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US-12622970-B2 - Photocurable reinforcement of 3D printed hydrogel objects

US12622970B2US 12622970 B2US12622970 B2US 12622970B2US-12622970-B2

Abstract

The present disclosure provides reinforced hydrogel structures, methods of reinforcing hydrogel structures, and methods of treating ischemic disorders using the reinforced hydrogel structures.

Inventors

  • Mora Carolynne Melican
  • Kalyan Vydiam
  • Aman Kaur
  • Lara Murcin
  • Barbara Nsiah
  • Richmon Lin
  • Derek Morris
  • Lina Trigg
  • Luis Alvarez
  • Mohammadali Safavieh
  • Masoud Modaresifar

Assignees

  • LUNG BIOTECHNOLOGY PBC

Dates

Publication Date
20260512
Application Date
20220506

Claims (16)

  1. 1 . A method of preparing a reinforced structure, comprising contacting a mesh immersed in an uncured photocurable bioink with a first hollow tube, an outer wall of the hollow tube being continuous, and irradiating the mesh immersed in the uncured photocurable bioink in contact with the hollow tube, thereby adhering the mesh to the hollow tube via a hydrogel formed from the photocurable bioink to form a tube reinforced by the mesh.
  2. 2 . The method of claim 1 , wherein the mesh has a thickness of about 0.1 μm to about 2 mm.
  3. 3 . The method of claim 1 , wherein the mesh spirals around a sublength of the hollow tube.
  4. 4 . The method of claim 1 , wherein the contacting comprises contacting an outside surface of the hollow tube with the mesh.
  5. 5 . The method of claim 1 , wherein the contacting and the irradiating are repeated more than once to form two or more layers of the mesh.
  6. 6 . The method of claim 5 , wherein the two or more layers are stacked.
  7. 7 . The method of claim 1 , wherein the photocurable ink comprises a photoinitiator and/or dye that reacts and/or absorbs light with a wavelength of about 100 to about 400 nm.
  8. 8 . The method of claim 1 , wherein the reinforced tube has a burst pressure of 1,000 mmHg or greater.
  9. 9 . The method of claim 1 , wherein the contacting comprises suturing the reinforced tube to a second hollow tube.
  10. 10 . The method of claim 9 , wherein the reinforced tube has a suture pullout force of a site of the suturing 2.5 times to 15 times greater than a non-reinforced hollow tube.
  11. 11 . The method of claim 9 , wherein the reinforced tube has a suture retention of 1.5 N or greater.
  12. 12 . The method of claim 1 , wherein the first hollow tube comprises a first subtube, a second subtube and a joint connecting the first subtube and the second subtube, wherein the contacting comprises contacting the mesh with the joint of the first hollow tube.
  13. 13 . The method of claim 1 , wherein the contacting comprises contacting the hollow tube with the mesh at a sublength constituting from 0.1% to 50% of the hollow tube.
  14. 14 . The method of claim 13 , wherein the sublength is from 1 mm to 2.5 cm.
  15. 15 . The method of claim 1 , wherein the reinforced tube is a vascular graft.
  16. 16 . A method of treating ischemic disease in a subject in need thereof, the method comprising implanting the reinforced tube produced by the method of claim 1 .

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63/185,305, filed May 6, 2021, the entire contents of which are incorporated herein by reference. BACKGROUND Three-dimensional (3D) hydrogel structures have increasing uses for various biomedical applications. However, the mechanical properties of a hydrogel construct can often lead to problems with the durability of these constructs. In the past, those in the field altered the mechanical properties by forming a “skin” on the surface of a hydrogel structure in a process that was tedious, time consuming, and hard to reproduce. In addition, the “skin” was sometimes fragile itself. For example, Raghavan et al., used a complex methodology employing concentric molds to create a hollow cylindrical structure. The delicate materials are difficult to remove from the molds, and in a second step, the surface of the tube is treated with an agent that causes polymer chains to crosslink in the gel structure. It is difficult to control the depth of this treatment. Others in the field have uses additives to elicit a chemical reaction throughout the hydrogel that changes the mechanical properties. This has several distinct disadvantages. One is that the beneficial properties of soft hydrogel scaffolds interacting with the cells is lost when the material properties are changed like this. A second disadvantage of this approach is the need to add an additional material type to the system, which may have a negative effect on cellular response. This more complex implant will also take longer to get regulatory approval. For example, Gaharwar has been able to increase a hydrogel's stiffness by 10 times and its toughness by 20 times through a process in which he adds a small amount of spherical, magnetic nanoparticles to the collagen-based hydrogels. Others toughen hydrogels by adding ceramic particles, such as Fukao (J. Mater. Chem. B, 2020, 8, 5184-5188). This approach would only work in limited applications in which the presence of a ceramic would not be detrimental to the healing of the tissue. Accordingly, there exists a need in the art to improve the mechanical properties of hydrogel structures in a manner that is repeatable and that does not create an overly complex device, and/or does not drastically alter the beneficial properties of soft hydrogel scaffolds. SUMMARY Some embodiments of the present disclosure are directed to a method of reinforcing a three-dimensional (3D) hydrogel structure, comprising contacting a mesh immersed in uncured photocurable bioink with the structure, and irradiating the mesh immersed in uncured photocurable bioink, thereby adhering it to the 3D hydrogel structure. Some embodiments of the present disclosure are directed to a composition comprising a three-dimensional (3D) hydrogel structure and a layer comprising a mesh immersed in a photocurable or photocured ink, and wherein the layer comprising a mesh immersed in a photocurable or photocured ink is in contact with the structure. Some embodiments of the present disclosure are directed to a method of treating ischemic disease in a subject in need thereof, the method comprising implanting the reinforced structure or composition disclosed herein. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1: Exemplary graph showing the mechanical properties of the tissue engineered vascular graft (TEVG) (burst pressure, suture retention, and compliance) compared with saphenous vein (SV). Burst pressure: 2134 mmHg=284 kPa; Suture retention strength: 1.92 N; and Compliance: 25.6%/100 mmHg. See Pashneh-Tala et al., Tissue Engineering: Part B, Volume 22, pg. 68, Number 1, 2016. FIGS. 2A-2I: Experimental apparatus for burst test development on hydrogel tubes. FIG. 2A: Formlabs through tube with plug and flare. FIG. 2B: Luer lock standard fitting with zip tie. FIG. 2C: Formlabs fixture reinforced with cohesive bandage, steri-strips, and glue/paper (sticks and rips tube). FIG. 2D: Glue and filter paper reinforcement of tube. FIG. 2E: Technical drawing of the construct shown in FIGS. 2A, 2B & 2C. FIG. 2F: Tube fixed to bottom of container to maintain horizontal configuration and eliminate tube-bend induced by tube buoyancy. FIG. 2G: Tube apparatus to eliminate glue usage. FIG. 2H: Tube with enhanced mounting ends. FIG. 2I: Tube with enhanced mounting ends R3=inner diameter and R6=outer diameter. FIGS. 3A-3E: Suture pull out test apparatus as described in Example 8. FIG. 3A: Clamped into a vice, a jig for mounting membrane for suture pull out test with u-shaped port for suture placement (FIG. 3B) in membrane inserted into the jig. FIG. 3C: submerged reinforced hydrogel. FIG. 3D: Jig with sandpaper support for gripping to exert force for suture pull out testing. FIG. 3E: Suture types, ⅜th circle was used in the suture pull out test. FIGS. 4A-4F: Porcine artery connection discussed in Example 5. FIG. 4A: Purse string suture technique. FIG. 4B: Connector attached to nativ