylate, alpha-methacrylate, norbornene, thiol, azide, alkene, alkyne, oxime, hydrozone, isocyanate tetrazine, maleimide, vinyl sulphone, dibenzocyclooctyne, NHS-ester.
- wherein at least one instance of R1 is
- m is an integer from 0 to 10;
- and
- n is an integer from 1 to 500.
An aggregated alveoli-like structure, comprising alveoli-like clusters comprising at least one polymer microsphere composition, wherein the at least one polymer microsphere composition comprises at least one multifunctional monomer, at least one peptide segment, at least one degradable crosslinker, and optionally further comprising at least one cell;
- and
- the alveoli-like clusters are encapsulated by the encapsulating matrix material composition of claim 93.
Dependencies are inferred from the claim text.