Fruit water content as an indication of sugar metabolism improves simulation of carbohydrate accumulation in tomato fruit.

Although fleshy fruit is mainly made up of water, little is known about the impact of its water status on sugar metabolism and its composition. In order to verify whether fruit water status is an important driver of carbohydrate composition in tomato fruit, an adaptation of the SUGAR model proposed previously by M. Génard and M. Souty was used. Two versions of the model, with or without integrating the influence of fruit water content on carbohydrate metabolism, were proposed and then assessed with the data sets from two genotypes, Levovil and Cervil, grown under different conditions. The results showed that, for both genotypes, soluble sugars and starch were better fitted by the model when the effects of water content on carbohydrate metabolism were taken into consideration. Water content might play a regulatory role in the carbon metabolism from sugars to compounds other than sugars and starch in Cervil fruit, and from sugars to starch in Levovil fruit. While water content influences tomato fruit carbohydrate concentrations by both metabolism and dilution/dehydration effects in the early developmental stage, it is mainly by dilution/dehydration effects in the late stage. The possible mechanisms underlying the effect of the fruit water content on carbohydrate metabolism are also discussed.

Ascorbate degradation in tomato leads to accumulation of oxalate, threonate and oxalyl threonate.

Ascorbate content in plants is controlled by its synthesis from carbohydrates, recycling of the oxidized forms and degradation. Of these pathways, ascorbate degradation is the least studied and represents a lack of knowledge that could impair improvement of ascorbate content in fruits and vegetables as degradation is non-reversible and leads to a depletion of the ascorbate pool. The present study revealed the nature of degradation products using [14 C]ascorbate labelling in tomato, a model plant for fleshy fruits; oxalate and threonate are accumulated in leaves, as is oxalyl threonate. Carboxypentonates coming from diketogulonate degradation were detected in relatively insoluble (cell wall-rich) leaf material. No [14 C]tartaric acid was found in tomato leaves. Ascorbate degradation was stimulated by darkness, and the degradation rate was evaluated at 63% of the ascorbate pool per day, a percentage that was constant and independent of the initial ascorbate or dehydroascorbic acid concentration over periods of 24 h or more. Furthermore, degradation could be partially affected by the ascorbate recycling pathway, as lines under-expressing monodehydroascorbate reductase showed a slight decrease in degradation product accumulation.

Putting primary metabolism into perspective to obtain better fruits.

Background: One of the key goals of fruit biology is to understand the factors that influence fruit growth and quality, ultimately with a view to manipulating them for improvement of fruit traits. Scope: Primary metabolism, which is not only essential for growth but is also a major component of fruit quality, is an obvious target for improvement. However, metabolism is a moving target that undergoes marked changes throughout fruit growth and ripening. Conclusions: Agricultural practice and breeding have successfully improved fruit metabolic traits, but both face the complexity of the interplay between development, metabolism and the environment. Thus, more fundamental knowledge is needed to identify further strategies for the manipulation of fruit metabolism. Nearly two decades of post-genomics approaches involving transcriptomics, proteomics and/or metabolomics have generated a lot of information about the behaviour of fruit metabolic networks. Today, the emergence of modelling tools is providing the opportunity to turn this information into a mechanistic understanding of fruits, and ultimately to design better fruits. Since high-quality data are a key requirement in modelling, a range of must-have parameters and variables is proposed.

Reduction of MDHAR activity in cherry tomato suppresses growth and yield and MDHAR activity is correlated with sugar levels under high light.

Ascorbate is oxidized into the radical monodehydroascorbate (MDHA) through ascorbate oxidase or peroxidase activity or non-enzymatically by reactive oxygen species. Regeneration of ascorbate from MDHA is ensured by the enzyme MDHA reductase (MDHAR). Previous work has shown that growth processes and yield can be altered by modifying the activity of enzymes that recycle ascorbate; therefore, we have studied similar processes in cherry tomato (Solanum lycopersium L.) under- or overexpressing MDHAR. Physiological and metabolic characterization of these lines was carried out under different light conditions or by manipulating the source-sink ratio. Independently of the light regime, slower early growth of all organs was observed in MDHAR silenced lines, decreasing final fruit yield. Photosynthesis was altered as was the accumulation of hexoses and sucrose in a light-dependent manner in plantlets. Sucrose accumulation was also repressed in young fruits and final yield of MDHAR silenced lines showed a stronger decrease under carbon limitation, and the phenotype was partially restored by reducing fruit load. Ascorbate and MDHA appear to be involved in control of growth and sugar metabolism in cherry tomato and the associated enzymes could be potential targets for yield improvement.

Neuregulin and BDNF induce a switch to NMDA receptor-dependent myelination by oligodendrocytes.

Myelination is essential for rapid impulse conduction in the CNS, but what determines whether an individual axon becomes myelinated remains unknown. Here we show, using a myelinating coculture system, that there are two distinct modes of myelination, one that is independent of neuronal activity and glutamate release and another that depends on neuronal action potentials releasing glutamate to activate NMDA receptors on oligodendrocyte lineage cells. Neuregulin switches oligodendrocytes from the activity-independent to the activity-dependent mode of myelination by increasing NMDA receptor currents in oligodendrocyte lineage cells 6-fold. With neuregulin present myelination is accelerated and increased, and NMDA receptor block reduces myelination to far below its level without neuregulin. Thus, a neuregulin-controlled switch enhances the myelination of active axons. In vivo, we demonstrate that remyelination after white matter damage is NMDA receptor-dependent. These data resolve controversies over the signalling regulating myelination and suggest novel roles for neuregulin in schizophrenia and in remyelination after white matter damage.

Remarkable reproducibility of enzyme activity profiles in tomato fruits grown under contrasting environments provides a roadmap for studies of fruit metabolism.

To assess the influence of the environment on fruit metabolism, tomato (Solanum lycopersicum 'Moneymaker') plants were grown under contrasting conditions (optimal for commercial, water limited, or shaded production) and locations. Samples were harvested at nine stages of development, and 36 enzyme activities of central metabolism were measured as well as protein, starch, and major metabolites, such as hexoses, sucrose, organic acids, and amino acids. The most remarkable result was the high reproducibility of enzyme activities throughout development, irrespective of conditions or location. Hierarchical clustering of enzyme activities also revealed tight relationships between metabolic pathways and phases of development. Thus, cell division was characterized by high activities of fructokinase, glucokinase, pyruvate kinase, and tricarboxylic acid cycle enzymes, indicating ATP production as a priority, whereas cell expansion was characterized by enzymes involved in the lower part of glycolysis, suggesting a metabolic reprogramming to anaplerosis. As expected, enzymes involved in the accumulation of sugars, citrate, and glutamate were strongly increased during ripening. However, a group of enzymes involved in ATP production, which is probably fueled by starch degradation, was also increased. Metabolites levels seemed more sensitive than enzymes to the environment, although such differences tended to decrease at ripening. The integration of enzyme and metabolite data obtained under contrasting growth conditions using principal component analysis suggests that, with the exceptions of alanine amino transferase and glutamate and malate dehydrogenase and malate, there are no links between single enzyme activities and metabolite time courses or levels.

Metabolomic profiling in tomato reveals diel compositional changes in fruit affected by source-sink relationships.

A detailed study of the diurnal compositional changes was performed in tomato (Solanum lycopersicum cv. Moneymaker) leaves and fruits. Plants were cultivated in a commercial greenhouse under two growth conditions: control and shaded. Expanding fruits and the closest mature leaves were harvested during two different day/night cycles (cloudy or sunny day). High-throughput robotized biochemical phenotyping of major compounds, as well as proton nuclear magnetic resonance and mass spectrometry metabolomic profiling, were used to measure the contents of about 70 metabolites in the leaves and 60 metabolites in the fruits, in parallel with ecophysiological measurements. Metabolite data were processed using multivariate, univariate, or clustering analyses and correlation networks. The shaded carbon-limited plants adjusted their leaf area, decreased their sink carbon demand and showed subtle compositional modifications. For source leaves, several metabolites varied along a diel cycle, including those directly linked to photosynthesis and photorespiration. These metabolites peaked at midday in both conditions and diel cycles as expected. However, transitory carbon storage was limited in tomato leaves. In fruits, fewer metabolites showed diel fluctuations, which were also of lower amplitude. Several organic acids were among the fluctuating metabolites. Diel patterns observed in leaves and especially in fruits differed between the cloudy and sunny days, and between the two conditions. Relationships between compositional changes in leaves and fruits are in agreement with the fact that several metabolic processes of the fruit appeared linked to its momentary supply of sucrose.

Effects of acute ozone stress on reproductive traits of tomato, fruit yield and fruit composition.

BACKGROUND: Tomato is sensitive to ozone. Fruit growth and composition are altered under ozone stress by modification of reproductive development. Fifty-one-day-old plants were exposed to three concentrations of ozone (200, 350 and 500 µg m(-3)) for 4 h. RESULTS: Ozone reduced well-developed fruit number and fruit size, but it did not significantly affect flowering rate and fruit setting rate. The effect of ozone depends on organ developmental stage at the time of ozone application, as flowers and young fruits at the time of ozone exposure were more affected. Contents of total soluble sugars (total SS), total organic acids (total OA) and ascorbic acid (AsA) increased in fruits harvested from ozone-treated plants. Tomato fruit composition was altered under ozone stress, leading to a lower sugar:acid ratio. These changes were mostly due to increased contents of malic acid, ascorbate and glucose despite a decrease in sucrose. CONCLUSION: Acute ozone exposure up to 500 µg m(-3) greatly influences tomato fruit quality. As final fruit yield was not significantly reduced, it highlighted that there may be compensatory mechanisms present in the reproductive structures of tomato. Further research would be necessary to determine how reproductive traits are affected by repeated ozone exposure or longer-term exposure.

Influence of physico-chemical properties of two lipoxin emulsion-loaded hydrogels on pre-polarized macrophages: a comparative analysis.

Inflammation, a crucial defense mechanism, must be rigorously regulated to prevent the onset of chronic inflammation and subsequent tissue damage. Specialized pro resolving mediators (SPMs) such as lipoxin A4 (LXA4) have demonstrated their ability to facilitate the resolution of inflammation by orchestrating a transition of M1 pro-inflammatory macrophages towards an anti-inflammatory M2 phenotype. However, the hydrophobic and chemically labile nature of LXA4 necessitates the development of a delivery system capable of preserving its integrity for clinical applications. In this study, two types of emulsion were formulated using different homogenization processes:mechanical overhead stirrer (MEB for blank Emulsion and MELX for LXA4 loaded-Emulsion) or Luer-lock syringes (SEB for blank Emulsion and SELX for LXA4 loaded-Emulsion)). Following characterization, including size and droplet morphology assessment by microscopy, the encapsulation efficiency (EE) was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). To exert control over LXA4 release, these emulsions were embedded within silanized hyaluronic acid hydrogels. A comprehensive evaluation, encompassing gel time, swelling, and degradation profiles under acidic, basic, and neutral conditions, preceded the assessment of LXA4 cumulative release using LC-MS/MS. Physicochemical results indicate that H-MELX (Mechanical overhead stirrer LXA4 Emulsion loaded-Hydrogel) exhibits superior efficiency over H-SELX (Luer-lock syringes LXA4 Emulsion loaded-Hydrogel). While both formulations stimulated pro-inflammatory cytokine secretion and promoted a pro-inflammatory macrophage phenotype, LXA4 emulsion-loaded hydrogels displayed a diminished pro-inflammatory activity compared to blank emulsion-loaded hydrogels. These findings highlight the biological efficacy of LXA4 within both systems, with H-SELX outperforming H-MELX in terms of efficiency. To the best of our knowledge, this is the first successful demonstration of the biological efficacy of LXA4 emulsion-loaded hydrogel systems on macrophage polarization. These versatile H-MELX and H-SELX formulations can be customized to enhance their biological activity making them promising tools to promote the resolution of inflammation in diverse clinical applications.

Light-dependent regulation of ascorbate in tomato by a monodehydroascorbate reductase localized in peroxisomes and the cytosol.

Ascorbate is a powerful antioxidant in plants, and its levels are an important quality criteria in commercial species. Factors influencing these levels include environmental variations, particularly light, and the genetic control of its biosynthesis, recycling and degradation. One of the genes involved in the recycling pathway encodes a monodehydroascorbate reductase (MDHAR), an enzyme catalysing reduction of the oxidized radical of ascorbate, monodehydroascorbate, to ascorbate. In plants, MDHAR belongs to a multigene family. Here, we report the presence of an MDHAR isoform in both the cytosol and peroxisomes and show that this enzyme negatively regulates ascorbate levels in Solanum lycopersicum (tomato). Transgenic lines overexpressing MDHAR show a decrease in ascorbate levels in leaves, whereas lines where MDHAR is silenced show an increase in these levels in both fruits and leaves. Furthermore, the intensity of these differences is light dependent. The unexpected effect of this MDHAR on ascorbate levels cannot be explained by changes in the expression of Smirnoff-Wheeler pathway genes, or the activity of enzymes involved in degradation (ascorbate peroxidase) or recycling of ascorbate (dehydroascorbate reductase and glutathione reductase), suggesting a previously unidentified mechanism regulating ascorbate levels.

A diminution in ascorbate oxidase activity affects carbon allocation and improves yield in tomato under water deficit.

The regulation of carbon allocation between photosynthetic source leaves and sink tissues in response to stress is an important factor controlling plant yield. Ascorbate oxidase is an apoplastic enzyme, which controls the redox state of the apoplastic ascorbate pool. RNA interference was used to decrease ascorbate oxidase activity in tomato (Solanum lycopersicum L.). Fruit yield was increased in these lines under three conditions where assimilate became limiting for wild-type plants: when fruit trusses were left unpruned, when leaves were removed or when water supply was limited. Several alterations in the transgenic lines could contribute to the improved yield and favour transport of assimilate from leaves to fruits in the ascorbate oxidase lines. Ascorbate oxidase plants showed increases in stomatal conductance and leaf and fruit sugar content, as well as an altered apoplastic hexose:sucrose ratio. Modifications in gene expression, enzyme activity and the fruit metabolome were coherent with the notion of the ascorbate oxidase RNAi lines showing altered sink strength. Ascorbate oxidase may therefore be a target for strategies aimed at improving water productivity in crop species.

Ascorbate as seen through plant evolution: the rise of a successful molecule?

Ascorbate is a widespread and efficient antioxidant that has multiple functions in plants, traditionally associated with the reactions of photosynthesis. This review aims to look at ascorbate from an evolutionary perspective. Cyanobacteria, algae, and bryophytes contain lower concentrations of ascorbate than higher plants, where the molecule accumulates in high concentrations in both photosynthetic and non-photosynthetic organs and tissues. This increase in ascorbate concentration is paralleled by an increase in the number of isoforms of ascorbate peroxidase and the ascorbate regenerating enzymes mono- and dehydroascorbate reductase. One way of understanding the rise in ascorbate concentrations is to consider ascorbate as a molecule among others that has been subject to selection pressures during evolution, due to its cost or benefit for the cell and the organism. Ascorbate has a low cost in terms of synthesis and toxicity, and its benefits include protection of the glutathione pool and proper functioning of a range of enzymes. The hypothesis presented here is that these features would have favoured increasing roles for the molecule in the development and growth of multicellular organisms. This review then focuses on this diversity of roles for ascorbate in both photosynthetic and non-photosynthetic tissues of higher plants, including fruits and seeds, as well as further functions the molecule may possess by looking at other species. The review also highlights one of the trade-offs of domestication, which has often reduced or diluted ascorbate content in the quest for increased fruit growth and yield, with unknown consequences for the corresponding functional diversity, particularly in terms of stress resistance and adaptive responses to the environment.

Light affects ascorbate content and ascorbate-related gene expression in tomato leaves more than in fruits.

Little is known about the light regulation of vitamin C synthesis in fruits. In contrast, previous studies in leaves revealed that VTC2 (coding for GDP-L: -galactose phosphorylase) was one of the key genes up-regulated by light in leaves. Our objective was to determine how the expression of ascorbate (AsA) synthesis genes in tomato (Solanum lycopersicum) was modified according to light irradiance in both leaves and fruits. Seven days of shading strongly decreased total ascorbate (reduced and oxidized form) content in leaves (50%) and to a lesser extent in fruits (10%). Among the last six steps of AsA biosynthesis, only two genes, VTC2 and GPP1 (one of the two unigenes coding for L: -galactose-1-P phosphatase in tomato), were down-regulated by long-term shading in red ripe fruits, compared to seven genes regulated in leaves. This underlines that light affects AsA-related gene expression more in leaves than in ripening fruits. Moreover, this study reveals strong daily changes in transcript levels of enzymes of the AsA biosynthetic pathway in leaves (11 of the 12 studied genes showed significant changes in their expression pattern). Among those genes, we found that diurnal variation in transcript levels of VTC2 and GME1 correlated to leaf AsA content measured 8 h later. This study provides a new hypothesis on the role of GME1 in addition to VTC2 in light-regulated AsA biosynthesis.

Conservation Biological Control of Codling Moth (Cydia pomonella): Effects of Two Aromatic Plants, Basil (Ocimum basilicum) and French Marigolds (Tagetes patula).

The addition of flowering companion plants within or around crop fields is a promising strategy to strengthen pest regulation by their natural enemies. Aromatic plants are frequently used as companion plants, but their effects on natural enemies remain unclear under field conditions. Here, we evaluated the effects of two aromatic plant species on the parasitism of the codling moth (Cydia pomonella) and the recruitment of predatory arthropods (spiders, earwigs) in a factorial field experiment. Apple trees were intercropped with basil (Ocimum basilicum), French marigolds (Tagetes patula), or ryegrass (Lolium perenne). The association between apple trees and O. basilicum increases codling moth parasitism, but does not affect arthropod predator abundances. Furthermore, we find a general negative effect of T. patula on arthropod diversities and abundances, including the pest and its natural enemies. Finally, changes in the parasitism rate and arthropod community structure due to the aromatic plants do not reduce codling moth density or associated apple damage. Further experiments are needed to determine the mechanisms involved in aromatic plant effects on pest repellence and on natural enemy recruitment (volatile organic compound composition, floral resource supply, or pest density dependence).

Virtual profiling: a new way to analyse phenotypes.

Simulation models can be used to perform virtual profiling in order to analyse eco-physiological processes controlling plant phenotype. To illustrate this, an eco-physiological model has been used to compare and contrast the status of a virtual fruit system under two situations of carbon supply. The model simulates fruit growth, accumulation of sugar, citric acid and water, transpiration, respiration and ethylene emission, and was successfully tested on peach (Prunus persica L. Batsch) for two leaf-to-fruit ratios (6 and 18 leaves per fruit). The development stage and the variation in leaf number had large effects of the fruit model variables dealing with growth, metabolism and fruit quality. A sensitivity analysis showed that changing a single parameter value, which could correspond to a genotypic change induced by a mutation, either strongly affects most of the processes, or affects a specific process or none. Correlation analysis showed that, in a complex system such as fruit, the intensity of many physiological processes and quality traits co-varies. It also showed unexpected co-variations resulting from emergent properties of the system. This virtual profiling approach opens a new route to explore the impact of mutations, or naturally occurring genetic variations, under differing environmental conditions.

Impact of temporary nitrogen deprivation on tomato leaf phenolics.

Reducing the use of pesticides represents a major challenge of modern agriculture. Plants synthesize secondary metabolites such as polyphenols that participate in the resistance to parasites. The aim of this study was to test: (1) the impact of nitrogen deficiency on tomato (Solanum lycopersicum) leaf composition and more particularly on two phenolic molecules (chlorogenic acid and rutin) as well as on the general plant biomass; and (2) whether this effect continued after a return to normal nitrogen nutrition. Our results showed that plants deprived of nitrogen for 10 or 19 days contained higher levels of chlorogenic acid and rutin than control plants. In addition, this difference persisted when the plants were once again cultivated on a nitrogen-rich medium. These findings offer interesting perspectives on the use of a short period of deprivation to modulate the levels of compounds of interest in a plant.

Non-host volatiles disturb the feeding behavior and reduce the fecundity of the green peach aphid, Myzus persicae.

BACKGROUND: The association of crops of value with companion plants could be one of the strategies to reduce the harmful effects of pests. We hypothesize that volatile organic compounds (VOCs) emitted by some aromatic plants may negatively impact M. persicae, disturbing its feeding behavior and consequently its reproduction. RESULTS: VOCs emitted from six potential companion plant species affected the reproduction of M. persicae feeding on pepper plants, Capsicum annuum. Reproduction of M. persicae was reduced when exposed to VOCs from leaves of Ocimum basilicum and flowers of Tagetes patula. Thus, species and phenology of the companion plant can influence the effect. The VOCs from O. basilicum and T. patula also reduced phloem feeding by the aphids based on electropenetrography (EPG). CONCLUSION: The reduced fecundity of M. persicae could be linked to aphid feeding disruption provoked by the VOCs emitted by O. basilicum in the vegetative stage or T. patula cv. Nana in the flowering stage. © 2020 Society of Chemical Industry.

Injectable silanized hyaluronic acid hydrogel/biphasic calcium phosphate granule composites with improved handling and biodegradability promote bone regeneration in rabbits.

Biphasic calcium phosphate (BCP) granules are osteoconductive biomaterials used in clinics to favor bone reconstruction. Yet, poor cohesivity, injectability and mechanical properties restrain their use as bone fillers. In this study, we incorporated BCP granules into in situ forming silanized hyaluronic acid (Si-HA) and hydroxypropylmethylcellulose (Si-HPMC) hydrogels. Hydrogel composites were shown to be easily injectable (F < 30 N), with fast hardening properties (<5 min), and similar mechanical properties (E∼ 60 kPa). In vivo, both hydrogels were well tolerated by the host, but showed different biodegradability with Si-HA gels being partially degraded after 21d, while Si-HPMC gels remained stable. Both composites were easily injected into critical size rabbit defects and remained cohesive. After 4 weeks, Si-HPMC/BCP led to poor bone healing due to a lack of degradation. Conversely, Si-HA/BCP composites were fully degraded and beneficially influenced bone regeneration by increasing the space available for bone ingrowth, and by accelerating BCP granules turnover. Our study demonstrates that the degradation rate is key to control bone regeneration and that Si-HA/BCP composites are promising biomaterials to regenerate bone defects.

hiPSC-Derived Neurons Provide a Robust and Physiologically Relevant In Vitro Platform to Test Botulinum Neurotoxins.

Botulinum neurotoxins (BoNTs) are zinc metalloproteases that block neurotransmitter release at the neuromuscular junction (NMJ). Their high affinity for motor neurons combined with a high potency have made them extremely effective drugs for the treatment of a variety of neurological diseases as well as for aesthetic applications. Current in vitro assays used for testing and developing BoNT therapeutics include primary rodent cells and immortalized cell lines. Both models have limitations concerning accuracy and physiological relevance. In order to improve the translational value of preclinical data there is a clear need to use more accurate models such as human induced Pluripotent Stem Cells (hiPSC)-derived neuronal models. In this study we have assessed the potential of four different human iPSC-derived neuronal models including Motor Neurons for BoNT testing. We have characterized these models in detail and found that all models express all proteins needed for BoNT intoxication and showed that all four hiPSC-derived neuronal models are sensitive to both serotype A and E BoNT with Motor Neurons being the most sensitive. We showed that hiPSC-derived Motor Neurons expressed authentic markers after only 7 days of culture, are functional and able to form active synapses. When cultivated with myotubes, we demonstrated that they can innervate myotubes and induce contraction, generating an in vitro model of NMJ showing dose-responsive sensitivity BoNT intoxication. Together, these data demonstrate the promise of hiPSC-derived neurons, especially Motor Neurons, for pharmaceutical BoNT testing and development.

In Situ Forming, Silanized Hyaluronic Acid Hydrogels with Fine Control Over Mechanical Properties and In Vivo Degradation for Tissue Engineering Applications.

In situ forming hydrogels that can be injected into tissues in a minimally-invasive fashion are appealing as delivery vehicles for tissue engineering applications. Ideally, these hydrogels should have mechanical properties matching those of the host tissue, and a rate of degradation adapted for neo-tissue formation. Here, the development of in situ forming hyaluronic acid hydrogels based on the pH-triggered condensation of silicon alkoxide precursors into siloxanes is reported. Upon solubilization and pH adjustment, the low-viscosity precursor solutions are easily injectable through fine-gauge needles prior to in situ gelation. Tunable mechanical properties (stiffness from 1 to 40 kPa) and associated tunable degradability (from 4 days to more than 3 weeks in vivo) are obtained by varying the degree of silanization (from 4.3% to 57.7%) and molecular weight (120 and 267 kDa) of the hyaluronic acid component. Following cell encapsulation, high cell viability (> 80%) is obtained for at least 7 days. Finally, the in vivo biocompatibility of silanized hyaluronic acid gels is verified in a subcutaneous mouse model and a relationship between the inflammatory response and the crosslink density is observed. Silanized hyaluronic acid hydrogels constitute a tunable hydrogel platform for material-assisted cell therapies and tissue engineering applications.