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Assignees
University of California San Diego UCSD
University of California, San Diego (UCSD)The University of California, San Diego (UCSD) is a leading public research university located in La Jolla, California. Known for its innovative and interdisciplinary approach, UCSD offers a wide range of undergraduate, graduate, and professional programs across various fields. The university is committed to fostering a diverse and inclusive community, promoting sustainability, and driving social mobility through education, research, and public service. UCSD is recognized for its contributions to research and innovation, particularly in areas such as climate science, health innovation, and artificial intelligence.
The University of California, San Diego (UCSD) is a leading public research university located in La Jolla, California. Known for its innovative and interdisciplinary approach, UCSD offers a wide range of undergraduate, graduate, and professional programs across various fields. The university is committed to fostering a diverse and inclusive community, promoting sustainability, and driving social mobility through education, research, and public service. UCSD is recognized for its contributions to research and innovation, particularly in areas such as climate science, health innovation, and artificial intelligence.
Publication Number
US-12364609-B2
Publication Date
2025-07-22
Expiration Date
2037-12-12
Abstract
Implantable devices for spinal cord and peripheral nerve injury are described. The implants include a three-dimensional printed structure having stem cells disposed therein. Also disclosed are methods of treating neuronal injuries with the disclosed implants.
Core Innovation
The invention relates to biomimetic implantable devices designed to treat spinal cord and peripheral nerve injuries. These implants include three-dimensional printed structures that mimic the natural architecture of the injury site, such as the spinal cord or peripheral nerve, and incorporate one or more channels. These channels guide regenerating axons through the lesion site and can be loaded with stem cells, including neural stem cells and mesenchymal stem cells, to promote tissue regeneration and functional recovery.
The implants are designed to overcome challenges in 3D bioprinting of functional neural tissue, particularly the difficulty of fabricating complex three-dimensional microarchitectures essential for guiding cell growth and tissue maturation in the central nervous system. Previous scaffolds faced limitations like foreign body responses, limited scalability, and lack of biomimicry. The invention addresses these by providing rapidly 3D printed structures with layerless architecture, biomimetic design replicating spinal cord gray and white matter or peripheral nerve structures, and suitable mechanical properties matching native tissue.
The implants are composed of biocompatible polymers such as polyethylene glycol diacrylate (PEGDA) and gelatin methacrylol (GelMa) in combinations that support structural integrity and cell attachment while reducing foreign body responses and glial scar formation. These implants can be customized to patient-specific injury geometries based on imaging and can extend across lesions with microchannels that guide axons linearly from one end of the implant to the other. Methods of treating neurological injuries with these implants include implantation into lesion sites with or without stem cell loading, promoting axonal regeneration, synaptic connectivity, and behavioral recovery.
Claims Coverage
The patent includes one independent claim that defines the biomimetic nerve or spinal cord implant and several dependent claims elaborating on various features. There is one independent claim.
Biomimetic implant body with linear channels mimicking host axon organization
A three-dimensional implant body having a first and second end formed in a biomimetic shape that mimics the structure of a nerve or spinal cord injury site to replicate host axon organization. The implant comprises a plurality of linear channels extending from the first to the second end that mimic host axon organization both ex vivo and in vivo. The channel walls have thickness up to 100 micrometers and retain pre-implantation structure for at least 4 weeks in vivo. The implant has an elastic modulus from about 260 kPa to about 300 kPa.
Production by 3D printing
The implant is produced by three-dimensional printing, enabling rapid fabrication of the biomimetic structure.
Inclusion of stem cells in channels
At least one type of stem cell, including neural stem cells, can be included in the linear channels to promote regeneration.
Stem cell types and engineering
The neural stem cells can be embryonic stem cells, induced pluripotent stem cell (iPSC) derived stem cells, directly differentiated neural stem cells, or combinations thereof. Stem cells can also be mesenchymal stem cells and may be engineered to express neurotrophic factors such as BDNF, NT3, or GDNF.
Composition of implant material
The implant is composed of polyethylene glycol diacrylate, gelatin methacrylol, or combinations thereof, providing biocompatibility and suitable mechanical properties.
Biomimicry to spinal cord or peripheral nerve injury
The implant mimics either spinal cord injury or peripheral nerve injury morphological characteristics.
Channel characteristics and organization
Channels are linear microchannels, typically about 200 micrometers in diameter, parallel to each other, and configured to guide regenerating axons linearly from the first end to the second end. Channels can have hexagonal cross-sections clustered as a honeycomb structure with wall thicknesses up to 100 micrometers and spacing around 66 micrometers.
Layerless structure and matrix composition
The implant is free of discrete layers, providing improved mechanical integrity, and composed of a matrix including gelatin methacrylate and PEGDA.
Long-term structural retention
Implants retain their pre-implantation structure for extended durations, with some embodiments showing structure retention for at least 6 months in vivo.
Core composition
The core of the implant comprises gelatin methacrylate, PEGDA, and a photoinitiator lithium phenyl-2,4,6-trimethylbenzoylphosphinate to enhance mechanical strength.
The independent claim defines a biomimetic 3D printed implant with linear channels that replicate host axon architecture and suitable mechanical properties for spinal cord or nerve repair. Dependent claims cover fabrication by 3D printing, stem cell inclusion, material composition, channel morphology and organization, and long-term structural stability, comprehensively defining the implant's inventive structural and functional attributes.
Stated Advantages
Rapid, layerless 3D printing enables fabrication of complex biomimetic implants with microscale resolution, providing improved mechanical integrity over traditional layered printed structures.
The implants reduce foreign body responses and glial scar formation compared to previous implants such as agarose scaffolds, promoting better host axon penetration and regeneration beyond lesion sites.
Customizable implant shape and size based on patient-specific imaging allows precise fitting of injury cavities, improving integration and therapeutic efficacy.
Incorporation of stem cells supports survival, differentiation, synapse formation, and functional regeneration, enabling relays across spinal cord lesions with significant motor recovery.
The implants are well vascularized and maintain structural integrity for months in vivo, supporting long-term tissue regeneration and remodeling.
Documented Applications
Treatment of spinal cord injury, including motor complete and motor incomplete spinal cord injuries.
Treatment of peripheral nerve injury, either complete or partial.
Promotion of axonal regeneration and remyelination across sites of spinal cord transection or peripheral nerve lesion.
Use in restoring motor function and electrophysiological transmission in damaged nervous tissue.
Potential treatment of sequelae of spinal cord injury such as bowel dysfunction, incontinence, impotence, sexual dysfunction, pain, numbness, and neuropathy by repairing the injury site.
Use in combination with physical therapy or other training modalities to improve neurological outcomes.
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