Electrospinning is an exceptional technology to fabricate sub-micrometric fiber scaffolds for regenerative medicine applications and to mimic the morphology and the chemistry of the natural extracellular matrix (ECM). Although most synthetic and natural polymers can be electrospun, gelatin frequently represents a material of choice due to the presence of cell-interactive motifs, its wide availability, low cost, easy processability, and biodegradability. However, cross-linking is required to stabilize the structure of the electrospun matrices and avoid gelatin dissolution at body temperature. Different physical and chemical cross-linking protocols have been described to improve electrospun gelatin stability and to preserve the morphological fibrous arrangement of the electrospun gelatin scaffolds. Here, we review the main current strategies. For each method, the cross-linking mechanism and its efficiency, the influence of electrospinning parameters, and the resulting fiber morphology are considered. The main drawbacks as well as the open challenges are also discussed.
Advances in regenerative medicine and in modern biomedical therapies are fast evolving and set goals causing an upheaval in the field of materials science. This review discusses recent developments involving the use of biopolymers as smart materials, in terms of material properties and stimulus-responsive behavior, in the presence of environmental physico-chemical changes. An overview on the transformations that can be triggered in natural-based polymeric systems (sol–gel transition, polymer relaxation, cross-linking, and swelling) is presented, with specific focus on the benefits these materials can provide in biomedical applications.
Opportunely arranged micro/nano-scaled fibers represent an extremely attractive architecture for tissue engineering, as they offer an intrinsically porous structure, a high available surface, and an ideal microtopography for guiding cell migration. When fibers are made with naturally occurring polymers, matrices that closely mimic the architecture of the native extra-cellular matrix and offer specific chemical cues can be obtained. Along this track, electrospinning of collagen or gelatin is a typical and effective combination to easily prepare fibrous scaffolds with excellent properties in terms of biocompatibility and biomimicry, but an appropriate cross-linking strategy is required. Many common protocols involve the use of swelling solvents and can result in significant impairment of fibrous morphology and porosity. As a consequence, the efforts for processing gelatin into a fiber network can be vain, as a film-like morphology will be eventually presented to cells. However, this appears to be a frequently overlooked aspect. Here, the effect on fiber morphology of common cross-linking protocols was analyzed, and different strategies to improve the final morphology were evaluated (including alternative solvents, cross-linker concentration, mechanical constraint, and evaporation conditions). Finally, an optimized, fiber-preserving protocol based on carbodiimide (EDC) chemistry was defined.
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