Photocrosslinkable and self-healable hydrogels of chitosan and hyaluronic acid.

Biocompatible and biodegradable hydrogels with biomimetic properties, such as self-repairing, are increasingly interesting for biomedical applications, particularly when they can be printed or in situ formed to mimic extracellular matrix or as personalized implantable devices in tissue regeneration or drug delivery. Photocrosslinkable hydrogels based on methacrylated chitosan (CHIMe) and hyaluronic acid that exhibit according with their composition, tuneable physico-chemical properties are here presented. The study of the conversion, gelation time, mechanical and rheological properties of photopolymerized CHIMe showed an optimal phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) initiator feed (0.1% w). These photocrosslinkable hydrogels demonstrated being able to promote doubly crosslinked hydrogels with similar Young Moduli regardless the cycles of self-healing processes, and tailored swelling (25-70 swelling factor), mechanical (1*10-4-2*10-2MPa) and rheological properties, as a function of polysaccharides relative content. Clear evidences have been found that fast photopolymerization of CHIMe/HA solutions leads to biocompatible (>80% cell viability), biodegradable (20-24days in hydrolytic medium) and robust self-healable hydrogels suitable for advanced biomedical and tissue engineering applications.The authors acknowledge funding by Spanish State Research Agency (AEI) and the European Regional Development Fund (ERFD) through the project PID2019-106099RB-C43/AEI/10.13039/501100011033, as well as, from the Basque Government Industry Department under the ELKARTEK program (KK-2021/00040). The authors thank Dra. Cristina Eguizabal for giving them access to the laboratory “Cell Therapy, Stem Cells and Tissue” at the Basque Center of Transfusion and Human at the Galdako hospital. Technical and human support provided by SGIker (UPV/EHU, MICINN, GV/EJ, EGEF and ESF) is gratefully acknowledged

Dynamic and Self-Healable Chitosan/Hyaluronic Acid-Based In Situ-Forming Hydrogels

In situ-forming, biodegradable, and self-healing hydrogels, which maintain their integrity after damage, owing to dynamic interactions, are essential biomaterials for bioapplications, such as tissue engineering and drug delivery. This work aims to develop in situ, biodegradable and self-healable hydrogels based on dynamic covalent bonds between N-succinyl chitosan (S-CHI) and oxidized aldehyde hyaluronic acid (A-HA). A robust effect of the molar ratio of both S-CHI and A-HA was observed on the swelling, mechanical stability, rheological properties and biodegradation kinetics of these hydrogels, being the stoichiometric ratio that which leads to the lowest swelling factor (×12), highest compression modulus (1.1·10−3 MPa), and slowest degradation (9 days). Besides, a rapid (3 s) self-repairing ability was demonstrated in the macro scale as well as by rheology and mechanical tests. Finally, the potential of these biomaterials was evidenced by cytotoxicity essay (>85%).This research was funded by Spanish State Research Agency (AEI) and the European Regional Development Fund (ERFD) through the project PID2019-106099RB-C43/AEI/10.13039/501100011033, as well as from the Basque Government Industry Department under the ELKARTEK (KK-2021/00040) program

pH-Induced 3D Printable Chitosan Hydrogels for Soft Actuation

Three-dimensional (3D) printing represents a suitable technology for the development of biomimetic scaffolds for biomedical and tissue engineering applications. However, hydrogel-based inks’ printability remains a challenge due to their restricted print accuracy, mechanical properties, swelling or even cytotoxicity. Chitosan is a natural-derived polysaccharide that has arisen as a promising bioink due to its biodegradability, biocompatibility, sustainability and antibacterial properties, among others, as well as its ability to form hydrogels under the influence of a wide variety of mechanisms (thermal, ionic, pH, covalent, etc.). Its poor solubility at physiological pH, which has traditionally restricted its use, represents, on the contrary, the simplest way to induce chitosan gelation. Accordingly, herein a NaOH strong base was employed as gelling media for the direct 3D printing of chitosan structures. The obtained hydrogels were characterized in terms of morphology, chemical interactions, swelling and mechanical and rheological properties in order to evaluate the influence of the gelling solution’s ionic strength on the hydrogel characteristics. Further, the influence of printing parameters, such as extrusion speed (300, 600 and 800 mm/min) and pressure (20–35 kPa) and the cytocompatibility were also analyzed. In addition, printed gels show an electro-induced motion due to their polycationic nature, which highlights their potential as soft actuators and active scaffolds.This research was funded by Spanish State Research Agency (AEI) and the European Regional Development Fund (ERFD) through the project PID2019-106099RB-C43/AEI/10.13039/501100011033, as well as the Basque Government Industry Department under the ELKARTEK programme (KK-2021/00040 and KK-2021/00082)

Polysaccharide-Based In Situ Self-Healing Hydrogels for Tissue Engineering Applications

In situ hydrogels have attracted increasing interest in recent years due to the need to develop effective and practical implantable platforms. Traditional hydrogels require surgical interventions to be implanted and are far from providing personalized medicine applications. However, in situ hydrogels offer a wide variety of advantages, such as a non-invasive nature due to their localized action or the ability to perfectly adapt to the place to be replaced regardless the size, shape or irregularities. In recent years, research has particularly focused on in situ hydrogels based on natural polysaccharides due to their promising properties such as biocompatibility, biodegradability and their ability to self-repair. This last property inspired in nature gives them the possibility of maintaining their integrity even after damage, owing to specific physical interactions or dynamic covalent bonds that provide reversible linkages. In this review, the different self-healing mechanisms, as well as the latest research on in situ self-healing hydrogels, is presented, together with the potential applications of these materials in tissue regeneration.This research was funded by the Spanish State Research Agency (AEI) and the European Regional Development Fund (ERFD) through the project PID2019-106099RB-C43/AEI/10.13039/501100011033. Spanish Ministry of Economy and Competitiveness (MINECO) through the project MAT2016-76039-C4-3-R (AEI/FEDER, UE) and from the Basque Government Industry and Education Department under the ELKARTEK (KK-2020/00068, KK-2020/00099, KK2019/00039 and KK2019/00101), HAZITEK and PIBA (PIBA-2018-06) programs, respectively

Hidrogel injektagarriak eta haien aplikazioak ehun ingeniaritzan

Ehun ingeniaritzak kaltetuta dauden ehunen ordezko funtzionalak sintetizatzeko helburua dauka. Horretarako, zelulaz, molekula bioaktiboz eta euskarri porotsuz osatutako matrizeak beharrezkoak dira, hazkuntza eta zelulen diferentziazio prozesuak gerta daitezen. Matrize hauek solidifikatzeko gai den aitzindari baten injekzioz eratu daitezke kaltetuta dauden ehunetan, hau dela eta, hidrogel injektagarriak ikerkuntza arlo biomedikoan izugarri hedatu dira azken urteotan. Biomaterial hauen injektagarriak izateko gaitasuna sare polimerikoen in-situ gurutzamenduan oinarritzen da. Gurutzamendu hauek, alde batetik, interakzio fisiko itzulgarrien bidez eman daitezke, hidrogel termosentikorrak, pH sentikorrak edo ionikoak eratuz. Bestaldetik, erreakzio kimikoetan ere oinarritu daitezke zeinetan hidrogel fotopolimerizagarriak edota entzimek katalizatutako gurutzamendu bidezko hidrogelak lor daitezkeen. Lan honek hidrogel injektagarriak sintetizatzeko erabiltzen diren estrategien eta ehun ingeniaritzan ikertutako sistema desberdinen aplikazioen berrikuspen bat egitea du helburu.; Tissue engineering aims to create functional substitutes for damaged or diseased tissues through complex constructions of living cells, bioactive molecules and three-dimensional porous scaffolds that support the union, proliferation and differentiation of cells. These constructions can be formed by injection of a precursor which can solidify into the defective tissue, which has converted biomaterials such as injectable hydrogels into one of the most promising biomedical research areas of recent years. Injectable hydrogels are based on the in-situ crosslinking of polymer networks. The mechanisms involved in the formation of these gels can be very varied, and are based on both reversible physical interactions, forming thermosensitive hydrogels, sensitive or ionic pH, and chemical reactions, as is the case of photocrosslinked hydrogels or enzymatically crosslinked. This paper aims to review the main strategies currently used for the formation of injectable hydrogels and, in addition, to show brief results on the formation of injectable hydrogels based on chitosan by physical and chemical crosslinking

Synthesis and Characterization of Covalently Crosslinked pH-Responsive Hyaluronic Acid Nanogels: Effect of Synthesis Parameters

Stable hyaluronic acid nanogels were obtained following the water-in-oil microemulsion method by covalent crosslinking with three biocompatible crosslinking agents: Divinyl sulfone, 1,4-butanediol diglycidyl ether (BDDE), and poly(ethylene glycol) bis(amine). All nanoparticles showed a pH-sensitive swelling behavior, according to the pKa value of hyaluronic acid, as a consequence of the ionization of the carboxylic moieties, as it was corroborated by zeta potential measurements. QELS studies were carried out to study the influence of the chemical structure of the crosslinking agents on the particle size of the obtained nanogels. In addition, the effect of the molecular weight of the biopolymer and the degree of crosslinking on the nanogels dimensions was also evaluated for BDDE crosslinked nanoparticles, which showed the highest pH-responsive response.This research was funded by the Government of the Basque Country (Grupos de Investigación, IT718-13, Frontiers, Programas Hazitek 2017–2018)

PCDD/PCDF, PCB, and Hexachlorobenzene in soil, bottom ash and products from brickmaking sites in developing countries - Results from surveys in Kenya, Mexico, and South Africa. A contribution to the Standardized Toolkit for Identification and Quantification of Dioxin and Furan Releases in support to the Stockholm Convention on Persistent Organic Pollutants

The report combines the results from soil sampling campaigns executed in Mexico, South Africa and Kenya in order to assess the impact of artisanal brick making on local environments. Moreover the study serves indirectly (through the comparison of the impact on soils), whether the emission factors for brick kilns obtained in in a separate study in Mexico can be applied to other developing countries. These emission factors will be introduced into the calculation scheme for the National Emission Inventories of unintentional POP's releases ("dioxin toolkit) which is the reporting tool under the reporting obligations laid down in the Stockholm Convention of POPs. Results revealed, that the soils in Mexico are higher contaminated then in South Africa and Kenya, most probably due to the practice of co-incineration of waste (oils), whereas in Africa coal or virgin biomass are used as fuels. In so far the emission factors obtained in Mexico apparently represent the upper range of emission factors for brick making.JRC.D.2-Water and Marine Resource

Gestational age-based reference ranges for cervical length and preterm birth prediction in triplet pregnancies: an observational retrospective study

Cervical length; Preterm delivery; Triplet pregnancyLongitud cervical; Parto prematuro; Embarazo de trillizosLongitud cervical; Part prematur; Embaràs de trillissosObjectives To develop gestational age-based reference ranges for cervical length in triplet pregnancies. The secondary objective was to assess the performance of cervical length measured between 18 and 20 + 6 days for the prediction of preterm delivery before 28 and 32 weeks, respectively. Methods Observational retrospective study of triplet pregnancies in three Spanish tertiary-care hospitals between 2001 and 2019. Cervical length measurements were consecutively obtained between 15 and 34 weeks of gestation. Pregnancies undergoing multifetal reduction or fetal surgery were excluded. Results Two hundred and six triplet pregnancies were included in the final analysis. There was a quadratic decrease in cervical length with gestational age. The median and fifth centiles for cervical length at 20 weeks were 35 and 13 mm. In the prediction of preterm birth < 28 weeks, for a false positive rate of 5%, and 10%, the detection rates were 40.9%, and 40.9%, respectively, and the prediction of preterm birth < 32 weeks, 22.0% and 26.0%, respectively. Conclusions In triplet pregnancies, cervical length decreases with gestational age. The performance of cervical length at 18–20 + 6 in screening for preterm birth before 28 and 32 weeks is poor

Electro and magnetoactive printed bi-functional actuators based on alginate hybrid hydrogels

Soft materials are attracting much attention for the development of biostructures able to mimic the movement of natural systems by remote actuation. Multi-sensitive hydrogels are among the best materials for obtaining dynamic and biocompatible soft structures for soft actuators and related biomedical devices. Nevertheless, bioinks based on naturally occurring and stimuli responsive hydrogels able to be 3D printed continues being a challenge for advanced applications. In this work 3D printable electrically and magnetically responsive, non-cytotoxic, hybrid hydrogels based on alginate and zero monovalent iron nanoparticles (NPs) are presented. The effect of NPs addition on the physico-chemical properties of the hydrogels is addressed, together with its effect on the functional electroactive and magnetoactive response. NPs concentration up to 10 % do not affect the mechanical stability of the gels, while promoting an increase actuation response.The authors acknowledge funding by Spanish State Research Agency (AEI) and the European Regional Development Fund (ERFD) through the project PID2019-106099RB-C43/AEI/10.13039/501100011033, as well as, from University of the Basque Country UPV/EHU (GIU 207075) , and from the Basque Government Industry Department under the ELKARTEK (KK-2021/00040) program. The authors thank Dra. Cristina Eguizabal for giving them access to the Basque Center for Transfusion and Human Tissues at the Galdakao hospital, to perform the biological assays. Technical and human support provided by SGIker (UPV/EHU, MICINN, GV/EJ, EGEF and ESF) is gratefully acknowledge

APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family

BACKGROUND: Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. METHODS: We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. RESULTS: A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. CONCLUSION: The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean famil