Multiphasic tissue scaffold constructs
Inventors
Vaquette, Cedryck • Lui, Hei Man Hayman • Ivanovski, Saso • Bindra, Randy
Assignees
Griffith University • Queensland University of Technology QUT
Publication Number
US-11752002-B2
Publication Date
2023-09-12
Expiration Date
2038-08-13
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Abstract
The present invention relates to a three-dimensional multiphasic synthetic tissue scaffold comprising first, second and third compartments, wherein: each said compartment comprises distinct microstructural, and/or chemical, and/or mechanical properties, and is connected with at least one other compartment of the scaffold via a continuous interface; the tissue scaffold is porous; and the external morphology of the tissue scaffold mimics that of a mammalian joint or a component thereof. The invention further relates to a method for producing the three dimensional multiphasic synthetic tissue scaffold using a polymeric material, the method comprising using a three-dimensional (3D) bioprinter to print the tissue scaffold by continuously deposit the polymeric material onto a platform until the tissue scaffold is produced in its entirety.
Core Innovation
The invention relates to a three-dimensional multiphasic synthetic tissue scaffold comprising first, second and third compartments. Each compartment has distinct microstructural, chemical, or mechanical properties and is connected with at least one other compartment via a continuous interface. The scaffold is porous, and its external morphology mimics that of a mammalian joint or a component thereof.
This scaffold may include compartments comprising a series of fibres or multiple fibre layers, where the second compartment mimics the external morphology of ligaments connecting the first and third compartments. The fibres in the ligament compartment are organized into layers aligned along axes rotated relative to each other, providing structural mimicry of natural tissue architecture.
The invention addresses challenges in tendon and ligament repair, particularly the difficulty in replicating joint architecture and achieving sufficient mechanical strength in synthetic scaffolds. Current treatments often rely on autografts that face issues such as donor site morbidity, size mismatching, and poor integration leading to suboptimal clinical outcomes, especially in small joints like the scapholunate interosseous ligament (SLIL) of the wrist.
The multiphasic scaffold is produced continuously using three-dimensional bioprinting technologies, enabling precise fabrication of interconnected compartments with distinct properties. This approach allows improved matching of native joint morphology and biomechanical function, facilitates tissue integration and vascularization, and eliminates donor morbidity associated with autografts. The scaffold can be seeded with mammalian cells to further promote tissue regeneration.
Claims Coverage
The claims define multiple inventive features covering the design of the multiphasic tissue scaffold, its composition, structure, production method, and therapeutic use.
Multiphasic synthetic tissue scaffold with distinct compartments connected via a porous continuous interface
A three-dimensional scaffold comprising first, second, and third compartments each with distinct microstructural, chemical, or mechanical properties, connected via a continuous interface, and the scaffold is porous with external morphology mimicking a mammalian joint or component thereof.
Ligament-mimicking second compartment with aligned multiple fibre layers at specific rotated angles
The second compartment comprises a series of fibres forming multiple layers aligned along axes where at least one axis is rotated at a defined angle (from about 2° to 50°) relative to another, enabling biomimicry of ligament architecture.
Triphasic fibre alignment with rotational orientation
The multiple fibre layers may include a third layer aligned along a third axis, rotated relative to the first and second axes, potentially at equal or substantially equal angles and directions (anticlockwise or clockwise) to replicate natural fibre orientations.
External morphology mimicking bone-ligament-bone arrangements and specific joints
The scaffold's compartments externally mimic bones and connecting ligaments, specifically including configurations mimicking the scapholunate joint, scaphoid, lunate, and scapholunate ligaments including dorsal ligaments.
Controlled scaffold porosity within defined pore size ranges
The scaffold comprises pores with maximum widths ranging from about 100 μM up to about 1000 μM, allowing for control over porosity to facilitate biological integration.
Incorporation of mammalian cells including stem cells within cell sheets
The scaffold may comprise mammalian cells selected from ligament-derived stem cells, cartilage stem cells, mesenchymal stem cells, and related progenitors, with cells embedded within cell sheets wrapped around or inserted into compartments.
Use of specific polymeric materials in compartments
Compartments comprise polymeric materials selected from collagen, chitosan, hyaluronic acid, alginate, gelatin, polyethylene glycol dimethacrylate, gelatin methacryloyl, matrigel, fibrinogen, agarose, polyurethane, and polycaprolactone.
Manufacture using continuous 3D bioprinting technology
A method of producing the scaffold uses a three-dimensional bioprinter to continuously deposit polymeric material onto a platform until completion, allowing integrated construction of scaffold compartments.
Use of scaffold in treatment of injured ligaments in mammals including humans
Methods include transplanting the scaffold into body compartments with injured ligaments, including joints such as the scapholunate joint and ligaments like the scapholunate interosseous ligament in humans.
The claims cover the innovative design of a multiphasic synthetic scaffold with structurally and functionally distinct compartments that mimic joint morphology, the specific fibre orientations to emulate ligaments, composition with biocompatible polymers and cells, manufacture by continuous 3D bioprinting, and therapeutic use in ligament repair.
Stated Advantages
The scaffold can withstand normal physiological forces for integrative and functional repair of soft tissue injuries.
It closely mimics existing joint architecture allowing accurate anatomical matching.
It permits manipulation to promote vascularization and tissue regeneration, reducing healing time.
It eliminates donor site morbidity associated with harvesting autografts.
Continuous manufacturing ensures mechanically strong cohesion and porous interfaces improving biomechanical stability and tissue integration.
The presence of aligned fibres provides guidance for ligament fibre alignment during tissue regeneration.
The scaffold supports the use of cell sheets promoting enhanced extracellular matrix deposition and improved regenerative outcomes.
Documented Applications
Reconstruction of the dorsal scapholunate interosseous ligament (SLIL) in wrist joints.
Use in small joint repair, specifically applications addressing scapholunate joint injuries.
Regeneration and repair of ligaments and composite musculoskeletal tissue in mammalian joints including knees, such as the medial collateral ligament (MCL) in rabbits as animal models.
Therapeutic transplantation of the scaffold into subjects with injured ligaments to facilitate tissue regeneration and restore biomechanical function.
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