Polymer-based piezoelectric biomaterials have already proven their relevance for tissue engineering applications. Furthermore, the morphology of the scaffolds plays also an important role in cell proliferation and differentiation. The present work reports on poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV), a biocompatible, biodegradable, and piezoelectric biopolymer that has been processed in different morphologies, including films, fibers, microspheres, and 3D scaffolds. The corresponding magnetically active PHBV-based composites were also produced. The effect of the morphology on physico-chemical, thermal, magnetic, and mechanical properties of pristine and composite samples was evaluated, as well as their cytotoxicity. It was observed that the morphology does not strongly affect the properties of the pristine samples but the introduction of cobalt ferrites induces changes in the degree of crystallinity that could affect the applicability of prepared biomaterials. Young’s modulus is dependent of the morphology and also increases with the addition of cobalt ferrites. Both pristine and PHBV/cobalt ferrite composite samples are not cytotoxic, indicating their suitability for tissue engineering applications.

Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) is a piezoelectric biodegradable and biocompatible polymer suitable for tissue engineering applications. The incorporation of magnetostrictive cobalt ferrites (CFO) into PHBV matrix enables the production of magnetically responsive composites, which proved to be effective in the differentiation of a variety of cells and tissues. In this work, PHBV and PHBV with CFO nanoparticles were produced in the form of films, fibers and porous scaffolds and subjected to an experimental program allowing to evaluate the degradation process under biological conditions for a period up to 8 weeks. The morphology, physical, chemical and thermal properties were evaluated, together with the weight loss of the samples during the in vitro degradation assays. No major changes in the mentioned properties were found, thus proving its applicability for tissue engineering applications. Degradation was apparent from week 4 and onwards, leading to the conclusion that the degradation ratio of the material is suitable for a large range of tissue engineering applications. Further, it was found that the degradation of the samples maintain the biocompatibility of the materials for the pristine polymer, but can lead to cytotoxic effects when the magnetic CFO nanoparticles are exposed, being therefore needed, for magnetoactive applications, to substitute them by biocompatible ferrites, such as an iron oxide (Fe 3 O 4 ).Polymers 2020, 12, 953 2 of 15In particular, smart polymers are gaining increasing attention as substrates and scaffolds for tissue engineering applications mainly as electroactive substrates-mostly piezoelectric ones-such as poly(l-lactic acid) (PLLA) [5,6], poly(hydroxybutyrate) (PHB) [7], poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) [8,9] and poly(vinylidene fluoride) (PVDF) [10,11], among others. The ability of those materials to actively enhance and stimulate cellular differentiation processes has been already proven [12,13], based on their mechano-transduction characteristics, generating voltage upon mechanical stimulation and vice-versa [14]. Piezoelectricity is a property that appears in a diversity of human tissues, including DNA, bones or tendons, emphasizing the relevance of electrical and mechano-electrical stimulation in physiological processes [15,16]. In a different approach to apply mechanical and/or mechano-electrical signals, magnetoelectric materials have also proven their aptness for tissue engineering applications, with the particularity of allowing electrical stimulation of the materials and, therefore, on the cells cultured on them, through magnetic solicitation [17,18]. These materials can generate voltage upon magnetic stimulation through the coupling of the magnetostrictive effect (magnetic to mechanical) and piezoelectric effect (mechanical to electric) [19,20]. Magnetoelectric composites are thus achieved combining a piezoelectric polymer with magnetostrictive particles [21][22][23], and their potential for tissue engineering and enhancement of cellular di...

Polymer-based piezoelectric biomaterials have already proven their relevance for tissue engineering applications. Further, the morphology of the scaffolds plays also an important role in cell proliferation and differentiation. The present work reports on poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV), a biocompatible, biodegradable and piezoelectric biopolymer that has been processed in different morphologies, including films, fibres, microspheres and 3D scaffolds. Further, the corresponding magnetically active PHBV-based composites were also produced. The effect of the morphology on physico-chemical, thermal, magnetic and mechanical properties of pristine and composites samples was evaluated, as well as their cytotoxicity. It was observed that the morphology does not strongly affect the properties of the pristine samples but the introduction of cobalt ferrites induces changes in the degree of crystallinity that could affect the applicability of prepared biomaterials. Young modulus is dependent of the morphology and also increases with the addition of cobalt ferrites. Both, pristine and PHBV/cobalt ferrite composite samples are no cytotoxic, indicating their suitability for tissue engineering applications.