Bioactive implant for myocardial regeneration and ventricular chamber restoration

Abstract

Bioactive implant for myocardial regeneration and ventricular chamber support including an elastomeric microporous membrane. The elastomeric microporous membrane being at least one non-degradable polymer and at least one partially degradable polymer. The non-degradable polymer is selected from polyethylacrylate and polyethylacrylate copolymerized with a hydroxyethylacrylate comonomer. The partially degradable polymer is selected from caprolactone 2-(methacryloyloxy)ethyl ester and caprolactone 2-(methacryloyloxy)ethyl ester copolymerized with ethylacrylate. The elastomeric microporous membrane further includes a nanofiber hydrogel, and cells. The bioactive implant, having one or two helical loops, contributes to the restauration of the heart conical shape. Cardiac wrapping by ventricular support bioprostheses of the present invention, having reinforcement bands spatially distributed as helicoids, recovers the sequential contraction of the myocardium resulting in the successive shortening and lengthening of the ventricles, therefore improving the ejection (systolic function) and suction of blood (diastolic function).

1 . A bioactive implant constituting a scaffold for myocardial regeneration and ventricular chamber support, comprising:
 I. an elastomeric microporous membrane comprising at least one non-degradable polymer and at least one partially degradable polymer, said membrane having a porosity comprised between 70% and 90%, the pores being interconnected and having diameters comprised between 50 microns and 500 microns, wherein   (a) Said non-degradable polymer is selected from the group consisting of polyethylacrylate and polyethylacrylate copolymerized with a 10% wt or a 20% wt hydroxyethylacrylate comonomer; and   (b) Said partially degradable polymer is selected from the group consisting of caprolactone 2-(methacryloyloxy)ethyl ester and caprolactone 2-(methacryloyloxy)ethyl ester copolymerized with ethylacrylate in weight proportions of this last comonomer comprised between 30% and 80%,   wherein the percentage of non-degradable polymers versus degradable polymers is comprised between 10% wt and 90% wt,   II. a nanofiber hydrogel and   III cells.   
     
     
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         20 . A method for preparing the bioactive implant of  claim 1 , comprising the steps of:
 filling an elastomeric microporous membrane with a nanofiber hydrogel, so as to obtain a bioactive construct;   culturing said construct under biophysical, mechanical conditions, and   seeding or implanting cells onto or into said bioactive construct.   
     
     
         21 . The method of  claim 20 , wherein the seeding or the implantation of the cells uses at least one of the following methods: mechanical, chemical, and/or physical. 
     
     
         22 . The method of  claim 20 , wherein the cells are myogenic, cardiomyogenic, angiogenic or pluripotent stem cells. 
     
     
         23 . A method for preparing the bioactive implant of  claim 1 , comprising the steps of:
 (a) obtaining cells;   (b) culturing said cells in vitro;   (c) mixing said cells with a nanofiber hydrogel; and   (d) filling an elastomeric microporous membrane with the cell containing nanofiber hydrogel of step (c).   Or   (a) obtaining cells;   (b) culturing said cells in vitro;   (c) filling an elastomeric microporous membrane with the nanofiber hydrogel;   (d) seeding or implanting the said cells within the microporous membrane loaded with the nanofiber hydrogel.   
     
     
         24 . The method of  claim 23  further comprising the step of (e) culturing said bioactive construct under local in vitro electrostimulation. 
     
     
         25 . The method of  claim 23 , wherein lowered oxygen tension is used during step (b). 
     
     
         26 . The method of  claim 23 , wherein the bioactive implant is manufactured so as to be adapted to left ventricular and/or right ventricular support and regeneration, for partial or complete ventricular wrappings. 
     
     
         27 . An elastomeric microporous membrane for use in a bioactive implant for myocardial regeneration and ventricular chamber support, comprising at least one non-degradable polymer, at least one partially degradable polymer, and at least one biomaterial of nanoporous or nanoscale fiber dimensions, said membrane having a porosity comprised between 70% and 90%, the pores being interconnected and having diameters comprised between 50 microns and 500 microns, wherein
 (a) said non-degradable polymer is selected from the group consisting of polyethylacrylate and polyethylacrylate copolymerized with a 10% wt or a 20% wt hydroxyethylacrylate comonomer; and   (b) said partially degradable polymer is selected from the group consisting of caprolactone 2-(methacryloyloxy)ethyl ester andcaprolactone 2-(methacryloyloxy)ethyl ester copolymerized with ethylacrylate in weight proportions of this last comonomer comprised between 30% and 80%,   wherein the percentage of non-degradable polymers versus degradable polymers is comprised between 10% wt and 90% wt.   
     
     
         28 . The elastomeric microporous membrane of  claim 27 , being surface-treated to graft adhesion molecules, said adhesion molecules being selected from the group consisting of functional peptides such as RGD peptides, functional sugars, lipids, and proteins,
 wherein said proteins are laminin or laminin fragments.   
     
     
         29 . The elastomeric microporous membrane of  claim 28  wherein said functional peptides are RGD peptides. 
     
     
         30 . A method for surgical myocardial repair, comprising:
 (a) mixing cells with a nanofiber hydrogel,   (b) positioning the elastomeric microporous membrane of  claim 27  at the intended location of the body, and   (c) injecting or spreading the mix obtained in step (a) into or onto the positioned elastomeric microporous membrane.   
     
     
         31 . A method for surgical myocardial repair, comprising:
 (a) mixing cells with a nanofiber hydrogel,   (b) injecting or spreading the mix obtained in step (a) into or onto the elastomeric microporous membrane of  claim 27 , so as to obtain a bioactive implant, and   (c) positioning the bioactive implant of step (b) at the intended location of the body.   
     
     
         32 . The method of  claim 31  further comprising the step of injecting cells through the epicardium. 
     
     
         33 . The method of  claim 31  wherein the injected cells are autologous stem cells cultured in hypoxic conditions. 
     
     
         34 . A method for treating a mammalian subject having injured myocardial tissue comprising the steps of:
 implanting a bioactive implant scaffold at a site of the injured myocardial tissue, said scaffold including an elastomeric microporous membrane comprising at least one non-degradable polymer and at least one partially degradable polymer, a nanofiber hydrogel and cells, said membrane having a porosity comprised between 70% and 90%, the pores being interconnected and having diameters comprised between 50 microns and 500 microns, said non-degradable polymer is selected from the group consisting of polyethylacrylate and polyethylacrylate copolymerized with 10% wt or 20% wt hydroxyethylacrylate comonomer; said partially degradable polymer is selected from the group consisting of caprolactone 2-(methacryloyloxy)ethyl ester and caprolactone 2-(methacryloyloxy)ethyl ester copolymerized with ethylacrylate in weight proportions of this last comonomer comprised between 30% and 80%, the percentage of non-degradable polymers versus degradable polymers is comprised between 10% wt and 90% wt.   
     
     
         35 . The method of  claim 34  wherein the bioactive implant scaffold further comprises a helical loop band including one or more loops, said helical loop band being formed of a non-degradable or semi-degradable material. 
     
     
         36 . The method of  claim 35  wherein said helical loop band is integrated into the bioactive implant scaffold. 
     
     
         37 . The method of  claim 34  further comprising the step of:
 fixing a helical loop band to said implanted bioactive implant, said helical loop band including one or more loops, said helical loop band being formed of a non-degradable or semi-degradable material. 
 
     
     
         38 . The method of  claim 34  wherein the bioactive implant scaffold is a patch. 
     
     
         39 . The method of  claim 37  wherein the patch further includes a helical loop band integrated into the patch. 
     
     
         40 . The method of  claim 34  wherein the scaffold is positioned at the left and right ventricles, wherein the injured myocardial tissue is in the right and left ventricles. 
     
     
         41 . The method of  claim 34  wherein the scaffold further comprises a biodegradable portion, the biodegradable portion being formed of a biodegradable or semi-degradable material. 
     
     
         42 . The method of  claim 41  wherein the biodegradable or semi-degradable portion is positioned at the left ventricle, wherein the injured myocardial tissue is the right ventricle. 
     
     
         43 . The method of  claim 41  wherein the biodegradable or semi-degradable portion is positioned at the right ventricle, wherein the injured myocardial tissue is the left ventricle.