Methods, substrates, and systems useful for cell seeding of medical grafts
Inventors
Hiles, Michael C. • Johnson, Chad E. • Fearnot, Neal E. • Payne, Thomas • Jankowski, Ronald
Assignees
Cook Myosite Inc • Cook Medical Technologies LLC • Muffin Inc • Cook Myosite Inc
Publication Number
US-12121631-B2
Publication Date
2024-10-22
Expiration Date
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Abstract
Described are methods, cell growth substrates, and devices that are useful in preparing cell-containing graft materials for administration to patients. Tubular passages can be defined in cell growth substrates to promote distribution of cells into the substrates. Also described are methods and devices for preparing cell-seeded graft compositions, methods and devices for preconditioning cell growth substrates prior to application of cells, and cell seeded grafts having novel substrates, and uses thereof.
Core Innovation
The invention provides methods, cell growth substrates, and devices useful in preparing cell-containing graft materials for administration to patients, including cell growth substrates defining tubular passages to promote distribution of cells during application of cell suspensions to the substrates. The disclosure includes methods and devices for preparing cell-seeded, flowable matrix graft compositions, methods and devices for pre-conditioning cell growth substrates prior to application of cell compositions, automated methods and devices for preparing cell-seeded implantable grafts including features for distributing cells throughout a volume of substrate materials, and particulate forms of cell growth substrates and their use to prepare flowable cellular graft materials. The invention further describes cell-seeded grafts having substrates comprising remodelable collagenous extracellular matrix sheet material that can retain growth factors, glycosaminoglycans, and proteoglycans from an animal source tissue.
The background identifies a need arising from slow clinical implementation of cell-containing graft materials and the need for more convenient and/or effective ways or materials for combining cells with cell growth substrates so that they are situated for survival and often expansion in the patient. The invention addresses these needs by providing substrate designs (for example sheets defining passages and substrates with primary and branching secondary passages), application devices (for example chambers, cannulae, spray nozzles, mixers and distribution assist devices), and particulate and gel-form substrate compositions to facilitate distribution, attachment, and delivery of cells to target tissues. The patent also describes devices and system features for assessing cell suspension conditions and for combining, mixing and transferring cellular compositions with substrate materials in a controlled manner.
Claims Coverage
The claims include three independent claims expressing three inventive features related to (1) a method for preparing a cell-seeded composition using a fluid extracellular matrix particulate composition combined with a liquid cell suspension, (2) a method for treating a patient by introducing cellularized particulate bodies into the patient, and (3) a cellular graft material comprising cellularized particulate bodies suspended in a liquid medium having certain cell types.
Formation of suspended cellularized particulate bodies
Providing a fluid extracellular matrix particulate composition comprising a suspension of particles of extracellular matrix material in a liquid medium; combining the fluid extracellular matrix composition with a liquid cell suspension to form a cellular fluid composition; mixing the cellular fluid composition; and causing cells of the liquid cell suspension to attach to the particles of extracellular matrix at least in part through a native capacity of the cells to attach to surfaces so as to form suspended cellularized particulate bodies each including a particle of extracellular matrix having some of the cells attached thereto.
Administration of cellularized particulate bodies
Introducing a cellular graft composition into the patient, wherein the cellular graft composition includes cellularized particulate bodies comprised of cells attached to extracellular matrix particles at least in part through a native capacity of the cells to attach to surfaces, the cellularized particulate bodies being suspended in a liquid medium of the cellular graft composition.
Cellularized particulate graft material comprising EPCs or muscle derived cells
A cellular graft material comprising cellularized particulate bodies suspended in a liquid medium, the cellularized particulate bodies each including a particle of a particulate cell growth substrate material and cells attached to the particle at least in part through a native capacity of the cells to attach to surfaces, wherein the cells comprise endothelial progenitor cells, muscle derived cells, or a combination thereof.
Collectively the independent claims cover (1) the in-liquid formation of cellularized particulate bodies by combining extracellular matrix particles with cell suspensions and mixing to permit native cell attachment, (2) the introduction of such cellularized particulate bodies into a patient as a treatment, and (3) a graft material product comprising suspended cellularized particulate bodies with specified cell types.
Stated Advantages
Features enabling enhanced combination with cell suspensions, including tubular passages defined in cell growth substrates to promote distribution of cells during application of cell-suspensions.
Ability to generate fluid pressure within blind-hole passages to more rapidly disperse a cell suspension and drive cells into adjacent regions of the substrate.
Interconnected or intersecting passage geometries that can create flow conditions (e.g., turbulence or redirection) to facilitate more rapid or efficient distribution of cells throughout the substrate volume.
Compact sheet-form particulate substrates provide advantageous suspension and cell attachment characteristics for flowable cellular graft materials and facilitate delivery (for example injectable delivery) and retention of cells at the targeted region.
Gellable matrix components that can transition to a higher viscosity after delivery to facilitate maintenance of the delivered graft material at the site of administration.
Documented Applications
Preparing cell-containing graft materials for administration to patients, including bedside autologous cellular treatment workflows where tissue is obtained, processed to a cellular composition, and re-introduced to the patient.
Preparing and delivering flowable, injectable cellular grafts (for example in a syringe and through a needle or catheter) for implantation into patient tissues.
Treating ischemic tissue by enhancing formation of blood vessels, including treatment of ischemic myocardial tissue and critical limb ischemia, via administration of vascularizing cellular grafts containing endothelial progenitor cells or ECFCs.
Enhancing healing of partial or full thickness dermal wounds such as diabetic ulcers and burns by administration of cellular grafts.
Generating or restoring muscle tissue, including delivery of muscle derived myoblasts to muscle tissue such as sphincter tissue to treat incontinence.
Preparing cellularized particulate bodies and other graft constructs for administration to a patient, and methods and devices for loading substrates, combining cells and substrates, and assessing adherence prior to administration.
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