Bioprinter devices, systems and methods for printing soft gels for the treatment of musculoskeletal and skin disorders

Inventors

TAMAYOL, Ali • Mostafavi, Azadeh • RUSSELL, Carina • Williams, Tyrell • Sinha, Indranil • Quint, Jacob

Assignees

NuTech Ventures Inc

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Publication Number

US-12270015-B2

Patent

Publication Date

2025-04-08

Expiration Date


Abstract

Systems and methods are described that utilize bioprinters to form scaffold structures in situ to facilitate treatment of the musculoskeletal or skin disorders in patients. A method for treating a musculoskeletal disorder of a patient includes positioning a bioprinter at a situs of the musculoskeletal disorder, or a situs of a skin injury, in the patient. The method includes extruding a hydrogel formulation from the bioprinter into the situs. The method includes curing the hydrogel formulation in the situs. The hydrogel formulation has a composition effective to generate, upon the curing, a scaffold structure in the situs to facilitate muscle hypertrophy and/or new muscle fibers, or skin wound healing, in the situs.

Core Innovation

The disclosure describes handheld/extrusion-based in situ bioprinting of photocrosslinkable adhesive hydrogel scaffolds at a targeted situs. A bioprinter extrudes a hydrogel scaffold material and cures it on-site using integrated light and/or chemical/heat-based curing to form an adhesive scaffold. The formed scaffold is intended to support tissue integration and cell viability while providing an adhesive interface to tissue.

The disclosed bioprinter system includes a housing and a syringe assembly inserted into a receptacle of the housing. The housing defines proximal and distal ends, with a first opening positioned distally to facilitate removable insertion of at least a portion of the syringe assembly, and a second opening positioned at or proximal to the proximal end to facilitate access to a nozzle from the exterior of the housing. An integrated power supply and electric actuator are coupled to a plunger of the syringe assembly, and a controller regulates power to facilitate regulating actuation of the plunger based on signals from at least one control device operable from the exterior of the housing.

The disclosure further describes system extensions and material formulation options for the printed hydrogel scaffold, including cell-laden hydrogel formulations such as GelMA with photoinitiator and shear thinning behavior, and optional additives including nanoparticles and bioceramics. Integrated or optional features include illumination and imaging/camera with remote/telemedicine capability and a temperature regulation device for maintaining the hydrogel liquid at or near a constant temperature. Example results described include adhesion/integration and cellular responses in a murine volumetric muscle loss model, and cell viability and myotube formation for C2C12 myoblasts encapsulated in the printed hydrogel.

Claims Coverage

The independent claims cover two inventive feature groupings: the housing/openings and syringe/nozzle access arrangement with actuator power regulation, and the system-level liquid-flow regulation through exterior nozzle access.

Distal-to-proximal syringe insertion with exterior nozzle access through housing openings

A housing defining a proximal end and a distal end, and the housing including a receptacle for receiving at least a portion of a syringe assembly within the housing, the receptacle defining a first opening and a second opening through a wall of the housing, where the first opening is positioned distally from the second opening to facilitate removable insertion of at least the portion of the syringe assembly into the receptacle through the first opening, and the second opening is positioned at, or proximal to, the proximal end to facilitate access to a nozzle of the syringe assembly from an exterior of the housing through the second opening upon the removable insertion.

Electric-actuator-driven plunger control based on exterior control signals

A power supply disposed within the housing, an electric actuator disposed within the housing operably coupled to at least a portion of a plunger of the syringe assembly upon insertion into the receptacle, a control interface positioned at least partially within the housing and including at least one control device operable from the exterior of the housing, and a controller disposed within the housing coupled to the power supply, the electric actuator, and the control interface, where the controller is configured to regulate a flow of power from the power supply to the electric actuator based on signals received from the at least one control device to facilitate regulating actuation of the plunger by the electric actuator.

Actuator-regulated liquid flow through nozzle to housing exterior

A housing defining a proximal end and a distal end, the housing including a receptacle with a first opening and a second opening through a wall of the housing, where the first opening is positioned distally from the second opening to facilitate access to a syringe assembly from an exterior of the housing and the second opening is positioned at, or proximal to, the proximal end to facilitate access to a nozzle from the exterior of the housing through the second opening, and where a flow of liquid from a barrel through the nozzle to the exterior of the housing is provided; the syringe assembly positioned at least partially in the receptacle including the barrel containing the liquid, the nozzle in flow communication with the barrel, and a plunger slidably disposed inside the barrel; an electric actuator coupled to the plunger; a control interface with at least one control device operable from the exterior of the housing; and a controller configured to regulate actuation of the plunger by regulating a flow of power from the power supply to the electric actuator based on signals from the at least one control device to facilitate regulating a flow of the liquid from the barrel through the nozzle and to the exterior of the housing.

Across the independent claims, coverage centers on a housing receptacle having a distal-to-proximal insertion opening arrangement and an exterior-access nozzle opening, together with controller-driven regulation of power to an electric actuator coupled to a syringe plunger to regulate liquid flow through a nozzle to the exterior of the housing.

Stated Advantages

The formed scaffold supports tissue integration and cell viability while providing an adhesive interface to tissue.

The disclosure describes adhesion/integration and cellular responses in a murine volumetric muscle loss model.

The disclosure describes cell viability and myotube formation for C2C12 myoblasts encapsulated in the printed hydrogel.

Documented Applications

Handheld/extrusion-based in situ bioprinting of photocrosslinkable adhesive hydrogel scaffolds at a targeted situs.

Cell-laden hydrogel formulations such as GelMA with photoinitiator and shear thinning behavior.

Remote/telemedicine capability through illumination and imaging/camera.

Maintaining the hydrogel liquid at or near a constant temperature.

Use in a murine volumetric muscle loss model.

Encapsulation of C2C12 myoblasts in the printed hydrogel.

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