Cytotoxicity and Inflammatory Effects of Chitin Nanofibrils Isolated from Fungi

Fungal nanochitin can assist the transition from the linear fossil-based economy to a circular biobased economy given its environmental benefits over conventional crustacean-nanochitin. Its real-world implementation requires carefully assessing its toxicity so that unwanted human health and environmental issues are avoided. Accordingly, the cytotoxicity and inflammatory effects of chitin nanofibrils (ChNFs) from white mushroom is assessed. ChNFs are few nanometers in diameter, with a 75.8% N-acetylation degree, a crystallinity of 59.1%, and present a 44:56 chitin/glucan weight ratio. Studies are conducted for aqueous colloidal ChNF dispersions (0–5 mg·mL–1) and free-standing films having physically entangled ChNFs. Aqueous dispersions of chitin nanocrystals (ChNCs) isolated via hydrochloric acid hydrolysis of α-chitin powder are also evaluated for comparison. Cytotoxicity studies conducted in human fibroblasts (MRC-5 cells) and murine brain microglia (BV-2 cells) reveal a comparatively safer behavior over related biobased nanomaterials. However, a strong inflammatory response was observed when BV-2 cells were cultured in the presence of colloidal ChNFs. These novel cytotoxicity and inflammatory studies shed light on the potential of fungal ChNFs for biomedical applications.E.L. acknowledges the funds from the “2021 Euskampus Missions 1.0. Programme” granted by Euskampus Fundazioa and from the University of the Basque Country (Convocatoria de Ayudas a Grupos de Investigación GIU21/010). The authors also acknowledge the Open Access funding provided by the University of Basque Country (UPV/EHU). A.L. is thankful for funds from the Basque Government, Department of Education (IT-1766-22). C.B.A. acknowledges the predoctoral grant from the UPV/EHU. Maria Angela Motta and Dr. Upashi Goswami are acknowledged for their support in cell culture

Role of Inorganic Fillers on the Physical Aging and Toughness Loss of PLLA/BaSO4 Composites

The addition of inorganic fillers has been reported to increase the toughness of poly(l-lactide) (PLLA), but the effect of physical aging in such composites has been neglected. The present work discusses the effect of the still ongoing segmental relaxation in PLLA-based composites filled with BaSO4 inorganic particles in regard of the filler quantity. By means of differential scanning calorimetry, X-ray diffraction, and tensile testing of progressively aged PLLA filled with particles ranging from 0.5–10 wt %, we observed an increase in the mechanical energy required to activate the plastic flow of the primary structure in the PLLA matrix, which resulted in the embrittlement of the majority of composites upon enough aging. Results further clarify the role of debonding in the activation process of PLLA, and the behavior of the composite is described at the segmental level. Only an addition of 10% of particles has effectively preserved a ductile behavior of the samples beyond 150 aging days; therefore, we strongly remark the significance of studying the effect of physical aging in such composites.The authors thank funding from the Basque Government (GV/EJ)-Department of Education, University and Research (consolidated research groups IT-1766-22 GIC21/131) and grant PID2019-106236 GB-I00 funded by MCIN/AEI/10.13039/501100011033 and PID2022-139821OB-I00 funded by MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe”. The Basque Government (GV/EJ) predoctoral grant for X.L. and SGIker technical services (UPV/EHU) for XRD and SEM support is also acknowledged

3D zelula-euskarri biodegradagarriak: diseinuaren garrantzia etorkizuneko biomedikuntza-aplikazioetan

Azken urte hauetan, polimero biodegradagarriez eginiko 3D zelula-euskarrien diseinuak garrantzi handia hartu du ehun-ingeniaritza arloaren barnean. Lan honen helburu nagusia da gai honi buruzko ikuspegi orokor bat ematea. Alde batetik, euskarriaren diseinuan polimero biodegradagarriaren hautapenak, mikroegiturak eta euskarriaren morfologiak duten garrantzia azaltzen da. Bestetik, atal honetan euskarriak lortzeko metodo ezberdinak ere deskribatzen dira. Bukatzeko, zelulen eta polimero-euskarriaren arteko elkarrekintzen ikerketak etorkizuneko medikuntza-aplikazioetarako duen garrantzia goraipatzen da

Lactide and Ethylene Brassylate-Based Thermoplastic Elastomers and Their Nanocomposites with Carbon Nanotubes: Synthesis, Mechanical Properties and Interaction with Astrocytes

Polylactide (PLA) is among the most commonly used polymers for biomedical applications thanks to its biodegradability and cytocompatibility. However, its inherent stiffness and brittleness are clearly inappropriate for the regeneration of soft tissues (e.g., neural tissue), which demands biomaterials with soft and elastomeric behavior capable of resembling the mechanical properties of the native tissue. In this work, both L- and D,L-lactide were copolymerized with ethylene brassylate, a macrolactone that represents a promising alternative to previously studied comonomers (e.g., caprolactone) due to its natural origin. The resulting copolymers showed an elastomeric behavior characterized by relatively low Young’s modulus, high elongation at break and high strain recovery capacity. The thermoplastic nature of the resulting copolymers allows the incorporation of nanofillers (i.e., carbon nanotubes) that further enable the modulation of their mechanical properties. Additionally, nanostructured scaffolds were easily fabricated through a thermo-pressing process with the aid of a commercially available silicon stamp, providing geometrical cues for the adhesion and elongation of cells representative of the nervous system (i.e., astrocytes). Accordingly, the lactide and ethylene brassylate-based copolymers synthesized herein represent an interesting formulation for the development of polymeric scaffolds intended to be used in the regeneration of soft tissues, thanks to their adjustable mechanical properties, thermoplastic nature and observed cytocompatibility.Grant PID2019-106236GB-I00 funded by MCIN/AEI/10.13039/501100011033. The authors are also thankful for funds from the Basque Government, Department of Education (IT-1766-22). C.B.-Á.: acknowledges the predoctoral grant funded by the UPV/EHU. Polimerbio and Y.P. have a Bikaintek Ph.D. grant (20-AF-W2-2018-00001)

Crystallization-Induced Gelling as a Method to 4D Print Low-Water-Content Non-isocyanate Polyurethane Hydrogels

[EN]The use of three-dimensional (3D) printable hydrogels for biomedical applications has attracted considerable attention as a consequence of the ability to precisely define the morphology of the printed object, allowing patients' needs to be targeted. However, the majority of hydrogels do not possess suitable mechanical properties to fulfill an adequate rheological profile for printability, and hence, 3D printing of cross-linked networks is challenging and normally requires postprinting modifications to obtain the desired scaffolds. In this work, we took advantage of the crystallization process of poly(ethylene glycol) to print non-isocyanate poly(hydroxyurethane) hydrogels with tunable mechanical properties. As a consequence of the crystallization process, the hydrogel modulus can be tuned up to 3 orders of magnitude upon heating up to 40 degrees C, offering an interesting strategy to directly 3D-print hydrogels without the need of postprinting cross-linking. Moreover, the absence of any toxicity makes these materials ideal candidates for biomedical applications.The authors acknowledge financial support from the European Commission through SUSPOL-EJD 642671 project. M.C.A. thanks the University of Birmingham for funding

Benefits of Polydopamine as Particle/Matrix Interface in Polylactide/PD-BaSO4 Scaffolds

This work reports the versatility of polydopamine (PD) when applied as a particle coating in a composite of polylactide (PLA). Polydopamine was observed to increase the particle–matrix interface strength and facilitate the adsorption of drugs to the material surface. Here, barium sulfate radiopaque particles were functionalized with polydopamine and integrated into a polylactide matrix, leading to the formulation of a biodegradable and X-ray opaque material with enhanced mechanical properties. Polydopamine functionalized barium sulfate particles also facilitated the adsorption and release of the antibiotic levofloxacin. Analysis of the antibacterial capacity of these composites and the metabolic activity and proliferation of human dermal fibroblasts in vitro demonstrated that these materials are non-cytotoxic and can be 3D printed to formulate complex biocompatible materials for bone fixation devices.The authors express thanks for technical and human support provided by SGIker of UPV/EHU and European funding: European Regional Development Fund (ERDF) and European Social Fund (ESF)

Advances and Perspectives in Dental Pulp Stem Cell Based Neuroregeneration Therapies

Human dental pulp stem cells (hDPSCs) are some of the most promising stem cell types for regenerative therapies given their ability to grow in the absence of serum and their realistic possibility to be used in autologous grafts. In this review, we describe the particular advantages of hDPSCs for neuroregenerative cell therapies. We thoroughly discuss the knowledge about their embryonic origin and characteristics of their postnatal niche, as well as the current status of cell culture protocols to maximize their multilineage differentiation potential, highlighting some common issues when assessing neuronal differentiation fates of hDPSCs. We also review the recent progress on neuroprotective and immunomodulatory capacity of hDPSCs and their secreted extracellular vesicles, as well as their combination with scaffold materials to improve their functional integration on the injured central nervous system (CNS) and peripheral nervous system (PNS). Finally, we offer some perspectives on the current and possible future applications of hDPSCs in neuroregenerative cell therapies.This research was supported by MICINN retos I+D+i (PID2019-104766RB-C21 and RYC-2013-13450, to J.R.P.) and UPV/EHU (GIU16/66 and PPGA20/22, to F.U., G.I.; and COLAB19/03 and IKERTU-2020.0155, to F.U., J.R.S.). Y.P. was funded by a Bikaintek PhD grant from the Basque Government (20-AF-W2-2018-00001)

Poly(alpha-hydroxy Acids)-Based Cell Microcarriers

Biodegradable poly(alpha-hydroxyacids) have gained increasing interest in the biomedical field for their use as cell microcarriers thanks to their biodegradability, biocompatibility, tunable mechanical properties/degradation rates and processability. The synthesis of these poly(alpha-hydroxyacids) can be finely controlled to yield (co) polymers of desired mechanical properties and degradation rates. On the other hand, by simple emulsion-solvent evaporation techniques, microspheres of controlled size and size distribution can be fabricated. The resulting microspheres can be further surface-modified to enhance cell adhesion and proliferation. As a result of this process, biodegradable microcarriers with advanced functionalities and surface properties that can be directly employed as injectable cell microcarriers are obtained.The authors are thankful for funds from the Spanish Ministry of Innovation and Competitiveness MINECO (MAT2013-45559-P) and the Basque Government, Department of Education, Linguistic politics and Culture (GIC12/161-IT-632-13). Editoria

3D zelula-euskarri biodegradagarriak: diseinuaren garrantzia etorkizuneko biomedikuntza-aplikazioetan

Azken urte hauetan, polimero biodegradagarriez eginiko 3D zelula-euskarrien diseinuak garrantzi handia hartu du ehun-ingeniaritza arloaren barnean. Lan honen helburu nagusia da gai honi buruzko ikuspegi orokor bat ematea. Alde batetik, euskarriaren diseinuan polimero biodegradagarriaren hautapenak, mikroegiturak eta euskarriaren morfologiak duten garrantzia azaltzen da. Bestetik, atal honetan euskarriak lortzeko metodo ezberdinak ere deskribatzen dira. Bukatzeko, zelulen eta polimero-euskarriaren arteko elkarrekintzen ikerketak etorkizuneko medikuntza-aplikazioetarako duen garrantzia goraipatzen da