US 11,696,972 B2
Process for the production of a hybrid structure consisting of coupled silk fibroin microfibers and nanofibers, hybrid structure thus obtained and its use as implantable medical device
Antonio Alessandrino, Como (IT)
Assigned to SILK BIOMATERIALS S.R.L., Lomazzo (IT)
Filed by SILK BIOMATERIALS S.R.L., Lomazzo (IT)
Filed on Jul. 28, 2020, as Appl. No. 16/941,273.
Application 16/941,273 is a division of application No. 15/522,397, granted, now 10,758,641, previously published as PCT/IB2015/058262, filed on Oct. 27, 2015.
Claims priority of application No. MI2014A001841 (IT), filed on Oct. 27, 2014.
Prior Publication US 2020/0353125 A1, Nov. 12, 2020
Int. Cl. A61L 27/36 (2006.01); A61F 2/02 (2006.01); A61L 27/54 (2006.01); A61L 27/22 (2006.01)
CPC A61L 27/3604 (2013.01) [A61F 2/02 (2013.01); A61L 27/227 (2013.01); A61L 27/54 (2013.01); A61L 2300/406 (2013.01); A61L 2300/414 (2013.01); A61L 2400/12 (2013.01)] 12 Claims
OG exemplary drawing
 
1. An implantable medical device comprising:
a hybrid structure comprising coupled microfibers and nanofibers of silk fibroin, said hybrid structure obtained according to the process comprising:
a) preparing of one or more parts made of microfibrous fibroin;
b) preparing of one or more parts made of nanofibrous fibroin;
c) treating of said one or more parts of nanofibrous fibroin and of said one or more parts of microfibrous fibroin, separately or after coupling, with a solvent for fibroin and/or with a solution comprising fibroin dissolved in the solvent;
c′) if in step c) the nanofibrous and microfibrous parts have been treated separately with a solvent for fibroin and/or with a solution comprising fibroin dissolved in a solvent, coupling of said parts;
d) consolidating the hybrid microfibrous/nanofibrous structure obtained in step c) or in step c′) by thermal treatment at a temperature between 10° C. and 150° C., for a time between 1 minute and 24 hours;
e) removing the solvent by washing with water or a water-alcohol mixture at a temperature between 10° C. and 100° C., or by evaporation at a temperature between 10° C. and 100° C.,
wherein the solvent for fibroin or the solvent of the solution comprising fibroin used in step c) is selected from:
(i) formic acid, 1,1,1,3,3,3-hexafluoro-2-propanol, trifluoroacetic acid, hexafluoroacetone, N-methylmorpholine N-oxide, ionic liquids, and mixtures thereof, wherein said solvents are pure or in mixture with water;
(ii) calcium chloride-ethanol-water mixtures, calcium nitrate-methanol-water mixtures, aqueous solutions of lithium salts and;
(iii) mixtures among the solvents of (i) and (ii).