Silk-based scaffold platform for engineering tissue constructs

Abstract

The inventions provided herein relate to silk-based scaffolds and methods of producing the same, which can be used for a range of tissue engineering applications. The fabrication methods described herein provide a versatile platform to incorporate hollow conduits (e.g., for nutrient/oxygen delivery) through three-dimensional silk-based scaffolds that have tunable bulk properties (e.g., but not limited to, porosity, mechanical, degradation rate) and allow endothelialization and/or cell compartmentalization, for engineering a variety of complex tissue equivalents.

1 .- 88 . (canceled) 
     
     
         89 . A degradable silk scaffold system comprising:
 a porous solid-state silk matrix body; and   a plurality of conduits comprising an array of linear channels arranged within the silk matrix body such that any part of the silk matrix body is spatially located from at least one conduit with a spacing that is within a diffusion limit within the range of several micrometers to about 3,000 micrometers.   
     
     
         90 . The degradable silk scaffold system of  claim 89 , wherein the linear channels span the entire scaffold in the matrix body. 
     
     
         91 . The degradable silk scaffold system of  claim 89 , wherein the linear channels have a diameter in the range of about 5 μm to about 3,000 μm, so that they are appropriately dimensioned for nutrient delivery sufficient to support confluent endothelialization. 
     
     
         92 . The degradable silk scaffold system of  claim 89 , wherein the linear channels have a diameter in the range of about 10 μm to about 2,000 μm, or about 50 μm to about 1,000 μm. 
     
     
         93 . The degradable silk scaffold system of  claim 89 , wherein the spacing is within a range of about 100 μm to about 2,000 μm. 
     
     
         94 . The degradable silk scaffold system of  claim 93 , wherein the spacing is within a range of about 250 μm to about 1,000 μm, or about 500 μm to about 750 μm. 
     
     
         95 . The degradable silk scaffold system of  claim 89 , further comprising an active agent. 
     
     
         96 . The degradable silk scaffold system of  claim 95 , wherein the active agent is selected from the group consisting of: proteins, peptides, antigens, immunogens, vaccines, antibodies or portions thereof, antibody-like molecules, enzymes, nucleic acids, siRNA, shRNA, aptamers, viruses, bacteria, small molecules, cells, therapeutic agents, nanoparticles and any combination thereof. 
     
     
         97 . The degradable silk scaffold system of  claim 96 , wherein the active agent is selected from the group consisting of: collagen type I, laminin, VEGF, PDGF, and any combination thereof. 
     
     
         98 . The degradable silk scaffold system of  claim 89 , wherein the pores in the porous solid-state silk matrix body have sizes within the range of about 25 μm to about 500 μm. 
     
     
         99 . The degradable silk scaffold system of  claim 89 , wherein the porous solid-state silk matrix body has a porosity of at least about 30%. 
     
     
         100 . The degradable silk scaffold system of  claim 89 , wherein the porous solid-state silk matrix body has a porosity between about 70% and about 95%. 
     
     
         101 . The degradable silk scaffold system of  claim 89 , wherein the porous solid-state silk matrix body is characterized by compressive modulus of about 10 kPa to about 1,000 kPa. 
     
     
         102 . The degradable silk scaffold system of  claim 89 , wherein the porous solid-state silk matrix body is characterized by compressive strength within the range of about 1 kPa to about 100 kPa. 
     
     
         103 . The degradable silk scaffold system of  claim 89 , wherein the porous solid-state silk matrix body is characterized by a degradation rate to no more than 30% of its original volume in at least about 3 months after implantation. 
     
     
         104 . The degradable silk scaffold system of  claim 89 , wherein the porous solid-state silk matrix body is characterized by a degradation rate to no more than 80% of its original volume in at least about 1 year after implantation. 
     
     
         105 . The degradable silk scaffold system of  claim 89 , wherein the porous solid-state silk matrix body is characterized by significant β-sheet structure. 
     
     
         106 . The degradable silk scaffold system of  claim 89 , further comprising one or more photothermal elements. 
     
     
         107 . The degradable silk scaffold system of  claim 106 , wherein the one or more photothermal elements comprises plasmonic nanoparticles. 
     
     
         108 . The degradable silk scaffold system of  claim 89 , further comprising a cell.