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

Targeted bacterial conjugation mediated by synthetic cell-to-cell adhesions

Genetic interventions on microbiomes, for clinical or biotechnological purposes, remain challenging. Conjugation-based delivery of genetic cargo is still unspecific and limited by low conjugation rates. Here we report an approach to overcome these problems, based on a synthetic bacterial adhesion system. Mating assemblers consist on a synthetic adhesion formed by the expression on the surface of donor and target cells of specific nanobodies (Nb) and their cognate antigen (Ag). The Nb?Ag bridge increased 1?3 logs transfer of a variety of plasmids, especially in liquid media, confirming that cell-cell docking is a main determinant limiting mating efficiency. Synthetic cell-to-cell adhesion allows efficient conjugation to targeted recipients, enhancing delivery of desired genes to a predefined subset of prey species, or even specific pathogenic strains such as enterohemorrhagic Escherichia coli (EHEC), within a bacterial community. The synthetic conjugation enhancer presented here optimizes plasmid delivery by selecting the target hosts with high selectivity.FUNDING: Spanish Science and Innovation Ministry (MCIN) [PID2020-117923GB-I00 to F.d.l.C.]; MCIN/AEI and FEDER [BIO2017-89081-R]; MCIN/AEI and NextGeneration EU/PRTR [PLEC2021-007739 to L.A.F.]. Conflict of interest statement. None declared ACKNOWLEDGEMENTS: We thank R. Fernandez-López for providing us with the BWmKate2 strain and, along with M. P. Garcillan-Barcia, for helpful discussions. We also thank E. Zechner for providing the pAR106 plasmid, and I. Rosenshine for EHEC strains and V. Campa for technical assistance in setting up the microscopy assay

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)

Reengagement of HIV-infected children lost to follow-up after active mobile phone tracing in a rural area of Mozambique

Introduction: Retention in care and reengagement of lost to follow-up (LTFU) patients are priority challenges in pediatric HIV care. We aimed to assess whether a telephone-call active tracing program facilitated reengagement in care (RIC) in the Manhiça District Hospital, Mozambique. Methods: Telephone tracing of LTFU children was performed from July 2016 to March 2017. Both ART (antiretroviral treatment) and preART patients were included in this study. LTFU was defined as not attending the clinic for ≥120 days after last attended visit. Reengagement was determined 3 months after an attempt to contact. Results: A total of 144 children initially identified as LTFU entered the active tracing program and 37 were reached by means of telephone tracing. RIC was 57% (95% CI, 39–72%) among children who could be reached versus 18% (95% CI, 11–26%) of those who could not be reached (p = 0.001). Conclusion: Telephone tracing could be an effective tool for facilitating reengagement in pediatric HIV care. However, the difficulty of reaching patients is an obstacle that can undermine the program

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

Pediatric HIV care cascade in southern mozambique: Missed opportunities for early ART and re-engagement in care

© 2020 Wolters Kluwer Health, Inc. All rights reserved. Background: There are 170,000 children living with HIV in 2017 in Mozambique. Scaling-up HIV care requires effective retention along the cascade. We sought to evaluate the pediatric cascade in HIV care at the Manhiça District Hospital. Methods: A prospective cohort of children <15 years was followed from enrollment in HIV care (January 2013 to December 2015) until December 2016. Loss to follow-up (LTFU) was defined as not attending the HIV hospital visits for ≥90 days following last visit attended. Results: From the 438 children included {median age at enrollment in care of 3,6 [interquartile range (IQR): 1.1-8.6] years}, 335 (76%) were antiretroviral therapy (ART) eligible and among those, 263 (78%) started ART at enrollment in HIV care. A total of 362 children initiated ART during the study period and the incidence rate of LTFU at 12, 24, and 36 months post-ART initiation was 41 [95% confidence interval (CI): 34-50], 34 (95% CI: 29-41), and 31 (95% CI: 27-37) per 100 children-years, respectively. Median time to LTFU was 5.8 (IQR: 1.4-12.7) months. Children 5-9 years of age had a lower risk of LTFU compared with children <1 year [adjusted subhazard ratio 0.36 (95% CI: 0.20-0.61)]. Re-engagement in care (RIC) was observed in 25% of the LTFU children. Conclusions: The high LTFU found in this study highlights the special attention that should be given to younger children during the first 6 months post-ART initiation to prevent LTFU. Once LTFU, only a quarter of those children return to the health unit. Elucidating factors associated with RIC could help to fine tune interventions which promote RIC