In the tissue engineering (TE) paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D) microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix, the composition of which varies as a function of the tissue, the degree of maturation, and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D) models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the “3Rs” guiding principles for a more ethical research. The design of 3D engineered tissue models is currently in its development stage, showing high potential in overcoming the limitations of already available models. However, many issues are still opened, concerning the identification of the optimal scaffold-forming materials, cell source and biofabrication technology, and the best cell culture conditions (biochemical and physical cues) to finely replicate the native tissue and the surrounding environment. In the near future, 3D tissue-engineered models are expected to become useful tools in the preliminary testing and screening of drugs and therapies and in the investigation of the molecular mechanisms underpinning disease onset and progression. In this review, the application of TE principles to the design of in vitro 3D models will be surveyed, with a focus on the strengths and weaknesses of this emerging approach. In addition, a brief overview on the development of in vitro models of healthy and pathological bone, heart, pancreas, and liver will be presented.

One of the main challenges in tissue engineering/regenerative medicine (TERM) is the repair of damaged heart tissue, avoiding or minimizing ventricular remodeling which leads to ventricular dilatation and hypertrophy, sphericity increase, and functionality loss. Several approaches have been described to restore or enhance the contractility of the failing heart. One of them is based on the fabrication of 3D substrates that can be implanted in the infarcted area to provide an efficient support to the regenerative process. This review focuses on the strategies adopted to design and realize polymeric scaffolds for heart TERM. The implementation of different polymers and the design of scaffold architecture are described.

Cardiac tissue engineering (TE) is an emerging field, whose main goal is the development of innovative strategies for the treatment of heart diseases, with the aim of overcoming the drawbacks of traditional therapies. One of these strategies involves the implantation of three-dimensional matrices (scaffolds) capable of supporting tissue formation. Scaffolds designed and fabricated for such application should meet several requirements, concerning both the scaffold-forming materials and the properties of the scaffold itself. A scaffold for cardiac TE should be biocompatible and biodegradable, mimic the properties of the native cardiac tissue, provide a mechanical support to the regenerating heart and possess an interconnected porous structure to favour cell migration, nutrient and oxygen diffusion, and waste removal. Moreover, the mimesis of myocardium characteristic anisotropy is attracting increasing interest to provide engineered constructs with the possibility to be structurally and mechanically integrated in native tissue. Several conventional and non-conventional fabrication techniques have been explored in the literature to produce polymeric scaffolds meeting all these requirements. This review describes these techniques, with a focus on their advantages and disadvantages, and their flexibility, with the final goal of providing the reader with the primal knowledge necessary to develop an effective strategy in cardiac TE.

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