# US 10,946,119 B2 · Systems and methods for an advanced medical device > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,946,119 B2 - Document ID: US10946119B2 - Status: Granted - Kind: B2 - Application number: 14/292,767 - Filed: 2014-05-30 - Published: 2014-09-18 - Granted: 2021-03-16 - Earliest claimed: 2006-02-02 - Applicants: Agathos Holdings LLC - Inventors: Milan Radojicic - Web page: https://patentgrep.com/patent/US10946119B2 ## CPC - A61L 27/227: {Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24} - A61L 31/005: {Ingredients of undetermined constitution or reaction products thereof} - A61L 31/047: {Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046} - A61M 27/006: {Cerebrospinal drainage; Accessories therefor, e.g. valves} - B33Y 80/00: Products made by additive manufacturing - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - B33Y: ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING ## Abstract The present invention relates to a biologically active medical device, which includes a matrix seeded with progenitor cells, and then covered by ciliated tissue. The matrix is capable of enabling cellular migration. The ciliated tissue is ependymal cells that express at least one of tight junctional complexes, zonula adherens, and gap junctions. The progenitor cells include subpendymal progenitor cells. In some cases the progenitor cells include stem cells, and the ciliated tissue includes at least one of Choroid cells, tanacytes, and circumventricular organs. In some embodiments, the medical device is oriented into a tubular structure in order to form a cerebrospinal shunt. Additional cells and structures may be imbedded within the matrix, such as glia, endothelial cells, stem cells, and blood vessels. The medical device may also be incorporated into a bioreactor including a flexible inner tube defining an anthropomorphically shaped lumen. ## Claims ### Claim 1 A method for generating robust cells in a bioreactor with a chamber comprising at least one fluid conduit said method comprising: seeding target cells in said chamber's at least one fluid conduit; applying pulsatile shear stresses to the target cells in a manner consistent with human cerebrospinal fluid physiological parameters, wherein said pulsatile shear stresses terminate at least some portion of the target cells, leaving behind viable cells; wherein said at least one fluid conduit and said pulsatile shear stresses are configured to simulate at least an impact of a human heartbeat pulse pressure on at least one human brain cerebrospinal fluid shear pathway; maturing said viable cells, thereby generating robust cells; and collecting or using said robust cells. ### Claim 2 (depends on 1) The method as recited in claim 1, further comprising applying at least one of metabolic perturbations, temperature stresses, chemical stresses, osmolality stresses, radiation stresses, acoustic stresses, and electromagnetic stresses to said target cells. ### Claim 3 (depends on 1) The method of claim 1, wherein said at least one fluid conduit comprises a plurality of cavities connected to form a branched chamber. ### Claim 4 (depends on 1) The method of claim 1, wherein said at least one fluid conduit comprises at least a portion of a 3D shape of any of a human brain ventricular system cerebrospinal fluid path and a human spine cerebrospinal fluid path. ### Claim 5 (depends on 4) The method of claim 4, wherein said at least a portion of a 3D shape of a human brain ventricular system cerebrospinal fluid path and a human spine cerebrospinal fluid path comprises any of a 3D shape of dura, arachnoid, nerve roots, and dentate ligament. ### Claim 6 (depends on 1) The method of claim 1, wherein said pulsatile shear stresses simulate pressures of any of human cardiac cycles and human respiratory cycles. ### Claim 7 (depends on 1) The method of claim 1, wherein said at least one fluid conduit further comprises at least one human Virchow-Robin space configured to simulate perivascular fluid flow. ### Claim 8 (depends on 1) The method of claim 1, wherein said bioreactor further includes at least one biologically active medical device; wherein said at least one biologically active medical device comprises at least some of said robust cells. ### Claim 9 (depends on 8) The method of claim 8, wherein said biologically active medical device comprises a biocompatible shunt or bioshunt for diversion of cerebrospinal fluid. ### Claim 10 A method for generating robust cells in a bioreactor with a chamber comprising at least one fluid conduit said method comprising: seeding target cells in said chamber's at least one fluid conduit; applying pulsatile shear stresses to the target cells in a manner consistent with human cerebrospinal fluid physiological parameters, wherein said pulsatile shear stresses terminate at least some portion of the target cells, leaving behind viable cells; wherein said at least one fluid conduit and said pulsatile shear stresses are configured to simulate at least an impact of a human heartbeat pulse pressure on at least one human brain cerebrospinal fluid shear pathway; maturing said viable cells, thereby generating robust cells; and collecting or using said robust cells; wherein said bioreactor further includes at least one medical device; wherein said at least one medical device comprises at least some of said robust cells. ### Claim 11 A method for generating robust cells in a bioreactor with a chamber comprising at least one fluid conduit said method comprising: seeding target cells in said chamber's at least one fluid conduit: wherein said at least one fluid conduit comprises a plurality of cavities connected to form a branched chamber; applying pulsatile shear stresses to the target cells in a manner consistent with human cerebrospinal fluid physiological parameters, wherein said pulsatile shear stresses terminate at least some portion of the target cells, leaving behind viable cells; wherein said at least one fluid conduit and said pulsatile shear stresses are configured to simulate at least an impact of a human heartbeat pulse pressure on at least one human brain cerebrospinal fluid shear pathway; maturing said viable cells, thereby generating robust cells; and collecting or using said robust cells; wherein said bioreactor further includes at least one medical device; wherein said at least one medical device comprises at least some of said robust cells.