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-12173310-B2
Publication Date
2024-12-24
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
Tissue engineering faces a major challenge due to the necessity of a vasculature system to supply nutrients and remove waste in thick constructs, which can be attributed to diffusion transport limitations resulting in necrotic cells and the lack of ability to recreate heterogeneous patterns of cells and matrix to obtain constructs with controlled shape and architectures. Existing methods yield macroporous templates or straight perfusable channels, but precise spatial control of scaffold architecture, physiologically relevant vessel geometry, multilayered interconnected microfluidic networks, and interpenetrating vascular networks are lacking in current technologies.
The present disclosure provides improved polymer compositions, such as a prepolymerization solution, and methods for use with digital light processing (DLP) 3D printers to fabricate thick, physiologically relevant vascular networks with and without cells. The invention employs a prepolymerization solution comprising a photosensitive polymer having a molecular weight greater than 2,000 Daltons, a photoinitiator, and a biocompatible, light-absorbing additive material suitable to control light penetration, and an automated additive-manufacturing apparatus that selectively patterns photosensitive biomaterials one layer at a time to yield a multi-layer hydrogel matrix comprising multiple perfusable, tubular channels that interpenetrate but do not intersect.
The disclosure further provides processes for manufacturing multi-layer hydrogel matrix constructs by creating a 3D model using computational algorithms or mathematical fractal, space-filling models, converting and slicing the model into 2D images, supplying the prepolymerization solution to a transparent vat, projecting patterned light onto the inner bottom surface of the vat to polymerize layer-by-layer, and repeating these steps to obtain final constructs, and includes embodiments where the hydrogel matrix and channels can be cell-lined and used for oxygenation of red blood cells.
Claims Coverage
The claim set includes one identified independent claim with two main inventive features.
Hydrogel matrix including a light-absorbing additive material
A composition comprising a hydrogel matrix that includes a light-absorbing additive material.
Interpenetrating first and second tubular channels that do not intersect
A composition comprising a first tubular channel and a second tubular channel defined in the hydrogel matrix, wherein the first tubular channel and the second tubular channel interpenetrate but do not intersect.
The independent claim covers a hydrogel matrix containing a light-absorbing additive material and at least two tubular channels that interpenetrate without intersecting.
Stated Advantages
Enables fabrication of thick, physiologically relevant vascular networks with multiple perfusable, tubular channels that closely resemble and function as native vascular networks.
Provides a photochemical means to achieve high z-resolution in bioprinted tissues while maintaining high cell viability.
Novel, unique, inexpensive, fast, efficient method that allows for creation of large, physiologically relevant model vasculature on the order of a few hours and lends itself to mass production of whole organ vasculature.
Control of light penetration via a biocompatible, light-absorbing additive material enables printing of horizontal and vertical channels and complex architectures.
Documented Applications
Tissue repair and regeneration.
Oxygenation of red blood cells using interpenetrating channels in a hydrogel matrix.
In vitro models of tissues or organs, including organ-on-a-chip or human-on-a-chip applications.
Mechanistic studies of organ development, angiogenesis, vascular remodeling, stem cell and vascular niches, and diseased states, such as in vitro models of cancer malignancy.
Tissue engineering and whole organ replacement, including mass production of whole organ vasculature.
Fabrication of microfluidic devices.
Lung applications and models comprising interpenetrating arterial (vascular) and airway networks with epithelial and endothelial cell lining.
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