Dermal micro-organs, methods and apparatuses for producing and using the same

• US 9,572,593 B2
• Filed: 07/01/2015
• Issued: 02/21/2017
• Est. Priority Date: 05/01/2003
• Status: Expired due to Fees

• Current Assignee: Medgenics Medical Israel Ltd.
• Original Assignee: Medgenics Medical Israel Ltd.
• Inventors: Bellomo, Stephen F., Okun, Alex, Fuerst, Yaron, Shalhevet, David, Amir, Elisha, Bukhman, Mordechay
• Primary Examiner(s): SZPIRA, JULIE ANN
• Application Number:
  US14/789,743
• Publication Number:
  US 20160000457A1
• Time in Patent Office: 601 Days
• US Class Current: 1/1
• CPC Class Codes: A61B 10/0275 with sample notch, e.g. on the side of inner stylet
• CPC Class Codes: A61B 17/32053 Punch like cutting instruments, e.g. using a cylindrical or oval knife A61B17/326 takes precedence; trepans A61B17/1695; for use on the cornea A61F9/007
• CPC Class Codes: A61B 17/322 Skin grafting apparatus
• CPC Class Codes: A61B 17/3468 for implanting or removing devices, e.g. prostheses, implants, seeds, wires devices for implanting seeds A61M37/0069
• CPC Class Codes: A61B 2017/0023 disposable
• CPC Class Codes: A61B 2017/00969 used for transplantation
• CPC Class Codes: A61B 2017/2808 Clamp, e.g. towel clamp
• CPC Class Codes: A61B 2017/320052 Guides for cutting instruments
• CPC Class Codes: A61B 2017/320064 with tissue or sample retaining means
• CPC Class Codes: A61B 2017/3225 with processing of harvested tissue
• CPC Class Codes: A61B 2217/005 with suction drainage system
• CPC Class Codes: A61F 2/105 Skin implants, e.g. artificial skin
• CPC Class Codes: A61K 35/36 Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells islets of Langerhans A61K35/39
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/2066 IL-10
• CPC Class Codes: A61K 38/215 IFN-beta
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61M 5/425 Protruding skin to facilitate piercing, e.g. vacuum cylinders, vein immobilising means
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: C12N 2502/094 : keratinocytes
• CPC Class Codes: C12N 2502/1323 : Adult fibroblasts
• CPC Class Codes: C12N 2510/00 : Genetically modified cells
• CPC Class Codes: C12N 5/0698 : Skin equivalents
• CPC Class Codes: Y10T 83/929 : Tool or tool with support

Abstract

Embodiments of the present invention provide Dermal Micro-organs (DMOs), methods and apparatuses for harvesting the same. Some embodiments of the invention provide a DMO including a plurality of dermal components, which substantially retain the micro-architecture and three dimensional structure of the dermal tissue from which they are derived. An apparatus for harvesting the DMO may include, according to some exemplary embodiments, a support configuration to support a skin-related tissue structure from which the DMO is to be harvested, and a cutting tool able to separate the DMO to from the skin-related tissue structure. Exemplary embodiments of the invention provide a genetically modified dermal micro-organ expressing at least one recombinant gene product. Some embodiments of the invention provide methods and apparatuses for implanting a genetically modified DMO.

Claims

1. An apparatus for directly harvesting a dermal micro-organ from a subject comprising:

(a) a support structure to support a skin-related tissue structure of a subject from which the dermal micro-organ is to be harvested;

(b) a cutting tool able to directly separate the dermal micro-organ from the skin-related tissue structure; and

(c) an introducer for puncturing the skin related tissue structure at a site of insertion of the cutting tool;

wherein the support structure comprises a guiding channel through which the cutting tool may be inserted, and which forms a trajectory for the cutting tool that enables the cutting tool to directly harvest the dermal micro-organ;

wherein the support structure comprises a vacuum chamber comprising an inner support surface able to maintain the skin-related tissue structure in a desired shape and position within the vacuum chamber when a vacuum condition is applied to the vacuum chamber, in order to enable the cutting tool to cut the dermal micro-organ directly from the skin-related tissue structure; and

wherein the harvested dermal micro-organ is an explant of living tissue consisting essentially of a plurality of dermal components located below the epidermis and lacking a complete epidermal layer.

2. The apparatus of claim 1, further comprising one or more vacuum channels to fluidically connect the vacuum chamber with at least one vacuum source.

3. The apparatus of claim 1, further comprising a drill stop configured to allow the cutting tool to advance a predetermined distance within said vacuum chamber.

4. The apparatus of claim 1, wherein the vacuum chamber further comprises an elevated protrusion able to maintain a plateau of skin generally above the trajectory of the cutting tool, such that the harvested dermal micro-organ is directly cut from the surrounding tissue by the advance of the cutting tool into a fat layer.

5. The apparatus of claim 4, wherein the elevated protrusion of the support structure allows the introducer to be pushed generally perpendicular to the skin-related tissue structure surface at the point of puncturing while the trajectory of the cutting tool is substantially linear and generally parallel to the skin-related tissue structure surface.

6. The apparatus of claim 4, wherein the vacuum chamber comprises two elevated protrusions, located proximal and distal to the trajectory of the cutting tool, each elevated protrusion able to maintain a plateau of skin generally above the trajectory of the cutting tool, such that the harvested dermal micro-organ is directly cut from the surrounding tissue by the advance of the cutting tool into a fat layer.

7. The apparatus of claim 6, further comprising a central channel located between the two elevated protrusions and co-serial with the guiding channel, wherein the central channel supports the skin-related tissue structure under vacuum conditions so that the dermal layer of the skin-related tissue structure is within the trajectory of the cutting tool.

8. The apparatus of claim 1, wherein the cutting tool is rotatable.

9. The apparatus of claim 1, wherein said introducer comprises:

a. an inner tubular element, and

b. an outer tubular element,

wherein the inner tubular element inserts through the outer tubular element and extends beyond the distal end of the outer tubular element, the inner and outer tubular elements together inserting at the site of puncturing coaxially within the guide channel; and

the outer tubular element capable of remaining coaxial and within the guiding channel upon withdrawal of the inner tubular element from the guiding channel after puncturing of the skin-related tissue structure.

10. The apparatus of claim 9, wherein the inner tubular element is a needle and the outer tubular element is an outer sleeve.

11. The apparatus of claim 1, wherein the trajectory of the cutting tool is substantially linear and generally parallel to the skin-related tissue structure surface.

12. A method of harvesting a dermal micro-organ directly from a subject using the apparatus of claim 1, comprising:

(1) supporting a skin-related tissue structure from which the dermal micro-organ is directly harvested with the support configuration;

(2) inserting the introducer through the guiding channel in the support structure and puncturing the surface of the skin-related tissue structure;

(3) inserting the cutting tool through the introducer and guiding channel and advancing the cutting tool along a trajectory that enables the cutting tool to directly cut the dermal micro-organ from the supported skin-related tissue structure; and

(4) recovering the dermal micro-organ, wherein the harvested dermal micro-organ is an explant of living tissue consisting essentially of a plurality of dermal components located below the epidermis and lacking a complete epidermal layer.

13. The method of claim 12, wherein only a single puncture is made on the surface of the skin-related tissue structure.

14. The method of claim 12, wherein the supporting comprises applying a vacuum condition to the vacuum chamber, wherein the vacuum condition causes the skin-related tissue structure to be held at an inner support surface of the vacuum chamber.

15. The method of claim 12, wherein the method comprises rotating the cutting tool, wherein the apparatus further comprises one or more vacuum channels to fluidically connect the vacuum chamber with at least one vacuum source.

16. The method of claim 12, wherein the vacuum chamber of the apparatus further comprises an elevated protrusion able to maintain a plateau of skin generally above the trajectory of the cutting tool, such that the harvested dermal micro-organ is directly cut from the surrounding tissue by the advance of the cutting tool into a fat layer.

17. The method of claim 16, wherein the elevated protrusion of the apparatus support structure allows the introducer to be pushed generally perpendicular to the skin-related tissue structure surface at the point of puncturing while the trajectory of the cutting tool is substantially linear and generally parallel to the skin-related tissue structure surface.

18. The method of claim 16, wherein the vacuum chamber of the apparatus comprises two elevated protrusions, located proximal and distal to the trajectory of the cutting tool, each elevated protrusion able to maintain a plateau of skin generally above the trajectory of the cutting tool, such that the harvested dermal micro-organ is directly cut from the surrounding tissue by the advance of the cutting tool into a fat layer.

19. The method of claim 18, wherein the apparatus further comprises a central channel located between the two elevated protrusions and co-serial with the guiding channel, wherein the central channel supports the skin-related tissue structure under vacuum conditions so that the dermal layer of the skin-related tissue structure is within the trajectory of the cutting tool.

20. The method of claim 12, wherein said introducer of the apparatus comprises:

a. an inner tubular element, and

b. an outer tubular element,

wherein the inner tubular element inserts through the outer tubular element and extends beyond the distal end of the outer tubular element, the inner and outer tubular elements together inserting at the site of puncturing coaxially within the guide channel; and

the outer tubular element capable of remaining coaxial and within the guiding channel upon withdrawal of the inner tubular element from the guiding channel after puncturing of the skin-related tissue structure.

21. The method of claim 12, wherein the trajectory of the cutting tool is substantially linear and generally parallel to the skin-related tissue structure surface.