Syneresis of self-crowded calcium-alginate hydrogels as a self-driven athermal aging process.

The assembly of biopolymers into a hydrated elastic network often goes along with syneresis, a spontaneous process during which the hydrogel slowly shrinks and releases solvent. The tendency to syneresis of calcium-alginate hydrogels, widely used biocompatible materials, is a hindrance to applications for which dimensional integrity is crucial. Although calcium-induced aggregation of specific block-sequences has been long known as the microscopic process at work in both primary cross-linking and syneresis, the nature of the coupling between these structural events and the global deswelling flow has remained so far elusive. We have tackled this issue within the regime of entangled pregels that yield highly cross-linked, self-crowded hydrogels with stiff networks. Using an original, stopped-flow extrusion experiment, we have unveiled a robust, stretched-exponential kinetics of shrinking, spanning more than six decades of time and quasi-independent of the alginate concentration. A careful analysis of the puzzling dynamical features of syneresis in these gels has led us to propose that due to the network rigidity, the calcium-fueled, random collapse events that drive solvent locally, are not thermally activated but rather controlled by the average poroelastic flow itself, according to a self-sustained mechanism described here for the first time.

Nanostructured Dense Collagen-Polyester Composite Hydrogels as Amphiphilic Platforms for Drug Delivery.

Associating collagen with biodegradable hydrophobic polyesters constitutes a promising method for the design of medicated biomaterials. Current collagen-polyester composite hydrogels consisting of pre-formed polymeric particles encapsulated within a low concentrated collagen hydrogel suffer from poor physical properties and low drug loading. Herein, an amphiphilic composite platform associating dense collagen hydrogels and up to 50 wt% polyesters with different hydrophobicity and chain length is developed. An original method of fabrication is disclosed based on in situ nanoprecipitation of polyesters impregnated in a pre-formed 3D dense collagen network. Composites made of poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA) but not polycaprolactone (PCL) exhibit improved mechanical properties compared to those of pure collagen dense hydrogels while keeping a high degree of hydration. Release kinetics of spironolactone, a lipophilic steroid used as a drug model, can be tuned over one month. No cytotoxicity of the composites is observed on fibroblasts and keratinocytes. Unlike the incorporation of pre-formed particles, the new process allows for both improved physical properties of collagen hydrogels and controlled drug delivery. The ease of fabrication, wide range of accessible compositions, and positive preliminary safety evaluations of these collagen-polyesters will favor their translation into clinics in wide areas such as drug delivery and tissue engineering.

Core-Shell Pure Collagen Threads Extruded from Highly Concentrated Solutions Promote Colonization and Differentiation of C3H10T1/2 Cells.

The elaboration of scaffolds able to efficiently promote cell differentiation toward a given cell type remains challenging. Here, we engineered dense type I collagen threads with the aim of providing scaffolds with specific morphological and mechanical properties for C3H10T1/2 mesenchymal stem cells. Extrusion of pure collagen solutions at different concentrations (15, 30, and 60 mg/mL) in a PBS 5× buffer generated dense fibrillated collagen threads. For the two highest concentrations, threads displayed a core-shell structure with a marked fibril orientation of the outer layer along the longitudinal axis of the threads. Young's modulus and ultimate tensile stress as high as 1 and 0.3 MPa, respectively, were obtained for the most concentrated collagen threads without addition of any cross-linkers. C3H10T1/2 cells oriented themselves with a mean angle of 15-24° with respect to the longitudinal axis of the threads. Cells penetrated the 30 mg/mL scaffolds but remained on the surface of the 60 mg/mL ones. After three weeks of culture, cells displayed strong expression of the tendon differentiation marker Tnmd, especially for the 30 mg/mL threads. These results suggest that both the morphological and mechanical characteristics of collagen threads are key factors in promoting C3H10T1/2 differentiation into tenocytes, offering promising levers to optimize tissue engineering scaffolds for tendon regeneration.

The physics and chemistry of silica-in-silicates nanocomposite hydrogels and their phycocompatibility.

Silicates-in-silica nanocomposite hydrogels obtained from sodium silicates/colloidal silica mixtures have previously been found to be useful for bacterial encapsulation. However the extension of synthesis conditions and the understanding of their impact on the silica matrix would widen the applicability of this process in terms of encapsulated organisms and the host properties. Here the influence of silicates and the colloidal silica concentration as well as pH conditions on the gel time, the optical properties, the structural and mechanical properties of silica matrices was studied. We show that gel formation is driven by silicate condensation but that the aggregation of silica colloids also has a major influence on the transparency and structure of the nanocomposites. Three different photosynthetic organisms, cyanobacteria Anabaena flos-aquae and two microalgae Chorella vulgaris and Euglena gracilis, were used as probes of the phycocompatibility of the process. The three organisms were highly sensitive to the silicate concentration, which impacts both the gelation time and ionic strength conditions. The Ludox content was crucial for cyanobacteria as it strongly impacts the Young's modulus of the matrices. The detrimental effect of acidic pH on cell suspension was compensated by the silica network. Overall, it is now possible to select optimal encapsulation conditions based on the physiology of the targeted cells, opening wide perspectives for the design of biosensors and bioreactors.

Transcription factor EGR1 directs tendon differentiation and promotes tendon repair.

Tendon formation and repair rely on specific combinations of transcription factors, growth factors, and mechanical parameters that regulate the production and spatial organization of type I collagen. Here, we investigated the function of the zinc finger transcription factor EGR1 in tendon formation, healing, and repair using rodent animal models and mesenchymal stem cells (MSCs). Adult tendons of Egr1-/- mice displayed a deficiency in the expression of tendon genes, including Scx, Col1a1, and Col1a2, and were mechanically weaker compared with their WT littermates. EGR1 was recruited to the Col1a1 and Col2a1 promoters in postnatal mouse tendons in vivo. Egr1 was required for the normal gene response following tendon injury in a mouse model of Achilles tendon healing. Forced Egr1 expression programmed MSCs toward the tendon lineage and promoted the formation of in vitro-engineered tendons from MSCs. The application of EGR1-producing MSCs increased the formation of tendon-like tissues in a rat model of Achilles tendon injury. We provide evidence that the ability of EGR1 to promote tendon differentiation is partially mediated by TGF-ß2. This study demonstrates EGR1 involvement in adult tendon formation, healing, and repair and identifies Egr1 as a putative target in tendon repair strategies.

Frictional dissipation and interfacial glass transition of polymeric solids.

We present single contact friction experiments between a glassy polymer and smooth silica substrates grafted with alkylsilane layers of different coverage densities and morphologies. This allows us to adjust the polymer-substrate interaction strength. We find that, when going from weak to strong interaction, the response of the interfacial junction where shear localizes evolves from that of a highly viscous threshold fluid to that of a plastically deformed glassy solid. This we analyze as resulting from an interaction-induced "interfacial glass transition" helped by pressure.

Solvent control of crack dynamics in a reversible hydrogel.

The resistance to fracture of reversible biopolymer hydrogels is an important control factor of the textural characteristics of food gels (such as gummy candies and aspic preparations). It is also critical for their use in tissue engineering, for which mechanical protection of encapsulated components is needed. Its dependence on loading rate and, recently, on the density and strength of crosslinks has been investigated. But, so far, no attention has been paid to solvent or to environment effects. Here we report a systematic study of crack dynamics in gels of gelatin in water/glycerol mixtures. We show in this model system that increasing solvent viscosity slows down cracks; moreover soaking with solvent markedly increases gel fragility; finally tuning the viscosity by adding a miscible liquid affects crack propagation through diffusive invasion of the crack tip vicinity. The results highlight the fact that fracture occurs by viscoplastic chain pull-out. This mechanism, as well as the related phenomenology, should be common to all reversibly crosslinked (physical) gels.

Self-healing slip pulses along a gel/glass interface.

We present experimental evidence of self-healing shear cracks at a gel/glass interface. This system exhibits two dynamical regimes depending on the driving velocity: steady sliding at high velocity (>V(c) approximately 100--125 microm/s), characterized by a shear-thinning rheology, and periodic stick-slip dynamics at low velocity. In this last regime, slip occurs by propagation of pulses that restick via a "healing instability" occurring when the local sliding velocity reaches the macroscopic transition velocity V(c). At driving velocities close below V(c), the system exhibits complex spatiotemporal behavior.