Patent Publication Number: US-2023145585-A1

Title: Pre-shaped allograft implant for reconstructive surgical use and methods of manufacture and use, and tools for forming a pre-shaped allograft implant for reconstructive surgical use

Description:
REFERENCE TO PENDING PRIOR PATENT APPLICATION 
     This patent application is a continuation of pending prior U.S. patent application Ser. No. 17/899,270, filed Aug. 20, 2022 by Ergun Kocak, et al., for PRE-SHAPED ALLOGRAFT IMPLANT FOR RECONSTRUCTIVE SURGICAL USE AND METHODS OF MANUFACTURE AND USE, AND TOOLS for FORMING A PRE-SHAPED ALLOGRAFT IMPLANT FOR RECONSTRUCTIVE SURGICAL USE (Attorney Docket No. 47413.830041.US1), which in turn is a continuation-in-part of pending prior U.S. patent application Ser. No. 16/707,681, filed Dec. 9, 2019 by Ergun Kocak, et al., for PRE-SHAPED ALLOGRAFT IMPLANT FOR RECONSTRUCTIVE SURGICAL USE AND METHODS OF MANUFACTURE AND USE (Attorney Docket No. 47413.830038.US1), which in turn claims the benefit under 35 U.S.C. 119 (e) of U.S. Provisional Patent Application No. 62/905,485, filed Sep. 25, 2019 by Ergun Kocak, et al. for PRE-SHAPED ALLOGRAFT IMPLANT FOR RECONSTRUCTIVE SURGICAL USE AND METHODS OF MANUFACTURE AND USE (Attorney Docket No. 47413.830038.US0). 
     Above-identified pending prior U.S. patent application Ser. No. 17/899,270, filed Aug. 20, 2022 by Ergun Kocak, et al., for PRE-SHAPED ALLOGRAFT IMPLANT FOR RECONSTRUCTIVE SURGICAL USE AND METHODS OF MANUFACTURE AND USE, AND TOOLS for FORMING A PRE-SHAPED ALLOGRAFT IMPLANT FOR RECONSTRUCTIVE SURGICAL USE (Attorney Docket No. 47413.830041.US1), claims the benefit under 35 U.S.C. 119 (e) of U.S. Provisional Patent Application No. 63/238,733, filed Aug. 30, 2021 by Ergun Kocak, et al. for PRE-SHAPED ALLOGRAFT IMPLANT FOR RECONSTRUCTIVE SURGICAL USE AND METHODS OF MANUFACTURE AND USE (Attorney Docket No. 47413.830041.US0) 
     The above-identified patent applications are hereby incorporated herein by reference. 
    
    
     BACKGROUND 
     An allograft includes bone, tendon, skin, or other types of tissue that is transplanted from one person to another. Allografts are used in a variety of medical treatments, such as knee replacements, bone grafts, spinal fusions, eye surgery, and skin grafts for reconstructive surgery and for the severely burned. Allografts come from voluntarily donated human tissue obtained from cadaveric donor-derived, living-related, or living-unrelated donors and can help patients regain mobility, restore function, enjoy a better quality of life, and even save lives in the case of cardiovascular tissue or skin. 
     An acellular dermal matrix (ADM) graft is a soft connective tissue graft generated by a decellularization process that preserves the intact extracellular skin matrix. Upon implantation, the ADM structure serves as a scaffold for donor-side cells to facilitate subsequent incorporation and revascularization. ADMs are manufactured utilizing known methods of decellularization by means of ionic and nonionic detergent methods, as well as those utilizing enzymatic processes and other techniques such as those listed in “Decellularization of Tissues and Organs,” Gilbert, et al, 2006 (https://www.ncbi.nlm.nih.gov/pubmed/16519932). 
     Currently, ADM grafts are primarily derived from decellularized cadaveric skin and must be shaped and/or cut as necessary by the surgeon either prior to or during a surgical procedure. Such grafts are also commonly formed from solid or perforated ADM. As a result, existing ADM grafts present efficiency, efficacy, and repeatability challenges when used for reconstructive surgery purposes. 
     SUMMARY 
     This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This Summary is not intended to identify key aspects or essential aspects of the claimed subject matter. Moreover, this Summary is not intended for use as an aid in determining the scope of the claimed subject matter. 
     One embodiment provides a method of manufacturing an acellular dermal matrix (ADM) graft product for use in a reconstructive surgical procedure. The method may include the following steps: (1) providing a portion of donor-derived skin, the portion of the donor-derived skin having a full thickness; (2) removing an epidermis layer and a fat layer from the portion of the donor-derived skin to form a portion of dermal tissue; (3) decellularizing the portion of the dermal tissue to form a portion of ADM graft material; (4) forming the portion of the ADM graft material into a pre-defined shape in anticipation of the reconstructive surgical procedure; (5) fenestrating the pre-defined shape into a mesh pattern; (6) verifying that a thickness of the pre-defined shape equals a specified thickness; (7) packaging the pre-defined shape in a medical sterilization pouch to form a packaged, pre-shaped, and meshed ADM graft; and (8) irradiating the packaged, pre-shaped, and meshed ADM graft to a sterility assurance level of 10 −6  to form the ADM graft product. 
     Another embodiment provides a pre-shaped, meshed acellular dermal matrix (ADM) graft stored as a packaged graft product prepared by a process comprising the steps of: (1) providing a portion of ADM tissue having a thickness between 1 mm and 2 mm; (2) fenestrating the portion of the ADM tissue in a mesh pattern extending over an entirety of the portion of the ADM tissue; (3) scoring the portion of the ADM tissue into a pre-defined shape to form the pre-shaped, meshed ADM graft; (4) verifying the thickness of the pre-shaped, meshed ADM graft; (5) packaging the pre-shaped, meshed ADM graft in a medical sterilization pouch; and (6) irradiating the pre-shaped, meshed ADM graft within the medical sterilization pouch to a sterility assurance level of 10 −6  to form the packaged graft product. 
     Yet another embodiment provides an acellular dermal matrix (ADM) graft product. The ADM graft product may include an ADM graft derived from full-thickness skin, the ADM graft having a pre-formed shape with a mesh pattern formed therein, as well as a medical sterilization pouch sealed about the ADM graft, wherein when the medical sterilization pouch and the ADM graft are irradiated to a sterility assurance level of 10 −6 , the ADM graft product has a shelf-life of two years. 
     In yet another embodiment, there is provided a method of manufacturing an acellular dermal matrix (ADM) graft product for use in a reconstructive surgical procedure. The method may include providing a portion of donor-derived skin, the portion of the donor-derived skin having a full thickness. The method may include removing an epidermis layer and a fat layer from the portion of the donor-derived skin to form a portion of dermal tissue. The method may include decellularizing the portion of the dermal tissue to form a portion of ADM graft material. The method may include forming the portion of the ADM graft material into a pre-defined shape in anticipation of the reconstructive surgical procedure, and the forming the portion of the ADM graft material into the pre-defined shape comprises at least one of scoring and cutting the portion of the ADM graft material into a domed shape ADM graft. The method may include verifying that a thickness of the pre-defined shape equals a specified thickness. The method may include packaging the domed shape ADM graft in a medical sterilization pouch to form a packaged and domed shape ADM graft. The method may include irradiating the packaged and domed shaped ADM graft to a sterility assurance level of 10 −6  to form the ADM graft product. 
     In still another embodiment there is provided a domed shaped acellular dermal matrix (ADM) graft stored as a packaged graft product prepared by a process. The process may include a step of providing a portion of ADM tissue having a thickness between 1 mm and 2 mm. The process may include a step of scoring the portion of the ADM tissue into a pre-defined shape to form the domed shape ADM graft. The process may include a step of verifying the thickness of the domed shape ADM graft. The process may include a step of packaging the domed shaped ADM graft in a medical sterilization pouch. The process may include a step of irradiating the domed shaped ADM graft within the medical sterilization pouch to a sterility assurance level of 10 −6  to form the packaged graft product. 
     And in yet another embodiment there is provided a tool or set of tools having a set of features for forming a domed ADM graft. The set of features may include a shaping tool feature having a shaping portion configured to shape a dome shaped ADM graft. The set of features may include a scoring tool feature having a scoring portion configured to impart a desired mesh pattern into the domed shaped ADM graft. 
     Other embodiments provide an ADM graft that combines the ADM as designed with antimicrobial elements that mitigate or prevent complications arising from post-surgical infections. Antimicrobial agents that are compatible with the ADM include silver in its colloidal, elemental or ionic form. The silver may be complexed with chelating agents or may be added directly to the ADM prior to final packaging. Similarly other antimicrobial agents may be combined with the ADM. Other agents well known to be used medically are chlorhexidine gluconate and antimicrobial peptides of various amino acid chain length. 
     Other embodiments are also disclosed. 
     Additional objects, advantages and novel features of the technology will be set forth in part in the description which follows, and in part will become more apparent to those skilled in the art upon examination of the following, or may be learned from practice of the technology. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Non-limiting and non-exhaustive embodiments of the present invention, including the preferred embodiment, are described with reference to the following figures, wherein like reference numerals refer to like parts throughout the various views unless otherwise specified. Illustrative embodiments of the invention are illustrated in the drawings, in which: 
         FIGS.  1 A- 1 B  illustrate respective front-plan and perspective views of one embodiment of a pre-shaped, meshed acellular dermal matrix (ADM) graft derived from full-thickness skin; 
         FIGS.  2 A- 2 B  illustrate respective top-perspective and bottom-perspective views of one embodiment of scoring tool for manufacturing the pre-shaped, meshed ADM graft of  FIGS.  1 A- 1 B ; 
         FIGS.  3 A- 3 B  illustrate front-plan views of an exemplary mesh, or fenestration, pattern of the pre-shaped, meshed ADM graft of  FIGS.  1 A- 1 B , shown in an open position and in a resting position, respectively; 
         FIG.  4    illustrates a perspective view of an exemplary skin mesher for forming the mesh pattern of  FIGS.  3 A- 3 B ; 
         FIG.  5    illustrates a first perforated prior art ADM graft for comparison to the pre-shaped, meshed ADM graft of  FIGS.  1 A- 1 B ; 
         FIG.  6    illustrates a second perforated prior art ADM graft for comparison to the pre-shaped, meshed ADM graft of  FIGS.  1 A- 1 B ; 
         FIGS.  7 A- 7 B  illustrate perspective views of a fluid egress testing device in respective first and second stages of fluid egress testing of the pre-shaped, meshed ADM graft of  FIGS.  1 A- 1 B , the first perforated ADM graft of  FIG.  5   , and the second perforated ADM graft of  FIG.  6   ; 
         FIGS.  8 A- 8 B  provide a table reflecting multiple sets of drainage time measurements captured during the fluid egress testing performed using the testing device of  FIGS.  7 A- 7 B ; 
         FIG.  9    provides a summary graft of the drainage time measurements shown in  FIGS.  8 A- 8 B ; 
         FIG.  10    illustrates a front perspective view of an ADM graft pocket formed by joining two of the pre-shaped, meshed ADM grafts of  FIGS.  1 A- 1 B  together; 
         FIG.  11    illustrates a front view of a pre-shaped, meshed ADM graft product in which the pre-shaped, meshed ADM graft of  FIGS.  1 A- 2 A  is packaged for storage in a sealed medical sterilization pouch; 
         FIG.  12    illustrates the pre-shaped, meshed ADM graft product of 
         FIG.  11    further packaged in a medical peel pouch; 
         FIG.  13    provides a flowchart depicting an exemplary method of manufacturing an embodiment of the pre-shaped, meshed ADM graft of  FIGS.  1 A- 1 B  and the packaged ADM graft product of  FIGS.  11 - 12   ; 
         FIG.  14    is a photograph of an embodiment of a domed shaped ADM graft product; 
         FIGS.  15 A and  15 B  illustrate an embodiment of a shaping and scoring tool for manufacturing of the domed shaped ADM graft product of  FIG.  15   ; and 
         FIG.  16    illustrates an alternative embodiment of a domed shaped ADM graft product having a multi-notched peripheral edge. 
     
    
    
     DETAILED DESCRIPTION 
     Embodiments are described more fully below in sufficient detail to enable those skilled in the art to practice the system and method. However, embodiments may be implemented in many different forms and should not be construed as being limited to the embodiments set forth herein. The following detailed description is, therefore, not to be taken in a limiting sense. 
     Various embodiments of the products and associated methods of manufacture and use described herein relate to a pre-shaped, meshed or fenestrated acellular dermal matrix (ADM) graft derived from full-thickness human, donor-derived skin for use in the surgical reconstruction of soft tissue defects resulting from trauma, disease, or surgical intervention. For example, embodiments of the ADM graft discussed herein may be used in the surgical specialty of plastic surgery, and particularly in prepectoral and post-mastectomy breast reconstruction, where the ADM graft is an adjunct to integumental repair of the surgical site. 
     Embodiments of the ADM graft may be packaged and irradiated for long-term sterile storage in a manner that allows them to be used in surgical procedures within two years of packaging. In use, embodiments of the pre-shaped, meshed ADM graft provide the surgeon with a mechanism to restore function to and support integumental tissue after surgical intervention in a manner that is repeatable, effective, and time efficient by leveraging a manufactured, pre-shaped and meshed ADM graft product that is derived from full-thickness skin. Embodiments of the ADM graft facilitate fluid drainage from the surgical site to discourage seroma formation, increase the rate of integration of the ADM graft with the body, and provide a reliable, repeatable solution the surgeon may use “off the shelf” rather than utilizing valuable time and resources for graft processing in preparation for or during the surgical procedure. 
     Turning to exemplary embodiments,  FIGS.  1 A- 1 B  illustrate respective front-plan and perspective views of one embodiment of a pre-shaped, meshed ADM graft  100  derived from decellularized, full-thickness skin. Using full-thickness skin as the source for the ADM graft  100  ensures that the ADM graft  100  has sufficient biomechanical properties to support varying surgical requirements, including, for example, a suitable ultimate tensile strength, suture pull-out resistance, and a Young&#39;s modulus indicative of a soft and supple graft. 
     In this embodiment, the pre-shaped, meshed ADM graft  100  may have a pre-formed shape approximating a circle with a portion of the top removed (i.e., slightly larger than a semi-circle). In one embodiment, as detailed in  FIGS.  1 A- 1 B , the pre-shaped ADM graft may form a generally semi-circular tissue portion  102  having a radius, r, of 9 cm. The semi-circular tissue portion  102  may approximate a circle having a top portion of the circle removed in a straight line disposed perpendicular to the radius, r, of the circle. The tissue portion  102  may have a total height, h, of 10 cm, and a material thickness, t, of 1.0-2.0 mm. Additional pre-shaped ADM graft embodiments may feature various circular or elliptical shapes with diameters ranging from 10 cm to 22 cm. The circular or elliptical tissue portion of the ADM graft may feature a removed top portion, as shown in FIGS.  1 A- 1 B, or an in-tact top portion, as necessary or desired for the intended surgical preparation. 
     In addition, the pre-shaped, meshed ADM graft  100  may include a notch  104  to indicate which surface provides a basement membrane surface  106 , or the dermal surface to be implanted towards the patient&#39;s vascular bed. In one embodiment, as shown in  FIGS.  1 A- 1 B , the notch  104  of the graft  100  may be disposed in the top left corner to indicate the basement membrane surface  106 . In other embodiments, the basement membrane may be removed. 
     The decellularized, full-thickness dermal tissue may be shaped and cut into the pre-shaped ADM graft  100  using an appropriately designed scoring tool along with a cutting tool such as, for example, a surgical scalpel or a surgical scissor.  FIGS.  2 A- 2 B  illustrate respective front and rear perspective views of one embodiment of a scoring tool  130  featuring a semi-circular edge pattern  132  that incorporates a raised notch  134  configured to form the indicator notch  104  in the pre-shaped ADM graft  100 . To manufacture the pre-shaped ADM graft  100 , an embodiment of the scoring tool  130  may be placed upon a portion of full-thickness dermal tissue and used to “stamp” out the notched, semi-circular tissue portion  102  from a larger ADM tissue portion. The cutting tool (not shown) may be used to trim excess tissue from around a perimeter of the scoring tool  130 . 
     The pre-shaped nature of the ADM graft  100  disclosed herein saves the surgeon valuable time during a surgical procedure because there is no (or minimal) need for the surgeon to shape, cut, or otherwise form the ADM graft into a desired shape during surgical preparation. Instead, the surgeon may simply select an appropriately pre-shaped ADM graft for the particular surgery and proceed. 
     Embodiments of the pre-shaped ADM graft  100  may additionally include a mesh or fenestration pattern to allow for increased fluid flow through the graft  100 , thereby reducing the chances of post-surgical seroma formation, a frequent complication after surgeries using existing ADM grafts. Pre-meshing also prevents the surgeon from having to perform any type or kind of meshing procedures during surgical preparation or during a surgical procedure and ensures an optimal mesh ratio to provide maximum fluid egress, or drainage, from the surgical site to prevent seroma formation and a maximum graft surface area for improved integration into the body post procedure. 
       FIGS.  3 A- 3 B  illustrate respective front views of an exemplary mesh, or fenestration, pattern  108  applied to the pre-shaped, meshed ADM graft  100 , shown in an open position, A, in which the mesh pattern appears as a series of holes  110  ( FIG.  3 A ) and in a resting position, B, in which the mesh pattern  108  appears as a series of straight slits or lines  112  ( FIG.  3 B ). In this embodiment, the mesh pattern  108  may feature a 1:1 graft:space ratio in which each mesh hole  110 /line  112  has a length, L, of 1.5 mm, an end-to-end offset, E o , of 1.5 mm, and a lateral offset, L o , of 1 mm. Alternative embodiments may feature a different mesh ratio and/or any appropriate and/or desired material and line dimensions. For example, in one embodiment the mesh pattern  108  may feature a 2:1 graft:space ratio, with a material thickness of 0.8-2.5 mm. 
     The mesh or fenestration pattern  108  may be formed in the pre-shaped, meshed ADM graft  100  using a standard “skin mesher”  140  such as, for example, a 4MED (or Rosenberg) Skin Graft Mesher (Distributed by Exsurco Medical, Wakeman, Ohio). As shown in  FIG.  4   , a portion of decellularized, full-thickness dermal tissue  101  or, alternatively, a pre-shaped semi-circular tissue portion  102  may be inserted into the skin mesher  140 , which has been adjusted to the appropriate mesh or fenestration settings, for application of the mesh pattern  108  to the tissue  101 . 
     A fluid egress study was completed to exhibit the increased fluid egress, or drainage, properties of the pre-shaped, meshed ADM graft  100 . In the study, the fluid drainage properties of the pre-shaped, meshed ADM graft  100  were compared to those of a prior art first perforated ADM graft  142 , shown in  FIG.  5   , having a first perforation density pattern  144  of 41 perforations per 320 cm 2 , or approximately 0.128 perforations per cm 2 , and a prior art second perforated ADM graft  146 , shown in  FIG.  6   , having a second perforation density pattern  148  of 80 perforations per 320 cm 2 , or approximately 0.25 perforations per cm 2  and approximately twice that of the first perforation density pattern  144 . Three samples of each were tested, each sample having a thickness between 0.9-2.0 mm. 
       FIGS.  7 A- 7 B  illustrate perspective views of a fluid egress testing device  150  in first and second stages of egress testing, respectively. Upon release of a valve  151 , a fluid  152  was passed from a fluid column  158 , through the respective tested ADM graft (i.e., the pre-shaped meshed ADM graft  100 , the first perforated ADM graft  142 , or the second perforated ADM graft  144 ) stretched across the fluid column  158  (not shown) and into a waste container  157 . An egress or drainage-time measurement was taken of the time required for a top surface  159  the fluid  152  to fall 8.5 inches from a first fluid-level line  154  to a second fluid-level line  156  along the fluid column  158  of the fluid egress testing device  150 , as shown in  FIGS.  7 A- 7 B , respectively. The drainage time for the fluid surface  159  to pass from the first line  154  to the second line  156  was measured in triplicate for each of the pre-shaped meshed ADM graft  100 , the first perforated ADM graft  142 , and the second perforated ADM graft  146 . The drainage time measurements are provided in the table of  FIGS.  8 A- 8 B . As summarized in the chart of  FIG.  9   , the fluid egress study showed that the pre-shaped, meshed ADM graft  100  having the 1:1 graft:space ratio demonstrated significantly improved fluid egress properties, namely approximately 3× and 5× faster fluid egress as compared to the first and the second perforation density patterns  144 ,  148  of the first and the second perforated grafts  142 ,  146 , respectively. 
     As discussed above, the mesh pattern  108  also increases the surface area of the pre-shaped, meshed ADM graft  100 , which, in turn, abets a rate of integration of the graft  100  during the healing process after surgical intervention. The surface area calculations below compare the pre-shaped, meshed ADM graft  100  with the first and the second perforated grafts  142 ,  146  having the first and the second perforation patterns  144 ,  148 , respectively, discussed above in relation to  FIGS.  5 - 6   . In summary, the surface area of a 2×2 cm 2  meshed ADM graft having a 1 mm thickness and  130 , 1.5 mm long mesh lines provides a 97.5% increase in surface area over a 2×2 cm 2  solid, non-meshed ADM graft, as shown below: 
     
       
         
           
             
               Surface 
               ⁢ 
                   
               Area 
             
             = 
             
               
                 ( 
                 
                   area 
                   ⁢ 
                       
                   of 
                   ⁢ 
                       
                   top 
                   ⁢ 
                       
                   of 
                   ⁢ 
                       
                   graft 
                 
                 ) 
               
               + 
               
                 
                   ( 
                   
                     #mesh 
                     ⁢ 
                         
                     lines 
                   
                   ) 
                 
                 ⁢ 
                 
                   ( 
                   
                     perimeter 
                     ⁢ 
                         
                     of 
                     ⁢ 
                         
                     mesh 
                     ⁢ 
                         
                     hole 
                   
                   ) 
                 
                 ⁢ 
                 
                   ( 
                   thickness 
                   ) 
                 
               
             
           
         
       
       
         
           
             
               Surface 
               ⁢ 
                   
               Area 
             
             = 
             
               
                 ( 
                 
                   4 
                   ⁢ 
                       
                   cm 
                 
                 ) 
               
               + 
               
                 
                   ( 
                   130 
                   ) 
                 
                 ⁢ 
                 
                   ( 
                   
                     2 
                     * 
                     1.5 
                         
                     mm 
                   
                   ) 
                 
                 ⁢ 
                 
                   ( 
                   
                     1 
                     ⁢ 
                         
                     mm 
                   
                   ) 
                 
               
             
           
         
       
       
         
           
             
               Surface 
               ⁢ 
                   
               Area 
             
             = 
             
               
                 
                   4 
                   ⁢ 
                       
                   cm 
                 
                 + 
                 
                   3.9 
                       
                   cm 
                 
               
               = 
               
                 7.9 
                     
                 cm 
               
             
           
         
       
       
         
           
             
               Orignal 
               ⁢ 
                   
               Solid 
               ⁢ 
                   
               Graft 
               ⁢ 
                   
               Area 
             
             = 
             
               
                 
                   ( 
                   
                     2 
                     ⁢ 
                         
                     cm 
                   
                   ) 
                 
                 ⁢ 
                 
                   ( 
                   
                     2 
                     ⁢ 
                         
                     cm 
                   
                   ) 
                 
               
               = 
               
                 4 
                 ⁢ 
                     
                 
                   cm 
                   2 
                 
               
             
           
         
       
       
         
           
             
               Increase 
               ⁢ 
                   
               in 
               ⁢ 
                   
               Surface 
               ⁢ 
                   
               Area 
               ⁢ 
                   
               from 
               ⁢ 
                   
               Meshing 
             
             = 
             
               
                 
                   
                     7.9 
                     - 
                     4 
                   
                   4 
                 
                 * 
                 100 
                 ⁢ 
                 % 
               
               = 
               
                 97.5 
                 % 
               
             
           
         
       
     
     The first perforated graft  142  having a 16 cm×20 cm perimeter and a 1 mm thickness, with a perforation density pattern  144  of 41 perforations per a 320 cm 2  area, each perforation having a 0.15 cm radius, provides only a 0.3% surface-area increase over a 16 cm×20 cm solid, non-meshed ADM graft, as shown below: 
     
       
         
           
             
               Surface 
               ⁢ 
                   
               Area 
             
             = 
             
               
                 ( 
                 
                   area 
                   ⁢ 
                       
                   of 
                   ⁢ 
                       
                   top 
                   ⁢ 
                       
                   of 
                   ⁢ 
                       
                   graft 
                 
                 ) 
               
               + 
               
                 ( 
                 
                   # 
                   ⁢ 
                       
                   holes 
                 
                 ) 
               
               ⁢ 
               
                 ( 
                 
                   surface 
                   ⁢ 
                       
                   area 
                   ⁢ 
                       
                   of 
                   ⁢ 
                       
                   inside 
                   ⁢ 
                       
                   of 
                   ⁢ 
                       
                   hole 
                 
                 ) 
               
             
           
         
       
       
         
           
             
               Surface 
               ⁢ 
                   
               Area 
             
             = 
             
               
                 ( 
                 
                   
                     320 
                     ⁢ 
                         
                     
                       cm 
                       2 
                     
                   
                   - 
                   
                     
                       ( 
                       41 
                       ) 
                     
                     ⁢ 
                     
                       ( 
                       
                         
                           π 
                           * 
                         
                         
                           .15 
                           2 
                         
                       
                       ) 
                     
                   
                 
                 ) 
               
               + 
               
                 
                   ( 
                   41 
                   ) 
                 
                 ⁢ 
                 
                   ( 
                   
                     
                       2 
                       * 
                     
                     ⁢ 
                     
                       π 
                       * 
                     
                     .15 
                         
                     cm 
                   
                   ) 
                 
                 ⁢ 
                 
                   ( 
                   
                     .1 
                         
                     cm 
                   
                   ) 
                 
               
             
           
         
       
       
         
           
             
               Surface 
               ⁢ 
                   
               Area 
             
             = 
             
               
                 
                   317.10188 
                       
                   
                     cm 
                     2 
                   
                 
                 + 
                 
                   3.86384 
                       
                   
                     cm 
                     2 
                   
                 
               
               = 
               
                 320.966 
                     
                 
                   cm 
                   2 
                 
               
             
           
         
       
       
         
           
             
               Orignal 
               ⁢ 
                   
               Solid 
               ⁢ 
                   
               Graft 
               ⁢ 
                   
               Area 
             
             = 
             
               
                 
                   ( 
                   
                     16 
                     ⁢ 
                         
                     cm 
                   
                   ) 
                 
                 ⁢ 
                 
                   ( 
                   
                     20 
                     ⁢ 
                         
                     cm 
                   
                   ) 
                 
               
               = 
               
                 320 
                 ⁢ 
                     
                 
                   cm 
                   2 
                 
               
             
           
         
       
       
         
           
             
               Increase 
               ⁢ 
                   
               in 
               ⁢ 
                   
               Surface 
               ⁢ 
                   
               Area 
               ⁢ 
                   
               from 
               ⁢ 
                   
               Perforating 
             
             = 
             
               
                 
                   
                     320.966 
                     - 
                     320 
                   
                   320 
                 
                 * 
                 100 
                 ⁢ 
                 % 
               
               = 
               
                 0.3 
                 % 
               
             
           
         
       
     
     The second perforated graft  146  having a 16 cm×20 cm perimeter and a 1 mm thickness, with a perforation density pattern  148  of 80 perforations per a 320 cm 2  area, each perforation having a 0.15 cm radius, provides only a 0.59% surface-area increase over a 16 cm×20 cm solid, non-meshed ADM graft, as shown below: 
     
       
         
           
             
               Surface 
               ⁢ 
                   
               Area 
             
             = 
             
               
                 ( 
                 
                   area 
                   ⁢ 
                       
                   of 
                   ⁢ 
                       
                   top 
                   ⁢ 
                       
                   of 
                   ⁢ 
                       
                   graft 
                 
                 ) 
               
               + 
               
                 
                   ( 
                   
                     # 
                     ⁢ 
                         
                     holes 
                   
                   ) 
                 
                 ⁢ 
                 
                   ( 
                   
                     surface 
                     ⁢ 
                         
                     area 
                     ⁢ 
                         
                     of 
                     ⁢ 
                         
                     inside 
                     ⁢ 
                         
                     of 
                     ⁢ 
                         
                     hole 
                   
                   ) 
                 
               
             
           
         
       
       
         
           
             
               Surface 
               ⁢ 
                   
               Area 
             
             = 
             
               
                 ( 
                 
                   
                     320 
                     ⁢ 
                         
                     
                       cm 
                       2 
                     
                   
                   - 
                   
                     
                       ( 
                       80 
                       ) 
                     
                     ⁢ 
                     
                       ( 
                       
                         
                           π 
                           * 
                         
                         
                           .15 
                           2 
                         
                       
                       ) 
                     
                   
                 
                 ) 
               
               + 
               
                 
                   ( 
                   80 
                   ) 
                 
                 ⁢ 
                 
                   ( 
                   
                     
                       2 
                       * 
                     
                     ⁢ 
                     
                       π 
                       * 
                     
                     .15 
                         
                     cm 
                   
                   ) 
                 
                 ⁢ 
                 
                   ( 
                   
                     .1 
                         
                     cm 
                   
                   ) 
                 
               
             
           
         
       
       
         
           
             
               Surface 
               ⁢ 
                   
               Area 
             
             = 
             
               
                 
                   314.34513 
                       
                   
                     cm 
                     2 
                   
                 
                 + 
                 
                   7.5392 
                       
                   
                     cm 
                     2 
                   
                 
               
               = 
               
                 321.884 
                     
                 
                   cm 
                   2 
                 
               
             
           
         
       
       
         
           
             
               Orignal 
               ⁢ 
                   
               Solid 
               ⁢ 
                   
               Graft 
               ⁢ 
                   
               Area 
             
             = 
             
               
                 
                   ( 
                   
                     16 
                     ⁢ 
                         
                     cm 
                   
                   ) 
                 
                 ⁢ 
                 
                   ( 
                   
                     20 
                     ⁢ 
                         
                     cm 
                   
                   ) 
                 
               
               = 
               
                 320 
                 ⁢ 
                     
                 cm 
               
             
           
         
       
       
         
           
             
               Increase 
               ⁢ 
                   
               in 
               ⁢ 
                   
               Surface 
               ⁢ 
                   
               Area 
               ⁢ 
                   
               from 
               ⁢ 
                   
               Perforating 
             
             = 
             
               
                 
                   
                     321.884 
                     - 
                     320 
                   
                   320 
                 
                 * 
                 100 
                 ⁢ 
                 % 
               
               = 
               
                 0.59 
                 % 
               
             
           
         
       
     
     Thus, the fenestration pattern  108  applied to the pre-shaped, meshed ADM graft  100  significantly increases the exposed surface area of the graft over both existing solid and perforated grafts. This increase causes the pre-shaped, meshed ADM graft  100  to integrate into the human body much more rapidly during the healing process after surgical intervention. 
     In one embodiment, the pre-shaped, meshed ADM graft  100  may be formed of the ADM derived from full-thickness skin, as discussed above, combined with antimicrobial elements that mitigate or prevent complications arising from post-surgical infections. Antimicrobial agents compatible with the ADM may include, for example, silver in its colloidal, elemental, or ionic form. The silver may be complexed with chelating agents or may be added directly to the ADM prior to final packaging. Similarly, other antimicrobial agents may be combined with the ADM. Other agents known to be used medically may include chlorhexidine gluconate and antimicrobial peptides having various amino acid chain lengths. 
     In one embodiment shown in  FIG.  10   , two pre-shaped, meshed ADM grafts  100  may be sutured together to form an ADM graft pocket  160 . In this embodiment, the two pre-shaped, meshed ADM grafts  100  may be sutured together around the curved portions each of the semi-circular tissue portions  102 , such that a breast implant  162  may be disposed within the ADM graft pocket  160  between the two pre-shaped, meshed ADM grafts  100 . The implant  162  is thus supported from the bottom, without the need to be covered at the top. In one embodiment, the ADM graft pocket  160  may be pre-sutured and then packaged and stored for later surgical use, as discussed below in relation to  FIGS.  11 - 12   , or the ADM graft pocket may be formed from two pre-shaped, meshed ADM grafts  100  and sutured by the surgeon prior to or during a surgical procedure. In another operative embodiment applicable to reconstructive surgery, the implant may be wrapped in the pre-shaped, meshed ADM graft  100  from an anterior side, and the graft  100  sutured to the chest wall. 
     After manufacture and to provide complete a shelf-stable, packaged ADM graft product  170 , the pre-shaped, meshed ADM graft  100  (or the ADM graft pocket  160 ) may be packaged along with two opposing pieces of backing material  172  and sterile water in a sealed medical sterilization pouch  174  such as, for example, a Kapak pouch (manufactured by AMPAK Technology Inc. of Larchmont, N.Y.), as shown in  FIG.  11   , or further into a sealed, peelable medical sterilization pouch  176  known as a “peel pouch” or a “chevron pouch,” as shown in  FIG.  12   . The packaged ADM graft product  170  may then be irradiated to a sterility assurance level (SAL) of 10 −6  such that it may be stored at room temperature for up to two years. The packaged ADM graft product  170  may be labeled in any appropriate manner and may include information pertaining to the raw material, the shape, a use by date, special requirements, results of a visual inspection, and so on. 
       FIG.  13    provides a flowchart depicting an exemplary method ( 200 ) of manufacturing an embodiment of the pre-shaped, meshed ADM graft  100 , the ADM graft pocket  160 , and the packaged ADM graft product  170 , discussed above. In this embodiment, the method may initiate with providing a portion of full-thickness donor-derived skin ( 202 ). Next, the epidermis layer and the fat layer adjacent to the dermis may be removed ( 204 ), and the dermal tissue may be decellularized according to a well-known or a proprietary decellularization process, resulting in the Acellular Dermal Matrix (ADM) ( 206 ). The ADM may then be shaped and/or cut into a pre-defined shape, such as the semi-circular tissue portion  102  or another appropriate shape, as necessary for an associated or pre-determined/assigned surgical procedure ( 208 ). The shaping may be accomplished using any appropriate scoring tool  130  or another appropriate shaping tool, and the graft may be cut out with the cutting tool. 
     The ADM may also be meshed/fenestrated in the desired mesh pattern (e.g., 1:1 graft:space ratio, 2:1 graft:space ratio) using any appropriate skin mesher  140  ( 210 ). The meshing or fenestrating process ( 210 ) may occur before or after the ADM is shaped into the pre-defined shape. The resulting pre-shaped, meshed ADM graft  100  may then be verified for its thickness to specification (e.g., 1 mm-2 mm) ( 212 ) using a thickness gauge, and one or more antimicrobial agents may be added to the pre-shaped, meshed ADM graft  100  to aid in post-surgical infection prevention ( 213 ). The graft  100  may then be packaged ( 214 ) between opposing pieces of backing material  172  within sterile water inside a self-sealing medical sterilization pouch  174  and/or a peelable pouch  176  such as, for example, a Kapak peel-pouch, forming the pre-shaped, meshed ADM graft product  170 . The packaged ADM graft product  170  may be irradiated to SAL 10 −6  ( 216 ). After irradiation ( 216 ), the packaged, pre-shaped, meshed ADM graft product  170  may be stored up to two years ( 218 ) before it is used in a surgical procedure ( 220 ). 
     In one embodiment, prior to packaging ( 214 ), two of the pre-shaped, meshed ADM grafts  100  may be joined (e.g., sutured) together about a curving portion of each individual graft  100  to form the ADM graft pocket  160  ( 222 ), discussed above in relation to  FIG.  10   . Alternatively, the ADM graft pocket  160  may be formed prior to a surgical procedure, within or prior to entering the operating theater. 
     The method of manufacturing the packaged, pre-shaped, meshed ADM graft product  170  provides a repeatable process for manufacturing the pre-shaped, meshed ADM graft  100  formed from full-thickness donor-derived skin such that surgeons may rely on the time-saving graft product in reconstructive surgical procedures to provide a graft solution that has the robust physical properties required of surgical skin grafts (as opposed to burn skin grafts), promotes healing in the form of effective drainage from the surgical site, and promotes integration of the graft into the patient&#39;s body. 
     In another embodiment, there may be provided a domed shaped ADM graft product  300  (see, for example  FIGS.  14  and  16   ).  FIGS.  15 A and  15 B  illustrate an embodiment of a shaping and scoring tool  400  for manufacturing of the domed shaped ADM graft product  300  as illustrated  FIG.  15   . The shaping and scoring tool  400  of  FIG.  15   , or a similar type of device or devices, may be provided with a shaping portion  405  to impart the dome shape  305  to the ADM graft product  300 . Furthermore, a scoring portion  410  integrated in the same device  305 , or provided separately, is configured to impart a desired mesh pattern  310  (which may be a concentric pattern formed on edges  315  of the ADM graft product  300 , or another desired mesh pattern, in addition to mesh patten  320 , across an entire surface of the ADM graft  300 , or the domed shaped ADM graft  300 may be shaped without a mesh pattern in a specific region or without any mesh pattern across the entire ADM graft  300 .) 
     With reference to  FIG.  16   , there is shown another embodiment  500  of an initial portion  325  of a domed shaped ADM graft product  300  having a multi-notched peripheral edge  505 . This multi-notched embodiment  500  may be one or both of shaped and/or scored using the shaping and scoring tool  400  of  FIG.  15    or other suitable apparatus and processing steps. 
     The decellularized, full-thickness dermal tissue  500  may be shaped and cut into the domed shaped ADM graft  300  using an appropriately designed scoring tool along with a cutting tool such as, for example, a surgical scalpel or a surgical scissor. 
     The pre-shaped nature of the domed shaped ADM graft disclosed herein saves the surgeon valuable time during a surgical procedure because there is no (or minimal) need for the surgeon to shape, cut, or otherwise form the ADM graft into a desired shape during surgical preparation. Instead, the surgeon may simply select an appropriately pre-shaped ADM graft for the particular surgery and proceed. 
     Embodiments of domed shaped ADM graft may additionally include a mesh or fenestration pattern to allow for increased fluid flow through the graft, thereby reducing the chances of post-surgical seroma formation, a frequent complication after surgeries using existing ADM grafts. Pre-meshing also prevents the surgeon from having to perform any type or kind of meshing procedures during surgical preparation or during a surgical procedure and ensures an optimal mesh ratio to provide maximum fluid egress, or drainage, from the surgical site to prevent seroma formation and a maximum graft surface area for improved integration into the body post procedure. 
     Although the above embodiments have been described in language that is specific to certain structures, elements, compositions, and methodological steps, it is to be understood that the technology defined in the appended claims is not necessarily limited to the specific structures, elements, compositions and/or steps described. Rather, the specific aspects and steps are described as forms of implementing the claimed technology. Since many embodiments of the technology can be practiced without departing from the spirit and scope of the invention, the invention resides in the claims hereinafter appended.