Aurelien Forget

From microporous regular frameworks to mesoporous materials with ultrahigh surface area: Dynamic reorganization of porous polymer networks

High surface area organic materials featuring both micro- and mesopores were synthesized under ionothermal conditions via the formation of polyaryltriazine networks. While the polytrimerization of nitriles in zinc chloride at 400 degrees C produces microporous polymers, higher reaction temperatures induce the formation of additional spherical mesopores with a narrow dispersity. The nitrogen-rich carbonaceous polymer materials thus obtained present surface areas and porosities up to 3300 m(2) g(-1) and 2.4 cm(3) g(-1), respectively. The key point of this synthesis relies on the occurrence of several high temperature polymerization reactions, where irreversible carbonization reactions coupled with the reversible trimerization of nitriles allow the reorganization of the dynamic triazine network. The ZnCl2 molten salt fulfills the requirement of a high temperature solvent, but is also required as catalyst. Thus, this dynamic polymerization system provides not only highly micro- and mesoporous materials, but also allows controlling the pore structure in amorphous organic materials.

Polysaccharide hydrogels with tunable stiffness and provasculogenic properties via α-helix to β-sheet switch in secondary structure

Mechanical aspects of the cellular environment can influence cell function, and in this context hydrogels can serve as an instructive matrix. Here we report that physicochemical properties of hydrogels derived from polysaccharides (agarose, κ-carrageenan) having an α-helical backbone can be tailored by inducing a switch in the secondary structure from α-helix to β-sheet through carboxylation. This enables the gel modulus to be tuned over four orders of magnitude (G′ 6 Pa–3.6 × 104 Pa) independently of polymer concentration and molecular weight. Using carboxylated agarose gels as a screening platform, we demonstrate that soft-carboxylated agarose provides a unique environment for the polarization of endothelial cells in the presence of soluble and bound signals, which notably does not occur in fibrin and collagen gels. Furthermore, endothelial cells organize into freestanding lumens over 100 μm in length. The finding that a biomaterial can modulate soluble and bound signals provides impetus for exploring mechanobiology paradigms in regenerative therapies.

Antibacterial and Anti-Inflammatory pH-Responsive Tannic Acid-Carboxylated Agarose Composite Hydrogels for Wound Healing

pH-sensitive hydrogels play an important role in controlled drug release applications and have the potential to impact the management of wounds. In this study, we report the fabrication of novel carboxylated agarose/tannic acid hydrogel scaffolds cross-linked with zinc ions for the pH-controlled release of tannic acid. The resulting hydrogels exhibited negligible release of tannic acid at neutral and alkaline pH and sustained release at acidic pH, where they also displayed maximum swelling. The hydrogels also displayed favorable antibacterial and anti-inflammatory properties, and a lack of cytotoxicity toward 3T3 fibroblast cell lines. In simulated wound assays, significantly greater cell migration and proliferation was observed for cells exposed to tannic acid hydrogel extracts. In addition, the tannic acid hydrogels were able to suppress NO production in stimulated human macrophages in a concentration-dependent manner, indicating effective anti-inflammatory activity. Taken together, the cytocompatibility, antibacterial, and anti-inflammatory characteristics of these novel pH-sensitive hydrogels make them promising candidates for wound dressings.

Mechanically Tunable Bioink for 3D Bioprinting of Human Cells

This study introduces a thermogelling bioink based on carboxylated agarose (CA) for bioprinting of mechanically defined microenvironments mimicking natural tissues. In CA system, by adjusting the degree of carboxylation, the elastic modulus of printed gels can be tuned over several orders of magnitudes (5-230 Pa) while ensuring almost no change to the shear viscosity (10-17 mPa) of the bioink solution; thus enabling the fabrication of 3D structures made of different mechanical domains under identical printing parameters and low nozzle shear stress. Human mesenchymal stem cells printed using CA as a bioink show significantly higher survival (95%) in comparison to when printed using native agarose (62%), a commonly used thermogelling hydrogel for 3D-bioprinting applications. This work paves the way toward the printing of complex tissue-like structures composed of a range of mechanically discrete microdomains that could potentially reproduce natural mechanical aspects of functional tissues.

Mechanically tailored agarose hydrogels through molecular alloying with β-sheet polysaccharides.

There is mounting evidence that the mechanical property of tissues provides important cues that control cell fate. However, implementation of hydrogels with tunable physicochemical properties is limited due to the challenges associated with crosslinking chemistries. It has been recently shown that mechanically well-defined injectable polysaccharide hydrogels can be engineered by switching their secondary structure from an α-helix to a β-sheet. Based on these findings, a new concept is presented to tailor the mechanical properties of agarose hydrogels via the blending with the β-sheet-rich carboxylated derivative. Using this simple strategy, gels with predictable roughness, fiber organization, and shear modulus ranging from 0.1 to 100 kPa can be formulated. Hydrogels whose mechanical properties can be precisely tailored in vivo without the recourse for chemical reactions are expected to play an important role in implementing mechanobiology paradigms in de novo tissue engineering.

Surface Functionality as a Means to Impact Polymer Nanoparticle Size and Structure

When polymeric nanoparticles (NPs) are formed by nanoprecipitation, which is a nucleation-growth process, the control over size requires changing the polymer concentration or solvent composition. Here, we demonstrate that the NP size can be controlled independent of polymer variables by introducing a polyelectrolyte (PE) in the aqueous phase. PEs that exhibit hydrogen bonding (H-bonding) yield a reduction in NP size, whereas PEs that do not possess this characteristic promote the formation of larger NPs. The observed effect can be attributed to the formation of a diffusional barrier around the NP in the form of a dense shell. This principle of controlling NP size is not limited to polymers and can also be employed in the production of lipid NPs.

Discovering Cell-Adhesion Peptides in Tissue Engineering: Beyond RGD

As an alternative to natural extracellular matrix (ECM) macromolecules, cell-adhesion peptides (CAPs) have had tremendous impact on the design of cell culture platforms, implants, and wound dressings. However, only a handful of CAPs have been utilized. The discrepancy in ECM composition strongly affects cell behavior, so it is paramount to reproduce such differences in synthetic systems. This Opinion article presents strategies inspired from high-throughput screening techniques implemented in drug discovery to exploit the potential of a growing CAP library. These strategies are expected to promote the use of a broader spectrum of CAPs, which in turn could lead to improved cell culture models, implants, and wound dressings.

Biomaterials based strategies for engineering tumor microenvironment

Tissue engineering aims to gain mechanistic insights into human diseases and to develop new treatment protocols. Although 2-dimensional (2-D) flat petri dish culture and in vivo disease-based models are the industrial gold standards for understanding the underlying disease pathophysiology and for drug screening/testing, they are associated with certain limitations. While the 2-D cell culture systems fail to mimic in vivo signaling, animal-based disease models are associated with long incubation period, high cost, ethical constraints as well as depiction of human pathology in different species. Therefore, there has been a paradigm shift towards the development of 3-dimensional (3-D) based in vitro disease models. These models act as bridging gaps between the aforementioned conventional strategies thereby fastening clinical translation. In this regard, biomedical engineering plays a key role towards the development of tissue engineering based 3-D disease models. These models have demonstrated success in recapitulating human diseases in terms of in vivo morphology and signaling. This chapter will present examples of biomaterials-based 3-D engineered disease models with a focus on cancer.