Javier Reguera

Biofunctional design of elastin-like polymers for advanced applications in nanobiotechnology

Elastin-like recombinant protein polymers are a new family of polymers which are captivating the attention of a broad audience ranging from nanotechnologists to biomaterials and more basic scientists. This is due to the extraordinary confluence of different properties shown by this kind of material that are not found together in other polymer systems. Elastin-like polymers are extraordinarily biocompatible, acutely smart and show uncommon self-assembling capabilities. Additionally, they are highly versatile, since these properties can be tuned and expanded in many different ways by substituting the amino acids of the dominating repeating peptide or by inserting, in the polymer architecture, (bio)functional domains extracted from other natural proteins or de novo designs. Recently, the potential shown by elastin-like polymers has, in addition, been boosted and amplified by the use of recombinant DNA technologies. By this means, complex molecular designs and extreme control over the amino-acid sequence can be attained. Nowadays, the degree of complexity and control shown by the elastin-like protein polymers is well beyond the reach of even the most advanced polymer chemistry technologies. This will open new possibilities in obtaining synthetic advanced bio- and nanomaterials. This review explores the present development of elastin-like protein polymers, with a particular emphasis for biomedical uses, along with some future directions that this field will likely explore in the near future.

Influence of the Amino-Acid Sequence on the Inverse Temperature Transition of Elastin-Like Polymers

This work explores the dependence of the inverse temperature transition of elastin-like polymers (ELPs) on the amino-acid sequence, i.e., the amino-acid arrangement along the macromolecule and the resulting linear distribution of the physical properties (mainly polarity) derived from it. The hypothesis of this work is that, in addition to mean polarity and molecular mass, the given amino-acid sequence, or its equivalent--the way in which polarity is arranged along the molecule--is also relevant for determining the transition temperature and the latent heat of that transition. To test this hypothesis, a set of linear and di- and triblock ELP copolymers were designed and produced as recombinant proteins. The absolute sequence control provided by recombinant technologies allows the effect of the amino-acid arrangement to be isolated while keeping the molecular mass or mean polarity under strict control. The selected block copolymers were made of two different ELPs: one exhibiting temperature and pH responsiveness, and one exhibiting temperature responsiveness only. By changing the arrangement and length of the blocks while keeping other parameters, such as the molecular mass or mean polarity, constant, we were able to show that the sequence plays a key role in the smart behavior of ELPs.

Genetic Engineering of Protein-Based Polymers: The Example of Elastinlike Polymers

In spite of the enormous possibilities of macromolecules as key elements in developing advancedmaterials with increased functionality and complexity, the success in this development is often limitedby the randomness associated with polymer synthesis and the exponential increase in technical difficultiescaused by the attempt to reach a sufficiently high degree of complexity in the molecular design.This paper describes a new approach in the design of complex and highly functional macromolecules,the genetic engineering of protein-based macromolecules. The exploitation of the efficient machineryof protein synthesis in living cells opens a path to obtain extremely well-defined and complexmacromolecules. Different molecular designs are presented, with increasing degree of complexity,showing how the controlled increase in their complexity yields (multi)functional materials with moreselect and sophisticated properties. The simplest designs show interesting properties already, butthe adequate introduction of given chemical functions along the polymer chain presents an opportunityto expand the range of properties to enhanced smart behavior and self-assembly. Finally, examplesare given where those molecular designs further incorporate selected bioactivities in order to developmaterials for the most cutting-edge applications in the field of biomedicine and nano(bio)technology.

Nanobiotechnological approach to engineered biomaterial design: the example of elastin-like polymers

Today, the development of advanced biomaterials is still lacking an appropriate tailored engineering approach. Most of the biomaterials currently used have their origin in materials developed for other technological applications. This lack of adequate biomaterial design is probably due to the peculiar environment where those materials must operate. On the one hand, this environment is dominated by the immune rejection system. On the other hand, the functionality of natural biomolecules is based on complex topological physical-chemical function distributions at the nanometer level. This review presents arguments concerning the role of biotechnology and nanotechnology in the future development of new advanced biomaterials and the potential of these biomaterials as a way to achieve highly biofunctional and truly biocompatible biomaterials for hot areas, such as regenerative medicine and controlled release. Recombinant protein-polymers will be presented as an example of candidates for this new paradigm in biomaterial design and production.

14 – Elastin-like systems for tissue engineering

Publisher Summary Modern biomaterials science is characterized by a growing emphasis on identification of specific design parameters that are critical to performance, and by a growing appreciation of the need to integrate biomaterials design with new insights emerging from studies of cell-matrix interactions, cellular signaling processes, and developmental and systems biology. Elastin-Like Polymers (ELPs) are non-natural polypeptides composed of repeating sequences. They have their origin in the repeating sequences found in the mammalian elastic protein elastin that confers elasticity to structures such as skin and blood vessels. The importance of these polymers reside in the fact that they show a versatile and ample range of interesting properties that are difficult to find together in other materials, and that goes beyond their simple mechanical performance. Certainly, ELPs show a set of properties that places them in an excellent position towards designing advanced polymers for many different applications, including the most cutting edge biomedical and nanobiotechnological uses. Regarding their properties, some of their main characteristics are derived from the natural protein on which they are based.