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Layered Double Hydroxides (LDH) are relevant inorganic materials for biomedical application thanks to both their tunable chemical composition and their lamellar structure allowing molecules or ions intercalation in the interlayer spaces. However, their brittleness and thermal sensibility limit the fabrication of 3D materials based on LDH, making it challenging, especially to prepare scaffolds for bone tissue engineering that require a macroporous structure for cell colonization and sufficient mechanical properties to be handled/cut by surgeons. To overcome these drawbacks, this study describes the preparation of 3D scaffolds based on the association of fully biocompatible LDH with an alginate matrix processed by freeze-casting, and leading to macroporous materials with a porosity compatible with cell colonization. To the best of our knowledge, the fabrication of such composite scaffolds by freeze-casting associated with a fine multiscale and systematic characterization was never described in the literature. Thus, this work first focused on the successful synthesis of Mg-Fe-CO3 layered double hydroxide nanoparticles, as confirmed by physicochemical characterizations (XRD, FTIR, SEM, DLS). Then, the resulting nano-LDH were associated with an alginate matrix to generate 3D composite scaffolds by freeze-casting. In order to evaluate the effect of nano-LDH content on the scaffold porous structure and mechanical properties, various compositions (nano-LDH/alginate ratio) were tested, and the structure and mechanical properties of the resulting scaffolds were characterized (SEM, X-Ray microtomography, compression tests). Results allowed us to identify an optimal nano-LDH/alginate composition (ratio 1:1) leading to 3D macroporous scaffolds combining suitable anisotropic microporosity for cell colonization and sufficient mechanical properties for non-bearing bone applications, while allowing for their manipulation without risks of collapse.

Layered Double Hydroxides (LDHs) are inorganic compounds of relevance to various domains, where their surface reactivity and/or intercalation capacities can be advantageously exploited for the retention/release of ionic and molecular species. In this study, we have explored specifically the applicability in the field of bone regeneration of one LDH composition, denoted “MgFeCO3”, of which components are already present in vivo, so as to convey a biocompatibility character. The propensity to be used as a bone substitute depends, however, on their ability to allow the fabrication of 3D constructs able to be implanted in bone sites. In this work, we display two appealing approaches for the processing of MgFeCO3 LDH particles to prepare (i) porous 3D scaffolds by freeze-casting, involving an alginate biopolymeric matrix, and (ii) pure MgFeCO3 LDH monoliths by Spark Plasma Sintering (SPS) at low temperature. We then explored the capacity of such LDH particles or monoliths to interact quantitatively with molecular moieties/drugs in view of their local release. The experimental data were complemented by computational chemistry calculations (Monte Carlo) to examine in more detail the mineral–organic interactions at play. Finally, preliminary in vitro tests on osteoblastic MG63 cells confirmed the high biocompatible character of this LDH composition. It was confirmed that (i) thermodynamically metastable LDH could be successfully consolidated into a monolith through SPS, (ii) the LDH particles could be incorporated into a polymer matrix through freeze casting, and (iii) the LDH in the consolidated monolith could incorporate and release drug molecules in a controlled manner. In other words, our results indicate that the MgFeCO3 LDH (pyroaurite structure) may be seen as a new promising compound for the setup of bone substitute biomaterials with tailorable drug delivery capacity, including for personalized medicine.

This review aims to highlight the importance of particle shape in the design of polymeric nanocarriers for drug delivery systems, along with their size, surface chemistry, density, and rigidity. Current manufacturing methods used to obtain non-spherical polymeric nanocarriers such as filomicelles or nanoworms, nanorods and nanodisks, are firstly described. Then, their interactions with biological barriers are presented, including how shape affects nanoparticle clearance, their biodistribution and targeting. Finally, their drug delivery properties and their therapeutic efficacy, both in vitro and in vivo, are discussed and compared with the characteristics of their spherical counterparts.

Bone infections are a key health challenge with dramatic consequences for affected patients. In dentistry, periodontitis is a medically compromised condition for efficient dental care and bone grafting, the success of which depends on whether the surgical site is infected or not. Present treatments involve antibiotics associated with massive bacterial resistance effects, urging for the development of alternative antibacterial strategies. In this work, we established a safe-by-design bone substitute approach by combining bone-like apatite to peroxide ions close to natural in vivo oxygenated species aimed at fighting pathogens. In parallel, bone-like apatites doped with Ag+ or co-doped Ag+/peroxide were also prepared for comparative purposes. The compounds were thoroughly characterized by chemical titrations, FTIR, XRD, SEM, and EDX analyses. All doped apatites demonstrated significant antibacterial properties toward four major pathogenic bacteria involved in periodontitis and bone infection, namely Porphyromonas gingivalis (P. gingivalis), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Fusobacterium nucleatum (F. nucleatum), and S. aureus. By way of complementary tests to assess protein adsorption, osteoblast cell adhesion, viability and IC50 values, the samples were also shown to be highly biocompatible. In particular, peroxidated apatite was the safest material tested, with the lowest IC50 value toward osteoblast cells. We then demonstrated the possibility to associate such doped apatites with two biocompatible polymers, namely gelatin and poly(lactic-co-glycolic) acid PLGA, to prepare, respectively, composite 2D membranes and 3D scaffolds. The spatial distribution of the apatite particles and polymers was scrutinized by SEM and µCT analyses, and their relevance to the field of bone regeneration was underlined. Such bio-inspired antibacterial apatite compounds, whether pure or associated with (bio)polymers are thus promising candidates in dentistry and orthopedics while providing an alternative to antibiotherapy.