MODULAR SYNTHETIC TISSUE-GRAFT SCAFFOLD
20210322632 · 2021-10-21
Inventors
- Luiz E. Bertassoni (Portland, OR, US)
- Avathamsa ATHIRASALA (Portland, OR, US)
- Anthony Tahayeri (Sherwood, OR, US)
Cpc classification
C12N2501/165
CHEMISTRY; METALLURGY
A61F2002/30607
HUMAN NECESSITIES
A61F2/2846
HUMAN NECESSITIES
B33Y80/00
PERFORMING OPERATIONS; TRANSPORTING
C12N2501/155
CHEMISTRY; METALLURGY
A61F2/30907
HUMAN NECESSITIES
A61F2002/30915
HUMAN NECESSITIES
A61L27/54
HUMAN NECESSITIES
C12N5/0691
CHEMISTRY; METALLURGY
A61F2/30942
HUMAN NECESSITIES
A61F2002/30331
HUMAN NECESSITIES
B29C64/124
PERFORMING OPERATIONS; TRANSPORTING
A61L2430/02
HUMAN NECESSITIES
C12N2533/18
CHEMISTRY; METALLURGY
International classification
B29C64/124
PERFORMING OPERATIONS; TRANSPORTING
B33Y70/10
PERFORMING OPERATIONS; TRANSPORTING
B33Y80/00
PERFORMING OPERATIONS; TRANSPORTING
Abstract
A modular synthetic tissue-graft scaffold (10) includes one or more nominally identical scaffold cages (12) configured to facilitate regrowth of tissue of an organism in and around the scaffold cages. Each scaffold cage comprises a volumetric enclosure (18) bounded by a perforated wall structure (40). A recess (24) formed at one end of the volumetric enclosure defines an inner stepped coupling surface. An annular raised portion (26) positioned at the other end of the volumetric enclosure forms an outwardly projecting stepped seating surface sized to form a complementary matable surface to the inner stepped coupling surface for whenever an inner stepped coupling surface of another one of the cages is placed on the outer stepped seating surface of the scaffold cage. Corridors (46) extending through the perforated wall structure and communicating with passageways (54) within the volumetric enclosure enable migration of material within and out of the scaffold cage.
Claims
1. In a modular, synthetic tissue-graft scaffold including a set of one or more nominally identical scaffold cages that are configured to facilitate regrowth of tissue of an organism in and around the scaffold cages, each scaffold cage in the set comprising: a volumetric enclosure bounded by a perforated wall structure and having interior and exterior surfaces and first and second opposite ends, the volumetric enclosure defining a central longitudinal axis that extends through the first and second opposite ends, the interior surface defining a boundary of an interior chamber of the volumetric enclosure, and the interior and exterior surfaces defining between them a thickness of the perforated wall structure; a perforated platform set within the volumetric enclosure and in transverse relation to the central longitudinal axis forms a recess at the first end of the volumetric enclosure, the recess defining an inner stepped coupling surface bounded by the interior surface of the perforated wall structure, the perforated platform providing a passageway within the interior chamber of the volumetric enclosure between its first and second opposite ends; an annular raised portion positioned at the second end of the volumetric enclosure and forming an outwardly projecting stepped seating surface including a first portion that is transverse to the central longitudinal axis and a second portion that is transverse to the first portion, and the outwardly projecting stepped seating surface sized to form a complementary matable surface to the inner stepped coupling surface whenever an inner stepped coupling surface of another one of the cages in the set is placed on the outer stepped seating surface of the scaffold cage; and corridors extending through the thickness of the perforated wall structure and communicating with the passageway within the interior chamber of the volumetric enclosure to enable migration of material within and out of the scaffold cage.
2. The modular scaffold of claim 1, in which the set includes an array of multiple nominally identical scaffold cages in the form of a scaffold cage sheet, the multiple scaffold cages oriented such that their associated central longitudinal axes are in generally parallel alignment and the exterior surfaces of mutually adjacent cages are fused to each other and thereby form a fused perforated wall structure, the fused perforated wall structure having a thickness through which spatially aligned corridors extend to allow migration of material between the interior chambers of the mutually adjacent scaffold cages.
3. The modular scaffold of claim 2, in which the scaffold cages forming the cage sheet include scaffold cages having annular raised portions positioned at first opposite ends and perforated platforms set to form recesses at second opposite ends.
4. The modular scaffold of claim 1, in which the modular scaffold is made of β-tricalcium phosphate.
5. The modular scaffold of claim 1, in which the modular scaffold is made of α-tricalcium phosphate, dicalcium phosphate, calcium carbonate, zirconium oxide or aluminum oxide.
6. The modular scaffold of claim 1, in which the modular scaffold is manufactured using a lithography-based three-dimensional printing technology.
7. The modular scaffold of claim 1, in which the modular scaffold is manufactured using a mold-based, a sculpting-based, or a subtractive manufacturing method.
8. The modular scaffold of claim 1, in which the inner stepped coupling surface is generally shaped as a circle, ellipse, or polygon.
9. The modular scaffold of claim 1, in which the annular raised portion is generally shaped as a circle, ellipse, or polygon.
10. The modular scaffold of claim 1, in which the perforated platform constitutes a first perforated platform, and further comprising a second perforated platform, the second perforated platform set transverse to the central longitudinal axis of the volumetric enclosure of the cage and proximal to the second end of the volumetric enclosure relative to the first perforated platform to define a platform pair, the platform pair providing a passageway within the interior chamber of the volumetric enclosure between the first and second ends.
11. The modular scaffold of claim 1, in which the exterior surface of the perforated wall structure constitutes one or more wall aspects, and the perforated wall structure includes no corridor extending through its thickness at one or more of the wall aspects.
12. The modular scaffold of claim 1, in which the passageway within the interior chamber terminates at and therefore does not extend through one of the first and second opposite ends of the volumetric enclosure.
13. The modular scaffold of claim 1, further comprising a tissue-graft material inserted into the interior chamber of the volumetric enclosure.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0014]
[0015]
[0016] FIG. 2A1 is an oblique isometric view showing a raised annular end, and FIG. 2A2 is an oblique isometric view showing an opposite, recessed end, of one embodiment of the disclosed scaffold cage.
[0017] FIG. 2B1 is a sectional view taken along lines 2B1-2B1 of FIG. 2A1, and FIG. 2B2 is a sectional view taken along lines 2B2-2B2 of FIGS. 2A2.
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DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0029]
[0030] FIGS. 2A1 and 2A2, 2B1 and 2B2, 2C, and 2D are, respectively, isometric, sectional, bottom plan, and top plan views of a preferred embodiment of scaffold cage 12.
[0031] As shown in FIGS. 2A1 and 2A2, scaffold cage 12 includes volumetric enclosure 18 that defines a central longitudinal axis 28 extending through first end 20 and second end 22 and has recess 24 positioned at first end 20 and annular raised portion 26 positioned at second end 22. Annular raised portion 26 includes an outwardly stepped seating surface 30 that has a first portion 32 and a second portion 34, with the surface of first portion 32 set transverse to central longitudinal axis 28 and the surface of second portion 34 set transverse to the surface of first portion 32. Volumetric enclosure 18 is bounded by a perforated wall structure 40 to provide flexural strength to scaffold cage 12. Perforated wall structure 40 has an interior surface 42 and an exterior surface 44 that are connected by a set of corridors 46. Interior surface 42 defines an interior chamber 48 of sufficient volume to receive tissue-graft material, and interior surface 42 and exterior surface 44 define between them a thickness 50 of perforated wall structure 40. The measure of thickness 50 varies along the length of perforated wall structure 40. Corridors 46 extend through thickness 50 of perforated wall structure 40 to facilitate movement of tissue-graft material (not shown) throughout interior chamber 48, other scaffold cages, and host tissues.
[0032] In some embodiments, interior chamber 48 receives and contains tissue-graft material that supports growth of tissue. Examples of tissue-graft material include hydrogel, microgel, extracellular suspension, pharmaceutical compound, or autologous tissue. The tissue-graft material may be cell-laden or acellular. The tissue-graft material may contain cellular growth factors including Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), or Bone Morphogenic Protein 2 (BMP-2); be pre-vascularized; or be geometrically micropatterned.
[0033] FIGS. 2B1 and 2B2 show interior chamber 48, thickness 50 of perforated wall structure 40, corridors 46, and recess 24, the last of which has a length set by a perforated platform 52. Perforated platform 52 is set inwardly of second end 22 and in transverse relation to central longitudinal axis 28 to form recess 24 at first end 20 of volumetric enclosure 18. Perforated platform 52 provides support for tissue-graft material placed in interior chamber 48 and includes passageways 54 for the movement of tissue-graft material within interior chamber 48 between first end 20 and second end 22. Recess 24 defines an inner stepped coupling surface 60 bounded by interior surface 42. Inner stepped coupling surface 60 and outwardly stepped seating surface 30 are mutually sized to form complementary matable surfaces for coupling adjacent scaffold cages by inserting an outer stepped seating surface of an annular raised portion of one of the scaffold cages into a recess of the other scaffold cage.
[0034] In a preferred embodiment, the complementary matable surfaces form a friction-fit to secure the coupling of scaffold cages. “Friction-fit” is described herein as a fastening between two surfaces that is achieved by friction after the surfaces are joined together. In other embodiments, an adhesive may be used to fasten the complementary matable surfaces together.
[0035]
[0036]
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[0038] In some embodiments, the dimensions of perforated wall structure 40 range between about (1,000 μm-3,000 μm)×(1,000 μm-3,000 μm)×(1,000 μm-3,000 μm), with thickness 50 ranging between about 100 μm-645 μm. In other embodiments, perforated platform 52 has a thickness ranging between about 125 μm-400 μm and is set to give recess 24 a length between about 225 μm-700 μm. In other embodiments, annular raised portion 26 has dimensions ranging between about (100 μm-645 μm)×(770 μm-3000 μm)× (770 μm-3000 μm) and an aperture leading to interior chamber 48 having a crosswise measure ranging between about 500 μm-2425 μm with first portion 32 having a thickness ranging between about 85 μm-320 μm. In further embodiments, corridors 46 have apertures having crosswise measures ranging between 190 μm-915 μm and are set in perforated wall structure 40 between 28 μm-86 μm from annular raised portion 26. These dimensional ranges are preferred to provide a therapeutically effective tissue-graft scaffold of sufficient flexural strength and permeability.
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[0046] In some embodiments, a cross-sectional surface area of the apertures of individual corridors 46 or spatially aligned corridors 74 ranges between about 10,000 μm.sup.2-810,000 μm.sup.2 to allow vascularization to develop within the tissue-graft material. Corridors 46 or spatially aligned corridors 74 may be of any cross-sectional shape, including circular, elliptical, or polygonal; and the crosswise dimensions of the apertures of corridors 46 and spatially aligned corridors 74 may range between about 1 μm-1,000 μm.
[0047] In a preferred embodiment, the scaffold cages and scaffold cage sheets are made of β-tricalcium phosphates (β-TCP) for increasing the Ca.sup.2+/PO.sub.4.sup.3−-dependent osteogenic signaling of human mesenchymal stem cells (hMSCs). LithaBone TCP 2000 (manufactured by Lithoz America LLC or “Lithoz”) is an example of a commercially prepared tri-calcium phosphate (Ca.sub.3(PO.sub.4).sub.2) product that is useful for bone replacement techniques. Moreover, tri-calcium phosphate materials generally are useful as bone replacement scaffolding because of their similarity to the mineral portion of human bone and have high biocompatibility, osteoconductivity, and resorbability. In some embodiments, the scaffold cages and scaffold cage sheets may be made from α-TCP, dicalcium phosphates, calcium carbonates, zirconium oxides or aluminum oxides. In other embodiments, they may be made of any material suitable for a specific function.
[0048] In a preferred embodiment, the scaffold cages and scaffold cage sheets are manufactured by lithography-based ceramic manufacturing (LCM) 3D printing technology. Examples of LCM 3D-printing instruments include the Lithoz Cera Fab 7500 and 8500 printers that have a printing resolution of about 40 μm. In one example of LCM 3D-printing, a ceramic powder (e.g., ASTM1088-04a certified β-TCP) is homogenously dispersed in a photocurable monomer and selectively polymerized via digital light projection (DLP) printing. The photolymerized slurry forms a composite of ceramic particles within a photopolymer matrix, and the organic matrix is removed via pyrolysis during sintering, which densifies the ceramic body to about 97% density. The resulting flexural strength of the printed material is about 35 MPa (similar to a trabecular bone), and its indentation modulus is generally equal to, or greater than, 100 GPa. In some embodiments, the scaffold cages and scaffold cage sheets may be manufactured using Osteoink™, which is a 3D-printable, osteoconductive calcium-phosphate material that sets in aqueous media without the need for sintering. In other embodiments, the scaffold cages and scaffold cage sheets may be manufactured by any other suitable three-dimensional printing technologies. In further embodiments, they may be made by any mold-based (such as reaction injection molding), sculpting-based, or subtractive manufacturing methods.
Example
[0049] The following example further describes and demonstrates use of preferred embodiments of the disclosed tissue-graft scaffold 10. The example is given solely for the purpose of illustration and is not to be construed as limiting use of tissue-graft scaffold 10 because many variations thereof are possible without departing from the spirit and scope of uses of tissue-graft scaffold 10. This example demonstrates the benefits of the disclosed modular synthetic tissue-graft scaffold to repair a large-volume bone defect.
[0050] A patient is brought to surgery presenting with a large-volume open fracture. After an evaluation of the soft tissue and adequate debridement of the wound, the surgeon evaluates the open fracture of diseased bone cavity 112 of upper bone 122 as shown in
[0051] After a study of the three-dimensional shape and size of the dead space remaining in diseased bone cavity 122, the surgeon selectively assembles multiple replicas of scaffold cage 12 as shown in FIGS. 2A1 and 2A2 to create synthetic tissue-graft scaffold 110 as shown in
[0052] Prior to inserting synthetic tissue-graft scaffold 110 into the dead space of diseased bone cavity 122, the surgeon places a suture around synthetic tissue-graft scaffold 110 and ties a knot to ensure it does not come apart after implantation. A first attempt at insertion into diseased bone cavity 122, as shown in
[0053] After determining that synthetic tissue-graft scaffold 110 suitably fits the dead space of diseased bone cavity 122, the surgeon secures synthetic tissue-graft scaffold 110 and the remaining vascularized host bone tissue together and closes the wound by suturing together the soft tissue surrounding diseased bone cavity 122 as represented by
[0054] It will be obvious to those having skill in the art that many changes may be made to the details of the above-described embodiments without departing from the underlying principles of the invention. For example, annular raised portion 26 and recess 24 of a scaffold cage 12 can be of other than square shape.