Hypothermic 3D bioprinting of living tissues supported by perfusable vasculature
Inventors
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Assignees
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Rice UniversityRice University is a leading research university in Houston, Texas, recognized for its emphasis on scientific discovery, innovation, and interdisciplinary collaboration. The institution is committed to academic excellence, impactful research, and community engagement, offering robust undergraduate and graduate programs in engineering, natural sciences, social sciences, humanities, business, and the arts. Rice is distinguished by its history of collaboration with organizations such as NASA, fostering advances in space science, biotechnology, energy research, and artificial intelligence.
Rice University is a leading research university in Houston, Texas, recognized for its emphasis on scientific discovery, innovation, and interdisciplinary collaboration. The institution is committed to academic excellence, impactful research, and community engagement, offering robust undergraduate and graduate programs in engineering, natural sciences, social sciences, humanities, business, and the arts. Rice is distinguished by its history of collaboration with organizations such as NASA, fostering advances in space science, biotechnology, energy research, and artificial intelligence.
Publication Number
US-11976294-B2
Publication Date
2024-05-07
Expiration Date
Abstract
The present disclosure provides compositions and methods for producing hydrogel matrix constructs. Methods of using hydrogel matrix constructs for tissue repair and regeneration and for the oxygenation of red blood cells are also disclosed.
Core Innovation
The disclosure provides compositions and methods for producing hydrogel matrix constructs using improved polymer compositions, such as a prepolymerization solution, for use with 3D printers that utilize digital light processing (DLP) to fabricate thick, physiologically relevant vascular networks with and without cells. The designed 3D printer is an automated, computer-aided 3D prototyping device with a mobile Z-axis stage and a transparent vat in which a prepolymerization solution containing photosensitive polymers, a photoinitiator, and a biocompatible, light-absorbing additive material is polymerized by projection of patterned light to yield a hydrogel matrix with multiple perfusable, tubular channels.
The invention addresses limitations in tissue engineering arising from diffusion transport limitations and the necessity of a vasculature system to supply nutrients and remove waste in thick constructs, as well as the inability of prior techniques to recreate heterogeneous patterns of cells and matrix and interpenetrating vascular networks. The disclosure employs photopolymerizable biomaterials, biocompatible light-absorbing additives to control light penetration for high z-resolution, and computational fractal and space-filling models to fabricate multiscale, branched, interpenetrating tubular networks that more closely resemble native vasculature.
Claims Coverage
Independent claim identified: one independent claim. Four main inventive features are extracted from the independent claim and dependent claims.
Photosensitive polymer
A photosensitive polymer is included in the prepolymerization solution as a core component of the claimed composition.
Photoinitiator
A photoinitiator is included in the prepolymerization solution as a core component of the claimed composition.
Biocompatible light-absorbing additive material
A biocompatible, light-absorbing additive material capable of absorbing light in a wavelength range encompassing the light absorption spectrum of the photoinitiator is included in the prepolymerization solution.
Controlled light penetration enabling horizontal and vertical channels
The biocompatible, light-absorbing additive material has the capability, by controlling light penetration, to cause printing of structures with horizontal and vertical channels.
The independent claim covers a prepolymerization solution composition comprising a photosensitive polymer, a photoinitiator, and a biocompatible, light-absorbing additive material that absorbs across the photoinitiator's spectrum; the disclosure further claims that controlling light penetration with the additive enables printing of horizontal and vertical channels.
Stated Advantages
Provides high z-resolution in bioprinted tissues while maintaining high cell viability.
Enables fabrication of thick, physiologically relevant vascular networks with complex, multiscale, branched, interpenetrating tubular architecture.
Allows printing of hydrogels with both horizontal and vertical channels by controlling light penetration.
Offers a novel, inexpensive, fast, efficient method with high throughput potential suitable for mass production of whole organ vasculature.
Permits embedding and patterning of multiple materials and cell types within a single construct and supports in vitro functional outcomes such as oxygenation of red blood cells.
Documented Applications
Tissue repair and regeneration using hydrogel matrix constructs.
Oxygenation of red blood cells using interpenetrating tubular channels within a hydrogel matrix.
Fabrication of microfluidic devices for organ-on-a-chip and human-on-a-chip applications.
In vitro models of tissues or organs, including models for lung applications with interpenetrating airway and vascular networks.
Mechanistic studies of organ development, angiogenesis, vascular remodeling, stem cell and vascular niches, and diseased states such as cancer malignancy.
Bone tissue engineering to produce complex porous architectures that mimic trabecular bone.
Tissue engineering and whole organ replacement, including mass production of whole organ vasculature.
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