Tissue and organ replacements and methods of making thereof

1 . A method of making a tissue or organ replacement composition to be attached to or implanted in a patient, the method comprising:

fabricating a biocompatible support structure including one or more external supports, one or more internal supports, or combinations thereof of a biocompatible material;

fabricating a tissue-engineered construct including one or more bio ink compositions, fabricating the tissue engineered construct comprising:

depositing the one or more bio ink compositions in or around the biocompatible support structure, wherein the one or more bio ink compositions includes living cells;

crosslinking the one or more bio ink compositions, and optionally repeating the depositing and crosslinking steps, to form the tissue-engineered construct; and curing the tissue or organ replacement composition;

wherein:

the tissue or organ replacement composition has a 3D shape;

the biocompatible material is present in an amount of about 1% to about 100% by weight of the biocompatible support structure;

wherein the one or more external supports partially cover outer surfaces of the tissue-engineered construct when the tissue or organ replacement composition is configured to be attached to or implanted in the patient and/or the one or more internal supports are partially encapsulated by the tissue-engineered construct when the tissue or organ replacement composition is configured to be attached to or implanted in the patient; and

wherein the organ is an ear and/or the biocompatible support structure is configured to be both internal and external to the body of the patient when attached to or implanted in the patient.

2 . The method of claim 1 , wherein the method of fabricating the biocompatible support structure comprises:

depositing one or more layers of the biocompatible material to a substrate; crosslinking the biocompatible material; and

separating the substrate from the one or more external supports, the one or more internal supports, or the combination thereof.

3 . The method of claim 2 , wherein the depositing comprises 3D printing the one or more bio ink compositions.

4 . The method of claim 3 , wherein the 3D printing is selected from the group consisting of ink-jet printing, layer-by-layer printing, extrusion printing, and bioprinting.

5 . The method of claim 2 , further comprising repeating the depositing and crosslinking steps to obtain the one or more external supports, the one or more internal supports, or the combination thereof.

6 . The method of claim 1 , wherein the method of fabricating the biocompatible support structure comprises injection molding, wherein the injection molding comprises:

depositing one or more layers of the biocompatible material to a substrate, wherein the substrate is a mold of the one or more external supports, internal supports, or combinations thereof;

crosslinking the biocompatible material in the mold; and

removing the one or more external supports, internal supports, or the combination thereof from the mold.

7 . The method of claim 1 , wherein the method of fabricating the biocompatible support structure comprises thermoforming, wherein the thermoforming comprises:

contacting a 2D sheet of the biocompatible material to a substrate, wherein the substrate is a mold of the one or more external supports, internal supports, or the combination thereof;

heating the 2D sheet of the biocompatible material to thermoform the 2D sheet into conformity with the shape of the mold to obtain the one or more external supports, internal supports, or the combination thereof;

removing the one or more external supports, internal supports, or the combination thereof from the mold.

8 . A tissue or organ replacement composition to be attached to or implanted in a patient, the tissue or organ replacement composition comprising:

a tissue-engineered construct comprising one or more bio ink compositions; and

a biocompatible support structure comprising one or more external supports, one or more internal supports, or combinations thereof of a biocompatible material;

wherein the tissue or organ replacement composition has a three-dimensional (3D) shape;

wherein the biocompatible material is present in an amount of 1% to 100% by weight of the biocompatible support structure;

wherein the one or more external supports partially cover outer surfaces of the tissue-engineered construct when the tissue or organ replacement composition is configured to be attached to or implanted in the patient and/or the one or more internal supports are partially encapsulated by the tissue-engineered construct when the tissue or organ replacement composition is configured to be attached to or implanted in the patient; and

wherein the organ is an ear and/or the biocompatible support structure is configured to be both internal and external to the body of the patient when attached to or implanted in the patient.

9 . The composition of claim 8 , wherein the one or more bio ink compositions comprise one or more of hydrogel, agarose, collagen, laminin, elastin, chitosan, fibrin, hyaluronic acid, carrageenan, polyethylene oxide, polypropylene oxide, polyethylene oxide-co-polypropylene oxide, hydroxypropyl methyl cellulose, poly(propylene fumarate-co-ethylene glycol), poly(ethylene glycol)-co-poly(lactic acid), poly(vinyl alcohol), KDLI 2 oligopeptides, poly(n-isopropyl acrylamide), or combinations of two or more thereof.

10 . The composition of claim 9 , wherein the one or more bio ink compositions comprise an alginate hydrogel present in an amount of 0.5% (w/v) to 10% (w/v).

11 . The composition of claim 8 , wherein the one or more bio ink compositions comprise 5 mg/ml to 200 mg/ml of collagen and/or comprise a carrier, a crosslinking agent, or a combination thereof.

12 . The composition of claim 8 , wherein the one or more bio ink compositions comprise collagen selected from type I collagen, type III collagen, type IV collagen, other fibrillary collagens, or a combination of two or more thereof.

13 . The composition of claim 8 , wherein the biocompatible material is selected from the group consisting of polysaccharides, biocompatible polymers, rubber, silicon, biocompatible metals, biocompatible ceramics, polyethylene glycol, polypropylene glycol, polyamino acids, natural and biopolymers, and combinations of two or more thereof and/or wherein the biocompatible material is selected from the group consisting of poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly (lactic-co-glycolic acid) (PLGA), polydioxanone (PDO), polycaprolactones, bioresorbable metal alloys, and combinations thereof.

14 . The composition of claim 8 , wherein the one or more internal supports have a 2D thickness from 10 μm to 2000 μm.

15 . The composition of claim 8 , wherein the biocompatible support structure has one or more of a flexural modulus of 0.2 GPa to 100 GPa, a modulus of elasticity of 0.02 GPa to 100 GPa, or a tensile strength of 1 MPa to 1000 MPa.

16 . The composition of claim 8 , wherein the composition withstands compression of 1 kN to 10,000 kN, a shear force of 0.2 kN to 1,000 kN, or a combination thereof.

17 . The composition of claim 8 , wherein the bio ink composition includes a cellular media containing a population of cells;

wherein the cellular media is a cellular hydrogel, and wherein the one or more bio ink compositions further comprise collagen.