Blanc Inter II SIMI 8 - Blanc International II - SIMI 8 - Chimie du solide, colloïdes, physicochimie

Tailoring of Cellulosic Aerogels for Biomedical Applications – CAP-BONE

Cellulosic aerogels : biomedical applications

Aérogels de Cellulose Ultra-légers Monolithiques : Modification de Surface, Fonctionnalisation et Applications Biomédicales <br /> <br />

CAP BONE

The main project idea focuses on the development of fundamental approaches for the preparation of novel, innovative, cellulose-based aerogels to render them even more promising materials for biomedical applications. A better understanding of hitherto puzzling surface and shrinking phenomena observed during previous work on the preparation of cellulose aerogels would further support the general objective and is therefore subject of the intended work, too. <br />The following work packages and milestones are envisaged: <br /> <br />• Study of the intriguing surface effects that distinguish bacterial cellulose aerogels from those obtained by regenerating plant cellulose from solution and that could be used for several applications such as controlled release of bioactive compounds. <br />• Investigation of the distinct differences in retaining the fragile network structure during scCO2 drying for the two types of aerogels . <br />• Advancing basic concepts for tailoring the properties (porosity, aggregate microstructure, hemocompatibility, mechanical and chemical properties) of cellulosic aerogels. The studied concepts comprise for example the use of porogens, surfactants, templating additives, scCO2 antisolvant precipitation, chemical modification and cross-linking etc.) <br />• Further development of analytical techniques for characterizing porous soft matter such as ultra-lightweight cellulosic aerogels with densities of down to 5 mg.cm-3. <br />• Tailoring cellulose and cellulose phosphate aerogels for selected, partly challenging biomedical applications such as bone grafting and controlled release of bioactive compounds. <br /> <br />

The scientific program will be divided as follows into one coordination task (task 1) plus four main scientific tasks (Tasks 2-5). Task 2 consists in the preparation of the various aerogels samples whereas Task 3 encompasses the modification of samples and their reinforcement. Task 4 is dedicated to the thorough characterization of all samples both from chemical, structural, textural and mechanical point of view.
Finally Task 5 is dedicated to the evaluation of properties of the new aerogels regarding biomedical applications (bone graft, support for tissue engineering and drug delivery).
Task 1 – Management
1.1. Progress report / Expenses
1.2. Consortium agreement / Final report
Task 2 – Aerogels with tailored surface properties, porosity and chemical structure
2.1. Understanding the differences between plant and bacterial cellulose with regard to surface properties and behaviour under scCO2 drying
2.2. Homogeneous and heterogenous chemical modification
2.3. Tailoring the porosity of bacterial and plant cellulose aerogels: Templating by additives, temporary scaffolds or porogens
Task 3 – Reinforcement / Modification
3.1. Interpenetrating organic polymers
3.2. Silica and siloxane modification
3.3 Reinforcement of meso- and macroporous CP aerogels
Task 4 – Characterization
4.1. Chemical characterization, cellulose integrity
4.2. Multi-scale characterization (porosity and structure)
4.3. Mechanical characterization of chemically modified and reinforced aerogels
Task 5 – Biomedical Applications
5.1. CP aerogels as bone graft materials
5.2. Biomineralization of CP aerogels
5.3. CA in controlled drug release applications

Divers aérogels de cellulose ont été préparés, puis modifiés pour introduire des groupements phosphates via différents mode de synthèse (POCl3, acide phosphorique, etc..).
En parallèle, la thermoporosimétrie a été développée pour caractériser ces matériaux. Des mesures complémentaires par adsorption de gaz et porosimétrie mercure sont venues compléter la caractérisation. Un comportement original des aérogels produits à partir de cellulose d’origine bactérienne et observé. Ces matériaux sont très stables en atmosphère humide contrairement à leurs analogues issus de cellulose d’origine végétale.

L’origine de ce comportement sera étudiée en détail par analyse thermogravimétique couplée avec un contrôle d’humidité grâce à l’équipement acquis grâce au projet CAP-BONE.
Des aérogels renforcés ont été préparés.
Pour le renforcement par un réseau inorganique, la silice a été utilisée. La chimie sol-gel a été utilisée pour polymériser in situ dans l’aérogel un réseau siloxane à partir d’alkoxides. Les conditions ont été optimisées pour obtenir le taux de silice le plus élevé et le meilleur renfort des propriétés mécaniques. Dans le même temps la TPM a été utilisée pour caractériser la porosité de ces matériaux hybrides. L’influence de la silice et des conditions opératoires est négligeable sur la structure des aérogels hybrides.

Pour le renforcement par des réseaux organiques, différents polymères ont été utilisés : acétate de cellulose (CA), PMMA, PLA. Les conditions de préparation ont été optimisées (température, solvant, antisolvant, concentration,…)
Pour les meilleurs matériaux, la densité augmente peu (de 10 mg/cm3 jusqu’à 170 mg/cm3), le module élastique augmente de 0,2 MPa jusqu’à 12 MPa pour CA, 24 MPa pour PMMA et 10 MPa pour PLA.
Le module spécifique augmente de 500 % pour le PMMA et de 300 % pour PLA et CA. Enfin la limite d’élasticité augmente de 10 kPa jusqu’à 0,4 MPa pour CA, 0,7 MPa pour PLA et 1,5 MPa pour PMMA.

Poursuite de la caractérisation des matériaux
Etude de la biominéralisation à la surface des échantillons
Mesure des propriétés mécaniques des aérogels renforcés
Compréhension du comportement à l’eau des aérogels d’origine bactérienne
Applications en système de relargage contrôlé.

Cellulosic aerogels: elaboration, chemical modification, characterization and biomedical applications, A. Hardy Dessources, F. Liebner, J.M. Nedelec et al., XVIIth Sol-Gel conference, Madrid, Spain (25th-30th August)

Pircher, N., Aigner, N.,

The “Chemistry NAWAROS group” at BOKU University was amongst the first groups that started re-search on cellulosic aerogels as the “young, third generation” of aerogels. Basic studies aiming at the preparation of highly porous aerogels from different pulps revealed that the fragile, open-porous struc-ture of alcogels can be largely retained if supercritical carbon dioxide (scCO2) is used in the final dry-ing step. This technique was later adapted for converting shaped bacterial cellulose (BC) aquogels into ultra-lightweight aerogels that quantitatively retained shape and porosity. Cellulose phosphate (CP) aerogels were prepared for the first time via the Lyocell approach and have been tested with regard to hemocompatibility, growth and differentiation of skeletal stem cells.
Based on previous work, the proposed project is intended to a) study the intriguing surface effects that distinguish bacterial cellulose aerogels from those obtained by regenerating plant cellulose from solu-tion, b) understand the distinct differences in retaining the fragile network structure during scCO2 dry-ing for the two types of aerogels, c) advance basic concepts (use of porogens, surfactants, templating, scCO2 antisolvent precipitation, chemical modification, cross-linking etc.) for tailoring the properties (porosity, aggregate microstructure, hemocompatibility, mechanical and chemical properties) of cellu-losic aerogels, d) to further develop analytical techniques for characterizing porous soft matter of such low densities (down to 5 mg cm-3), and e) to investigate the tailored cellulosic aerogels regarding their use in selected biomedical applications.
The application of mechanically sufficiently stable, cellulose phosphate-based hemocompatible aero-gels with spread porosity including a sufficient percentage of macropores with diameters in the range of 50 = x = 400 µm as a novel cell scaffolding material for bone grafting is one main target of the proposed project. The envisaged work has been motivated by several recent findings: 1) cellulose phosphates can be safely processed to aerogels via the Lyocell route 2) cellulose phosphates are hemocompatible and non-toxic in cultured human osteoblasts and fibroblasts, 3) cellulose phosphorylation (moderate DS only) is a pre-requisite to biomineralization, i.e. the formation of calcium deficient hydroxyapatite (cdHap), 4) moderate calcification activates blood platelets without inducing an inflammatory response, 5) calcified cellulose phosphates support robust growth and spontaneous osteogenic differentiation of skeletal stem cells.
Tailoring the properties of cellulosic aerogels for controlled release of bioactive compounds is a second main objective of the proposed work. Preliminary studies have shown that bioactive compounds can be homogenously loaded into cellulose aerogels by scCO2 antisolvent precipitation. Full retention of porosity and quantitative rewettability of BC aerogels render them promising matrices for controlled release application in wound treatment, skin care or drug dehabituation. Through a better understanding of the above-mentioned microstructural differences and hitherto puzzling surface effects it is expected that aerogels from commercial pulps can also be used in a multitude of applications (catalysis, filters, separation techniques, etc.) beyond the controlled release of bioactive compounds.



Project coordinator

Monsieur Jean-Marie NEDELEC (UNIVERSITE BLAISE PASCAL - CLERMONT-FERRAND II) – j-marie.nedelec@univ-bpclermont.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LPMM UNIVERSITE BLAISE PASCAL - CLERMONT-FERRAND II
LMI UNIVERSITE BLAISE PASCAL - CLERMONT-FERRAND II

Help of the ANR 292,240 euros
Beginning and duration of the scientific project: February 2012 - 36 Months

Useful links