MEMBRANOUS TISSUE WITH EVENLY SPACED ELEVATED PROJECTIONS ON ONE SIDE AND CONCAVE DEPRESSIONS ON THE OTHER SIDE METHOD AND USE

Abstract

The present invention discloses the method of preparation and use of soft tissue membranous structures into slip resistant membranes with regularly spaced surface projections on one side and concave depressions on the other side with perforations or without perforations which enhance vascular ingrowth and tissue incorporation.

Claims

1. A three-dimensional membrane structure comprises: a smooth two-sided biological membrane with regular or irregularly spaced surface concave depressions on a first side and projections on an opposite second side.

2. The three-dimensional membrane structure of claim 1 wherein at least one or more of the surface projections on the second side and concave depressions on the first side in the membranes form open perforations at an end of the at least one or more projections of the three-dimensional membrane structure.

3. The three-dimensional membrane structure of claim 1 wherein the three-dimensional membrane is a dried membrane.

4. The three-dimensional membrane structure of claim 3 wherein the dried membrane has been freeze-dried.

5. The three-dimensional membrane structure of claim 1 wherein the biological membrane material is one of dermis, full thickness skin, amniotic membrane, pericardium, dura mater or fascia.

6. The three-dimensional membrane structure of claim 5 wherein the dermis can be intact or decellularized.

7. The three-dimensional membrane structure of claim 5 wherein the dermis, full-thickness skin, amniotic membrane, fascia, pericardium, dura mater or other membranes can be human or animal.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The invention will be described by way of example and with reference to the accompanying drawings in which:

[0018] FIG. 1 is a photograph of a metal plate with perforations on which the membrane is placed, frozen and then freeze-dried. The perforations are placed in a predetermined geometric pattern, but this can vary.

[0019] FIG. 2 provides a comparison between dermis freeze-dried on a smooth metal plate (right) and on a perforated metal plate (left). The projections on one side and concave depressions on the other side are produced by tissue being forced into the metal plate perforations by the vacuum in the freeze-drying chamber.

[0020] FIG. 2A is a cross-section showing a wetted membrane on the perforated plate between two smooth plates.

[0021] FIG. 3 shows dermis after being freeze-dried on the plate shown in FIG. 1.

[0022] FIG. 4 is a photograph of freeze-dried dermis laid upside down on the metal plate on which it was freeze-dried. The protrusions are concave on the inside.

[0023] FIG. 5 provides a close-up view of the protrusions with perforations of dermis having been freeze-dried on the perforated metal plate.

[0024] FIG. 6 shows a membrane with a combination of protrusions and concave depressions on each surface side.

DETAILED DESCRIPTION OF THE INVENTION

[0025] The invention is directed to the finding that when membranous tissue 10, when fresh is placed and frozen on a perforated metal plate 20, shown in FIG. 1, in the chamber of a freeze dryer and then freeze-dried, the smooth structure is converted into a structure with regularly spaced projections 14 on one side and concave depressions 15 on the other side on the surface. The stainless-steel plate 20 shown in FIG. 1 with perforations 22 on which the membrane 10 is frozen and freeze-dried can be made of a variety of metals. This biomechanical change is irreversible; freeze-dried membrane 10 will retain its shape on rehydration, illustrated in FIG. 2.

[0026] With reference to FIG. 2, on the left side is pictured the membrane 10, in this picture dermis freeze-dried on the plate 20 shown in FIG. 1. On the right side of FIG. 2, dermis freeze dried on a solid metal plate is shown. The wetted or non-dried membrane is shown in FIG. 2A on the plate 20 and pressed between two smooth plates 40, 50.

[0027] Skin dermis is prepared by separating it from the epidermis by a dermatome, any cutting devise or by chemical dissolution of the epidermis. Dermis (fresh) is placed on a perforated metal grid or plate 20 which is inserted into the chamber of a freeze drier at room temperature. The shelf cooling is turned on concomitantly with turning on the vacuum in the chamber. The shelf is cooled to at least 15 C. and the membrane 10 placed on it is frozen. Freeze-drying commences after the membrane 10 is frozen. The vacuum in the chamber is maintained at 100 millitorr or below. After freeze-drying is completed with residual moisture in the membrane 10 reduced to about 15%, the chamber is returned to atmospheric pressure, and the membrane 10 whose shape was altered is removed, illustrated in FIG. 3. Membranous tissue such as fascia lata, dura mater or pericardium are treated intact in an identical manner.

[0028] In general, amniotic membrane is produced by drying not freeze-drying, fresh amniotic membrane. The latter can be used as a substitute membrane for a membrane tissue in a living body. The amniotic membrane is useful as a medical substitute membrane such a dura meter, pericardium, pleura, peritoneum and for coverage of non-healing wounds, such as those of the extremities associated venous stasis. The method used for drying amniotic membrane involves heating the amniotic membrane under reduced pressure to 50 C. (U.S. Pat. No. 8,414,929). The heating is produced by a far-infrared heater and a microwave irradiator. The fragmentation of the amniotic membrane, said to occur with conventional freeze-drying, is prevented by repeating pressure reducing step. In the present invention potential convenience freeze-drying damage is avoided by rapidly freezing amniotic membrane on perforated metallic plate before placing it in the freeze-drying chamber and reducing the pressure in the freeze-drying chamber to room millitorr or below. In another embodiment, the amniotic membrane is covered with perforated cellophane to keep it flat during the freeze-drying process. In still another embodiment, the amniotic membrane 10 is covered with a heavy plate, metal, plastic, Teflon or any other material to keep it flat. Adequate drying is achieved through holes 22 of the perforated metal plate 20. Preferably the entire process is performed aseptically, but if aseptic technique is not used the membrane 10 can be secondarily sterilized by irradiation, ethylene-oxide sterilization, peracetic acid or any other generally acceptable methods. Freeze-dried amniotic membrane with artificial regularly spaced bumps, produced by the described technique can be stored in sterile packages. Since cellular components are left intact in the amniotic membrane produced by the described method, rehydrated amniotic membrane would maintain biologic properties similar to those of fresh amnion. Irregular surface would prevent slippage of the implant and facilitate vascular ingrowth. With reference to FIG. 4, the freeze-dried dermis 10 is laid upside down on the metal plate 20 on which it was freeze-dried to show the protrusions 14 which are concave depressions 15 on the opposite side.

[0029] Perforations 16 in the projections 14 produced by the above-described method would enhance vascular ingrowth and accelerate incorporation of the membranous grafts. These can be made by pressing the membrane 20 with a solid plate 40, 50 to maintain it in place on the perforated metal plate 20, and cutting off the ends of the cover with a sharp blade. In another embodiment the holes in the cover can be made by needles superimposed over the perforations 22 in the perforated metal plate 20.

[0030] FIG. 5 shows a close up view of the protrusions 15 with perforations 16. These facilitate vascular ingrowth and incorporation of the membranous allograft. Centers of the projections 14 on one side and concave depressions 15 on the other side are pitted.

[0031] With reference to FIG. 6, an alternative embodiment shows a combination of the projections 14 and concave depressions 15 may be made on a same side or surface of the membrane 10 such that the resultant three-dimensional structures have traction and flow features from both surfaces.

[0032] Variations in the present invention are possible in light of the description of it provided herein. While certain representative embodiments and details have been shown for the purpose of illustrating the subject invention, it will be apparent to those skilled in this art that various changes and modifications can be made therein without departing from the scope of the subject invention. It is, therefore, to be understood that changes can be made in the particular embodiments described, which will be within the full intended scope of the invention as defined by the following appended claims.