Vascularized tissue graft

Abstract

The present invention relates to improved methods for tissue engineering including tissue transplantation, augmentation and regeneration, and more particularly, a method for the generation of donor vascularized tissue suitable for use in tissue transplantation, augmentation and/or repair. The present invention enables the use of a support matrix in the generation of an anatomical construct comprising the donor vascular tissue. The support matrix may be devised such that it has dimensions of a size and shape adapted to simulate those of tissue to be transplanted, augmented and/or repaired. The methods and support matrix of the present invention may also find application as a means for delivering a desirable gene product to a subject. The method and support matrix of the present invention is conveniently made available in the form of a kit, for use in the field of tissue engineering.

1 . A method of augmenting volume or structure or repairing a deficit of a tissue in a subject at a desired site, comprising the steps of:
 a) creating a functional circulation on a vascular pedicle in the subject at the desired site, wherein said functional circulation is comprised of vessels capable of sustaining bloodflow with no impediments to said bloodflow;   b) enclosing the vascular pedicle within a fabricated chamber, the chamber having internal dimensions which are of a size and shape that simulate those of the tissue to be augmented by volume or structure or repaired tissue deficit of the desired site;   c) seeding the chamber with isolated adipocytes or pieces of adipose tissue;   d) filling the chamber with an extracellular matrix without added cells, said extracellular matrix being selected from the group consisting of reconstituted basement membrane preparations not derived from the isolated cells or pieces of tissue of step (c), laminin, polylactic-polyglycolic acid variants (PLGA), fibrin or plasma glue, collagen, and sea sponge; and   e) leaving the chamber at the desired site for a period sufficient for vascularized tissue to grow to the size and shape of the tissue to be augmented by volume or structure or deficit repaired.   
     
     
         2 . The method according to  claim 1 , comprising the step of: after step (b) adding growth factors, drugs, antibodies, inhibitors or other chemicals to the chamber. 
     
     
         3 . The method according to  claim 1 , wherein the vascular pedicle comprises an arterio-venous (AV) loop or shunt. 
     
     
         4 . The method according to  claim 1 , wherein the vascular pedicle comprises a ligated artery and vein. 
     
     
         5 . The method according to  claim 1 , wherein said created vascular pedicle contained within the chamber is connected to an extracorporeal circulation. 
     
     
         6 . The method according to  claim 1 , wherein said subject is a human. 
     
     
         7 . The method according to  claim 2 , wherein the additional growth factors, drugs, antibodies, inhibitors or other chemicals added to the chamber are selected from the group consisting of: growth factors, homing factors to attract stem cells from the circulation, and promoters of angiogenesis or vasculogenesis. 
     
     
         8 . The method according to  claim 1 , wherein the functional circulation on a vascular pedicle of step (a) comprises an artery, a venous graft, and a vein. 
     
     
         9 . The method according to  claim 1 , wherein the functional circulation on a vascular pedicle of step (a) comprises an artery, a venous graft, an arterial graft, and a vein. 
     
     
         10 . The method according to  claim 1 , wherein the functional circulation on a vascular pedicle of step (a) comprises the ligated stumps of an artery and a vein placed side by side. 
     
     
         11 . The method of  claim 1 , wherein said extracellular matrix without added cells is a reconstituted basement membrane preparation.