Tissue engineering is considered one of the most important therapeutic strategies of regenerative medicine. The main objective of these new technologies is the development of substitutes made with biomaterials that are able to heal, repair or regenerate injured or diseased tissues and organs. These constructs seek to unlock the limited ability of human tissues and organs to regenerate. In this review, we highlight the convenient intrinsic properties of gelatin for the design and development of advanced systems for tissue engineering. Gelatin is a natural origin protein derived from collagen hydrolysis. We outline herein a state of the art of gelatin-based composites in order to overcome limitations of this polymeric material and modulate the properties of the formulations. Control release of bioactive molecules, formulations with conductive properties or systems with improved mechanical properties can be obtained using gelatin composites. Many studies have found that the use of calcium phosphate ceramics and diverse synthetic polymers in combination with gelatin improve the mechanical properties of the structures. On the other hand, polyaniline and carbon-based nanosubstrates are interesting molecules to provide gelatin-based systems with conductive properties, especially for cardiac and nerve tissue engineering. Finally, this review provides an overview of the different types of gelatin-based structures including nanoparticles, microparticles, 3D scaffolds, electrospun nanofibers and in situ gelling formulations. Thanks to the significant progress that has already been made, along with others that will be achieved in a near future, the safe and effective clinical implementation of gelatin-based products is expected to accelerate and expand shortly.

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Introduction: Biomaterials have provided a wide range of exciting opportunities in tissue engineering and regenerative medicine. Gelatin, a collagen-derived natural biopolymer, has been extensively used in regenerative medicine applications over the years, due to its cell-responsive properties and the capacity to deliver a wide range of biomolecules. Areas covered: The most relevant properties of gelatin as biomaterial are presented together with its main therapeutic applications. The latter includes drug delivery systems, tissue engineering approaches, potential uses as ink for 3D/4D Bioprinting and its relevance in organ-on-a-chip platforms. Expert Opinion: Advances in polymer chemistry, mechanobiology, imaging technologies and 3D biofabrication techniques have expanded the application of gelatin in multiple biomedical research applications ranging from bone and cartilage tissue engineering, to wound healing and anti-cancer therapy. Here, we highlight the latest advances in gelatin-based approaches within the fields of biomaterial-based drug delivery and tissue engineering together with some of the most relevant challenges and limitations.

The innate graded structural and compositional profile of musculoskeletal tissues interfaces is disrupted and replaced by fibrotic tissue in the context of disease and degeneration. Tissue engineering strategies focused on the restoration of the transitional complexity found in those junctions present special relevance for regenerative medicine. Herein, we developed a gelatinbased multiphasic hydrogel system where sections with distinct composition and microstructure were integrated in a single unit. In each phase, hydroxyapatite (HA) particles or cellulose nanocrystals (CNC) were incorporated into an enzymatically crosslinked gelatin network to mimic bone or tendon tissue, respectively. Stiffer hydrogels were produced with the incorporation of mineralized particles and magnetic alignment of CNC resulted in anisotropic structure formation. The evaluation of the biological commitment with human adipose-derived stem cells (hASCs) towards tendon-to-bone interface, revealed an aligned cell growth and higher synthesis and deposition of tenascin (TNC) in the anisotropic phase, while the activity of the secreted alkaline phosphatase (ALP) and the expression of osteopontin (OPN) were induced in the mineralized phase. These results highlight the potential versatility offered by gelatintransglutaminase enzyme tandem for the development of strategies that mimic the graded, composite and complex intersections of the connective tissues.