Bone and ligament injuries present the greatest challenges in connective tissue regeneration. The design of materials for these applications lies at the forefront of material science and is the epitome of its current ambition. Indeed, its goal is to design and fabricate reproducible, bioactive and bioresorbable 3D scaffolds with tailored properties that are able to maintain their structure and integrity for predictable times, even under load-bearing conditions. Unfortunately, the mechanical properties of today's available porous scaffolds fall short of those exhibited by complex human tissues, such as bone and ligament. The manipulation of structural parameters in the design of scaffolds and their bioactivation, through the incorporation of soluble and insoluble signals capable of promoting cell activities, are discussed as possible strategies to improve the formation of new tissues both in vitro and in vivo. This review focuses on the different approaches adopted to develop bioactive composite systems for use as temporary scaffolds for bone and anterior ligament regeneration.

Only recently polymers with intrinsic conductive properties have been studied in relation to their incorporation into bioactive scaffolds for use in tissue engineering. The reason for this interest is that such scaffolds could electrically stimulate cells and thus regulate specific cellular activities, and by this means influence the process of regeneration of those tissues that respond to electrical impulses. In our work, macroporous hydrogels are developed with controlled pore morphology and conductive properties to enable sufficient cell signaling to supply events inherent to nerve regeneration. A hybrid material has been prepared by in situ precipitation of polyaniline (PANi) in polyethyleneglycol diacrylate (PEGDA) solution, followed by crosslinking via UV irradiation. A porous architecture, characterized by macropores from 136 μm to 158 μm in size, has been achieved by sodium chloride particle leaching. In this work, we demonstrate that PANi synthesis and hydrogel crosslinking combine to enable the design of materials with suitable conductive behaviour. The presence of PANi evidently increased the electrical conductivity of the hybrid material from (1.1 ± 0.5) × 10(-3) mS/cm with a PANi content of 3wt%. The hydrophilic nature of PANi also enhanced water retention/proton conductivity by more than one order of magnitude. In vitro studies confirmed that 3 wt% PANi also improve the biological response of PC12 and hMSC cells. Hybrid PANi/PEGDA macroporous hydrogels supplement new functionalities in terms of morphological and conductive properties, both of which are essential prerequisites to drive nerve cells in regenerative processes.

In scaffold aided regeneration of muscular tissue, composite materials are currently utilized as a temporary substrate to stimulate tissue formation by controlled electrochemical signals as well as continuous mechanical stimulation until the regeneration processes are completed. Among them, composites from the blending of conductive (CPs) and biocompatible polymers are powerfully emerging as a successful strategy for the regeneration of myocardium due to their unique conductive and biological recognition properties able to assure a more efficient electroactive stimulation of cells. Here, different composite substrates made of synthesized polyaniline (sPANi) and polycaprolactone (PCL) were investigated as platforms for cardiac tissue regeneration. Preliminary, a comparative analysis of substrates conductivity performed on casted films endowed with synthesized polyaniline (sPANi) short fibres or blended with emeraldine base polyaniline (EBPANi) allows to study the attitude of charge transport, depending on the conducting filler amount, shape and spatial distribution. In particular, conducibility tests indicated that sPANi short fibres provide a more efficient transfer of electric signal due to the spatial organization of electroactive needle-like phases up to form a percolative network. On the basis of this characterization, sPANi/PCL electrospun membranes have been also optimized to mimic either the morphological and functional features of the cardiac muscle ECM. The presence of sPANi does not relevantly affect the fibre architecture as confirmed by SEM/image analysis investigation which shows a broader distribution of fibres with only a slight reduction of the average fibre diameter from 7.1 to 6.4 μm. Meanwhile, biological assays--evaluation of cell survival rate by MTT assay and immunostaining of sarcomeric α-actinin of cardiomyocites-like cells--clearly indicate that conductive signals offered by PANi needles, promote the cardiogenic differentiation of hMSC into cardiomyocite-like cells. These preliminary results concur to promise the development of electroactive biodegradable substrates able to efficiently stimulate the basic cell mechanisms, paving the way towards a new generation of synthetic patches for the support of the regeneration of damaged myocardium.

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Polycaprolactone (PCL) is one of the earliest, commercially available, synthetic polymers characterized by a large set of biodegradation and mechanical properties that can be finely controlled by regulating the local environmental driving forces (ie, microorganisms, enzymes, hydrolysis). Owing to their faster resorbability and long‐term degradation in the presence of water (up to 3 to 4 years), PCL has been widely investigated as a bioinspired material able to target selective cell response via controlled intracellular resorption pathways. In comparison with other aliphatic polyesters, the superior rheological and viscoelastic properties render PCL easy to manufacture and manipulate into a wide range of three‐dimensional platforms (ie, porous scaffold, micro‐ and nanocarriers, and implantable devices). In this article, we discuss the main relationships between polymer synthesis, physical/chemical properties, and processing conditions to optimize the fabrication of biodegradable devices made of PCL, putting particular focus on drug delivery, tissue engineering. and green chemistry applications.