Supramolecular structures are of great interest due to their applicability in various scientific and industrial fields. These fields of scientific action include promising applications i biomedical areas, in sensing, and in conductive and electrical phases. The sensible definition of supramolecular molecules is being set by investigators, who, because of the different sensitivities of their methods and observational timescales, may have different views as to what constitute these supramolecular structures. Besides, diverse polymers can be found to offer unique avenues for multifunctional systems with properties in medicine industrial applications. Aspects of this review provide different conceptual strategies to address molecular design, properties, and potential applications of self-assembly materials and the use of metal coordination as a feasible and useful strategy for constructing complex supramolecular structures. In this order of appreciations and ideas order, it is that this review report involves classic topics such as hydrogels that range from their relationship with drug delivery systems, to metallo-supramolecular materials, through applications in ophthalmic systems, in applications that require adhesiveness and electrically conductive hydrogels. This review also addresses systems that are largely based on hydrogel chemistry and the enormous opportunities to design very specific structures for applications that demand enormous specificity.

Disease, trauma, and aging account for a significant number of clinical disorders. Regenerative medicine is emerging as a very promising therapeutic option. The design and development of new cell-customized biomaterials able to mimic ECM functionalities represent one of the major strategy to control the cell fate and stimulate tissue regeneration. Recently, hydrogels have received a considerable interest for their use in the modulation and control of cell fate during regeneration processes. Several synthetic bioresponsive hydrogels are being developed in order to facilitate cell-matrix and cell-cell interactions. In this review new strategies and future perspectives of such synthetic cell microenvironment will be highlighted.

Shape-shifting polymers usually require not only reversible stimuli-responsive ability, but also strong mechanical properties. A novel shape-shifting photochromic hydrogel system was designed and fabricated through embedding hydrophobic spiropyran (SP) into double polymeric network (DN) by micellar copolymerization. Here, sodium alginate (Alg) and poly acrylate-co-methyl acrylate-co-spiropyran (P(SA-co-MA-co-SPMA)) were employed as the first network and the second network respectively to realize high mechanical strength. After soaked in the CaCl2 solution, the carboxyl groups in the system undergo metal complexation with Ca2+ to enhance the hydrogel. Moreover, after the hydrogel is exposed to UV-light, the closed isomer of spiropyran in the hydrogel network can be converted into an open zwitterionic isomer MC, which is considered to interact with Ca2+ ions. Interestingly, Ca2+ and UV-light responsive programmable shape of the copolymer hydrogel can recover to its original form by immersing in pure water. Since its excellent metal ion and UV-light stimuli-responsive and mechanical properties, the hydrogel has potential applications in the field of soft actuators.

Mucus is a critical part of the human body’s immune system which traps and carries away various particulates such as anthropogenic pollutants, pollen, viruses etc. Various synthetic hydrogels have been developed to mimic mucus, using different polymers as their backbones. Common to these simulants is a three-dimensional gel network which is physically crosslinked and is capable of loosely entrapping water within. Two of the challenges in mimicking mucus using synthetic hydrogels include the need to mimic the rheological properties of the mucus and its ability to capture particulates (its adhesion mechanism). In this paper, we review the existing mucus simulants and discuss their rheological, adhesive and tribological properties. We show that most, but not all, simulants indeed mimic the rheological properties of the mucus but only one mimics the ability of mucus to capture particulates.

Following the general aim of recapitulating the native mechanical properties of tissues and organs in vitro, the field of materials science and engineering has benefited from recent progress in developing compliant substrates with similar physical and chemical properties. In particular, in the field of mechanobiology, soft hydrogels can now reproduce the precise range of stiffnesses of healthy and pathological tissues to study the mechanisms behind cell response to mechanics. However, it was shown that biological tissues are not only elastic but also relax at different timescales. Cells can indeed perceive and actually need this dissipation because it is a critical signal integrated with other signals to define adhesion, spreading and even more complicated functions. The mechanical definition of hydrogels used in mechanobiology is however commonly limited to the elastic stiffness (Young’s modulus) and this value is known to depend greatly on the measurement conditions that are rarely reported. Here, we report that a simple relaxation test performed under well defined conditions can provide all the necessary information to characterize soft materials mechanically, by fitting the dissipation behavior with a generalized Maxwell model (GMM). The method was validated using soft polyacrylamide hydrogels and proved to be very useful to unveil precise mechanical properties of gels that cells can sense and offer a set of characteristic values that can be compared with what is typically reported from microindentation tests.

Polymer hydrogels are 3D networks consisting of hydrophilic crosslinked macromolecular chains, able to swell and retain water. Since their invention in the 1960s, they have become an outstanding pillar in the design, development, and application of engineered polymer systems suitable for biomedical and pharmaceutical applications (such as drug or cell delivery, regeneration of hard and soft tissues, wound healing, and bleeding prevention, among others). Despite several well-established synthetic routes of polymer hydrogels based on batch polymerization techniques, about fifteen years ago academia started to look for alternative methods involving simpler reaction paths, shorter reaction times, and lower energy consumption. In this context, frontal polymerization (FP) undoubtedly has become an alternative and efficient reaction model that allows for converting monomers into polymers via a localized and propagating reaction, by exploiting the formation and propagation of a “hot” polymerization front, able to self-sustain and propagate throughout the monomeric mixture. Therefore, the present work aims to summarize the main research outcomes, achieved during the last years, concerning the design, preparation, and application of FP-derived polymeric hydrogels, demonstrating the feasibility of this technique for the obtainment of functional 3D networks, and providing the reader with some perspectives for the forthcoming years.

Focal cartilage defects are a prevalent knee problem affecting people of all ages. Due to its avascular nature, cartilage has limited self-repair capacity, and osteochondral defects can lead to pain and long-term complications such as osteoarthritis. Autologous chondrocyte implantation (ACI) has been a successful surgical approach for repairing osteochondral defects over the past two decades. However, a major drawback of ACI is the de-differentiation of chondrocytes during their in vitro expansion. In this study, we isolated ovine chondrocytes and cultured them in a two-dimensional environment as for ACI procedures. We hypothesised that the 3D scaffolds would support the cells re-differentiation without the need for growth factors and so we encapsulated them into soft collagen and alginate (col/alg) hydrogels. Chondrocytes embedded into hydrogels were viable and proliferated. After 7 days they acquired a rounded morphology and started to aggregate. Gene expression studies showed that the genes associated with chondrogenesis started to be up regulated as early as day one. At 21 days chondrocytes had extensively colonized the hydrogel, forming large cell clusters and started to deposit collagen II and aggrecan with limited collagen type I deposition. These findings highlight the potential of soft col/alg hydrogels to enhance ACI outcomes by creating a favourable microenvironment for chondrocyte reprogramming and re-differentiation, eliminating the dependency on growth factors.

Herein, we report a stimuli responsive hydrogel with inhibitory activity against Escherichia coli prepared by chemical crosslinking of carboxymethyl chitosan (CMCs) and hydroxyethyl cellulose (HEC). The hydrogels were prepared by esterification of chitosan (Cs) with monochloroacetic acid to produce CMCs which was then chemically crosslinked to HEC using citric acid as the crosslinking agent. To impart a stimuli responsiveness property to the hydrogels, polydiacetylene-zinc oxide (PDA-ZnO) nanosheets were synthesized in-situ during the crosslinking reaction followed by photopolymerization of the resultant composite. To achieve this, ZnO was anchored on carboxylic groups in 10,12-pentacosadiynoic acid (PCDA) layers to restrict movement of alkyl portion of PCDA during crosslinking CMCs and HEC hydrogels. This was followed by irradiating the composite with UV radiation to photopolymerize the PCDA to PDA within the hydrogel matrix so as to impart thermal and pH responsiveness to the hydrogel. From the results obtained, the prepared hydrogel had a pH dependant swelling capacity as it absorbed more water in acidic media as compared to basic media. Incorporation of PDA-ZnO resulted in a thermochromic composite responsive to pH evidenced by a visible colour transition from pale purple to pale pink. Upon swelling, PDA-ZnO-CMCs-HEC hydrogels had inhibitory activity against E. coli attributed to the slow release of the ZnO nanoparticles as compared to CMCs-HEC hydrogels.

Hydrogels can provide instant relief to pain and facilitate the fast recovery of wounds. Currently the incorporation of medicinal herbs/plants in polymer matrix is being investigated due to their anti-bacterial and wound healing properties. Herein, we investigated the novel combination of chitosan (CS), chondroitin sulfate (CHI) and garlic (Gar) to synthesize hydrogels through freeze gelation process for faster wound healing and resistance to microbial growth at the wound surface. The synthesized hydrogels were characterized via Fourier transform infrared spectroscopy (FTIR), which confirmed the presence of relevant functional groups. The scanning electron microscopy (SEM) images exhibited the porous structure of the hydrogels, which is useful for the sustained release of Gar from the hydrogels. The synthesized hydrogels showed significant inhibition zones against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore, cell culture studies confirmed the cyto-compatibility of the synthesized hydrogels. Thus, the novel hydrogels presented in this study can offer antibacterial effect during wound healing and promote tissue regeneration.

The control of the three-dimensional (3D) polymer network structure is important for permselective materials when specific biomolecules detection is needed. Here we investigate conditions to obtain a tailored hydrogel network that combine both molecular filtering and molecular capture capabilities for biosensing applications. Along this line short oligonucleotide detection in a displacement assay is set within PEGDA hydrogels synthetized by UV radical photopolymerization. To provide insights on the molecular filter capability, diffusion studies of several probes (sulforhodamine G and dextrans) with different hydrodynamic radii were carried out using NMR technique. Moreover, fluorometric analyses of hybridization of DNA oligonucleotides inside PEGDA-hydrogels shed light on the mechanisms of recognition in 3D, highlighting that mesh size and crowding effect greatly impact of hybridization mechanism onto polymer network. Finally, we found the best probe density and diffusion transport conditions to allow the specific oligonucleotide capture and detection inside PEGDA-hydrogels for oligonucleotide detection and the filtering out of higher molecular weight molecules.

Innovative tissue engineering biomimetic hydrogels based on hydrophilic polymers have been investigated for their physical and mechanical properties. 5% to 25% by volume loading PHEMA-nanosilica glassy hybrid samples were equilibrated at 37°C in aqueous physiological isotonic and hypotonic saline solutions (0.15 and 0.05 M NaCl) simulating two limiting possible compositions of physiological extracellular fluids. The glassy and hydrated hybrid materials were characterized both for dynamo-mechanical properties and equilibrium absorptions in the two physiological-like aqueous solutions. Mechanical and the morphological modifications occurring in the samples have been described. The 5% volume nanosilica loading hybrid nanocomposite composition showed mechanical characteristics in the dry and hydrated states that were comparable to those of cortical bone and articular cartilage, respectively, and then chosen for further sorption kinetics characterization. Sorption and swelling kinetics were monitored up to equilibrium. Changes in water activities and osmotic pressures in the water-hybrid systems equilibrated at the two limiting solute molarities of the physiological solutions have been related to the observed anomalous sorption modes using the Flory-Huggins interaction parameter approach. The bulk modulus of the dry and glassy PHEMA-5% nanosilica hybrid at 37°C has been observed to be comparable with the values of the osmotic pressures generated from the sorption of isotonic and hypotonic solutions. The anomalous sorption modes and swelling rates are coherent with the difference between osmotic swelling pressures and hybrid glassy nano-composite bulk modulus: the lower the differences the higher the swelling rate and equilibrium solution uptakes. Bone tissue engineering benefits of use of tuneable biomimetic scaffold biomaterials that can be “designed” to act as biocompatible and biomechanically active hybrid interfaces are discussed.

3D bioprinting holds great promise in the field of regenerative medicine as it can create complex structures in a layer-by-layer manner using cell-laden bioinks, making it possible to imitate native tissues. Current bioinks lack both the high printability and the biocompatibility required in this respect. Hence, the development of bioinks that are capable of both properties is needed. In our previous study, a furfuryl-gelatin based bioink, crosslinkable by visible light, was used for creating mouse mesenchymal stem cell-laden structures with high fidelity. In this study, lattice mesh geometries were printed in a comparative study to test against the properties of a traditional rectangular-sheet. After 3D printing and crosslinking, both structures were analysed for swelling and rheological properties, and their porosity estimated using scanning electron microscopy. Results showed that the lattice structure was relatively more porous but sturdy and exhibited a lower degradation rate compared to the rectangular-sheet. Further, the lattice allowed encapsulation of a greater number of cells, allowing them to proliferate to a greater extent compared to the rectangular-sheet that retained a lesser number of cells initially. All of these results collectively affirmed that the lattice poses as a superior scaffold design for tissue engineering applications.

The reproductive health of women is governed by an optimal balance between the host-microbiota interaction. Depletion in the beneficial vaginal microflora caused by depletion of Lactobacillus species and increased proliferation of pathogens results in gynecological infections. Among women of reproductive age, vaginal infections are increasingly prevalent. Attaining therapeutic efficacy using conventional formulations remains a challenge as vaginal fluids quickly remove or dilute the therapeutic formulations. Hydrogels have been widely exploited for targeted delivery of therapeutics directly into the vaginal mucus. With careful choice of polymers (natural, synthetic or semi-synthetic) hydrogels with specific properties such as stimuli-responsiveness, antimicrobial, and muco-adhesiveness can be tailored for higher therapeutic efficacy. In this review, the advnances in hydrogel strategies for the treatment of vaginal infections is presented with emphasis on the types and properties that play a significant role in vaginal drug delivery systems.

Extensive damage to peripheral nerves is a health problem with few therapeutic alternatives. In this context, the development of tissue engineering seeks to obtain materials that can help recreate environments conducive to cellular development and functional repair of peripheral nerves. Different hydrogels have been studied and presented as alternatives for future treatments to emulate the morphological characteristics of nerves. Along with this, other research proposes the need to incorporate electrical stimuli into treatments as agents that promote cell growth and differentiation; however, no precedent correlates the simultaneous effects of the types of hydrogel and electrical stimuli. In this research, the neural differentiation of PC12 cells we are evaluated, relating the effect of collagen, alginate, GelMA, and PEGDA hydrogels with electrical stimulation modulated in four different ways. Our results show significant correlations for different culture conditions, allowing us to develop new experimental schemes for new materials in peripheral nerve engineering.

Our previous study found that intravesical perfusion metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel for-mulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong in-hibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and expression of tumour biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPK/mTOR signalling pathway compared with metformin alone. These findings highlighted the potential of this novel formulation as an efficient candidate for managing BC via intravesical ad-ministration.

Hydrogels (gels) are attractive tools for tissue engineering and regenerative medicine due to their potential for drug delivery and ECM-like composition. In this study, we use rheology to characterize GelMA/alginate gels loaded with human platelet lysate (PL). We then characterize these gels from a physicochemical perspective and evaluate their ability to transport PL proteins, their pore size, and their rate of degradation. Finally, their biocompatibility is evaluated. We describe how alginate changes the mechanical behavior of the gels from elastic to viscoelastic after ionic (calcium-mediated) crosslinking. In addition, we positively report the release of PL proteins and relate it to the degradation profile of the gels and the biocompatibility of the gels. Thus, the developed gels represent attractive substrates for both cell studies and bioactive materials.

Polymeric hydrogels are promising polymeric functional materials that have been widely used in the biomedical field as an emerging carrier of various therapeutic agents. Polymeric hydrogels as a carrier of therapeutics can leverage therapeutically beneficial outcomes of drug delivery than systemic chemotherapy and can provide spatial and temporal control over the release of various therapeutic agents. Polymeric hydrogels are cross-linked three-dimensional networks constructed by hydrophilic polymers and they are capable of absorbing and re-taining a large amount of water. Polymeric hydrogels share many physiochemical features with natural tissues due to their water abundance, biomimetic microstructure, and intrinsic flexibility. Polymeric hydrogels have excellent biocompatibility, biodegradability, and lower toxicity. Polymeric hydrogels enhance the convenience and efficiency of drug delivery by assisting in situ gelation and controlling drug release by changing their volume and other properties when it encounters some stimuli (e.g., heat, pH, light, and ultrasound). This review aims to outline the overview of polymeric hydrogels, properties, types, advantage, disadvantages, characteri-zation, and their application with present status and future perspective used for the delivery of therapeutics in pharmaceutical and biomedical sciences.

Two antimicrobial agents such as silver nanoparticles (AgNPs) and titanium dioxide (TiO2) have been formulated with natural polysaccharides (chitosan or alginate) to develop innovative inks for the rapid, customizable, and extremely accurate manufacturing of 3D printed scaffolds useful as dressings in the treatment of infected skin wounds. Suitable chemical-physical properties for the applicability of these innovative devices were demonstrated through the evaluation of water content (88-93%), mechanical strength (Young’s modulus 0.23-0.6 MPa), elasticity, and morphology. The antimicrobial tests performed against Staphylococcus Aureus and Pseudomonas Aeruginosa demonstrated the antimicrobial activities against Gram+ and Gram– bacteria of AgNPs and TiO2 agents embedded in the CH or ALG macroporous 3D hydrogels (AgNPs MIC starting from 5 µg/ml). The biocompatibility of chitosan was widely demonstrated by cell viability tests and was higher than that observed for alginate. Constructs containing AgNPs at 10 µg/ml concentration level did not significantly alter cell viability as well as the presence of titanium dioxide; cytotoxicity towards human fibroblasts was observed starting with AgNPs concentration of 100 µg/ml. In conclusions, the 3D printed dressings here developed own the features to be cheap, highly defined, easy to be manufactured and further applied in personalized antimicrobial medicine applications.

Dental pulp tissue engineering (TE) quests to regenerate dentin/pulp complex by combining a suitable supporting matrix, stem cells, and biochemical stimuli. Such procedures foresee a matrix that can be easily introduced into the root canal system (RCS) and tightly adhere to dentin walls to assure the dentin surface's proper colonization with progenitor cells capable of restoring the dentin/pulp complex. Herein was investigated an injectable self-setting hyaluronic acid-based (HA) hydrogel system, formed by aldehyde-modified (a-HA) with hydrazide-modified (ADH), enriched with platelet lysate (PL), for endodontic regeneration. The hydrogels' working (wT) and setting (sT) times, the adhesion to the dentine walls, the hydrogel's microstructure, and the delivery of human Dental Pulp Cells (DPCs) were studied in vitro. Hydrogels incorporating PL showed a suitable wT and sT and a porous microstructure. The tensile tests showed that the breaking point occurs after 4.13 mm deformation. While in the indentation test after 1.3 mm deformation. Both breaking points occur in the hydrogel extension. The HA/PL hydrogels exhibited supportive properties and promoted cell migration toward dentin surfaces in vitro. Overall, these results support using PL-laden HA injectable hydrogels (HA/PL) as a biomaterial for DPCs encapsulation, thereby displaying great clinical potential towards endodontic regenerative therapies.

Hydrogels obtained from the combination of different polymers are an interesting strategy for the development of controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using different concentration of the components. The hydrogels were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and swelling degree; betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay shown that almost all hydrogels are cytocompatibles and an increase the proliferation in both cell types after one week of incubation was observed by Live/Dead® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics and biocompatibility.

Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. Aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner. The therapeutical peptide and proteins are remarkable therapeutic agents in today’s world that allows the treatment of severe, chronic and life‐threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis in an easy manner. Despite few limitations, hydrogels provide fine tuning of proteins and peptides delivery with enormous impact in clinical medicine. The primary objective of this article is to review current issues concerned with the therapeutics peptides and proteins and impact of remarkable properties of hydrogels on these therapeutic agents. Different routes for pharmaceutical peptides and proteins and superiority over other drugs candidates are presented. The article will also review literature concerning classification of hydrogels on different basis, polymers used, release mechanisms their physical and chemical characteristics and diverse applications.

Cellulose nanofibrils (CNFs) are materials with high aspect ratio. Typically, TEMPO-oxidised, or cationic CNFs consist of long fibrils (up to 2 μm) with very low thickness (less than 10 nm). Derived from their high aspect ratio, CNFs form strong hydrogels with high elasticity at low concentrations. Thus, CNF suspensions appear as an interesting rheology modifier to be applied in cosmetics, paints, foods, as a mineral suspending agent, among other applications. The high viscosity results from the strong 3D fibril network, which is related to good fibrillation of the material, allowing the nanofibrils to overlap. The overlap concentration (c*) was found to vary from ca. 0.13 to ca. 0.60 wt.% depending on the type and intensity of the pre-treatment ap-plied during the preparation of the CNFs. The results confirm the higher tendency for the fibres treated with CHPTAC (cationic) and TEMPO to form a 3D network, resulting in the lowest c*. For the TEMPO-oxidised CNF suspensions, it was also found that aggregation is improved at acidic pH conditions due to lower charge repulsion among fibrils, leading to an increase in the suspension viscosity, as well as higher apparent yield stresses. TEMPO CNF suspensions with low content of carboxylic groups tend to precipitate at moderate acidic pH values.

Azobenzene photoswitches are fundamental components in contemporary approaches aimed at light-driven control of intelligent materials. Significant endeavors are directed towards enhancing the light-triggered reactivity of azobenzenes for such applications and obtaining water-soluble molecules able to act as crosslinkers in a hydrogel. Here, we report the rational design and the synthesis of azobenzene/alginate photoresponsive hydrogels endowed with fast reversible sol-gel transition. We started with the synthesis of three cationic azobenzenes (AZO A, B, and C) and then incorporated them in sodium alginate (SA) to obtain photoresponsive supramolecular hydrogels (SMHGs). The photoresponsive properties of the azobenzenes were investigated by UV-Vis and ¹H NMR spectroscopy. Upon irradiation with 365 nm UV light, the azobenzenes demonstrated efficient trans-to-cis isomerization, with complete isomerization occurring within seconds. The return to the trans form took several hours, with AZO C exhibiting the fastest return, possibly due to higher trans isomer stability. In the photoresponsive SMHGs, the minimum gelation concentration (MGC) of azobenzenes was determined for different compositions, indicating that small amounts of azobenzenes could induce gel formation, particularly in 5 wt% SA. Upon exposure to 365 nm UV light, the SMHGs exhibited reversible gel-sol transitions, underscoring their photoresponsive nature. This research offers valuable insights into the synthesis and photoresponsive properties of cationic, water-soluble azobenzenes, as well as their potential application in the development of photoresponsive hydrogels.

Traumatic brain injury (TBI) is among the leading causes of mortality and long-term impairment globally. TBI has a dynamic pathology encompassing a variety of metabolic and molecular events that occur in two phases, primary and secondary. An external forceful blow to the brain initiates the primary phase, which is followed by a secondary phase that involves the release of calcium ions (Ca2+) and the initiation of a cascade of inflammatory processes, including mitochondrial dysfunction, rise in oxidative stress, activation of glial cells, and damage to the blood-brain barrier (BBB), resulting in paracellular leakage. There is currently no FDA-approved drug for TBI, but existing approaches rely on delivering small and macromolecular treatments, which are severely constrained by the BBB, poor retention, off-target toxicity, and complex pathology of TBI. Therefore, there is a demand for innovative and alternative therapeutics with effective delivery tactics for diagnosis and treatment of TBI. Tissue engineering and use of biomaterials is one such alternative approach. With this approach, neuronal stem cell therapy is combined with synthetically generated tissue materials such as hydrogels, self-assembling peptides, and electrospun nanofibers, which may induce neurite outgrowth, differentiation of human neural stem cells, and nerve gap bridging in TBI. This review examines tissue engineering and the use of biomaterials as potential treatments for TBI, including their synthesis, mechanisms of action, and limitations. The review also discusses challenges facing tissue engineering and biomaterial technology including survival rate of transplanted stem cells and the development of biodegradable, biocompatible, and mechanically flexible biomaterials. A better understanding of the mechanisms and drawbacks of these novel therapeutic approaches will help guide the design of future TBI therapies.

Regenerative endodontic procedures (REPs) aim at recreating dental pulp tissue using biomaterials such as hydrogels. Their bioactivity is mostly linked to the nature of biomolecules or chemical compounds that will compose the endodontic hydrogel. However, many other parameters, such as hydrogel concentration, type, bioactive molecules solubility, of apex size were reported to influence the hydrogel behavior, leading to the inability to predict the clinical outcome. This lack of knowledge and the various parameters that should be considered, suggest that biological activity of endodontic hydrogel is impossible to anticipate and could hinder the bench to bedside transition. We formulated in this article our opinion that most of these parameters could be identified, described, and studied. A second part of the document lists some challenges and perspectives, including development of future mathematical models able to explain and predict the bioactivity of these endodontic hydrogel in clinic.

Extensive experimental and theoretical research over the past several decades has culminated in the understanding of the mechanisms behind nanoparticle-mediated enhancements on the mechanical properties of hydrogels. This information is not only crucial to realizing applications that directly benefit from developing hydrogels with high mechanical strength, but also to guide the development of strategies to further enhance hydrogel properties by combining different approaches. In our study, we investigated the effect of combining two approaches – addition of nanoparticles and crosslinking two different polymers (to create double-network hydrogels) – on the mechanical properties of hydrogels. Our studies revealed that these approaches may be combined to synthesize hydrogel composites with enhanced properties; however, both polymers in the double-network hydrogel must strongly interact with the nanoparticles to fully benefit from the addition of nanoparticles. Moreover, the concentration of hydrogel monomers used for the preparation of the double-network hydrogels had a significant effect on the extent of nanoparticle-mediated enhancements; double-network hydrogel nanocomposites prepared using lower monomer concentrations showed higher enhancements in elastic moduli compared to those prepared using high monomer concentrations. Collectively, these results demonstrate that the hypotheses previously developed to understand the role of nanoparticles on the mechanical properties of hydrogel nanocomposites may be extended to double-network hydrogel systems and guide the development of next generation hydrogels with extraordinary mechanical properties through a combination of orthogonal approaches.

One-dimensional nanostructures such as silver nanowires (AgNWs) have attracted considerable attention owing to their outstanding electrical, thermal and antimicrobial properties; however, their application in the prevention of infections linked to bone tissue regeneration interventions has not yet been explored. Here we report on the development of an innovative scaffold prepared from chitosan, composite hydroxyapatite and AgNWs (CS-HACS-AgNWs) having both bioactive and antibacterial properties. In vitro results highlighted the antibacterial potential of AgNWs against both gram-positive and gram-negative bacteria. The CS-HACS-AgNWs composite scaffold demonstrated suitable Ca/P deposition, improved gel strength, reduced gelation time, and sustained Ag+ release within therapeutic concentrations. Antibacterial studies showed that the composite formulation was capable of inhibiting bacterial growth in suspension and of completely preventing biofilm formation on the scaffold in the presence of resistant strains. The hydrogels were also shown to be biocompatible, allowing cell proliferation. In summary, the developed CS-HACS-AgNWs composite hydrogels demonstrated significant potential as a scaffold material to be employed in bone regenerative medicine, as it presents enhanced mechanical strength combined with the ability to allow calcium salts deposition, while efficiently decreasing the risk of infections. The results presented justify further investigations into potential clinical applications of these materials.

A novel chemically cross-linked hydrogel was prepared through the utilization of the nor-bornene (Nb)-methyl tetrazine (mTz) click reaction, derived from carboxymethyl cellulose (CMC) and alginate (Alg). The hydrogel was designed to generate reactive oxygen species (ROS) from NIR-dye, indocyanine green (ICG) for a combined photothermal and photodynamic ther-apy (PTT/PDT). The cross-linking of Nb and mTz moieties occurred via an inverse elec-tron-demand Diels-Alder reaction under physiological conditions avoiding the need for a cata-lyst. The resulting hydrogels exhibited viscoelastic properties (G′ ~ 492-270 Pa) and high porosi-ty. The hydrogels were found to be injectable with tunable mechanical characteristics. The ICG encapsulated hydrogels demonstrated ROS generation ability under NIR exposure. The ROS production was investigated through DPBF assays to access photodynamic effect (with NIR irra-diation at 1-2W for 5-15 min). The temperature of the ICG-loaded hydrogels was also raised up-on the NIR irradiation to eradicate tumor cells photothermally. In vitro cytocompatibility as-sessments revealed the non-toxic nature of CMC-Nb and Alg-mTz towards HEK-293 cells. Fur-thermore, the ICG-loaded hydrogels effectively inhibited the metabolic activity of Hela cells following NIR exposure. This innovative hydrogel system holds promise for applications in combined PTT and PDT.

Nanotechnology and polymer engineering are steering towards a new development to invade deleterious mysteries. In the last few decades, polymer engineering has grabbed researchers’ attention and similarly, polymeric network-engineered structures have been vastly studied. Prior to therapeutic application, early and quick detection analyses are critical. Therefore, developing nanoscale sensors to manage the acute expression of feeble states and malignancies to draw therapeutic lines demands advanced nanoengineering. In spite of nano-therapeutics have emerged as an alternative approach to tackling strenuous diseases. Also, studies have shown highly biocompatible biomedical engineering has emerged with sheer progression. Moreover, hydrogels have emerged as a three-dimensional (3D) polymeric network that consists of hydrophilic natural or synthetic polymers. The resemblance of hydrogels with tissue structure makes it more unique to study inquisitively. Preceding studies have shown a vast spectrum of synthetic and natural polymer deployment in the field of biotechnology and molecular diagnostics. This review explores recent studies on synthetic and natural polymer engineered hydrogel-based biosensors and their applications in multipurpose diagnostics and therapeutics. We reviewed the latest studies on hydrogel-engineered biosensors, exclusively DNA-based and DNA hydrogels fabricated biosensors.

The prospective applications of chitosan-based hydrogels (CBHs), a category of biocompatible and biodegradable materials, in biomedical disciplines such as tissue engineering, wound healing, drug delivery, and biosensing have garnered great interest. The synthesis and characterization processes used to create CBHs play a significant role in determining their characteristics and effectiveness. The processing procedure could be tailored to obtain specific features like porosity, swelling, mechanical strength, degradation rate, and bioactivity, affecting the properties of CBHs to a great extent. Additionally, characterization methods aid in gaining access to the microstructures and properties of CBHs. Especially, this review provides a comprehensive assessment of the state-of-the-art with a focus on the affiliation between particular properties and application domains. The main obstacles and prospects for the future of CBH development for biomedical applications are also covered in the review.

Novel advanced biomaterials have recently gained great attention, especially in surgical minimally invasive techniques. Applying sophisticated design and engineering methods, various elastomer-hydrogel systems (EHS) with outstanding performance have been developed in last decades. Those systems composed of elastomers and hydrogels are very attractive due to their high biocompatibility, injectability, controlled porosity and often antimicrobial properties. Moreover, elastomeric properties and bioadhesiveness are making them suitable for soft tissue engineering. Herein, we present the advances in current state-of-the-art design principles and strategies for strong interface formation inspired by nature (bio-inspiration), diverse properties and applications of elastomer-hydrogel systems in different medical fields, in particular, in tissue engineering. Functionalities of those systems, including adhesive properties, injectability, antimicrobial properties and degradability applicable to tissue engineering will be discussed in a context of future efforts towards development of advanced biomaterials.

The current pandemic is urgently demanding to discover alternative materials capable of inactivate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus 2019 (COVID-19) disease. Calcium alginate is a crosslinked hydrophilic biopolymer with an immense range of biomedical applications due to its excellent chemical, physical and biological properties. In this study, the cytotoxicity and antiviral activity of calcium alginate in the form of films were studied. The results showed that these films are biocompatible in human keratinocytes and are capable of inactivating enveloped viruses such as bacteriophage phi 6 with a 1.43-log reduction (94.92% viral inactivation) and SARS-CoV-2 Delta variant with a 1.64-log reduction (96.94% viral inactivation) in virus titers. The antiviral activity of these calcium alginate films can be attributed to its negative charge density that may bind to viral envelopes inactivating membrane receptors.

Biomaterials play an important role in the development of advancing three dimensional (3D) in vitro skin models, providing valuable insights for drug testing and tissue-specific modeling. Commercial materials, such as collagen, fibrin or alginate, have been widely used in skin modelling. However, they do not adequately represent the molecular complexity of skin components. On this regard, the development of novel biomaterials that represent the complexity of tissues are becoming more important in the design of advanced models. In this study, we have obtained aged human decellularized dermal extracellular matrix (dECM) hydrogels extracted from cadaveric human skin and demonstrated their potential as scaffold for advanced skin models. These dECM hydrogels effectively reproduce the complex fibrillar structure of other common scaffolds, exhibiting similar mechanical properties, while preserving the molecular composition of the native dermis. It is worth noting that fibroblasts embedded within human dECM hydrogels exhibit behavior more representative of natural skin compared to commercial collagen hydrogels, where uncontrolled cell proliferation leads to material shrinkage. The described human dECM hydrogel is able to be used as scaffold for dermal fibroblasts in a skin aging on chip model. These results demonstrate that dECM hydrogels preserve essential components of the native human dermis making them a suitable option for the development of 3D skin aging models that accurately represent the cellular microenvironment, improving existing in vitro skin models and allowing for more reliable results in dermatopathological studies.

Nature has always been a source of inspiration for the development of novel materials and devices. In particular, polymer actuators that mimic the movements and functions of natural organisms have been of great interest due to their potential applications in various fields, such as biomedical engineering, soft robotics, and energy harvesting. During recent years, the development and actuation performance of electrospun fibrous meshes with the advantages of high permeability, surface area and easy functional modification, has received extensive attention from researchers. This review covers the recent progress in the state-of-the-art electrospun actuators based on commonly used polymers such as stimuli-sensitive hydrogels, shape-memory polymers (SMPs), and electroactive polymers. The design strategies inspired by nature such as hierarchical systems, layered structures, responsive interfaces to enhance the performance, and functionality of these actuators including the role of biomimicry to create devices that mimic the behavior of natural organism are discussed. Finally, the challenges and future directions in the field, with a focus on the development of more efficient and versatile electrospun polymer actuators that can be used in a wide range of applications, are addressed. The insights gained from this review can contribute to the development of advanced and multifunctional actuators with improved performance and expanded application possibilities.

Bone fractures are very common in the geriatric population and poses a great economic burden worldwide. While traditional methods for repairing bone defects have primarily been autografts, there are several drawbacks limiting its use. Bone graft substitutes have been used as alternative strategies to improve bone healing. However, there remains several impediments to achieving the desired healing outcomes. Injectable hydrogels have become attractive scaffold materials for bone regeneration given their high performance in filling irregularly sized bone defects, ability to encapsulate cells and bioactive molecules, and mimic the native ECM of bone. We investigated the use of an injectable chitosan-based hydrogel scaffold to promote differentiation of preosteoblasts in vitro. The hydrogels were characterized by evaluating cell homogeneity, cell viability, rheological and mechanical properties, and differentiation ability of preosteoblasts in hydrogel scaffolds. Cell-laden hydrogel scaffolds exhibited shear thinning behavior and the ability to maintain shape fidelity after injection. The CNC-CS hydrogels exhibited higher mechanical strength and significantly upregulated the osteogenic activity and differentiation of preosteoblasts as shown by ALP activity assays and histological analysis of hydrogel scaffolds. These results suggest that this injectable hydrogel is suitable for cell survival, can promote osteogenic differentiation of preosteoblasts, and structurally support new bone growth.

Nanocomposite hydrogels offer remarkable potential for applications in bone tissue engineering. They are synthesized through the chemical or physical crosslinking of polymers and nanomaterials, allowing for the enhancement of their behaviour by modifying the properties and compositions of the nanomaterials involved. However, their mechanical properties require further enhancement to meet the demands of bone tissue engineering. Here, we present an approach to improve the mechanical properties of nanocomposite hydrogels by incorporating polymer grafted silica nanoparticles into a double network inspired hydrogel (gSNP Gels). The gSNP Gels were synthesised via a graft polymerization process using a redox initiator. gSNP Gels were formed by grafting 2-acrylamido-2-methylpropanesulfonic acid (AMPS) as the first network gel followed by a sequential second network acrylamide (AAm) onto amine functionalized silica nanoparticles (ASNPs). We utilized glucose oxidase (GOx), to create an oxygen-free atmosphere during polymerization resulting in higher polymer conversion compared to argon degassing. The gSNP Gels showed excellent compressive strengths of 13.9 ± 5.5 MPa, a strain of 69.6 ± 6.4%, and a water content of 63.4% ± 1.8. The synthesis technique demonstrates a promising approach to enhance the mechanical properties of hydrogels, which can have significant implications for bone tissue engineering and other soft tissue applications.

Abstract: This study aims to analyze the physico-mechanical properties and dynamic models of tissue-simulating hydrogels, specifically the photoacoustic (PA) response signals, by varying the concentrations of polyvinyl alcohol (PVA) and molecular weight (MW). A state space model (SSM) is proposed to study the PVA hydrogels to retrieve the PA-related signal's damping ratio and nat-ural frequency. Nine box-shaped PVA hydrogels containing saline solution were used, with five concentrations of PVA (7, 9, 12, 15, 20%) for MW1 and four for MW2. The results indicated that the concentration of PVA and MW played an important role in the PA wave's amplitude, arrival time, and speed of sound over the hydrogels. The SSM parameters showed that increasing PVA and MW concentrations improved the hydrogels' ability to absorb and transfer energy under the PA effect. These parameters were also found to be correlated with density and modulus of elasticity. Addi-tionally, the concentrations of PVA and MW affected the absorption and optical scattering coeffi-cients. The physical-mechanical properties, including porosity, density, and modulus of elasticity, improved as the concentration of PVA and MW increased. The ultimate goal of this study is to develop hydrogels as phantoms that can be used for tissue simulation and imaging.

Decomposition of natural and synthetic polymeric materials (peat, humates, biochar, strongly swelling hydrogels and other soil conditioners) in a biologically- and chemically- active soil environment inevitably leads to their degradation and ability to improve the structure, water-retention, absorptive capacity and actual fertility of artificial soil constructions in urbanized ecosystems and agro landscapes (constructozems). Quantitative assessment of the biodegradation process using field and laboratory incubation experiments, as well as mathematical modeling, showed the possibility of significant (up to 30-50% per year) losses of organic matter of constructozems and a corresponding deterioration in their quality. Incubation experiments with the analysis of carbon dioxide emission for polymeric materials under given thermodynamic conditions allow to estimate the potential rates of their decomposition (half-life) and their dependence on the dose of inhibitors of microbial activity. Special nomographs provide an opportunity to determine the optimum depth of the arrangement of organic components in soil constructions to ensure their stable functioning during a fixed operating time in urban conditions. The results of the study are useful for geo-engineers and landscaping practitioners.

The distribution of noble metal nanoparticles in hydrogels are influencing their nanoplasmonic response and signal used for biosensor purposes. By controlling the particle distribution, it is possible to obtain new nanoplasmonic features with new sensing modalities. Particle distributions can be characterized by using volume-imaging methods such as the focused ion beam-scanning electron microscope (FIB-SEM) and the serial block-face scanning electron microscopy (SBFSEM) techniques . Since the pore structure of hydrogels is contained by the water absorbed in the polymer network it may pose challenges for volume-imaging based on electron microscope techniques since the sample must be in a vacuum chamber. The structure of hydrogels can be conserved by choosing appropriate preparation methods, which also depends on the composition of the hydrogel used. In this paper, we have prepared low-weight percentage hydrogels, with and without gold nanorods (GNR) for conventional SEM imaging by using two different drying techniques; (1) the critical point drying (CPD) technique and (2) hexamethyldisilazane (HMDS) drying of hydrogels. A qualitative characterization of the GNR-hydrogels was carried out to study the GNRs positioned in the polymer network. The effect of the two different drying methods on the hydrogel morphology were also compared. The use of HMDS as an alternative to the CPD has several advantages involving less parametrical variables for drying, involving less effort, being cost-effective, and requires no equipment use. In addition, choosing an optimized sample preparation method for SEM with optimized imaging parameters is highly important for obtaining accurate information about materials that is not correlated to artifacts. Hence, the results obtained from the preparation methods and SEM imaging parameters in this paper are useful for developing methods for mapping the metal particle distributions in micro-hydrogels by using FIB-SEM and SBFSEM techniques.

This study focuses on enhancing controllable fibrin-based hydrogels for tissue engineering, addressing existing weaknesses. By integrating a novel copolymer, we improve the foundation for cell-based angiogenesis with adaptable structural features. Tissue engineering often faces challenges like waste disposal and nutrient supply beyond the 200 µm diffusion limit. Angiogenesis breaks through this limitation, allowing the construction of larger constructs. Our innovative scaffold combination significantly boosts angiogenesis, resulting in longer branches and more capillary network junctions. The copolymer attached to fibrin fibers enables precise adjustment of hydrogel mechanical-dynamic properties for specific applications. Our material proves effective for angiogenesis, even under suppression factors like suramin. In our study, we prepared fibrin-based hydrogels with and without the copolymer PVP12400-co-GMA10mol%. Using a co-culture system of human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), we analyzed angiogenetic behavior on and within the modified hydrogels. Capillary-like structures were reproducibly formed on different surfaces, demonstrating the general feasibility of three-dimensional endothelial cell networks in fibrin-based hydrogels. This highlights the biomaterial's suitability for in vitro pre-vascularization of biohybrid implants.

Carrageenan (car-), used in the pharmaceutical as well as food industry, is marine sulfated polysaccharides. The carrageenan blends (CB) of kappa (κ-), iota (ι-), and lambda (λ-) of 50/50 weight by weight are multipurpose and biocompatible hydrophilic polymers. They were subjected to adsorption of copper (Cu2+) ions. The aim of the study was to conduct extensive rheological and mechanical studies rendering them suitable for biological purposes. The rheology was conducted at various temperatures using a frequency curve, frequency sweep, loss modulus, and storage modulus analysis. Models of rheology like Ostwald, Bingham, and Modified Bingham models were utilized. The rheological results demonstrated non-Newtonian/pseudo-plastic behavior at various temperatures. The models of rheology demonstrated good flow properties and rheological performance of these materials. These materials could be exploited for their application in pharmaceuticals, food, and cosmetics. Thus, our study reflects that these CB can be safely exploited in the healthcare, pharmaceutical, and food industry. However, further studies should be conducted to evaluate their effectiveness in clinical studies.

Understanding cell migration is a key step to unravel many physiological phenomena and predict several pathologies, like cancer metastasis. In particular, mechanical confinement has been proved to be a key factor in the cellular migration strategy choice. As our insight in the field improves, new tools are needed in order to empower biologists’ analysis capabilities. In this framework, microfluidic devices have been used to engineer the mechanical stimuli and to investigate cellular migration response in a more controlled way. In this work, we will review the existing technologies employed in the realization of microfluidic cellular migration assays, namely soft lithography of PDMS and hydrogels and femtosecond laser micromachining. We will give an overview of the state of the art of these devices, focusing on the different geometrical configurations that have been exploited to study specific aspects of cellular migration. Our scope is to highlight the advantages and possibilities given by each approach and to envisage the future developments in in-vitro migration studies under mechanical confinement in microfluidic devices.

Novel pH responsive semi-interpenetrating polymer hydrogels based on tamarind gum-co-poly(acrylamidoglycolic acid) (TMGA) polymers have been synthesized using simple free radical polymerization in the presence of bis[2-(methacryloyloxy)ethyl] phosphate as a crosslinker and potassium persulfate as a initiator. In addition, these hydrogels have been used as templates for green synthesis of silver nanoparticles (13.4±3.6 nm in diameter, TMGA-Ag) by using leaf extract of Teminalia bellirica as reducing agent. Swelling kinetics and equilibrium swelling behavior of the TMGA hydrogels have been investigated in various pH environment the maxium % equilibrium swelling behavior observed i.e., 2882±1.2. The synthesized hydrogels and silver nanocomposites have been characterized by the UV, FTIR, XRD, SEM and TEM. TMGA and TMGA-Ag hydrogels have been investigated to study the characteristics of drug delivery and antimicrobial study. Doxorubicin hydrochloride, a chemotherapeutic agent successfully encapsulated with maximum encapulstaion efficiency i.e., 69.20±1.2 and performed in vitro release studies in pH physiological and gastric environment at 37 ℃. The drug release behavior is examined with kinetic models such as zero order, first order, Higuchi, Hixson Crowell, Korsmeyer-Peppas. These release data was the best fitted with the Korsemeyer-Peppas transport mechanism with n=0.91. Treatment effect on HCT116 Cell, human colon cancer cells were assessed with cell viability and cell cycle analysis. Antimicrobial activity of TMGA-Ag hydrogels is studied against to Staphylococcus aureus and Klebsiella pneumonia. Finally, the results demonstrate that TMGA and TMGA-Ag are promising candidates for anti-cancer drug delivery and inactivation of pathogenic bacteria, respectively.

Resveratrol is currently considered an option for chemoprevention and treatment of oral cancer, but the instability and unfavorable pharmacokinetics hinder its use in clinical practice. The present study deals with the preparation of resveratrol liposomes by a method that preserves stability and provides payload high enough for chemoprevention and/or treatment of oral cancer. Different temperatures, RSV concentrations and molar fractions, as well as the presence or absence of vitamin C in the hydration media were assayed. Liposome hydrodynamic diameter, polydispersity and zeta potential were evaluated by dynamic light scattering. In vitro biocompatibility, antioxidant activity and permeability were evaluated using TR146 cells and PermeaPad® membranes. Liposomes were included in hydrogels and films, and their suitability for buccal application was evaluated. According to the results, a temperature of 37ºC was optima to efficiently produce the resveratrol liposomes. Vitamin C was found to influence the liposome size, while resveratrol concentration significantly influenced the entrapment efficiency. High cell biocompatibility and potent intracellular antioxidant activity were observed and the inclusion of vitamin C reinforced the antioxidant effects. High permeation across PermeaPad® membranes and efficient uptake by TR146 cells was proved for resveratrol loaded liposomes. Liposomal hydrogels and films appropriated for buccal application were obtained and the payload of the formulations was high enough to produce mucosa concentrations above resveratrol IC50 values reported for cancer cells.

The genetic code evolved by parallel tracks of chaotic and ordered processes. Liquid-liquid phase separation (hydrogels), a chaotic process, constructs diverse membraneless compartments within cells, resulting in regulated hydration and sequestration and concentration of reaction components. Hydrogels relate to chaotic amyloid fiber production. We propose that polyglycine and related hydrogels (i.e. GADV; G is glycine), phase separations, membraneless droplets and amyloid accretions organized protocell domains to drive the earliest evolution of the genetic code and the pre-life to cellular life transition. By contrast, evolution of tRNA, tRNAomes, aminoacyl-tRNA synthetases and translation systems followed highly ordered and systematic pathways, described by well-defined mechanisms and rules. The pathway of evolution of aminoacyl-tRNA synthetases, which tracked evolution of the genetic code, is clarified. Hydrogels and amyloids form a chaotic component, therefore, that complemented otherwise systematic processes. We describe with detail a pre-life world in which hydrogels and amyloids provided the selections of the first life.

Neural tissue engineering, nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system (CNS) repair. It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes, making development of CNS therapeutics challenging. Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society, it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels. Extracellular vesicles (EVs), also known as exosomes, when derived from mesenchymal stem cells, are one of the most promising approaches that have been attempted thus far, as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation. At the same time, advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur, as well as the release of biomolecules facilitating or inducing the reparative processes. This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels. The rationale behind this hypothesis is presented, analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain. This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur. Finally, the importance of including non-human primate (NHP) models in the clinical translation pipeline, as well as the added benefit of multi-modal neuroimage analysis to establish non-invasive, in vivo, quantifiable imaging-based biomarkers for CNS repair are discussed, aiming for more effective and safe clinical translation of such regenerative therapies to humans.

Functional articular cartilage regeneration remains an unmet medical challenge, increasing the interest for innovative biomaterial-based tissue engineering (TE) strategies. Hydrogels, 3D macromolecular networks with hydrophilic groups, present articular cartilage-like features such as high water content and load-bearing capacity. In this study, 3D porous polyethylene glycol diacrylate (PEGDA) hydrogels were fabricated combining the gas foaming technique and an UV-based crosslinking strategy. The 3D porous PEGDA hydrogels were characterized in terms of their physical, structural and mechanical properties. Our results showed that the size of the hydrogels pores can be modulated by varying the initiator concentration. In vitro cytotoxicity tests showed that 3D porous PEGDA hydrogels presented high biocompatibility both with human chondrocytes and osteoblast-like cells. Importantly, the 3D porous PEGDA hydrogels supported the viability and chondrogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells (hBM-MSCs)-based spheroids as demonstrated by the positive staining of typical cartilage extracellular matrix (ECM) (glycosaminoglycans (GAGs)) and upregulation of chondrogenesis marker genes. Overall, the produced 3D porous PEGDA hydrogels presented cartilage-like mechanical properties and supported MSC-spheroid chondrogenesis, highlighting their potential as suitable scaffolds for cartilage TE or disease modelling strategies.

The peril of a 3-dimensional, robust and sustained myocardial restoration by means of Tissue Engineering is that it still remains a largely experimental approach. Prolific protocols have been developed and tested in small and large animals, but as clinical cardiac surgeons, we have not come to the privilege of utilizing any of them in our clinical practice. The question arises: why? The heart is a unique organ, anatomically and functionally. It is not an easy target to replicate with current techniques, or even to support its viability and function. Currently available therapies fail to reverse the loss of functional cardiac tissue, the fundamental pathology remains unaddressed and a heart transplantation is an ultima ratio treatment option. Owing to equivocal results of cell-based therapies, several strategies have been pursued to overcome limitations of the current treatment options. Preclinical data as well as first-in-human studies conducted to date have provided important insights into the understanding of injection-based approaches for myocardial restoration. In the light of the available data, injectable biomaterials suitable for transcatheteter delivery appear to have the highest translational potential,. This article presents a current state-of-the-art in the field of hydrogel-based myocardial restoration therapy.

The necessity to reduce the effect of the greenhouse phenomenon imposed the turn of the food packaging technology to the use of biobased raw materials decreasing the carbon dioxide fingerprint. In this direction alginates derived from brown algae species are of the most promising biobased biopolymers, used for development of edible active coatings, capable to protect food from oxidation/bacterial spoilage. In this study sodium alginate, which was plasticized with glycerol and mixed with a biobased thymol/natural halloysite nanohybrid, was used to develop novel edible active coatings. Active nanocomposite coatings developed by mixing of pure halloysite with sodium alginate/glycerol matrix were produced for comparison purposes. X-Ray and Fourier Transform Infrared Spectroscopy indicated higher compatibility of thymol/halloysite nanohybrid with sodium alginate/glycerol matrix compared to the relevant of pure halloysite. This increased compatibility led to higher tensile properties, water/oxygen barrier properties, and total antioxidant activity. All coating samples were applied as edible active coatings for “tsalafouti” spreadable soft cheese, exhibited a reduction of mesophilic microbial population of more than one log10(cfu/g) unit comparing with uncoated cheese. Moreover, the reduction of mesophilic microbial population was increased by increasing halloysite and thymol content which indicates the sodium alginate/glycerol/thymol/halloysite as promising edible active coatings for “tsalafouti”.