Angélica Díaz

Synthesis, Properties and Applications of Biodegradable Polymers Derived from Diols and Dicarboxylic Acids: From Polyesters to Poly(ester amide)s

Poly(alkylene dicarboxylate)s constitute a family of biodegradable polymers with increasing interest for both commodity and speciality applications. Most of these polymers can be prepared from biobased diols and dicarboxylic acids such as 1,4-butanediol, succinic acid and carbohydrates. This review provides a current status report concerning synthesis, biodegradation and applications of a series of polymers that cover a wide range of properties, namely, materials from elastomeric to rigid characteristics that are suitable for applications such as hydrogels, soft tissue engineering, drug delivery systems and liquid crystals. Finally, the incorporation of aromatic units and α-amino acids is considered since stiffness of molecular chains and intermolecular interactions can be drastically changed. In fact, poly(ester amide)s derived from naturally occurring amino acids offer great possibilities as biodegradable materials for biomedical applications which are also extensively discussed.

Study on the crystallization of poly(alkylene dicarboxylate)s derived from 1,9-nonanediol and mixtures with different ratios of azelaic acid and pimelic acid units

Polyalkylene dicarboxylates derived from 1,9-nonanediol and mixtures with different ratios of pimelic acid and azelaic acid were synthesized by thermal polycondensation. All samples had a high degree of crystallinity although it was found to decrease with the comonomer content. Crystallization kinetics of the two homopolymers and the copolymer with the eutectic composition was studied by calorimetric and optical microscopy techniques. Similar Avrami parameters were determined for the three samples and a spherulitic growth with heterogeneous nucleation was deduced. Spherulites showed negative birefringence and a fibrillar or ringed texture depending on the sample. Furthermore, clear differences were found in the primary nucleation density, the spherulitic growth rate and even in the secondary nucleation constant deduced from the Lauritzen-Hoffman treatment. The three studied samples had a similar arrangement of molecular chains, and consequently their WAXD patterns showed the same strong reflections related to the molecular packing. SAXS data revealed that a lamellar insertion mechanism was characteristic for non-isothermal crystallization from the melt. In addition, significant differences were found between the crystal lamellar thicknesses of the homopolymer and copolymer samples. Diffraction and spectroscopic data suggested that the lamellar crystals of the eutectic copolymer were mainly constituted by azelate units whereas the pimelate units were preferentially located in the amorphous regions including the interlamellar amorphous layer associated with the chain folds.

Polylactide nanofibers loaded with vitamin B6 and polyphenols as bioactive platform for tissue engineering

AbstractElectrospun polylactide nanofibers loaded with different antioxidants (i.e. vitamin B6 in pyridoxine and pyridoxal form, p-coumaric acid and caffeic acid) are prepared from N,N-dimethylformamide/dimethylsulfoxide solutions. Morphology, structure and crystallinity of the nanofibers are evaluated by transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray diffraction and differential scanning calorimetry (DSC) techniques. Fibers are highly amorphous but able to crystallize easily due to the high molecular orientation induced by the electrospinning process. The drug molecules are incorporated into the polymeric matrix or formed isolated crystals. A fast release of loaded drug occurs within the first 8 h in hydrophobic medium; but, a slow and sustained release during several days occurs in a hydrophilic medium. Cell attachment on the loaded scaffolds was unaffected by the incorporation of the antioxidants. In contrast, cell proliferation increases with high antioxidative activity against free radicals responsible for cell damage. These new electrospun scaffolds provide high protection of cells against oxidative stress and resulting in innovative 3D fibrous platforms for tissue growth and proliferation.

Hydrogels for Biomedical Applications: Cellulose, Chitosan, and Protein/Peptide Derivatives

Hydrogels based on polysaccharide and protein natural polymers are of great interest in biomedical applications and more specifically for tissue regeneration and drug delivery. Cellulose, chitosan (a chitin derivative), and collagen are probably the most important components since they are the most abundant natural polymers on earth (cellulose and chitin) and in the human body (collagen). Peptides also merit attention because their self-assembling properties mimic the proteins that are present in the extracellular matrix. The present review is mainly focused on explaining the recent advances on hydrogels derived from the indicated polymers or their combinations. Attention has also been paid to the development of hydrogels for innovative biomedical uses. Therefore, smart materials displaying stimuli responsiveness and having shape memory properties are considered. The use of micro- and nanogels for drug delivery applications is also discussed, as well as the high potential of protein-based hydrogels in the production of bioactive matrices with recognition ability (molecular imprinting). Finally, mention is also given to the development of 3D bioprinting technologies.

Self‐Assembly of Tetraphenylalanine Peptides

Three different tetraphenylalanine (FFFF) based peptides that differ at the N- and C-termini have been synthesized by using standard procedures to study their ability to form different nanoassemblies under a variety of conditions. The FFFF peptide assembles into nanotubes that show more structural imperfections at the surface than those formed by the diphenylalanine (FF) peptide under the same conditions. Periodic DFT calculations (M06L functional) were used to propose a model that consists of three FFFF molecules defining a ring through head-to-tail NH3(+)⋅⋅⋅(-)OOC interactions, which in turn stack to produce deformed channels with internal diameters between 12 and 16 Å. Depending on the experimental conditions used for the peptide incubation, N-fluorenylmethoxycarbonyl (Fmoc) protected FFFF self-assembles into a variety of polymorphs: ultra-thin nanoplates, fibrils, and star-like submicrometric aggregates. DFT calculations indicate that Fmoc-FFFF prefers a parallel rather than an antiparallel β-sheet assembly. Finally, coexisting multiple assemblies (up to three) were observed for Fmoc-FFFF-OBzl (OBzl = benzyl ester), which incorporates aromatic protecting groups at the two peptide terminals. This unusual and noticeable feature is attributed to the fact that the assemblies obtained by combining the Fmoc and OBzl groups contained in the peptide are isoenergetic.

New poly(ester urea) derived from L-leucine: electrospun scaffolds loaded with antibacterial drugs and enzymes.

Electrospun scaffolds from an amino acid containing poly(ester urea) (PEU) were developed as promising materials in the biomedical field and specifically in tissue engineering applications. The selected poly(ester urea) was obtained with a high yield and molecular weight by reaction of phosgene with a bis(α-aminoacyl)-α,ω-diol-diester monomer. The polymer having L-leucine, 1,6-hexanediol and carbonic acid units had a semicrystalline character and relatively high glass transition and melting temperatures. Furthermore it was highly soluble in most organic solvents, an interesting feature that facilitated the electrospinning process and the effective incorporation of drugs with bactericidal activity (e.g. biguanide derivatives such as clorhexidine and polyhexamethylenebiguanide) and enzymes (e.g. α-chymotrypsin) that accelerated the degradation process. Continuous micro/nanofibers were obtained under a wide range of processing conditions, being diameters of electrospun fibers dependent on the drug and solvent used. Poly(ester urea) samples were degradable in media containing lipases and proteinases but the degradation rate was highly dependent on the surface area, being specifically greater for scaffolds with respect to films. The high hydrophobicity of new scaffolds had repercussions on enzymatic degradability since different weight loss rates were found depending on how samples were exposed to the medium (e.g. forced or non-forced immersion). New scaffolds were biocompatible, as demonstrated by adhesion and proliferation assays performed with fibroblast and epithelial cells.

Ontogenetic changes in the digestive system of Pleoticus muelleri (Decapoda, Penaeoidea)

Summary The present study describes the ontogenetic changes observed in the histology and in total protease, trypsin, and chymotrypsin activities of the digestive system in the shrimp Pleoticus muelleri (Decapoda, Penaeoidea) under culture conditions. The stomach development follows the typical pattern described for other decapods. The gland filter develops during larval stages, while the astric mill takes the adult shape during postlarval metamorphosis and juvenile stages. During early larval stages, the histological structure of the anterior and lateral caeca is similar to that of the adult midgut gland, with R, F and B cells. During late larval stages, the anterior caeca decline and take a structure similar to that of the mesodeum and the lateral caeca expand to form the adult midgut gland by proliferation of tubules in antero-posterior direction and from the cortical region to the medullar region. Total protease activity was higher in postlarvae 45, no significant differences was found in the others larval and p larval stages. Trypsin activity was lowest in early postlarval stages (PL1 and PL6), coinciding with the metamorphosis; enzyme activity increased in postlarvae 10 followed by a significant decrease in postlarvae 26. Chymotrypsin showed a significantly lower activity in protozoea 3, a peak of activity between postlarvae 1 and 10, and a decrease in the following postlarval stages. The inhibition of trypsin and chymotrypsin activities were confirmed the presence of these serine proteases during developmental stages. The ontogenetic pattern of P. muelleri digestive system morphology is similar to those described of others penaeoids. The recorded variation in enzyme activity during developmental stages may be associated with the unique postlarval life history. This research has implications for artificial diet development in crustacean culture and understanding of dietary shifts during larval development.

Preparation of micro-molded exfoliated clay nanocomposites by means of ultrasonic technology

Ultrasound micro-molding technology has been tested as a new method to get polymer/clay nanocomposites. Biodegradable polylactide (PLA) and poly (nona-methylene azelate) (PE99) have been used as polymer matrices, whereas different silicate clays have been assayed. The new technology is able to get specimens without evidences of degradation during processing. Only the use of organo-modified clays could give rise to a slight molecular weight decrease when the poly (alkylene dicarboxylate) sample was considered. Ultrasonic micro-molding has revealed effective to get directly nanocomposites with the final form required for a selected application, a homogeneous clay distribution up to a load of 6 wt-% and more interestingly exfoliated structures without being necessary the use of a compatibilizer agent between the organic polymer and the inorganic silicate clay. Transmission electron micrographs and X-ray diffraction profiles revealed exfoliated structure when N757, C20A, C25A, and N848 clays were employed.Crystallization behavior of exfoliated PLA nanocomposites was highly peculiar since clay particles had an antinucleating effect that decreased the overall crystallization rate respect to the neat polymer. In addition, the incorporation of layers into growing spherulites increased the crystal growth rate. A typical crystallization effect was on the contrary observed for nanocomposites derived from the poly (alkylene dicarboxylate) sample.

Dual-functionalization device for therapy through dopamine release and monitoring

A dual-functional device is fabricated to release progressively dopamine (DA) from a biohydrogel under real-time monitoring via electrochemical detection. For this purpose, a poly-γ-glutamic acid biohydrogel is assembled with a poly(3,4-ethylenedioxythiophene) (PEDOT) layer, previously deposited onto a screen printed electrode. The biohydrogel is formulated to achieve dimensional stability and maximum DA-loading capacity. Conditions for DA-loading are influenced by the oxidation of the neurotransmitter in acid environments and the poor resistance of PEDOT to the lyophilization. The performance of the device is proved in a medium with the physiological pH of blood and the cerebrospinal fluid. The progressive release of DA is successfully monitored by the device, the limit of detection and sensitivity of the integrated sensor being 450 × 10-9 m and 8 × 10-5 mA µm-1 , respectively. The effect of electrochemical stimulation in the kinetics of the DA release is also investigated applying potential ramps in cyclic phase to alter the biohydrogel morphology.

Bio-based aliphatic polyesters from dicarboxylic acids and related sugar and amino acid derivatives

Great efforts are nowadays focused to get valuable chemicals and polymers from renewable natural resources and to decrease the high dependence on petrochemicals. Bioproduction of various platform chemicals is a reality, and products such as ethanol, butanol, diols, succinic acid, glutaric acid, or sebacic acid can be easily attained. These are also the monomers involved in the preparation of poly(alkylene dicarboxylate)s, which constitute one of the main families of biodegradable polymers. Characteristics of polyesters and polycarbonates can also be modified by incorporation of other natural units such as amino acids and sugars-based monomers. In the first case, it is clear that additional amide groups are incorporated in the main chain, allowing the establishment of strong intermolecular hydrogen bonding interactions that could modify both physical properties and biodegradation rates, as well as give an improved compatibility with tissues. In the same way, final characteristics can also be modified by the presence of rigid cyclic units in the main chain as it is the case of the sugar derivatives, which in addition can provide an ideal functionality through hydroxyl and amine groups for being used as drug delivery systems.