Polymeric scaffold for myocardial regeneration and protection

The object of this disclosure is to provide a polymeric scaffold effective in the cardiac tissue regeneration and protection, in particular following myocardial infarction. This scaffold has improved mechanical and electrically conductive capabilities compared to known scaffolds; it is also characterized by an optimized angiogenic, cardioinductive and cell recruitment effect and by the ability to limit ventricular remodelling. It can be used to promote the cardiac tissue regeneration and revascularization both after acute and chronic infarction. Furthermore, this scaffold can be used for a controlled release of active ingredients (drugs) which not only have cardioprotective activity against reperfusion damage or which are able to promote cell recruitment, but which can also perform anti-fibrotic, antiinflammatory, anti-apoptotic/anti-necrotic, pro-angiogenic and pro-regenerative functions, which improve the contractile capacity of the myocardium and limit tissue remodeling, also in order to treat a series of other genetic or acquired pathologies that alter the cardiac tissue. The aforementioned purpose is achieved thanks to the subject-matter specifically referred to in the following claims, which are intended as an integral part of this disclosure. In particular, this disclosure refers to a polymeric scaffold for myocardial regeneration and protection, comprising a support structure which comprises at least a first and a second support layers and at least one inner layer interposed between said first and second support layers, - wherein said first and second support layers comprise at least one polymeric material selected from the group consisting of poly(lactic-co-glycolic acid) (PLGA), poly(dioxanone) (PDS), polycaprolactone (PCL), polyhydroxyalkanoates (PHA), among the polyhydroxyalkanoates (PHA) preferably poly(3-hydroxybutyric-co-3- hydroxyvaleric acid), optionally in combination with at least one biological polymer, - wherein at least one of said support layers further comprises at least one organic and biodegradable semiconducting material, preferably an organic and biodegradable semiconducting peptide, - wherein said at least one inner layer comprises a hydrogel, preferably comprising at least one organic and biodegradable semiconducting material, more preferably one organic and biodegradable semiconducting peptide. The support layers comprise a surface sculpture which includes a plurality of cavities arranged according to a regular frame, said cavities being defined by an array of longitudinal linear projections and an array of transversal linear projections intersecting each other respectively, said first and second support layers having cavities respectively facing opposite sides of the support structure. In one or more embodiments, the support structure can further comprise at least one intermediate layer, said intermediate layer comprising at least one polymeric material selected from the group consisting of polydioxanone (PDS), polyhydroxyalkanoates (PHA), and polycaprolactone (PCL), and optionally at least one organic and biodegradable semiconducting material, preferably an organic and biodegradable semiconducting peptide. The polymeric material of the at least one support layer and of the at least one intermediate layer is a biodegradable material. The intermediate layer can comprise at least one polymeric material that biodegrades more slowly than the polymeric material contained in at least one of the first and second support layers. In particular, for example, the at least one support layer can comprise PLGA optionally in combination with a biological polymer and the intermediate layer can comprise a polymer which has a lower degradation rate than PLGA, preferably at least one polymer selected from polydioxanone (PDS), polycaprolactone (PCL), polyhydroxyalkanoates (PHA), preferably poly(3-hydroxybutyric-co-3-hydroxyvaleric acid). In this way, the intermediate layer will degrade more slowly than at least one or both support layers, so that the scaffold will release active ingredients/MIPs gradually. In one or more embodiments, the support structure can comprise a first and a second inner layers, and the intermediate layer can be interposed between the first and second inner layers. The at least one biological polymer optionally included in at least one of the two support layers can be selected from the group consisting of gelatin, hyaluronic acid, collagen, gellan. The hydrogel of the at least one inner layer can comprise at least one biological polymer which can be selected from the group consisting of gelatin, hyaluronic acid, collagen, gellan. The organic and biodegradable semiconducting material can be selected from the group consisting of self-assembling N-fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) peptides, self-assembling N-fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) peptides functionalized with carbohydrate moieties, Fmoc-FF-glucosamine- 6 sulfate (Fmoc-GlcS) or Fmoc-FF-glucosamine-6 phosphate (Fmoc-GlcP), combinations thereof. Advantageously, the support structure further comprises molecularly imprinted particles included in at least one of the two support layers and/or in at least one intermediate layer. These particles can be accommodated in one or more of the cavities of the support layers and/or be located on the projections of the support structure. Such molecularly imprinted particles can be selective for at least one enzyme belonging to the metalloprotease (MMP) family, preferably selected from the group consisting of MMP-9, MMP-8, MMP-2, MMP-14 or TGFβ, thrombospondins (TSP-1, TSP-2, TSP-3). Furthermore, such molecularly imprinted particles can comprise at least one water soluble polymer preferably selected from the group consisting of polyvinylpyrrolidone (PVP), poly-n-isopropylacrylamide copolymers (PNIPAAm). These particles can have a diameter between 20 nm and 2 μm, preferably between 80 nm and 700 nm. In one or more embodiments, the scaffold can further comprise at least one active ingredient which can be included in at least one of the support layers and/or in the at least one inner layer, and/or in the at least one intermediate layer. The active ingredient may be encapsulated in particles which can comprise at least one biodegradable polymer preferably selected from the group consisting of polyhydroxybutyrate (PHB), poly-3-hydroxybutyrate (P3HB) and related copolymers. The diameter of the particles can be between 20 nm and 2 μm, preferably between 90 nm and 700 nm. Such particles can be accommodated in one or more of the cavities of the support layers or on at least one projection of the support layers. Furthermore, in one or more embodiments, the at least one intermediate layer may comprise at least one preferably anti-fibrotic active ingredient and at least one molecularly imprinted particle. Preferably, the scaffold of this disclosure may be an acellular scaffold. The absence of an in vitro culture phase presents a series of advantages that make this specific solution extremely attractive and more rapidly applicable for transfer to a biomedical industry, in particular since: 1) the use of the scaffold is independent from the individuality of the patient; 2) once produced, the scaffold can be immediately implanted (the time for in vitro culture of the cells is not necessary); 3) transport and storage are simpler than those of cellularized scaffolds; 4) in the absence of cellular, therefore vital, components, the reproducibility of the product in an industrial context is significantly favored. The results of a physico-chemical, morphological, mechanical and functional characterization have demonstrated for the scaffold of this disclosure a mechanical anisotropy typical of a cardiac tissue, good mechanical properties, an optimization in terms of conductivity, a controlled release of active ingredients included in the layers of the assembled system and/or within microfibers and micro-nanoparticles and the possibility of incorporating molecularly imprinted micro-nanoparticles (MIPs) selective for molecules and enzymes involved in the alteration of the matrix leading to ventricular remodeling. Advantageously, the scaffold of this disclosure has a different composition of its layers and consequently a different degradation rate thereof, as described below.