Integrating novel technologies to fabricate smart scaffolds

Tissue engineering aims at restoring or regenerating a damaged tissue by combining cells, derived from a patient biopsy, with a 3D porous matrix functioning as a scaffold. After isolation and eventual in vitro expansion, cells are seeded on the 3D scaffolds and implanted directly or at a later stage in the patient's body. 3D scaffolds need to satisfy a number of requirements: (i) biocompatibility, (ii) biodegradability and/or bioresorbability, (iii) suitable mechanical properties, (iv) adequate physicochemical properties to direct cell-material interactions matching the tissue to be replaced and (v) ease in regaining the original shape of the damaged tissue and the integration with the surrounding environment. Still, it appears to be a challenge to satisfy all the aforementioned requisites with the biomaterials and the scaffold fabrication technologies nowadays available. 3D scaffolds can be fabricated with various techniques, among which rapid prototyping and electrospinning seem to be the most promising. Rapid prototyping technologies allow manufacturing scaffolds with a controlled, completely accessible pore network--determinant for nutrient supply and diffusion--in a CAD/CAM fashion. Electrospinning (ESP) allows mimicking the extracellular matrix (ECM) environment of the cells and can provide fibrous scaffolds with instructive surface properties to direct cell faith into the proper lineage. Yet, these fabrication methods have some disadvantages if considered alone. This review aims at summarizing conventional and novel scaffold fabrication techniques and the biomaterials used for tissue engineering and drug-delivery applications. A new trend seems to emerge in the field of scaffold design where different scaffolds fabrication technologies and different biomaterials are combined to provide cells with mechanical, physicochemical and biological cues at the macro-, micro- and nano-scale. If merged together, these integrated technologies may lead to the generation of a new set of 3D scaffolds that satisfies all of the scaffolds' requirements for tissue-engineering applications and may contribute to their success in a long-term scenario.