Hybrid heterogeneous hydrogel, manufacturing method and use as an in-situ non-degradable filler implant

A method for fabricating a hybrid heterogeneous hydrogel comprising:

• forming microbeads by phase separation induced by copolymerization at a temperature between 45° C. and 55° C. from a reaction mixture comprising the following compounds:
• a dendrimer monomer having a plurality of branches and in which only a single branch is functionalized with an unsaturated ethylene radical, the other branches being devoid of ethylene radicals,
• an acrylamide compound chosen from an N-substituted methacrylamide and N-substituted acrylamide, and
• at least one bifunctional unsaturated ethylene cross-linking agent comprising two reactive vinyl bonds, and
• a free radical initiator,
• the microbeads defining closed non-communicating micropores having a size that is smaller than 20 nm,
• the microbeads having a diameter of more than 1.5 microns and less than 10 microns,
• the microbeads being assembled to one another to form aggregates between 5 and 50 microbeads, the aggregates being joined to one another by cross-linking points to define a hybrid heterogeneous hydrogel having a through porous array defining three-dimensional percolating paths and pores, a majority of said pores having a diameter between 10 and 30 microns and a fraction of pores having a diameter between 30 and 300 microns is more than 20% and
• wherein the hybrid heterogeneous hydrogel has a viscoelastic nature and has a modulus of elasticity between 1 and 200 kPa;
• wherein copolymerization is performed with a first temperature plateau followed by a second plateau or a temperature gradient to form the microbeads, the temperature of the first plateau being between 45° C. and 55° C. and the second plateau or the temperature gradient having temperatures at least 5° C. higher than the temperature of the first plateau and
• wherein the reaction mixture is injected into cylindrical-shaped, heat-conducting molds.