Resorbable, macro-porous, non-collapsing and flexible membrane barrier for skeletal repair and regeneration

• US 5,919,234 A
• Filed: 08/19/1996
• Issued: 07/06/1999
• Est. Priority Date: 08/19/1996
• Status: Expired due to Term

• Current Assignee: Macropore, Inc.
• Original Assignee: Macropore, Inc.
• Inventors: Calhoun, Christopher J., Lemperle, Stefan M.
• Primary Examiner(s): Yu, Mickey
• Assistant Examiner(s): KOH, CHOON P
• Application Number:
  US08/699,673
• Time in Patent Office: 1,051 Days
• Field of Search: 623/1, 623/11, 623/15, 623/12, 623/16, 606/69, 606/70, 606/71, 606/74, 606/86, 606/154, 600/37, 128/898, 433/173-176, 433/215
• US Class Current: 623/23.72
• CPC Class Codes: A61B 17/06166 Sutures suture materials A61L17/00; manufacture of artificial threads D01D; treatment of threads D06M
• CPC Class Codes: A61B 17/0642 for bones, e.g. for osteosynthesis or connecting tendon to bone
• CPC Class Codes: A61B 17/08 Wound clamps or clips, i.e. not or only partly penetrating the tissue suture bridges A61B17/0466; Devices for bringing together the edges of a wound
• CPC Class Codes: A61B 17/64 Devices extending alongside the bones to be positioned
• CPC Class Codes: A61B 17/68 Internal fixation devices , including fasteners and spinal fixators, even if a part thereof projects from the skin bone staples A61B17/0642
• CPC Class Codes: A61B 17/688 for reattaching pieces of the skull
• CPC Class Codes: A61B 17/72 Intramedullary pins, nails or other devices A61B17/744 takes precedence
• CPC Class Codes: A61B 17/80 Cortical plates , i.e. bone plates; Instruments for holding or positioning cortical plates, or for compressing bones attached to cortical plates
• CPC Class Codes: A61B 17/8071 for the jaw
• CPC Class Codes: A61B 17/8085 with pliable or malleable elements or having a mesh-like structure, e.g. small strips A61B17/8071, A61B17/8076 take precedence
• CPC Class Codes: A61B 17/86 Pins or screws or threaded wires; nuts therefor A61B17/72 take precedence
• CPC Class Codes: A61B 2017/00004 (bio)absorbable, (bio)resorbable, resorptive for implantable prostheses A61F2210/0004
• CPC Class Codes: A61B 2017/0647 having one single leg, e.g. tacks
• CPC Class Codes: A61B 2017/0648 threaded, e.g. tacks with a screw thread
• CPC Class Codes: A61C 8/0006 Periodontal tissue or bone regeneration support means for endoprosthetic bone substitute or bone graft implants A61F2/2846
• CPC Class Codes: A61F 2/0063 Implantable repair or support meshes, e.g. hernia meshes
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/2803 for mandibular reconstruction temporo-mandibular joints A61F2/3099; bone plates for the jaw A61B17/8071
• CPC Class Codes: A61F 2/2846 Support means for bone substitute or for bone graft implants, e.g. membranes or plates for covering bone defects nets or sleeves applied to surface of endoprostheses A61F2/30907; bone plates A61B17/80; bone regeneration in dental surgery A61C8/0006
• CPC Class Codes: A61F 2/2875 Skull or cranium A61F2/2803 and A61F2/3099 take precedence
• CPC Class Codes: A61F 2/468 : Testing instruments for artificial joints for testing non-implantable prostheses A61F2/76
• CPC Class Codes: A61F 2002/2817 : Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/2835 : Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
• CPC Class Codes: A61F 2002/2878 : for orbital repair
• CPC Class Codes: A61F 2002/2889 : Maxillary, premaxillary or molar implants
• CPC Class Codes: A61F 2002/30062 : (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30235 : tubular, e.g. sleeves
• CPC Class Codes: A61F 2002/30428 : made by inserting a protrusion into a slot
• CPC Class Codes: A61F 2002/30785 : parallel
• CPC Class Codes: A61F 2002/30787 : inclined obliquely with respect to each other
• CPC Class Codes: A61F 2002/4649 : Bone graft or bone dowel harvest sites
• CPC Class Codes: A61F 2210/0004 : bioabsorbable
• CPC Class Codes: A61F 2220/0025 : Connections or couplings between prosthetic parts, e.g. between modular parts; Connecting elements
• CPC Class Codes: A61F 2230/0069 : cylindrical
• CPC Class Codes: A61L 2300/40 : characterised by a specific therapeutic activity or mode of action
• CPC Class Codes: A61L 2300/412 : Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2300/414 : Growth factors
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/146 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/148 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

A resorbable, flexible implant in the form of a continuous macro-porous sheet is disclosed. The implant is adapted to protect biological tissue defects, especially bone defects in the mammalian skeletal system, from the interposition of adjacent soft tissues during in vivo repair. The membrane has pores with diameters from 20 microns to 3000 microns. This porosity is such that vasculature and connective tissue cells derived from the adjacent soft tissues including the periosteum can proliferate through the membrane into the bone defect. The thickness of the sheet is such that the sheet has both sufficient flexibility to allow the sheet to be shaped to conform to the configuration of a skeletal region to be repaired, and sufficient tensile strength to allow the sheet to be so shaped without damage to the sheet. The sheet provides enough inherent mechanical strength to withstand pressure from adjacent musculature and does not collapse.

Claims

1. An implant for protecting a biological tissue defect from a prolapse of adjacent soft tissues during in vivo repair of the biological tissue defect, the implant having a pre-implant configuration, which is defined as a configuration of the implant immediately before the implant if formed around and implanted over the biological tissue defect and placed into contact with any adjacent soft tissue, the implant comprising:

a substantially planar sheet of resorbable polymer base material excluding paper and having a first side and a second side, the substantially planar sheet of resorbable polymer base material comprising a single layer of resorbable polymer base material between the first side and the second side, the single layer of resorbable polymer base material having a substantially uniform composition; and

a plurality or apertures disposed in the substantially planar sheet or resorbable polymer base material, the plurality of apertures being substantially uniformly distributed over both the first side and the second side of the substantially planar sheet or resorbable polymer base material, each of the plurality of apertures of the implant when the implant is in the pre-implant configuration having a diameter which is between about 500 microns and about 3000 microns and which defines an isolated, non-intersecting, fluid-flow path from the first side to the second side;

wherein the implant comprises a configuration and strength sufficient to prevent prolapse of adjacent soft tissues into the biological tissue defect, when the implant is formed around and implanted over the biological tissue defect and placed into contact with any adjacent soft tissue; and

wherein each of the plurality of apertures of the substantially planar sheet or resorbable polymer base material immediately after implanting of the substantially planar sheet of resorbable polymer base material over the biological tissue defect, has a diameter sufficient in size to allow a proliferation of vasculature and connective tissue cells, derived from adjacent soft tissues, to permeate through the aperture and substantially into the biological tissue defect.

2. The implant as recited in claim 1, wherein the connective tissue cells comprise mesenchymal cells.

3. The implant as recited in claim 1, wherein the implant is impregnated with at least one substance for cellular control.

4. The implant as recited in claim 2, wherein the implant is impregnated with at least one of a chemotactic substance for influencing cell-migration, an inhibitory substance for influencing cell-migration, a mitogenic growth factor for influencing cell proliferation, a growth factor for influencing cell differentiation, and factors which promote neoangiogenesis (formation of new blood vessels).

5. The resorbable membrane as recited in claim 1, wherein the implant comprises a thickness within a range between about 10 microns and about 2000 microns.

6. The implant as recited in claim 1, wherein the implant is adapted for being resorbed into the mammalian body, and not remodeled, within a period of approximately 24 months from an initial implantation of the implant into the mammalian body.

14. The implant as recited in claim 1, wherein each of plurality of apertures of the implant when the implant is in the pre-implant configuration has a diameter greater than approximately 1000 microns.

15. The implant as recited in claim 1, wherein each of the plurality of apertures of the implant when the implant is in the pre-implant configuration has a diameter of approximately 1500 microns.

22. The implant as recited in claim 5, wherein the substantially planar sheet of resorbable polymer base material has a thickness of approximately 1 millimeter.

7. A method of facilitating protected bone regeneration, comprising the following steps:

providing a substantially planar sheet of resorbable polymer base material excluding paper, the substantially planar sheet of resorbable polymer base material having a first side and a second side and comprising a single layer of resorbable polymer base material between the first side and the second side, the single layer of resorbable polymer base material having a substantially uniform composition, the substantially planar sheet of resorbable polymer base material further having a thickness and a plurality of non-intersecting apertures penetrating completely through the thickness of the substantially planar sheet of resorbable polymer base material from the first side to the second side, the plurality of non-intersecting apertures being substantially uniformly distributed over the substantially planar sheet of resorbable polymer base material, each of the non-intersecting apertures defining an isolated fluid-flow path extending through the thickness of the substantially planar sheet of resorbable polymer base material and having a diameter from about 500 microns to about 3000 microns in a pre-implant configuration of the substantially planar sheet of resorbable polymer base material, the pre-implant configuration being defined as a configuration of the substantially planar sheet of resorbable polymer base material immediately before the substantially planar sheet of resorbable polymer base material is formed around and implanted over a biological tissue defect and placed into contact with any adjacent soft tissue; and

securing the substantially planar sheet of resorbable polymer base material over and around a bone defect area, to thereby cover and protect the entire bone defect area and to overlap adjacent areas of bone near the bone defect area, the substantially planar sheet of resorbable polymer base material having a configuration and strength sufficient to prevent prolapse of adjacent soft tissues into the bone defect area and to facilitate protected bone regeneration independently, without any aid from a fixation device, when the substantially planar sheet of resorbable polymer base material is secured over the bone defect area and secured to the adjacent areas of bone near the bone defect area, wherein each of the non-intersecting apertures of the secured substantially planar sheet of resorbable polymer base material has a diameter sufficient in size to allow a proliferation of vasculature and connective tissue cells, derived from adjacent soft tissues, to permeate through the plurality of non-intersecting apertures and into the biological tissue defect.

8. The method as recited in claim 7, wherein the step of securing the substantially planar sheet of resorbable polymer base material over and around a bone defect area comprises the following steps:

forming the substantially planar sheet of resorbable polymer base material into a tubular configuration; and

wrapping the substantially planar sheet of resorbable polymer base material around the bone defect area.

9. The method as recited in claim 8, wherein the step of wrapping the substantially planar sheet of resorbable polymer base material around the bone defect area comprises a step of frictionally securing the substantially planar sheet of resorbable polymer base material around the bone defect area.

10. The method as recited in claim 8, wherein the step of wrapping the substantially planar sheet of resorbable polymer base material around the bone defect area comprises a step of securing the substantially planar sheet of resorbable polymer base material around the bone defect area with at least one of clamps, staples, screws, sutures and tacks.

11. The method as recited in claim 8, wherein the step of wrapping the substantially planar sheet of resorbable polymer base material around a bone defect area comprises a step of wrapping the substantially planar sheet of resorbable polymer base material around the bone defect area without any aid from any one of a plate, a screw, an intramedullary rod, and an external fixation device.

12. The method as recited in claim 11, wherein the step of wrapping the substantially planar sheet of resorbable polymer base material around the bone defect area comprises a step of wrapping the substantially planar sheet of resorbable polymer base material around a long bone.

13. The method as recited in claim 8, wherein the step of wrapping the substantially planar sheet of resorbable polymer base material around the bone defect area comprises a step of wrapping a substantially planar sheet of resorbable polymer base material, having 1 millimeter to 1.5 millimeter diameter non-intersecting apertures, around a bone defect area, wherein the resorbability of the substantially planar sheet of resorbable polymer base material avoids long-term stress shielding of the bone defect area and thereby avoids subsequent bone resorption of new bone in and near the bone defect area.

16. An implant for protecting a biological tissue defect from a prolapse of adjacent soft tissues during in vivo repair of the biological tissue defect, the implant having a pre-implant configuration, which is defined as a configuration of the implant immediately before the implant is implanted over the biological tissue defect and placed into contact with any adjacent soft tissue, the implant comprising;

a substantially planar sheet of resorbable polymer base material excluding paper and having a first side and a second side, the substantially planar sheet of resorbable polymer base material comprising a single layer of resorbable polymer base material between the first side and the second side, the single layer of resorbable polymer base material further having a substantially uniform composition; and

a plurality of apertures disposed in the substantially planar sheet of resorbable base material, each of the plurality of apertures of the implant when the implant is in the pre-implant configuration having a diameter from about 500 microns to about 3000 microns and defining an isolated fluid-flow path which extends from the first side to the second side, each isolated fluid-flow path being defined along an individual path axis, which comprises a substantially straight line, and having a substantially constant cross-sectional area at every point along a length of the path axis between the first side and the second side;

wherein the implant comprises a configuration and strength sufficient to prevent gross prolapse of adjacent soft tissue into the biological tissue defect; and

wherein each of the plurality of apertures of the implant, immediately after the implant is implanted over the biological tissue defect and placed into contact with any adjacent soft tissue, has a diameter sufficient in size to allow a proliferation of vasculature and connective tissue cells, derived from the adjacent soft tissues, to permeate through the aperture and substantially into the biological tissue defect.

17. An implant for protecting a biological tissue defect from a prolapse of adjacent soft tissues during in vivo repair of the biological tissue defect, the implant having a pre-implant configuration, which is defined as a configuration of the implant immediately before the implant is implanted over the biological tissue defect and placed into contact with any adjacent soft tissue, the implant comprising:

a substantially planar sheet of resorbable polymer base material excluding paper and having a first side and a second side, the substantially planar sheet of resorbable polymer base material comprising a single layer of resorbable polymer base material between the first side and the second side, the single layer of resorbable polymer base material having a substantially uniform composition; and

a plurality of tunnels disposed in the substantially planar sheet of resorbable base material, each of the plurality of tunnels of the implant when the implant is in the pre-implant configuration having a diameter from about 500 microns to about 3000 microns and defining an isolated fluid-flow path which extends from the first side to the second side, each of the plurality of tunnels of the implant, immediately after the implant is implanted over the biological tissue defect and placed into contact with any adjacent soft tissue, having a diameter sufficient in size to allow a proliferation of vasculature and connective tissue cells, derived from the adjacent soft tissues, to permeate through the tunnel and into the biological tissue defect, the implant comprising a configuration and strength sufficient to prevent gross prolapse of adjacent soft tissue into the biological tissue defect;

wherein none of the fluid-flow paths intersect; and

wherein none of the fluid-flow paths share any common volume.

18. An implant for protecting a biological tissue defect from a prolapse of adjacent soft tissues during in vivo repair of the biological tissue defect, the implant having a pre-implant configuration, which is defined as a configuration of the implant immediately before the implant is implanted over the biological tissue defect and placed into contact with any adjacent soft tissue, the implant comprising:

a substantially planar sheet of resorbable polymer base material excluding paper and having a first side and a second side, the substantially planar sheet of resorbable polymer base material comprising a single layer of resorbable polymer base material between the first side and the second side, the single layer of resorbable polymer base material having a substantially uniform composition; and

a plurality of apertures disposed in the substantially planar sheet of resorbable polymer base material, each of the plurality of apertures of the implant when the implant is in the pre-implant configuration being surrounded by and defined by an aperture wall within the substantially planar sheet of resorbable polymer base material, each of the plurality of apertures defining a fluid flow path from the first side to the second side;

wherein each aperture wall of the implant when the implant is in the pre-implant configuration extends substantially and continuously from the first side to the second side, to thereby define a corresponding aperture which extends substantially and continuously from the first side to the second side;

wherein each of the plurality of apertures of the implant when the implant is in the pre-implant configuration has a diameter within a range from approximately 500 microns to approximately 3000 microns, the diameter of each of the plurality of apertures of the implant, immediately after the implant is implanted over the biological tissue defect and placed into contact with any adjacent soft tissue, having a diameter sufficient in size to allow a proliferation of vasculature and connective tissue cells, derived from the adjacent soft tissues, to permeate through the aperture and into the biological tissue defect; and

wherein the implant comprises a configuration and strength sufficient to prevent gross prolapse of the adjacent soft tissue into the biological tissue defect.

19. The implant as recited in claim 18, wherein the substantially planar sheer of resorbable base material is impregnated with at least one of a chemotactic substance for influencing cell-migration, an inhibitory substance for influencing cell-migration, a mitogenic growth factor for influencing cell proliferation, a growth factor for influencing cell differentiation, and factors which promote neoangiogenesis (formation of new blood vessels).

20. The implant as recited in claim 18, wherein:

each aperture extends along a straight axis from the first side of the substantially planar sheer of resorbable polymer base material to the second side of the substantially planar sheet of resorbable polymer base material; and

a diameter of each aperture is substantially constant along a length of the straight axis along which the aperture extends.

21. The implant as recited in claim 18, wherein each straight axis is substantially perpendicular to a plane formed by the substantially planar sheet of resorbable polymer base material.