Bioactive scaffold for therapeutic and adhesion prevention applications

Abstract

A device for inhibiting adhesion of apposing human body tissue layers includes a scaffold having a designated mean pore size, relative density, and degradation half-life. The scaffold may be operably positioned between apposing tissue layers, such as proximate adhesiogenic layers at a wound site, so as to permit remesothelialization of the tissue without formation of fibrous adhesions. The scaffold device of the invention inhibits adhesion formation by promoting contractile cell migration away from the wound site for a predetermined period of time. The invention further relates to device and methods for promoting internal tissue regeneration, and for provision and/or dispensation of therapeutic and/or diagnostic agents in vivo.

1 . A method for inhibiting adhesion of apposing internal human body tissue layers, said method comprising: 
 (a) providing a scaffold prepared by co-precipitation of collagen and a glycosaminoglycan, followed by lyophilization; and    (b) positioning said scaffold between said apposing tissue layers.    
     
     
         2 . A method as in  claim 1 , further including incorporating a dispensable therapeutic agent with said scaffold.  
     
     
         3 . A method as in  claim 2  wherein said dispensable therapeutic agent is selected from the group consisting of antibiotics, cytokines, anti-inflammatory drugs, cytostatic agents, fibrinolytic agents, corticosteroids, and combinations thereof.  
     
     
         4 . A method as in  claim 1  wherein a bioadhesive is disposed on at least one surface of said scaffold.  
     
     
         5 . A method as in  claim 1  wherein a first portion of said scaffold is more porous than a second portion of said scaffold.  
     
     
         6 . A method as in  claim 1  wherein said tissue layers are selected from the group consisting of organs of the peritoneal cavity, pericaradium, pleural cavity, pelvic cavity, tendons, and nerves.  
     
     
         7 . A method as in  claim 1  wherein said scaffold is non-immunogenic and non-antigenic.  
     
     
         8 . A method as in  claim 1 , including grafting said scaffold to at least one of said tissue layers.  
     
     
         9 . A method as in  claim 1 , further including incorporating a diagnostic agent with said scaffold.  
     
     
         10 . A method for inhibiting adhesion of apposing internal human body tissue layers, said method comprising: 
 (a) providing a scaffold having: 
 (i) a mean pore size of between about 5 and about 200 μm;  
 (ii) a relative density of between about 0.5 and about 10%; and  
 (iii) a predetermined degradation rate when disposed in vivo; and  
   (b) positioning said scaffold between said apposing tissue layers.    
     
     
         11 . A method as in  claim 10  wherein at least a portion of said scaffold has a predetermined degradation half life of between about 1 and 6 weeks.  
     
     
         12 . A method for inhibiting adhesion of apposing internal human body tissue layers, said method comprising: 
 (a) providing a scaffold having: 
 (i) a mean pore size of between about 5 and about 200 μm;  
 (ii) a relatively density of between about 0.5 and about 10%; and  
 (iii) a predetermined degradation rate; and  
   (b) positioning said scaffold between said apposing tissue layers.    
     
     
         13 . A method as in  claim 12  wherein at least a portion of said scaffold has a degradation half life of between 1 and 6 weeks when disposed in vivo.  
     
     
         14 . A method for permitting remesothelialization at an internal wound site without formation of fibrous adhesions, said method comprising: 
 (a) providing a scaffold having: 
 (i) a mean pore size of between about 5 and about 200 μm;  
 (ii) a relative density of between about 0.5 and about 10%; and  
 (iii) a degradation half life of between 1 and 6 weeks when disposed in vivo; and  
   (b) positioning said scaffold between proximate adhesiogenic tissue layers at the wound site.    
     
     
         15 . A method for reducing incidence of contraction and scar tissue formation at an internal wound site, said method comprising: 
 (a) providing a scaffold having: 
 (i) a mean pore size of between about 5 and about 200 μm;  
 (ii) a relative density of between about 0.5 and about 10%; and  
 (iii) a degradation half life of between 1 and 6 weeks when disposed in vivo; and  
   (b) positioning said scaffold between proximate adhesiogenic tissue layers at the wound site.    
     
     
         16 . A method for preventing adhesion of apposing tissue layers at an internal wound site, said method comprising promoting contractile cell migration away from the wound site.  
     
     
         17 . A method as in  claim 15  wherein said contractile cells include fibroblasts.  
     
     
         18 . A method for inhibiting adhesion of apposing tissue layers at an internal wound site, wherein said method comprises diverting fibroblast invasion from the wound site to a porous scaffold device disposed at an adhesiogenic surface which is located at or adjacent to the wound site.  
     
     
         19 . A method for inhibiting adhesion of apposing human body tissue layers at a wound site, said method comprising inhibiting contractile cell incursion into the wound site for a predetermined period of time.  
     
     
         20 . A method as in  claim 19  wherein said predetermined period of time is about equal to the duration of regeneration of respective said tissue layers at the wound site.  
     
     
         21 . A method as in  claim 19  wherein said predetermined period of time is less than a period of time required for a chronic foreign body response.  
     
     
         22 . A device for promoting regeneration of internal tissues of the human body, said device comprising a scaffold prepared from collagen.  
     
     
         23 . A device as in  claim 22  wherein said scaffold is prepared by co-precipitation of collagen and a glycosaminoglycan, followed by lyophilization.  
     
     
         24 . A device for promoting regeneration of internal tissues of the human body, said device comprising a scaffold having: 
 (i) a mean pore size of between about 5 and about 200 μm;    (ii) a relative density of between about 0.5 and about 10%. and    (iii) a predetermined degradation rate when disposed in vivo.    
     
     
         25 . A device as in  claim 24  wherein at least a portion of said biodegradable scaffold has a degradation half life of between 1 and 6 weeks when said scaffold is disposed in vivo.  
     
     
         26 . A method for promoting regeneration of internal tissues of the human body at a tissue damage site, said method comprising: 
 (a) providing a scaffold having: 
 (i) a mean pore size of between about 5 and about 200 μm;  
 (ii) a relative density of between about 0.5 and about 10%; and  
 (iii) a degradation half life of between 1 and 6 weeks when disposed in vivo; and  
   (b) positioning said scaffold at the tissue damage site.    
     
     
         27 . A method for dispensing a therapeutic agent, said method comprising: 
 (a) providing a scaffold prepared from collagen;    (b) incorporating said therapeutic agent with said scaffold; and    (c) positioning said scaffold in vivo.    
     
     
         28 . A method for dispensing a therapeutic agent, said method comprising: 
 (a) providing a scaffold having: 
 (i) a mean pore size of between about 5 and about 200 μm;  
 (ii) a relative density of between about 0.5 and about 10%; and  
 (iii) a predetermined degradation rate when disposed in vivo;  
   (b) incorporating said therapeutic agent with said scaffold; and    (c) positioning said scaffold in vivo.    
     
     
         29 . A method for providing a diagnostic agent in vivo, said method comprising: 
 (a) providing a scaffold having: 
 (i) a mean pore size of between about 5 and about 200 μm;  
 (ii) a relative density of between about 0.5 and about 10%; and  
 (iii) a predetermined degradation rate when disposed in vivo.  
   (b) incorporating said diagnostic agent with said scaffold; and    (c) positioning said scaffold in vivo.    
     
     
         30 . A method as in  claim 29  wherein at least a portion of said biodegradable scaffold has a degradation half life of between about  1  and  6  weeks when disposed in vivo.  
     
     
         31 . A method for inhibiting adhesion of apposing internal human body tissue layers, said method comprising: 
 (a) providing a scaffold prepared from collagen; and    (b) positioning said scaffold between said apposing tissue layers.