Elastin provides structural integrity, biological cues and persistent elasticity to a range of important tissues including the vasculature and lungs. Its critical importance to normal physiology makes it a desirable component of biomaterials that seek to repair or replace these tissues. The recent availability of large quantities of the highly purified elastin monomer, tropoelastin, have allowed for a thorough characterization of the mechanical and biological mechanisms underpinning the benefits of mature elastin. While tropoelastin is a flexible molecule, a combination of optical and structural analyses has defined key regions of the molecule that directly contribute to the elastomeric properties and control the cell interactions of the protein. Insights into the structure and behavior of tropoelastin have translated into increasingly sophisticated elastin-like biomaterials, evolving from classically manufactured hydrogels and fibers to new forms, stabilized in the absence of incorporated cross-linkers. Tropoelastin is also compatible with synthetic and natural co-polymers, expanding the applications of its potential use beyond traditional elastin-rich tissues and facilitating finer control of biomaterial properties and the design of next-generation tailored bioactive materials.

There remains a significant clinical need for an alternative to autologous vein grafts in small-diameter applications such as coronary bypass, but no clinically viable, synthetic small-diameter vascular grafts have been developed. While ePTFE and Dacron have long been used for large diameter grafts, it is likely that in small-diameter, low flow conditions, alternative materials and techniques are required, which have shown promising experimental results through enhancing compliance, biocompatibility, and endothelialization of vascular grafts. It is likely that the integration of synthetic materials that possess optimized mechanical properties combined with techniques for improved biocompatibility, such as the use of pure extracellular matrix proteins, will be the impetus for the creation of a new generation of clinically viable, smalldiameter vascular substitutes.

The mechanical stability, elasticity, inherent bioactivity, and self-assembly properties of elastin make it a highly attractive candidate for the fabrication of versatile biomaterials. The ability to engineer specific peptide sequences derived from elastin allows for precise control of these physicochemical and organizational characteristics, and further broadens the diversity of elastin-based applications. Elastin and elastin-like peptides can also be modified or blended with other natural or synthetic moieties, including peptides, proteins, polysaccharides and polymers, to augment existing capabilities or confer additional architectural and biofunctional features to compositionally pure materials. Elastin and elastin-based composites have been subjected to diverse fabrication processes, including heating, electrospinning, wet spinning, solvent casting, freeze-drying, and cross-linking, for the manufacture of particles, fibers, gels, tubes, sheets and films. The resulting materials can be tailored to possess specific strength, elasticity, morphology, topography, porosity, wettability, surface charge and bioactivity. This extraordinary tunability of elastin-based constructs enables their use in a range of biomedical and tissue engineering applications such as targeted drug delivery, cell encapsulation, vascular repair, nerve regeneration, wound healing, and dermal, cartilage, bone and dental replacement.

Following penetrating injury of the skin, a highly orchestrated and overlapping sequence of events helps to facilitate wound resolution. Inflammation is a hallmark that is initiated early, but the reciprocal relationship between cells and matrix molecules that triggers and maintains inflammation is poorly appreciated. Elastin is enriched in the deep dermis of skin. We propose that deep tissue injury encompasses elastin damage, yielding solubilized elastin that triggers inflammation. As dermal fibroblasts dominate the deep dermis, this means that a direct interaction between elastin sequences and fibroblasts would reveal a proinflammatory signature. Tropoelastin was used as a surrogate for elastin sequences. Tropoelastin triggered fibroblast expression of the metalloelastase MMP-12, which is normally expressed by macrophages. MMP-12 expression increased 1056 ± 286-fold by 6 h and persisted for 24 h. Chemokine expression was more transient, as chemokine C-X-C motif ligand 8 (CXCL8), CXCL1, and CXCL5 transcripts increased 11.8 ± 2.6-, 10.2 ± 0.4-, and 8593 ± 996-fold, respectively, by 6-12 h and then decreased. Through the use of specific inhibitors and protein truncation, we found that transduction of the tropoelastin signal was mediated by the fibroblast elastin binding protein (EBP). In silico modeling using a predictive computational fibroblast model confirmed the up-regulation, and simulations revealed PKA as a key part of the signaling circuit. We tested this prediction with 1 μM PKA inhibitor H-89 and found that 2 h of exposure correspondingly reduced expression of MMP-12 (63.9±12.3%) and all chemokine markers, consistent with the levels seen with EBP inhibition, and validated PKA as a novel node and druggable target to ameliorate the proinflammatory state. A separate trigger that utilized C-terminal RKRK of tropoelastin reduced marker expression to 65.0-76.5% and suggests the parallel involvement of integrin αVβ3. We propose that the solubilization of elastin as a result of dermal damage leads to rapid chemokine up-regulation by fibroblasts that is quenched when exposed elastin is removed by MMP-12.