**1. Introduction**

Amplifying efforts towards a more bio-based economy have recently revived the urge for novel smart processes capable of efficiently transforming biomass or its constituents into functional materials.

Among the broad variety of biopolymers, cellulose is probably the most valuable renewable resource, since it is an abundant unique source of energy, chemicals, and materials. It is easy to access in high purity [1], biocompatible [2,3], and is not a food competitor.

In context with the increasing awareness for a more responsible use of energy and materials in all areas of life, it is easy to understand that research on lightweight, open-porous, and bio-based materials optimized in stiffness-to-weight proportion has greatly advanced in the last decade [4]. This development has been boosted by the nowadays broader availability of supercritical carbon dioxide technologies. The latter allow—besides chemical modification, coating, or foaming—for largely non-destructive drying of biopolymer gels [5]. This gives access to a new family of ultra-lightweight aerogels which would not be accessible with the same features using classical drying techniques [6–8]. Even though not having conquered industrial production yet, cellulose-derived aerogels are promising candidates for a wide range of applications. This includes thermal super-insulation [9], specific sorption of gases or solutes [10], carrier support in catalysis [11], morphological templating [12], energy generation and storage [13], as well as wound dressings [14–16], transdermal drug delivery [17,18], or tissue engineering [19–21].

Depending on the target application, cellulosic aerogels can be required to feature a broad spectrum of specific properties. The demands are rather simple for thermal superinsulation panels. The latter would require low apparent density, narrow mesopore distribution, sufficient dimensional stability in humid atmosphere, resistance towards microbial degradation, and facile processability [22]. Cell scaffolding materials, however, have to meet complex requirements [19,23,24]. Dual-porosity, i.e., interconnected micron-size pores accommodated in networks of nanoporous struts, and biocompatibility for example are key features. While biocompatibility is inherent to cellulose, dual-porosity can be provided, such as using temporary scaffolds of packed beds of porogens [25]. Besides dual-porous architecture, appropriate nanotopology, surface chemistry, electrical charge density, mechanical properties, or availability of growth factors are further important prerequisites [26]. This is complemented by purity and preservation of chemical integrity of cellulose throughout processing into the desired cell scaffolding materials.

Solution casting and subsequent coagulation of cellulose by an antisolvent is one of the most facile and efficient approaches towards shaped open-porous materials [27,28]. However, the choice of solvents able to solubilize cellulose is rather limited [7]. The complex requirements of cell scaffolding materials in terms of purity, morphology, or surface properties further narrow the range of potentially applicable solvents. Reasons include potential derivatization as demonstrated for common ionic liquids [29], hydrolytic cleavage [30], and formation of undesired by-products [31].

Recently we reported about the impact of different cellulose solvents and antisolvents on nanomorphological and -topological features (e.g., crystallinity, size and shape of pores, dimension, organization, and surface roughness of network building nanoparticles) of cellulose II aerogels [32]. Both nanomorphology and nanotopography play a crucial role in tissue engineering. This has been recently demonstrated for neurite extension by neuronal PC12 cells grown on collagen-coated mesoporous silica aerogels [33,34] and on electrically conductive carbon aerogels [35]. Based on the finding that the non-derivatizing solvent system tetrabutylammonium fluoride / dimethylsulfoxide (TBAF/DMSO) affords the formation of particularly small particles, and hence, finely substructured cellulose II networks [32], we extended the exploration of this solvent for processing different types of pulp into cellulose aerogels [36]. Simultaneously we were aiming to improve the dissolution performance of TBAF·xH2O/DMSO. Optimization of the water-to-fluoride ratio was one target, since the latter is a sensitive parameter governing dissolution kinetics. It turned out that the optimum of cellulose dissolution is reached at water-to-fluoride molar ratios of (0.8 ≤ χwf ≤ 2). Water contents outside this range impede cellulose dissolution either by *E2*-type Hofmann decomposition of TBAF into but-1-ene, tributylamine and thermodynamically stable HF2- ions (χwf ≤ 0.8) [37] or simply by insufficient rearrangemen<sup>t</sup> capabilities for the hydrogen bonding network in cellulose (χwf ≥ 2) [38].

This study investigates the utilization of TBAF·xH2O/DMSO for the preparation of cellulose phosphate aerogels since the latter have shown promise as cell sca ffolding materials. Recently, cross-linked aerogels obtained from cellulose nanocrystals carrying a low count of phosphate halfester groups on their surface were reported to fulfil many requirements of viable bone tissue sca ffolds [21]. This complements the results of earlier attempts aiming at the preparation of cellulose II phosphate aerogels via shaping and coagulation of cellulose phosphates from *Lyocell* dopes, i.e., using the solvent system *N*-methylmorpholine-*N*-oxide (NMMO)/water. Already at low degrees of phosphorylation (DSP ca. 0.2), biomineralization and good hemocompatibility in terms of hemostasis and inflammatory response were observed [39]. However, some shortcomings of NMMO related to its elevated melting point, its proneness towards autocatalytic degradation (in the presence of acidic phosphate groups) and the specific solidification behavior of cooling dopes were reasons enough to look for alternatives.

This study investigates the preparation of cellulose phosphate aerogels using TBAF·xH2O/DMSO as a non-derivatizing solvent for the preparation of cellulose phosphate aerogels of low degree of phosphorylation. It has been tested with the example of two representative cellulosic source materials. The exploratory work was expected to provide data for developing a cellulose phosphate 3D printing approach for cell sca ffolding materials.

### **2. Results and Discussion**
