Non-Uniformly Stiff Polymeric Scaffolds and Methods for Producing Thereof

Abstract

The invention relates to methods for producing a polymeric scaffold for use in tissue engineering applications or soft tissue surgery, as well as to the produced scaffolds and an associated kit. The method features a first fast drying step of applying a mechanical compression on a polymeric gel layer and a second slow drying step of the gel up to reach a polymer mass fraction of at least 60% w/w in the final scaffold. The method allows the production of scaffolds with high regeneration and healing properties of a grafted tissue via host cell invasion and colonization, and a good suturability. These goals are achieved through the formation within the scaffold of a non-uniform architecture creating softer and stiffer areas, which is maintained even upon re-swelling of the scaffold upon hydration of the final dried product.

1 - 25 . (canceled) 
     
     
         26 . A polymeric scaffold having a non-uniform density for use in tissue engineering, diagnostics, or surgical procedures,
 wherein the polymeric scaffold has a polymer mass fraction of at least 60% w/w of a total scaffold weight, and   wherein the polymeric scaffold has a density at a surface that is denser as compared to a density at a core.   
     
     
         27 . The polymeric scaffold of  claim 26 , wherein a pore diameter at the core is between 0.2 μm and 200 μm. 
     
     
         28 . The polymeric scaffold of  claim 26 , wherein an average pore diameter at the surface is less than 0.2 μm. 
     
     
         29 . The polymeric scaffold of  claim 26 , wherein a Young's modulus at the core is between 0.1 kPa and about 20 kPa. 
     
     
         30 . The polymeric scaffold of  claim 26 , wherein a Young's modulus at the surface is between 5 kPa and 1500 kPa. 
     
     
         31 . The polymeric scaffold of  claim 26 , wherein the polymeric scaffold is suturable. 
     
     
         32 . The polymeric scaffold of  claim 26 , wherein the polymeric scaffold is at least 1 cm long. 
     
     
         33 . The polymeric scaffold of  claim 26 , wherein the polymeric scaffold includes a bioactive agent. 
     
     
         34 . The polymeric scaffold of  claim 26 , wherein the polymeric scaffold is cell-free. 
     
     
         35 . The polymeric scaffold of  claim 26 , wherein the polymeric scaffold includes cells. 
     
     
         36 . The polymeric scaffold of  claim 26 , wherein the polymeric scaffold is immersed in an aqueous solution. 
     
     
         37 . The polymeric scaffold of  claim 26 , wherein the polymeric scaffold does not include a crosslinking agent. 
     
     
         38 . The polymeric scaffold of  claim 26 , wherein the polymeric scaffold is configured to reswell in an aqueous solution by more than 4% w/w to reach a steady-state water content. 
     
     
         39 . The polymeric scaffold of  claim 38 , wherein the polymeric scaffold is configured to reswell in a range of 5% to 48% w/w to reach a steady-state water content. 
     
     
         40 . The polymeric scaffold of  claim 26 , comprising one or more polymeric material layers. 
     
     
         41 . The polymeric scaffold of  claim 26 , comprising one or more polymeric tubes. 
     
     
         42 . The polymeric scaffold of  claim 26 , wherein a polymeric material of the polymeric scaffold includes gelatin, elastin, collagen, agar/agarose, chitosan, fibrin, methyl cellulose, hyaluronic acid, proteoglycans, polyamino-acids or derivative thereof, polysaccharides or derivatives thereof, glycosaminoglycans or derivatives thereof, or any combination of the foregoing. 
     
     
         43 . An implant kit comprising:
 a container;   an aqueous solution located inside the container;   a polymeric scaffold immersed by the aqueous solution inside the container, wherein
 the polymeric scaffold has a polymer mass fraction of at least 60% w/w of a total scaffold weight, and 
 the polymeric scaffold has a density at a surface that is denser as compared to a density at a core. 
   
     
     
         44 . A graft made of a polymeric scaffold having a non-uniform density for surgical applications,
 wherein the polymeric scaffold has a polymer mass fraction of at least 60% w/w of a total scaffold weight, and   wherein the polymeric scaffold has a density at a surface that is denser as compared to a density at a core.   
     
     
         45 . The polymeric scaffold of  claim 44 , wherein the polymeric scaffold is configured to reswell in an aqueous solution by more than 4% w/w to reach a steady-state water content.