Abstract:
A shaped transplant product  10  derived from human umbilical cord  2  has a collagenous tissue membrane  20  derived from an umbilical cord  2  made essentially of thick collagenous tissue which is shaped to form a soft tissue barrier or wound covering or other internal or external wound healing attachment. The shaped transplant product  10 S has a defined memory shape that can be configured to pass through a hollow cylindrical trocar or arthroscopy device for implantation. The defined memory shape can be a hollow elongated split tube. The split tube along the split can have abutting edges. The split tube can have an open split forming a gap between edges adjacent the open slit. The split tube can have overlapping edges. The split tube can have an elongated body having a center portion tapering toward opposing smaller ends to form a pre-set shape.

Description:
RELATED APPLICATIONS 
       [0001]    This application is a continuation in part of co-pending U.S. application Ser. No. 14/827,445 entitled “Umbilical Cord Transplant Product” filed on Aug. 17, 2015. 
     
    
     TECHNICAL FIELD 
       [0002]    This invention relates to a transplant product derived from human umbilical cord and shaped for use as a soft tissue barrier or wound covering or other internal or external healing attachment and the products method of manufacture. 
       BACKGROUND OF THE INVENTION 
       [0003]    The use of placental tissue to harvest thin membranes of amnion or chorion is well known. The use of umbilical cords to harvest stem cells is also well documented. However, the use of the umbilical cord tissue as a source for wound covering has been avoided because of the very thick nature of the tubular umbilical cord tissue and the fact that it is such a thick material it is not considered readily absorbable during a normal soft tissue healing. All of these adverse preconceived notions in the medical community may be unwarranted, if not wrong, in many applications wherein the healing time is long or the thickness of the material can be an advantage. The inventors of the present invention have discovered a remarkable way to process the harvested umbilical cord that not only benefits from the otherwise perceived drawbacks, but in fact provides embodiments with heretofore unachievable attachment features that make suture tissue tears issue completely disappear while at the same time making the material easier to pass sutures compared to using thin amniotic membranes. All of this is accomplished without requiring an additional structural layers to prevent tissue suture tearouts. 
       SUMMARY OF THE INVENTION 
       [0004]    A shaped transplant product derived from human umbilical cord has a collagenous tissue membrane derived from an umbilical cord made essentially of thick collagenous tissue which is shaped to form a soft tissue barrier or wound covering or other internal or external wound healing attachment. The shaped transplant product has a defined memory shape that can be configured to pass through a hollow cylindrical trocar or arthroscopy device for implantation. The defined memory shape can be a hollow elongated split tube. The split tube along the split can have abutting edges. The split tube can have an open split forming a gap between edges adjacent the open slit. The split tube can have overlapping edges. The split tube can have an elongated body having a center portion tapering toward opposing smaller ends to form a pre-set shape. The shaped transplant can have a shape imparted by a mandrel or core during manufacture, the mandrel or core, when removed, leaving the shaped transplant product with a pre-set shape. 
         [0005]    The structural, chemical and biochemical properties are retained, the collagenous tissue membrane is cleaned removing the veins, arteries and Wharton&#39;s jelly without exposure to harsh chemicals. The collagenous tissue membrane is soaked in normal saline solution under mild agitation for a predetermined time to structurally increase tear resistance of the membrane. The collagenous tissue membrane is free of meconium. The collagenous tissue membrane has a general transparent or translucent appearance of a clear or slightly pink color. 
         [0006]    The collagenous tissue membrane is subjected to a vacuum drying process under vacuum at a prescribed vacuum over a predetermined time at room temperature sufficient to dry without altering the structural and chemical properties of the tissue, preferably being placed in a freeze dryer which is set to run for 19 hours at 1100 mT and 25 degrees C. The collagenous tissue membrane, after drying, has a thickness between 100 microns to 1000 microns, typically averaging a thickness between 250 and 800 microns. The collagenous tissue membrane is cut into round, oval, square or rectangular shapes. After drying, the cut collagenous tissue membrane has at least one suture entry site formed integrally as a structurally enhanced peripheral wall that acts and performs like a grommet but without any additional parts. The suture entry site is formed by a heated tip that forms a toughened tissue membrane wall encircling each of the at least one sites. The suture entry site is heat formed having a reduced thickness puncture center or an opening either of which are surrounded by the toughened tissue membrane wall. The toughened tissue membrane wall is rigid, wherein the grommet-like feature is thickened relative to exterior surfaces of the adjacent collagenous tissue membrane. The cut collagenous tissue membrane can have two or more suture entry sites. The cut collagenous tissue membrane can be cut into a small size formed as a pledget for suturing through and attachment to a thin tissue. 
         [0007]    In one embodiment, the cut collagenous tissue membrane has the at least one suture entry site positioned in a corner of the square or rectangular cut membrane. Each corner of the cut collagenous tissue membrane can be folded over to make a double thickness cut collagenous tissue membrane at the suture entry site. In another embodiment, the cut collagenous tissue membrane has two opposite edges, adjacent each edge is a plurality of suture entry sites. The number of the plurality of suture entry sites adjacent one edge is equal to the number of suture entry sites of the opposite edge. Preferably, the suture entry sites of one edge are offset relative to the suture entry sites of the opposite edge wherein the offset is arranged and positioned so the suture entry sites on one edge are interposed between the suture entry sites of the other edge when the cut collagenous tissue membrane is rolled or folded such that the two opposing edges are aligned. In this embodiment, the suture entry sites are configured to pass a suture helically wrapped to form a cylindrical cut collagenous tissue membrane for wrapping about a nerve, vein, artery or any other tubular or round tissue vessel. 
       DEFINITIONS 
       [0008]    Meconium—is the earliest stool of a mammalian infant. Unlike later feces, meconium is composed of materials ingested during the time the infant spends in the uterus: intestinal epithelial cells, lanugo, mucus, amniotic fluid, bile, and water. 
         [0009]    Pledget—compress or small flat mass usually of gauze or absorbent cotton that is laid over a wound or into a cavity to apply medication, exclude air, retain dressings, or absorb the matter discharged, as used herein, the pledget is made from the cut umbilical cord tissue. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0010]    The invention will be described by way of example and with reference to the accompanying drawings in which: 
           [0011]      FIG. 1  is a photograph of a technician holding a cut lengthwise umbilical cord exposing the veins, arteries and Wharton&#39;s jelly. 
           [0012]      FIG. 2  is a photograph of a technician holding a length of umbilical cord during recovery. 
           [0013]      FIG. 3  is a photograph of the longitudinal dissection of the umbilical cord tissue. 
           [0014]      FIG. 4  is a photograph showing the umbilical cord after cleaning and soaking in normal saline. 
           [0015]      FIG. 5  is an example of the transplant product after cutting. 
           [0016]      FIG. 6  is a microscoped photograph at × magnification showing the epithelial layer no longer intact. 
           [0017]      FIG. 7  is a photograph of the transplant product showing a suture passing through a folded over end. 
           [0018]      FIG. 8  is a schematic diagram of the cleaning steps. 
           [0019]      FIG. 9  is a schematic diagram of the drying steps. 
           [0020]      FIG. 10  is a schematic diagram of the cutting steps. 
           [0021]      FIG. 11  is a schematic diagram of the packaging steps. 
           [0022]      FIG. 12  is an embodiment of the transplant product derived from umbilical cord having folded over corners with suture entry sites. 
           [0023]      FIG. 13  is an embodiment of the transplant product having suture entry sites in a single layer. 
           [0024]      FIG. 14  is another embodiment having a plurality of suture entry sites adjacent along each side. 
           [0025]      FIG. 15  is the embodiment shown in  FIG. 14  rolled into a cylinder or tubular shape with a suture woven through the circumferentially offset suture entry sites. 
           [0026]      FIG. 16  shows a plurality of mandrels or cores for imparting a pre-set shape to the collagenous tissue membrane of the present invention. 
           [0027]      FIG. 17  is an exploded view of the membrane, an exemplary mandrel and a drying chamber for shaping the transplant product of the present invention. 
           [0028]      FIG. 18A  is a schematic view showing the core or mandrel assembly. 
           [0029]      FIG. 18B  is a schematic showing the membrane initially a flat rectangle later being shown shaped into a split tube. 
           [0030]      FIG. 19  is an end view of a first shaped transplant product. 
           [0031]      FIG. 20  is a perspective view of the embodiment of  FIG. 19 . 
           [0032]      FIG. 21  is an end view of a second embodiment shaped transplant product formed as a split tube with overlapping edges. 
           [0033]      FIG. 22  is a partial perspective view of the embodiment of  FIG. 21 . 
           [0034]      FIG. 23  is a third embodiment of the shaped transplant product formed as a split tube have gapped edges. 
           [0035]      FIG. 24  shows a fourth embodiment wherein the membrane when cut into elongated strips can be shaped into a spiral wrapped tube. 
           [0036]      FIGS. 25-25C  show the shaped transplant products corresponding to the mandrels shown in  FIG. 16 . 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0037]    The present invention encompasses both the manufacturing of various embodiments of final transplant products  10  and the transplant products derived from human umbilical cords (UC)  2 . The final umbilical cord product  10  is categorized as a thick layer of a collagenous membrane  20  of dried umbilical cord  2 . The transplant product  10  is a semi-transparent collagenous membrane. All donated umbilical cords, preferably, are derived from cesarean section delivered placentas recovered from young, healthy consenting mothers according to established procedures from a recovering facility. Application of final processed transplant products is for homologous use as a soft tissue barrier or wound covering or for other internal wound healing applications. The tissue is for single patient use and is to only be handled by a licensed physician. 
         [0038]    Processing of the transplant products, as shown in the photographs of  FIGS. 1-7 , was conducted at approved biomedical facilities. During the processing of the final transplant product, the structural, chemical, and biochemical components of the tissue remained intact. The only solution the umbilical cord was exposed to during processing was a physiological grade normal saline solution (0.9% Sodium Chloride). This solution was used to aid in the cleaning of the tissue to remove all traces of blood and extraneous umbilical membrane tissue. The umbilical cord segments then underwent a gentle vacuum cycle shaping if desired to obtain a final product that was dried. The dried tissue  20  makes the final transplant product  10  by cutting and packaging in final packaging that is to be delivered to the end user. The final product can be to be stored at room temperature. The current shelf life of the final processed transplant product is expected to be 5 years based on the validation of the final packaging material used for storage. 
         [0039]    As with all manufacturing processes, cleaning and further processing of the umbilical cord is performed using aseptic technique. Pre-cleaning microbiology cultures are taken of the umbilical cord prior to initiating the cleaning process. Once the cultures are taken, the umbilical cord is cut lengthwise and flattened exposing the inner lining. Removal of the vein, arteries and Wharton&#39;s Jelly are accomplished manually with the aid of forceps and/or razors. The umbilical cord is then exposed to a normal saline solution (0.9% Sodium Chloride) and soaked for 4-8 hours with slight agitation during this period. Acceptable cleaned umbilical cord segments of the collagenous tissue membrane  20  must be transparent in color, free of meconium, not fragile, and exhibit normal tissue integrity. 
         [0040]    The cleaning process of the umbilical cord is performed inside an ISO Class 5, Class II biological safety cabinet (BSC) that is located inside an ISO Class 5 suite in a cleanroom. The process of cleaning the umbilical cord is performed as such to leave the structural and chemical properties of the membrane  20  intact. 
         [0041]    Once the umbilical cord segments of the collagenous tissue membrane  20  are cleaned and meet the aforementioned acceptable criteria, they are then prepared to undergo the vacuum drying process. The cleaned umbilical cord membranes  20  are placed on a sterile plastic tray with the inner lining of the umbilical cord facing upwards and the epithelial side facing downward. A layer of medical grade foam is then gently placed on top surface or side  22  of the tissue membrane  20  and lightly pressed to ensure the membrane  20  has completely adhered to the foam. The foam is gently lifted off the plastic tray and turned over exposing the epithelial side  21  of the umbilical cord. Another layer of medical grade foam is placed over the umbilical cord membrane  20  sandwiching the tissue membrane  20  in place. The sandwiched tissues are placed into sterile drying trays with the epithelial layer side  21  facing upwards. The drying trays are then placed inside of a freeze dryer which is set to run for 19 hours at 1100 mT and 25° C. This cycle has shown to sufficiently dry the tissue without affecting the structural and chemical properties of the tissue. 
         [0042]    The cutting of the tissue membrane  20  is performed once the vacuum drying process is complete. The dried tissue membrane  20  is removed from the freeze dryer and subsequently carefully removed from the medical grade foams. The dried umbilical cord segments are then placed on a sterile plastic cutting board. The collagenous tissue membrane  20 , after drying, has a thickness between 100 microns to 1000 microns, typically averaging a thickness between 250 and 800 microns. Table 1 below exhibits the final product sizes for flat membranes. Once the umbilical cord segments are cut into their designated sizes using a scalpel and ruler, an orientation notch is made for the end user to denote the sidedness of the allograft. Using a sterile 5 mm skin gauge, a notch can be placed in the upper left hand corner of the membrane denoting that the epithelial side is facing upward. 
         [0043]    Final umbilical cord product  10  sizes are provided as an exemplary list: 1 cm×1 cm, 1 cm×2 cm, 2 cm×2 cm, 2 cm×3 cm, 3 cm×3 cm, 3 cm×4 cm, 3 cm×6 cm, 3 cm×8 cm. 
         [0044]    Final processed umbilical cord membrane  20  tissues when cut form the transplant product  10  which are packaged in validated final packaging. The membrane  20  is aseptically double pouched; each pouch sealed using an impulse heat sealer. The outer packaging used is a chevron type pouch allowing the end user to easily present the sterile inner pouch containing the product to a sterile field. The packaged final product  10  is stored at room temperature until it is distributed to the end user. 
         [0045]    In one embodiment, the collagenous tissue membrane  20  is subjected to a vacuum drying process under vacuum at a prescribed vacuum over a predetermined time at room temperature sufficient to dry without altering the structural and chemical properties of the tissue, preferably being placed in a freeze dryer which is set to run for 19 hours at 1100 mT and 25 degrees C. Due to the thickness of the collagenous tissue membrane  20 , which is typically much thicker than the thickness of tissue membranes derived from a placenta, make the umbilical cord derived membrane ideal for suturing. The collagenous tissue membrane  20  is cut into round, oval, square or rectangular shapes. After drying, the cut collagenous tissue membrane  20  can be made structurally enhanced for suturing by having at least one suture entry site  30  formed integrally as a structurally enhanced peripheral wall  32  that acts and performs like a grommet but without any additional parts. The suture entry site  30  is formed by a heated tip that forms a toughened tissue membrane wall  32  encircling each of the at least one sites  30 . The suture entry site  30  is heat formed having a reduced thickness puncture center or an opening  31  either of which are surrounded by the toughened tissue membrane wall  32 . The toughened tissue membrane wall  32  is rigid or generally tear resistant, wherein the grommet-like feature is thickened relative to exterior surfaces of the adjacent collagenous tissue membrane  20 . The cut collagenous tissue membrane  20  can have two or more suture entry sites  30 . The cut product  10  of collagenous tissue membrane  20  can be cut into a small size formed as a pledget for suturing through and attachment to a thin tissue. 
         [0046]    In one embodiment illustrated in  FIG. 13 , the cut collagenous tissue membrane  20  has the at least one suture entry site  30  positioned in a corner  12  of the square or rectangular cut membrane  20 . Each corner  12  of the cut collagenous tissue membrane  20  can be folded over to make a double thickness cut collagenous tissue membrane  20  at the suture entry site  30  wherein the top surface or side  22  is covered at the corners  12  by the epithelial side  21 , as shown in  FIG. 12 . In another embodiment, the cut collagenous tissue membrane  20  has two opposite edges  26 ,  27 , adjacent each edge  26 ,  27  is a plurality of suture entry sites. The number of the plurality of suture entry sites adjacent one edge  26  either one less, equal to or one more than the number of suture entry sites  30  of the opposite edge  27 , as shown  8  and  9  suture entry sites  30  on the respective edges  26 ,  27  in  FIG. 14 . Preferably, the suture entry sites  30  of one edge  27  are offset relative to the suture entry sites  30  of the opposite edge  26  wherein the offset is arranged and positioned so the suture entry sites on one edge are interposed between the suture entry sites  30  of the other edge when the cut collagenous tissue membrane  20  is rolled or folded such that the two opposing edges  26 ,  27  are aligned. In this embodiment, the suture entry sites  30  are configured to pass a suture  40  helically wrapped to form a cylindrical cut collagenous tissue membrane  20  for wrapping about a nerve, vein, artery or any other tubular or round tissue vessel. 
         [0047]    With reference to  FIGS. 16-24 , an important variation from the flat, round, rectangular or square transplant product  10  is described and shown hereinafter. The flat shaped product  10 , while ideal for wound bandaging and covering is not necessarily the best for wrapping blood vessels or peripheral nerves. As was mentioned in reference to  FIG. 15 , the flat tissue product  10  could be sutured to form a tube. 
         [0048]    In  FIG. 16 , there are shown a variety of mandrels or cores that allow the collagenous tissue membrane to be pre-shaped during the manufacturing process. 
         [0049]    As shown in  FIGS. 19-24 , various split tube shapes can be made that have been dried to have the tubular shape formed during manufacturing. This shape has a memory so that when implanted, the split tube  10 S will revert back to the pre-set shape. 
         [0050]    Preferably, this is achieved by wrapping the collagenous tissue membrane  10  prior to drying about a mandrel or core  100 A,  100 B,  100 C,  100 D or  100 E. As shown in  FIG. 16 , the mandrel or core  100 A has a center portion diameter  101  that steps down at ends  102 . When the membrane is placed on this mandrel, that shape is imparted to it during drying, see  FIG. 25A . 
         [0051]    The mandrel or core  100 B is generally cylindrical, the mandrel or core  100 C has slightly tapered ends  102  and mandrel or core  100 D has a greater slope to create even smaller tapered ends  102 . This results in the shaped product  10 S as shown in  FIGS. 25B, 25C and 25  respectively. 
         [0052]    With reference to  FIGS. 17, 18A and 18B , the inventors that in drying the grafts, and dehydrating the materials seeking a flat membrane for placement, real value is being missed for deployment via trocar and arthroscopic implementation. They realized that an umbilical sheet when wrapped on a mandrel, compressed with a clam shell sleeve, can be formed within a clam shell that can have a surface roughness that is either random or defined, and that the dried graft retains its shape following removal. This graft is intended to be formed by clamping a clam-shell like fixture for repeat use as a tool, with the option of being vacuum desiccated from the inside which provides conduit and varying thicknesses for delivery and remoistening. 
         [0053]    As shown schematically in  FIG. 18A , the mandrel  100 E, or any of the mandrels  100 A- 100 D as well, can be placed inside a sleeve  200 , the sleeve  200  can be a clam shell construct that is compressed against the mandrel  100 A- 100 E during drying. A vacuum can be pulled on the assembly, preferably through the mandrel to draw the membrane tightly on the mandrel to impart the desired shape. 
         [0054]    The sleeve  100  can have heating rods  203  for drying, or the entire assembly placed in a heated drying oven, or simply room temperature dried. In any event, the goal is to make a pre-set shape, preferably of a split tube or a wrapped tube, to allow easing the covering on blood vessels or nerves. Once shaped, as shown in  FIG. 18B , the transplant product  10  is transformed into a shaped transplant product  10 S. 
         [0055]    With reference to  FIGS. 19 and 20 , the split tube shaped transplant product  10 S can have abutting edges. Alternatively, as shown in  FIGS. 21 and 22 , the membrane  20  can have overlapping edges  26 ,  27 . The term “overlapping” implies the membrane, when placed on a mandrel  100 A- 100 E is wrapped greater than 360 degrees or greater than once. “Abutting” means the wrap is 360 degrees or close to it, and as shown in  FIG. 23 , is wrapped less than once and a gap is formed as the edges  26  and  27  did not fully encircle the mandrel on shaping. Each style has distinct advantages depending on the procedure. 
         [0056]    With reference back to  FIG. 15 , the pre-set shaped product can be used without the suture holes, or when desired, can be provided with this feature as shown. 
         [0057]    With reference to  FIGS. 25A, 25B, 25C and 25 , the shaped products  10 S are shown corresponding to the mandrels  100 A- 100 D respectively. 
         [0058]    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.