Reconstruction of urologic structures with polymeric matrices

Abstract

A method for repairing defects and reconstructing urothelial structures in vivo has been developed using a fibrous, open synthetic, biodegradable polymeric matrix which is configured to provide the desired corrective structure. The matrix is shaped to correct the defect, then implanted surgically to form a scaffolding for the patient's own cells to grow onto and into. The implantation of the matrix initiates an inflammatory reaction, resulting in urothelial cells, endothelial cells and mesenchymal cells, to migrate into the matrix. The polymer forming the matrix is selected to be biocompatible and degradable in a controlled manner over a period of one to six months, in the preferred embodiment. A preferred material is a poly(lactic acid-glycolic acid) in a fibrous form, such as a woven or non-woven mesh. Examples demonstrate the repair of defects in bladder in rabbits.

We claim:  
     
         1 . A method for correcting urothelial defects comprising implanting at the site to be corrected a matrix of a biodegradable, biocompatible synthetic polymeric fibers forming a matrix having an interstitial spacing of at least 100 microns, shaped to correct the defect.  
     
     
         2 . The method of  claim 1  wherein the defect is in the bladder.  
     
     
         3 . The method of  claim 1  wherein the defect is in the ureter or urethra.  
     
     
         4 . The method of  claim 1  wherein the defect is in the gastrointestinal tract.  
     
     
         5 . The method of  claim 1  further comprising providing with the matrix factors selected from the group consisting of nutrients, growth factors, inducers of differentiation or de-differentiation, products of secretion, immunomodulators, inhibitors of inflammation, biologically active compounds which enhance or allow ingrowth of the lymphatic network or nerve fibers, vascular growth factors, attachment peptides, and combinations thereof.  
     
     
         6 . The method of  claim 1  wherein the matrix is coated with a material selected from the group consisting of basement membrane components, agar, agarose, gelatin, gum arabic, collagens types I, II, III, IV and V, fibronectin, laminin, glycosaminoglycans, and mixtures thereof.  
     
     
         7 . A fibrous matrix formed of biodegradable synthetic polymer having an interstitial spacing between 100 and 300 microns which is shaped to repair a tissue defect.  
     
     
         8 . The matrix of  claim 7  wherein the defect is in a urological structure.  
     
     
         9 . The matrix of  claim 8  where the urological structure is selected from the group consisting of ureters, urethras, bladders and renal pelvis.  
     
     
         10 . The matrix of  claim 7  wherein synthetic polymer is selected from the group consisting of polyanhydrides, polyorthoesters, polyphosphazenes, and polyhydroxy acids.  
     
     
         11 . The matrix of  claim 10  wherein the polymer is a polyhydroxy acid is selected from the group consisting of polylactic acid, polyglycolic acid, and copolymers thereof.  
     
     
         12 . The matrix of  claim 7  wherein the matrix degrades over a period of between one and six months following implantation.