RESUMO
Printable hydrogels have attracted significant attention as versatile, tunable, and spatiotemporally controlled biomaterials for tissue engineering (TE) applications. Several chitosan-based systems are reported presenting low or no solubility in aqueous solutions at physiological pH. Herein, a novel neutrally charged, biomimetic, injectable, and cytocompatible dual-crosslinked (DC) hydrogel system based on a double functionalized chitosan (CHT) with methacryloyl and tricine moieties (CHTMA-Tricine), completely processable at physiological pH, with promising three-dimensional (3D) printing potential is presented. Tricine, an amino acid typically used in biomedicine, is capable of establishing supramolecular interactions (H-bonds) and is never explored as a hydrogel component for TE. CHTMA-Tricine hydrogels demonstrate significantly greater toughness (ranging from 656.5 ± 82.2 to 1067.5 ± 121.5 kJ m-3 ) compared to CHTMA hydrogels (ranging from 382.4 ± 44.1 to 680.8 ± 104.5 kJ m-3 ), highlighting the contribution of the supramolecular interactions for the overall reinforced 3D structure provided by tricine moieties. Cytocompatibility studies reveal that MC3T3-E1 pre-osteoblasts cells remain viable for 6 days when encapsulated in CHTMA-Tricine constructs, with semi-quantitative analysis showing ≈80% cell viability. This system's interesting viscoelastic properties allow the fabrication of multiple structures, which couple with a straightforward approach, will open doors for the design of advanced chitosan-based biomaterials through 3D bioprinting for TE.
Assuntos
Bioimpressão , Quitosana , Glicina/análogos & derivados , Engenharia Tecidual/métodos , Hidrogéis/farmacologia , Hidrogéis/química , Quitosana/farmacologia , Quitosana/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Impressão Tridimensional , Bioimpressão/métodos , Alicerces Teciduais/químicaRESUMO
Polysaccharides are among the most abundant bioresources on earth and consequently need to play a pivotal role when addressing existential scientific challenges like climate change and the shift from fossil-based to sustainable biobased materials. The Research Roadmap 2040 of the European Polysaccharide Network of Excellence (EPNOE) provides an expert's view on how future research and development strategies need to evolve to fully exploit the vast potential of polysaccharides as renewable bioresources. It is addressed to academic researchers, companies, as well as policymakers and covers five strategic areas that are of great importance in the context of polysaccharide related research: (I) Materials & Engineering, (II) Food & Nutrition, (III) Biomedical Applications, (IV) Chemistry, Biology & Physics, and (V) Skills & Education. Each section summarizes the state of research, identifies challenges that are currently faced, project achievements and developments that are expected in the upcoming 20 years, and finally provides outlines on how future research activities need to evolve.
Assuntos
PolissacarídeosRESUMO
Dynamic G-quadruplex supramolecular hydrogels have aroused great interest in a broad range of bioapplications. However, neither the development of native extracellular matrix (ECM)-derived natural biopolymer-functionalized G-quadruplex hydrogels nor their use to create perfusable self-supporting hydrogels has been explored to date, despite their intrinsic potential as carrier vehicles of therapeutic agents, or even living cells in advanced regenerative therapies, or as platforms to enable the diffusion of nutrients and oxygen to sustain long-term cell survival. Herein, we developed a dynamic co-assembling multicomponent system that integrates guanosine (G), 3-aminophenylboronic acid functionalized hyaluronic acid (HA-PBA), and potassium chloride to bioengineer strong, homogeneous, and transparent HA-functionalized G-quadruplex hydrogels with injectable, thermo-reversible, conductive, and self-healing properties. The supramolecular polymeric hydrogels were developed by hydrogen bonding and π-π stacking interactions between G coupled via dynamic covalent boronate ester bonds to HA-PBA and stabilized by K+ ions, as demonstrated by a combination of experiments and molecular dynamics simulations. The intrinsic instability of the self-assembled G-quadruplex structures was used to bioengineer self-supporting perfusable multicomponent hydrogels with interconnected size and shape-tunable hollow microchannels when embedded in 3D methacrylated gelatin supporting matrices. The microchannel-embedded 3D constructs have shown enhanced cell viability when compared to the bulk hydrogels, holding great promise for being use as artificial vessels for enabling the diffusion of nutrients and oxygen essential for cell survival. The proposed approach opens new avenues on the use of ECM-derived natural biopolymer-functionalized dynamic G-quadruplex hydrogels to design next-generation smart systems for being used in tissue regeneration, drug screening, or organ-on-a-chip.
Assuntos
Ácido Hialurônico , Hidrogéis , Ácido Hialurônico/química , Hidrogéis/química , Matriz Extracelular/química , Gelatina/químicaRESUMO
The design of dynamically crosslinked hydrogel bioinks for three-dimensional (3D) bioprinting is emerging as a valuable strategy to advance the fabrication of mechanically tuneable cell-laden constructs for 3Din vitrodisease modelling and tissue engineering applications. Herein, a dynamic bioink comprising boronic acid-functionalised laminarin and alginate is explored for bioprinting 3D constructs under physiologically relevant conditions. The formulated bioink takes advantage of a double crosslinked network that combines covalent but reversible boronate ester bonds and ionic gelation via divalent cations. Moreover, it exhibits suitable rheological properties and improved mechanical features owing to its modular crosslinking chemistry, yielding stable constructs with user-programmable architecture. We explored such dynamic bioink as a supporting matrix for different cell classes, namely osteoblast precursors, fibroblasts and breast cancer cells. The resulting cell-laden bioprinted hydrogels display a homogeneous cell distribution post-printing and exceptional cell viability (>90%) that can be maintained for prolonged time periods in culture (14 days) for all cell lines. This simple and chemically versatile approach is envisaged to accelerate the development of multifunctional bioinks and contribute towards the fabrication of biomimetic 3D scaffolds with applicability in a wide range of predictive or exploratory biomedical platforms.
Assuntos
Bioimpressão , Engenharia Tecidual , Alicerces Teciduais , Alginatos , Boro , Glucanos , Hidrogéis , Impressão TridimensionalRESUMO
The ocean is par excellence a fertile territory of biodiversity on our planet. Marine-derived polysaccharides have been applied as functional materials in biomedicine due to their attractive bioactive properties, safety, high availability and low-cost production. Laminarin (or laminaran), a low molecular weight ß-glucan storage polysaccharide present in brown algae, can be (bio-) chemically modified to enhance its biological activity and employed in cancer therapies, drug/gene delivery, tissue engineering, antioxidant and anti-inflammatory functions. This review provides a brief overview on laminarin characteristics, modification strategies and highlights its pivotal biomedical applications.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Pesquisa Biomédica , Glucanos/farmacologia , Neoplasias/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/química , Antioxidantes/química , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Glucanos/química , Humanos , Neoplasias/patologia , Engenharia TecidualRESUMO
Biologically inspired materials with tunable bio- and physicochemical properties provide an essential framework to actively control and support cellular behavior. Cell membrane remodeling approaches benefit from the advances in polymer science and bioconjugation methods, which allow for the installation of un-/natural molecules and particles on the cells' surface. Synthetically remodeled cells have superior properties and are under intense investigation in various therapeutic scenarios as cell delivery systems, bio-sensing platforms, injectable biomaterials and bioinks for 3D bioprinting applications. In this review article, recent advances in the field of cell surface remodeling via bio-chemical means and the potential biomedical applications of these emerging cell hybrids are discussed. STATEMENT OF SIGNIFICANCE: Recent advances in bioconjugation methods, controlled/living polymerizations, microfabrication techniques and 3D printing technologies have enabled researchers to probe specific cellular functions and cues for therapeutic and research purposes through the formation of cell spheroids and polymer-cell chimeras. This review article highlights recent non-genetic cell membrane engineering strategies towards the fabrication of cellular ensembles and microtissues with interest in 3D in vitro modeling, cell therapeutics and tissue engineering. From a wider perspective, these approaches may provide a roadmap for future advances in cell therapies which will expedite the clinical use of cells, thereby improving the quality and accessibility of disease treatments.
Assuntos
Bioimpressão , Membrana Celular/química , Membranas Artificiais , Impressão Tridimensional , Esferoides Celulares/química , Engenharia Tecidual , Membrana Celular/metabolismo , Humanos , Esferoides Celulares/citologia , Esferoides Celulares/metabolismoRESUMO
This work is a proof of concept study establishing the potential of electrosprayed Janus particles for combined photodynamic therapy-chemotherapy. Sub-micron-sized particles of polyvinylpyrrolidone containing either an anti-cancer drug (carmofur) or a photosensitiser (rose bengal; RB), and Janus particles containing both in separate compartments were prepared. The functional components were present in the amorphous form in all the particles, and infrared spectroscopy indicated that intermolecular interactions formed between the different species. In vitro drug release studies showed that both carmofur and RB were released at approximately the same rate, with dissolution complete after around 250 min. Cytotoxicity studies were undertaken on model human dermal fibroblasts (HDF) and lung cancer (A549) cells, and the influence of light on cell death explored. Formulations containing carmofur as the sole active ingredient were highly toxic to both cell lines, with or without a light treatment. The RB formulations were non-toxic to HDF when no light was applied, and with photo-treatment caused large amounts of cell death for both A549 and HDF cells. The Janus formulation containing both RB and carmofur was non-toxic to HDF without light, and only slightly toxic with the photo-treatment. In contrast, it was hugely toxic to A549 cells when light was applied. The Janus particles are thus highly selective for cancer cells, and it is hence proposed that such electrosprayed particles containing both a chemotherapeutic agent and photosensitiser have great potential in combined chemotherapy/photodynamic therapy.
Assuntos
Fluoruracila/análogos & derivados , Fotoquimioterapia/métodos , Povidona , Rosa Bengala , Células A549/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/farmacologia , Fluoruracila/química , Fluoruracila/farmacologia , Humanos , Tamanho da Partícula , Excipientes Farmacêuticos/química , Excipientes Farmacêuticos/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Povidona/química , Povidona/farmacologia , Rosa Bengala/química , Rosa Bengala/farmacologiaRESUMO
Cell surface engineering has emerged as a powerful approach to forming cell aggregates/spheroids and cell-biomaterial ensembles with significant uses in tissue engineering and cell therapeutics. Herein, we demonstrate that cell membrane remodeling with a thermoresponsive boronic acid copolymer induces the rapid formation of spheroids using either cancer or cardiac cell lines under conventional cell culture conditions at minute concentrations. It is shown that the formation of well-defined spheroids is accelerated by at least 24 h compared to non-polymer-treated controls, and, more importantly, the polymer allows for fine control of the aggregation kinetics owing to its stimulus response to temperature and glucose content. On the basis of its simplicity and effectiveness to promote cellular aggregation, this platform holds promise in three-dimensional tissue/tumor modeling and tissue engineering applications.
Assuntos
Ácidos Borônicos/química , Materiais Biocompatíveis , Técnicas de Cultura de Células , Polímeros , Esferoides Celulares , Engenharia TecidualRESUMO
We report the synthesis of two simple copolymers that induce rapid cell aggregation within minutes in a fully reversible manner. The polymers can act as self-supporting "cellular glues" or as "drivers" of 3D cell spheroids/aggregates formation at minute concentrations.