The advances in 3D printed silicone (PDMS: Polydimethylsiloxane) implants provide an outlook for personalized implants with highly accurate anatomical conformity. However, a potential adverse effects such as granuloma formation due to immune reactions still exists. One potential way of overcoming this problem is the control of implant/host interface using immunomodulatory coatings.In this study, a new cytokine cocktail composed of interleukin 10 and prostaglandin-E2 was designed to decrease the adverse immune reaction and promote tissue integration by fixing macrophage into M2 pro-healing phenotype for a long term. In vitro, the cytokine cocktail was able to keep the secretion of pro-inflammatory cytokines (TNF-α and IL-6) at a low level and induced the secretion of IL-10 and the upregulation of stabilin-1 (endocytotic scavenger receptor expressed by M2 macrophage). This cocktail was then loaded in a gelatin based hydrogel to develop an immunomodulatory material that can be used as a coating of a medical device. The efficacy of this coating was demonstrated in an in vivo rat model during reconstruction of a tracheal defect by 3D printed silicone implants. The coating was stable on silicone implants over 2 weeks and the controlled release of cocktail components was achieved for at least 14 days. In vivo, only 33% of the animals with bare silicone implant survived whereas 100% survived with the implant equipped with the immunomodulatory hydrogel. The presence of the hydrogel and the cytokine cocktail diminished the thickness of the inflammatory tissue, the intensity of both acute and chronic inflammation, overall fibroblastic reaction, oedema presence and fibrinoid formation (assessed by histology) and lead to a 100% survival rate. At systemic level, the presence of immunomodulatory hydrogel decreased significantly pro-inflammatory cytokines like TNF-α, IFN-γ, CXCL1 and MCP-1 levels at day 7 and IL-1α, IL-1β, CXCL1 and MCP-1 levels at day 21. The ability of this new immunomodulatory hydrogel to control the level of inflammation once applied on a 3D printed silicone implant has been demonstrated. Such thin coatings can be applied to any implants or scaffolds used in tissue engineering to diminish the initial immune response, improve integration and functionality of these materials and finally decrease potential complications related to their presence.
Polyester-based composites with silica nanoparticles fillers are promising candidates as biomaterials due to improved mechanical and biological properties. However, nanofillers use generally leads to an inhomogeneous distribution inside the polymer matrix because of agglomeration, decreasing composites overall performances. In view of improving nanofillers dispersion, we developed a synthesis and characterization method to design poly(D, L-lactide)-grafted silica nanoparticles using "grafting to" method and to quantify the amount of grafted poly(D,Llactide). Firstly, well-defined N-hydroxysuccinimide ester poly(D,L-lactide)s were synthesized through a new pathway. Then, amino-functionalized silica nanoparticles were grafted with those customized polyesters yielding an amide covalent bond between both reagents. Such PDLLA-grafted nanoparticles were precisely characterized and the grafting amount was quantified using a dual approach based on TGA and FTIR analysis. The synthesis and the characterization methods developed constitute a robust and reproducible way to design well-defined polymer-grafted silica nanoparticles that could be used as nanofillers in polymer matrix nanocomposites for biomedical applications.
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.
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.
This paper focuses on an integrative “bricks-and-mortar” approach involving bioactive glass nanoparticles (bricks) covalently functionalized with a customized polymer (mortar) combined with the freeze-casting process. With the aim of obtaining a macroporous composite for bone substitution, composed of a spatially homogeneous assembly of nanoscale objects, we establish a method for the systematic elaboration of nanocomposite scaffolds. It was implemented through several steps from the synthesis of functionalized poly(d,l-lactide) (PDLLA) and SiO2–CaO binary bioactive glass nanoparticles (diameter around 164 nm) to the unidirectional freeze-casting process. The different stages include the first description of controlled PDLLA (M n 8400 g·mol–1) grafting onto bioactive glass nanoparticle surfaces, their fine characterization and grafting quantification, and their mixing with free PDLLA chains (83 400 g·mol–1) during suspension formulation. This paper emphasizes the effect of the working temperature during the freeze-casting process on the multiscale spatial organization of resulting scaffolds such as the porosity morphology (lamellar and tubular), size (from 30 to 380 μm), anisotropy, and orientation. In addition to porosity, our results demonstrate a rosary-like organization of PDLLA-grafted nanoparticles in pore walls. The higher homogeneity in the spatial distribution of grafted nanoparticles over the height of scaffolds and at a micron scale confirms the validity of the “bricks-and-mortar” concept to prevent or limit aggregation. In particular, this study highlights the correlation between nanoparticle functionalization and mechanical properties, especially the recovery rate after compression tests. These results lay the foundation for the development of tunable materials for bone substitution, via potential enhancement of bioactivity and cell colonization.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.