Materials and methods for accelerating cardiovascular tissue regeneration
AssigneeThe Florida International University Board of Trustees
InventorsSharan D. Ramaswamy, Brittany Gonzalez, Ariadna Herrera, Alexander Williams
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Abstract
Provided are elastin-rich bioscaffolds, enhanced via stem cell pre-seeding and flow-based mechanical conditioning followed by subsequent removal of stem cells. The bioscaffolds may accelerate cardiovascular tissue regeneration and can be used in the surgical repair/reconstruction in various cardiovascular and other surgical applications including heart valves, cardiovascular grafts, and patches. The provided acellular, elastin-rich bioscaffold will pose minimal immune risk and reduced FDA regulatory hurdles as a non-living biologic product.
Claims16
An enriched decellularized bioscaffold implant for implantation in a patient, the bioscaffold implant comprising:
- a decellularized tissue matrix;
- and
- an engineered extracellular matrix (ECM) component generated by stem cells and comprising elastin and collagen,
- the bioscaffold implant being decellularized,
- the decellularized bioscaffold implant having a percentage elastin after decellularization not less than its percentage elastin before decellularization,
- the decellularized bioscaffold implant having a percentage collagen after decellularization not less than its percentage collagen before decellularization,
- the bioscaffold implant having a cell count includign the stem cells after decellularization at least 50% less than its cell count including the stem cells after generation of the elastin and collegen but before decellularization,
- the decellularized tissue matrix being syngeneic or xenogeneic to the patient, and
- the stem cells being allogeneic, autologous, or syngeneic to the patient.
A method of fabricating an enriched decellularized bioscaffold implant for implantation in a patient, the method comprising:
- providing a tissue matrix;
- exposing the tissue matrix to stem cells in a bioreactor under conditions sufficient to generate an engineered extracellular matrix (ECM) component in the tissue matrix and comprising elastin and collagen;
- and
- decellularizing the tissue matrix to remove the stem cells while maintaining the engineered ECM component in the tissue matrix,
- the conditions sufficient to generate an engineered ECM component in the tissue matrix comprising mechanical stimulation at a targeted fluid-induced oscillatory shear stress range having an oscillatory shear index (OSI) in a range of from 0.18 to 0.23.
A decellularized bioscaffold implant for implantation in a patient, the bioscaffold implant comprising:
- a decellularized tissue matrix;
- and
- an engineered extracellular matrix (ECM) component generated by stem cells,
- the engineered ECM component comprising elastin and collagen,
- the patient being a human patient,
- the stem cells being allogeneic to the patient,
- the decellularized tissue matrix being porcine small intestinal submucosa (PSIS),
- the decellularized tissue matrix having a cylindrical shape comprising a radial direction and a circumferential direction,
- the decellularized tissue matrix having a measurable average maximum tensile stress in the circumferential direction, which is at least 80% of a measurable average maximum tensile stress of the decellularized tissue matrix in the radial direction,
- the decellularized bioscaffold implant having a percentage elastin after decellularization not less than its percentage elastin before decellularization,
- the decellularized bioscaffold implant having a percentage collagen after decellularization not less than its percentage collagen before decellularization, and
- the decellularized bioscaffold implant having a cell count after decellularization at least 50% less than its cell count after generation of the elastin and collagen but before decellularization.
Dependencies are inferred from the claim text.