Biofabrication techniques for the implementation of intrinsic tissue geometries to an in vitro collagen hydrogel
Inventors
Yost, Michael John • Rodriguez-Rivera, Veronica
Assignees
University of South Carolina • Medical University of South Carolina MUSC • MUSC Foundation for Research and Development
Publication Number
US-10730928-B2
Publication Date
2020-08-04
Expiration Date
2035-09-28
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Abstract
Methods for reaction electrospinning are provided to form collagen fibers. The method can include: acidifying a collagen in an acidic solvent to form an acidic collagen solution; electrospinning the acidic collagen solution within an alkaline atmosphere (e.g., including ammonia vapor) to form collagen fibers; and collecting the collagen fibers within a salt bath (e.g., including ammonium sulfate). The acidic solvent can include water and an alcohol, and can have a pH of about 2 to about 4 (e.g., including a strong acid, such as HCl). An albumin rubber is also provided, which can include albumin crosslinked with glutaraldehyde.
Core Innovation
The invention provides methods for reaction electrospinning of collagen fibers and for forming engineered bio-scaffolds that mimic the spatial arrangement and geometrical intricacy of in vivo tissue. This is achieved by creating a sacrificial albumin rubber (comprising albumin crosslinked with glutaraldehyde) that can be molded into complex tissue-inspired shapes. The albumin rubber is injected and set within a mold to create a precise rubber blank, which is then coated with collagen using either casting or an electrospinning process, transferring intricate architectural features to the collagen scaffold.
After coating with collagen, the albumin rubber is selectively dissolved and removed using an enzyme, such as trypsin, which digests the rubber while leaving the collagen structure intact. This process results in a collagen-based scaffold containing internal flow channels and branch points, closely reflecting the complex geometries and architectures found in natural tissues such as blood vessels and organs. The collagen hydrogels can be formulated to include laminin to enhance cell signaling properties.
The problem addressed by the invention is the lack of fabrication technologies that can re-create in vitro the true 3D architecture and geometrical complexity of native tissue, especially scaffolds with branched or intricate flow channels, which are crucial for mimicking physiological functions and supporting proper cell behavior and tissue regeneration. The described approach overcomes limitations of prior scaffolding methods that could not achieve such fine, biologically relevant features or required toxic crosslinkers, enabling the creation of biocompatible, structurally accurate, and cell-instructive scaffolds.
Claims Coverage
There is one independent claim capturing the primary inventive aspect of the invention.
Bio-scaffold formation using an enzymatically removable albumin rubber template
A method comprising: 1. Filling a mold with an albumin rubber so that the rubber conforms to the shape of the mold, producing a rubber blank with the mold's geometry. 2. Removing the albumin rubber from the mold to obtain a free-standing rubber blank with the desired spatial features. 3. Coating the rubber blank with collagen, allowing the collagen to take the shape of the rubber blank. 4. Selectively dissolving the rubber blank from within the collagen using an enzyme, wherein the enzyme digests only the rubber template while leaving the collagen unaffected, thus forming internal flow channels inside the bio-scaffold that replicate the geometrical features of the original mold.
The independent claim establishes an inventive process for creating engineered bio-scaffolds with complex internal geometries by using an albumin rubber template that is selectively removed enzymatically, leaving a collagen structure that mimics in vivo tissue architecture.
Stated Advantages
Enables the creation of 3D scaffolds that faithfully recapitulate complex in vivo tissue geometries, including internal flow channels and branch points.
Utilizes biocompatible and cell-instructive materials, such as collagen and laminin, providing superior chemical and physical cues to support cell viability and tissue remodeling.
Allows fine control over scaffold elasticity and mechanical properties to match those of native tissues.
Employs a sacrificial rubber template that can be selectively removed without damaging the collagen scaffold using mild enzymatic digestion.
Eliminates the need for toxic chemical crosslinkers, reducing the risk of cytotoxicity and preserving collagen's native structure.
Facilitates rapid, easy, and high-fidelity transfer of intricate architectural features from a digital model or tissue image into a physical scaffold.
Documented Applications
Formation of in vitro platforms that mimic intrinsic tissue geometries for therapeutic research and regenerative medicine.
Creation of engineered bio-scaffolds for studying disease processes and cell behaviors in a physiologically relevant 3D environment.
Generation of scaffolds for transplantation and replacement of damaged or malformed soft tissues.
Fabrication of vascular tissue constructs with branched architectures suitable for culturing vascular endothelial and bone marrow stromal cells.
Development of tissue models for engineering organs such as heart and kidney, including their branched flow channels for transplantation studies.
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