Apparatus for building complex 3d biomimetic scaffolds

Abstract

A system and apparatus for constructing complex three-dimensional scaffolds that takes advantage of the physical and chemical properties of gelatin-sugar hydrogels. Novel apparatus for building complex three-dimensional scaffolds for biomimetic applications such as in vitro organ growth, using a gelatin/sugar/water gel, ultraviolet radiation, and heat or enzyme are described. The apparatus produce gelatin-sugar hydrogels demonstrating greater thermal stability, mechanical strength, and resistance to enzymatic degradation. The invention also provides a means to assemble the gelatin sugar hydrogel films into complex three-dimensional structures (scaffolds). To account for the native biochemical factors present in natural scaffolds, methods of conjugating such factors to the gelatin-sugar hydrogel are described. These scaffolds can then be applied for tissue culturing and organ growth.

1 . An apparatus for building three dimensional biomimetic scaffolds comprising a plurality of processing units treating a mixture of gelatin and water with UV radiation to produce a biomimetic scaffold having a plurality of cross-linked gel layers. 
     
     
         2 . An apparatus for building three dimensional biomimetic scaffolds comprising a plurality of processing units treating a mixture of gelatin, sugar, and water with UV radiation to produce a biomimetic scaffold having a plurality of cross-linked gel layers. 
     
     
         3 . The apparatus of  claim 1  wherein each said processing unit performs one or more of the following steps: (a) selectively irradiating said mixture to form cross-linked gel layers having at least one non-irradiated region; (b) removing the non-irradiated material from the non-irradiated regions to leave cross-linked gel layers demonstrating a predetermined irregular shape; and (c) fusing a plurality of said cross-linked gel layers together to form a biomimetic scaffold. 
     
     
         4 . The apparatus of  claim 3  wherein one of the processing units performs the additional step of conjugating select biochemical factors to said layers prior to said layers being fused together to stimulate cellular processes. 
     
     
         5 . The apparatus of  claim 3 , wherein one of the processing units performs the additional step of applying thermal radiation to said layers to modulate the gel layer's stiffness. 
     
     
         6 . The apparatus of  claim 1  further comprising a computational unit that calculates parameters for the construction of said biomimetic scaffold and instructs said processing units in the construction of said biomimetic scaffolds. 
     
     
         7 . The apparatus of  claim 6  wherein said computational unit divides a three-dimensional representation of said scaffold into two-dimensional layers of user-supplied thickness which thickness defines the thickness of said cross-linked gel layers. 
     
     
         8 . The apparatus of  claim 7  wherein said computational unit also determines the locations within said two-dimensional layers of one or more of the following parameters: (a) photomasking material to selectively block UV irradiation cross-linking; (b) biochemical factors to modulate cellular processes; (c) cross-linkers to conjugate said biochemical factors to the mixture; and (d) radiation to increase the cross-linked gel layers' stiffness. 
     
     
         9 . An apparatus for building three dimensional biomimetic scaffolds, said apparatus comprising:
 (a) a computational unit which slices a three-dimensional model of said scaffold into two-dimensional slices and determines the spatial and temporal placement of building components of said scaffold within each said two-dimensional slice;   (b) a first processing unit that selectively irradiates a mixture comprising gelatin and water in accordance with the instructions of said computational unit to produce cross-linked gel layers with at least one non-irradiated region;   (c) a second processing unit that selectively dissolves the non-irradiated material from the non-irradiated regions of said cross-linked gel layer: and   (d) a third processing unit which arranges the selectively dissolved cross-linked gel layers and fuses said layers together.   
     
     
         10 . The apparatus of  claim 9 , wherein said mixture also includes sugar. 
     
     
         11 . The apparatus of  claim 9 , wherein said second processing unit dissolve the non-irradiated material with heated solvent while holding said gel layers in place. 
     
     
         12 . The apparatus of  claim 9 , wherein the means by which said third processing unit fuses said layers together is selected from a group comprising sugar glaze and heat, and an enzyme. 
     
     
         13 . The apparatus of  claim 9 , further comprising a processing unit used between the computational and third processing units that selectively applies biochemical factors to said gel layers in accordance with the instructions of said computational unit to modulate select cellular processes and cross-links these factors to said layers. 
     
     
         14 . The apparatus of  claim 9 , further comprising a processing unit used between the first and the third processing units that selectively applies thermal radiation in accordance with the instructions of said computational unit to locally modulate said cross-linked layers' stiffness. 
     
     
         15 . The apparatus of  claim 9 , further comprising an additional processing unit that arranges the fused gel layers. 
     
     
         16 . The apparatus of  claim 9 , further comprising an additional processing unit that perfuses said layers with select biochemical factors to modulate select cellular processes and to cross-link these factors to said gel layers. 
     
     
         17 . The apparatus of  claim 9  wherein one or more units of said apparatus are automated.