Oral tissue regeneration and repair

Abstract

A method for treating an oral condition of a subject by grafting cultured tissue constructs to the oral tissue. The cultured tissue constructs comprise cultured cells and endogenously produced extracellular matrix components without the requirement of exogenous matrix components or network support or scaffold members. Some tissue constructs of the invention are comprised of multiple cell layers or more than one cell type. The tissue constructs of the invention have morphological features and functions similar to tissues their cells are derived and their strength makes them easily handleable. Preferred cultured tissue constructs of the invention comprise cells derived from human tissue.

We claim: 
     
         1 . A method for treating an oral condition of a subject, said method comprising:
 grafting a cultured tissue construct to an oral tissue of the subject wherein said cultured tissue construct comprises a layer of extracellular matrix and said extracellular matrix comprises cultured fibroblast cells in the absence of exogenous matrix components or scaffold supports.   
     
     
         2 . The method of  claim 1  wherein the oral condition is selected from the group consisting of recessed oral gingiva, loss of interdental papilla, alveolar ridge deficiency, failed oral implant, dental furcation defect and maxillofacial tumor resection. 
     
     
         3 . The method of  claim 1 , wherein the extracellular matrix comprises:
 (i) fibrillar collagen showing a packing organization of fibrils and fibril bundles exhibiting a quarter-staggered 67 nm banding pattern;   (ii) decorin; and,   (iii) glycosaminoglycans.   
     
     
         4 . The method of  claim 1 , wherein the cultured fibroblast cells are derived from tissue selected from the group consisting of neonate male foreskin, dermis, tendon, lung, urethra, umbilical cord, corneal stroma, oral mucosa, and intestine. 
     
     
         5 . The method of  claim 1 , wherein the cultured fibroblast cells are dermal fibroblasts. 
     
     
         6 . The method of  claim 1 , wherein the cultured fibroblast cells are derived from human tissue. 
     
     
         7 . A method for treating an oral condition of a subject, said method comprising:
 grafting a cultured tissue construct to an oral tissue of the subject, wherein said cultured tissue construct comprises a first layer of extracellular matrix and a second layer of cells disposed on said first layer,
 said extracellular matrix comprising cultured fibroblast cells in the in the absence of exogenous matrix components and scaffold supports, and 
 said second layer of cells comprising epithelial cells. 
   
     
     
         8 . The method of  claim 7  wherein the oral condition is selected from the group consisting of recessed oral gingiva, loss of interdental papilla, alveolar ridge deficiency, failed oral implant, dental furcation defect and maxillofacial tumor resection. 
     
     
         9 . The method of  claim 7  wherein the extracellular matrix comprises:
 (i) fibrillar collagen showing a packing organization of fibrils and fibril bundles exhibiting a quarter-staggered 67 nm banding pattern; 
 (ii) decorin; and, 
 (iii) glycosaminoglycans. 
 
     
     
         10 . The method of  claim 7 , wherein the epithelial cells are selected from the group consisting of keratinocytes, corneal epithelial cells, epithelial cells from oral mucosa, esophageal epithelial cells, and uroepithelial cells. 
     
     
         11 . The method of  claim 7 , wherein said cultured fibroblast cells contained within said first layer are derived from tissue selected from the group consisting of neonate male foreskin, dermis, tendon, lung, cartilage, urethra, corneal stroma, oral mucosa, and intestine. 
     
     
         12 . The method of  claim 7 , wherein the cultured fibroblast cells contained within said first layer are dermal fibroblasts. 
     
     
         13 . The method of  claim 12 , wherein the extracellular matrix further comprises fibronectin and tenascin. 
     
     
         14 . The method of  claim 7 , wherein the cultured fibroblast cells and the epithelial cells are derived from human tissue. 
     
     
         15 . The method of  claim 7 , wherein the cultured tissue construct comprises a second layer of keratinocyte cells disposed on the first layer to form an epidermal cell layer. 
     
     
         16 . The method of  claim 15 , wherein the epidermal cell layer is a multilayered, stratified, differentiated and exhibits a basal layer, suprabasal layer, a granular layer and a stratum corneum; and wherein the bilayered cultured skin construct has a basement membrane present at the junction of the first and second layers. 
     
     
         17 . A method for treating an oral condition of a subject, said method comprising:
 grafting a cultured tissue construct to an oral tissue of the subject, wherein said cultured tissue construct comprises a gel mixture of a collagen solution and a contractile agent.   
     
     
         18 . The method of  claim 17  wherein the oral condition is selected from the group consisting of recessed oral gingiva, loss of interdental papilla, alveolar ridge deficiency, failed oral implant, dental furcation defect and maxillofacial tumor resection. 
     
     
         19 . The method of  claim 17 , wherein said contractile agent comprises fibroblast cells. 
     
     
         20 . The method of  claim 19 , wherein the fibroblast cells are derived from human tissue. 
     
     
         21 . The method of  claim 19 , wherein the fibroblast cells are derived from tissue selected from the group consisting of neonate male foreskin, dermis, tendon, lung, urethra, umbilical cord, corneal stroma, oral mucosa and intestine. 
     
     
         22 . A method for treating an oral condition of a subject, said method comprising:
 grafting a cultured tissue construct to an oral tissue of the subject, wherein said cultured tissue construct comprises
 a first layer comprising a collagen gel in the absence of cells, and 
 a second layer disposed on said first layer, said second layer comprising a second collagen gel containing collagen and a contractile agent. 
   
     
     
         23 . The method of  claim 22  wherein the oral condition is selected from the group consisting of recessed oral gingiva, loss of interdental papilla, alveolar ridge deficiency, failed oral implant, dental furcation defect and maxillofacial tumor resection. 
     
     
         24 . The method of  claim 22 , wherein the contractile agent comprises fibroblast cells. 
     
     
         25 . The method of  claim 24 , wherein the fibroblast cells are derived from tissue selected from the group consisting of neonate male foreskin, dermis, tendon, lung, urethra, umbilical cord, corneal stroma, oral mucosa and intestine. 
     
     
         26 . The method of  claim 22 , wherein the second layer comprises human epidermal cells. 
     
     
         27 . The method of  claim 24 , wherein the fibroblast cells are derived from human tissue. 
     
     
         28 . The method of any of  claims 1 ,  7 ,  17 , and  22  wherein the fibroblast cells are genetically modified to produce extracellular matrix components. 
     
     
         29 . The method of  claim 28 , wherein the fibroblast cells are genetically modified to produce a growth factor, hormone, peptide, or protein.