Milena Lama

Relation structure-propriétés de gels denses de collagène produits par injection de collagène séché par atomisation: Injecter des gels denses de collagène pour obtenir des matériaux 3D, biomimétiques en termes d’architecture et de propriétés mécaniques, est un enjeu pour la régénération tissulaire car cela pourrait éviter des chirurgies lourdes. Des solutions de collagène très concentrées ont la capacité de former des mésophases dont la géométrie mime celle des tissus biologiques. Ainsi, il est possible d’obtenir des gels de collagène en 3D possédant une meilleure tenue mécanique, sans utiliser de réticulant chimique qui peut induire des inflammations. Cependant, l’injection de solutions de collagène très concentrées est empêchée par l’augmentation drastique de leur viscosité. Comment associer biomimétisme et injectabilité de gels denses de collagène ? Nous proposons de concentrer des solutions acides de collagène par atomisation, produisant des billes denses de collagène. Une simple pesée de ces billes permet de déterminer la concentration des gels. Mélangées à un solvant aqueux, elles sont injectées dans un moule imitant un défaut tissulaire. La fibrillogénèse, induite in vitro dans les solutions de collagène, forme des gels rigides. Les microscopies optique et électroniques révèlent des organisations issues de l’auto-assemblage du collagène à l’échelle macroscopique, selon la concentration en collagène (de 3wt% à 8wt%). Le comportement mécanique des gels imite celui des tissus biologiques, et est fortement lié à l’ultrastructure des fibrilles de collagène. Cette étude ouvre des perspectives dans le domaine de la régénération tissulaire en dessinant le cadre d’une librairie tissulaire, contenant des matériaux en collagène biomimétiques, injectables et denses, permettant l’usage de procédures chirurgicales moins invasives.

While carboxymethyl cellulose (CMC)—a biocompatible and water-soluble cellulose derivative—holds promise for biomedical applications, challenges remain in synthesizing CMC-based hydrogels with covalent crosslinking through free radical polymerization without requiring complex, multi-step processes. In this study, we introduce a facile one-pot strategy that combines CMC with acrylamide (AAm) under cryogelation and low-intensity UV irradiation to achieve covalent bonding and a high polymerization yield. The resulting polyacrylamide/carboxymethyl cellulose (PAAm/CMC) porous gels were systematically evaluated for their chemical, physical, thermal, and drug-release properties, with a focus on the effects of AAm concentration and polymerization temperature (frozen vs. room temperature). Notably, the cryogel synthesized with 2.5 M AAm (PC2.5) exhibited significantly enhanced mechanical properties—that is, an 8.4-fold increase in tensile modulus and a 26-fold increase in toughness—compared with the non-cryo gel. Moreover, PC2.5 demonstrated excellent cyclic compression stability in water and phosphate-buffered saline (PBS), with less than 10% reduction in modulus after 100 cycles. These increases in the mechanical properties of PC2.5 are attributed to the formation of macropores with high polymer density and high crosslinking density at the pore walls. PC2.5 also showed slower drug release in PBS and good cytocompatibility. This study presents a simplified and efficient route for fabricating mechanically robust, covalently crosslinked PAAm/CMC cryogels, highlighting their strong potential for biomedical applications in drug delivery systems.

Mineralized biological tissues rich in type I collagen (e.g., bone and dentin) exhibit complex anisotropic suprafibrillar organizations in which the organic and inorganic moieties are intimately coassembled over several length scales. Above a critical size, a defect in such tissue cannot be self-repaired. Biomimetic materials with a composition and microstructure similar to that of bone have been shown to favorably influence bone regeneration. This highlights the value of developing a similar formulation in an injectable form to enable minimally invasive techniques. Here, we report on the fabrication and application potential of an injectable collagen/CHA (carbonated hydroxyapatite) cell-free hydrogel. The organic part consists of spray-dried nondenatured and dense collagen microparticles, while the inorganic part consists of biomimetic apatite mineral. By mixing both powders at desired tissue-like ratios with an aqueous solvent in one step, spontaneous co-self-assembly occurs, leading to the formation of a mineralized matrix with suprafibrillar tissue-like features thanks to the induced liquid crystalline properties of collagen on one hand and apatite on the other hand. When injected into soft tissue, the mineralized collagen hydrogel free of chemical cross-linking agents exhibits suitable cohesion and is biocompatible. Preliminary in vitro tests in a tooth cavity model show its integration onto dentin with a biomimetic interface. Based on the results, this versatile injectable mineralized collagen hydrogel shows promising potential as a biomaterial for bone tissue repair and mineralized tissue-like ink for bioprinting applications.

Bone, consisting of calcium phosphate minerals, rigid collagen fibrils, and acidic proteins, exhibits stiff and tough mechanical properties. On a molecular scale, covalent cross-linking in proteins and ionic interactions within proteins and at the protein-mineral boundary contribute to bone's toughness. In addition, hierarchical structures, like the sponge-like arrangement, are also crucial for the energy dissipation system in bone. Inspired by the multiple sacrificial bonds found in bone, we developed a soft/hard composite made up of two components with contrasting mechanical properties: a porous calcium phosphate skeleton and an acidic polymer hydrogel matrix. The porous ceramic skeleton alone is extremely rigid but brittle. However, the presence of the hydrogel matrix transforms the brittle nature of the porous ceramic skeleton into a soft/hard composite with stretchable and tough characteristics. The composite exhibits significant energy dissipation due to the fracture of the ceramic skeleton under small deformation, while catastrophic failure of the composite is prevented because the hybridized matrix disperses the damage throughout the entire sample. The Ca²⁺-mediated ionic bonding within the matrix hydrogel and at the boundary between the gel and skeleton effectively transfers the stress, enhancing the composite's toughness. Furthermore, the cyclic deformation generates new bare surfaces on the ceramic skeleton, leading to increased interaction between the matrix and these new surfaces, which enhances the composite's healing capability. This study demonstrates that the concept of multiple sacrificial bonds in bone is a smart strategy for designing polymer–ceramic composites with excellent mechanical properties.

Structurally colored materials with a color mixing effect are developed using SiO₂–ZrN core–shell particles, where ZrN nanoparticles used as shells exhibited localized surface plasmon resonances (LSPRs). ZrN nanoparticles (10–30 nm) are attached to monodispersed SiO₂ particles by modifying SiO₂ particles with polymers. The attached ZrN nanoparticles exhibited a plasmon resonance absorption band at 700 nm. These SiO₂–ZrN core–shell particles have a highly monodisperse particle size and assemble into a particle‐stacked film with Bragg diffraction light in the visible spectrum. The particle‐stacked film of the SiO₂–ZrN core–shell particles exhibited the maximum reflection depending on the particle size of the SiO₂ core. The ratio of the reflection intensity in the long‐wavelength region corresponding to the ZrN absorption to that in the short‐wavelength region of the particle‐stacked film containing the ZrN shell is less than that of the ratio in only SiO₂ particle‐stacked film. The results reveal that these particle‐stacked films exhibit a “color mixing effect” that combines specific wavelength absorption through plasmon resonance and specific wavelength diffraction owing to the periodic structure without using precious metals.

Anisotropic photonic hydrogels with alternatively stackedpoly(dodecylglyceryl itaconate) (PDGI) bilayers and polyacrylamide (PAAm) gellayers are unique soft materials with various functions. It is knownthat to form the lamellar phase of bilayers, a small amount of co-surfactantsodium dodecyl sulfate (SDS) should be present in the precursor monomersolutions of the gels. However, little is known about the influenceof the co-surfactant on the structure of bilayers and on the mechanicalproperties of such photonic hydrogels. Herein, we chose several co-surfactantsand studied the effect of the co-surfactants on the self-assemblybehavior of the bilayers and on the mechanical properties of the resultingphotonic hydrogels. A macroscopically aligned lamellar phase couldbe induced for all the co-surfactants. Interestingly, the mechanicalresponse of the photonic hydrogels sensitively depends on the chemicalstructure of the co-surfactant, especially at large deformation. Wehypothesize that doping by small amounts of co-surfactants dramaticallychanges the anchoring strength and density of PAAm strands onto thebilayer surface, thereby influencing the load transfer efficiencyfrom the bilayer to the PAAm gel layer at large deformation and therupture of the bilayer. This work provides new understanding in themolecular mechanisms of deformation and strengthening in this softand anisotropic nanocomposite, helping to design more robust photonichydrogels.

Biological tissues rich in type I collagen exhibit specific hierarchical fibrillar structures together with remarkable mechanical toughness. However, the role of collagen alone in their mechanical response at different structural levels is not fully understood. Here, it is proposed to rationalize such challenging interplay from a materials science perspective through the subtle control of this protein self‐assembly in vitro. It is relied on a spray‐processing approach to readily use the collagen phase diagram and set a palette of biomimetic self‐assembled collagen gels in terms of suprafibrillar organization. Their mechanical responses unveil the involvement of mechanisms occurring either at fibrillar or suprafibrillar scales. Noticeably, both modulus at early stage of deformations and tensile toughness probe the suprafibrillar organization, while durability under cyclic loading and stress relaxation reflect mechanisms at the fibril level. By changing the physicochemical environment, the interfibrillar interactions are modified toward more biomimetic mechanical responses. The possibility of making tissue‐like materials with versatile compositions and toughness opens perspectives in tissue engineering.

Significance: Disordered materials with heterogeneities at scales ranging from nano- to micrometers usually scatter visible light and become opaque beyond a certain thickness. However, transparent materials are found in nature. The physical origin of transparency in natural and artificial biopolymer materials is still not fully understood. Here, a gap of transparency is found in synthetic fibrillar collagen matrices within a very narrow range of concentration. The transparency results from structural partial order inhibiting light scattering, while preserving mechanical stability, stiffness, and nonlinearity. The potential to produce biomimetic hydrogels with such striking optical properties by self-assembly opens an interesting route in the study of photonic materials and provides new elements in the understanding of the appearance of transparency in natural materials.

Extracellular matrices (ECM) rich in type I collagen exhibit characteristic anisotropic ultrastructures. Nevertheless, working in vitro with this biomacromolecule remains challenging. When processed, denaturation of the collagen molecule is easily induced in vitro avoiding proper fibril self‐assembly and further hierarchical order. Here, an innovative approach enables the production of highly concentrated injectable collagen microparticles, based on collagen molecules self‐assembly, thanks to the use of spray‐drying process. The versatility of the process is shown by performing encapsulation of secretion products of gingival mesenchymal stem cells (gMSCs), which are chosen as a bioactive therapeutic product for their potential efficiency in stimulating the regeneration of a damaged ECM. The injection of collagen microparticles in a cell culture medium results in a locally organized fibrillar matrix. The efficiency of this approach for making easily handleable collagen microparticles for encapsulation and injection opens perspectives in active tissue regeneration and 3D bioprinted scaffolds.