Additive Manufacturing of Nanocellulose Aerogels with Structure-Oriented Thermal, Mechanical, and Biological Properties.

Additive manufacturing (AM) is widely recognized as a versatile tool for achieving complex geometries and customized functionalities in designed materials. However, the challenge lies in selecting an appropriate AM method that simultaneously realizes desired microstructures and macroscopic geometrical designs in a single sample. This study presents a direct ink writing method for 3D printing intricate, high-fidelity macroscopic cellulose aerogel forms. The resulting aerogels exhibit tunable anisotropic mechanical and thermal characteristics by incorporating fibers of different length scales into the hydrogel inks. The alignment of nanofibers significantly enhances mechanical strength and thermal resistance, leading to higher thermal conductivities in the longitudinal direction (65 mW m-1  K-1 ) compared to the transverse direction (24 mW m-1  K-1 ). Moreover, the rehydration of printed cellulose aerogels for biomedical applications preserves their high surface area (≈300 m2  g-1 ) while significantly improving mechanical properties in the transverse direction. These printed cellulose aerogels demonstrate excellent cellular viability (>90% for NIH/3T3 fibroblasts) and exhibit robust antibacterial activity through in situ-grown silver nanoparticles.

Synthesis of Highly Luminescent Silica-Coated Upconversion Nanoparticles from Lanthanide Oxides or Nitrates Using Co-Precipitation and Sol-Gel Methods.

Upconversion nanoparticles (UCNPs) are under consideration for their use as bioimaging probes with enhanced optical performance for real time follow-up under non-invasive conditions. Photostable and core-shell NaYF4:Yb3+, Er3+-SiO2 UCNPs obtained by a novel and simple co-precipitation method from lanthanide nitrates or oxides were herein synthesized for the first time. The sol-gel Stöber method followed by oven or supercritical gel drying was used to confer biocompatible surface properties to UCNPs by the formation of an ultrathin silica coating. Upconversion (UC) spectra were studied to evaluate the fluorescence of UCNPs upon red/near infrared (NIR) irradiation. ζ-potential measurements, TEM analyses, XRD patterns and long-term physicochemical stability were also assessed and confirmed that the UCNPs co-precipitation synthesis is a shape- and phase-controlling approach. The bio- and hemocompatibility of the UCNPs formulation with the highest fluorescence intensity was evaluated with murine fibroblasts and human blood, respectively, and provided excellent results that endorse the efficacy of the silica gel coating. The herein synthesized UCNPs can be regarded as efficient fluorescent probes for bioimaging purposes with the high luminescence, physicochemical stability and biocompatibility required for biomedical applications.

Biological Thermal Performance of Organic and Inorganic Aerogels as Patches for Photothermal Therapy.

Aerogels are materials with unique properties, among which are low density and thermal conductivity. They are also known for their exquisite biocompatibility and biodegradability. All these features make them attractive for biomedical applications, such as their potential use in photothermal therapy (PTT). This technique is, yet, still associated with undesirable effects on surrounding tissues which emphasizes the need to minimize the exposure of healthy regions. One way to do so relies on the use of materials able to block the radiation and the heat generated. Aerogels might be potentially useful for this purpose by acting as insulators. Silica- and pectin-based aerogels are reported as the best inorganic and organic thermal insulators, respectively; thus, the aim of this work relies on assessing the possibility of using these materials as light and thermal insulators and delimiters for PTT. Silica- and pectin-based aerogels were prepared and fully characterized. The thermal protection efficacy of the aerogels when irradiated with a near-infrared laser was assessed using phantoms and ex vivo grafts. Lastly, safety was assessed in human volunteers. Both types presented good textural properties and safe profiles. Moreover, thermal activation unveils the better performance of silica-based aerogels, confirming the potential of this material for PTT.

Preparation of Vancomycin-Loaded Aerogels Implementing Inkjet Printing and Superhydrophobic Surfaces.

Chronic wounds are physical traumas that significantly impair the quality of life of over 40 million patients worldwide. Aerogels are nanostructured dry porous materials that can act as carriers for the local delivery of bioactive compounds at the wound site. However, aerogels are usually obtained with low drug loading yields and poor particle size reproducibility and urges the implementation of novel and high-performance processing strategies. In this work, alginate aerogel particles loaded with vancomycin, an antibiotic used for the treatment of Staphylococcus aureus infections, were obtained through aerogel technology combined with gel inkjet printing and water-repellent surfaces. Alginate aerogel particles showed high porosity, large surface area, a well-defined spherical shape and a reproducible size (609 ± 37 µm). Aerogel formulation with vancomycin loadings of up to 33.01 ± 0.47 µg drug/mg of particle were obtained with sustained-release profiles from alginate aerogels for more than 7 days (PBS pH 7.4 medium). Overall, this novel green aerogel processing strategy allowed us to obtain nanostructured drug delivery systems with improved drug loading yields that can enhance the current antibacterial treatments for chronic wounds.

3D-Printed, Dual Crosslinked and Sterile Aerogel Scaffolds for Bone Tissue Engineering.

The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. However, these aerogels are usually fragile, with fast biodegradation rates in biological aqueous fluids, and they lack the sterility required for clinical practice. In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. Nitrogen adsorption-desorption (BET) and SEM analyses were performed to assess the textural parameters of the resulting alginate-HA aerogel scaffolds. The biological evaluation of the aerogel scaffolds was performed regarding cell viability, hemolytic activity and bioactivity for BTE. The impact of scCO2-based post-sterilization treatment on scaffold properties was also assessed. The obtained aerogels were dual porous, bio- and hemocompatible, as well as endowed with high bioactivity that is dependent on the HA content. This work is a step forward towards the optimization of the physicochemical performance of advanced biomaterials and their sterilization.

3D-printed alginate-hydroxyapatite aerogel scaffolds for bone tissue engineering.

3D-printing technology allows the automated and reproducible manufacturing of functional structures for tissue engineering with customized geometries and compositions by depositing materials layer-by-layer with high precision. For these purposes, the production of bioactive gel-based 3D-scaffolds made of biocompatible materials with well-defined internal structure comprising a dual (mesoporous and macroporous) and highly interconnected porosity is essential. In this work, aerogel scaffolds for bone regeneration purposes were obtained by an innovative strategy that combines the 3D-printing of alginate-hydroxyapatite (HA) hydrogels and the supercritical CO2 drying of the gels. BET and SEM analyses were performed to assess the textural parameters of the obtained aerogel scaffolds and the dimensional accuracy to the original computer-aided design (CAD) design was also evaluated. The biological characterization of the aerogel scaffolds was also carried out regarding cell viability, adhesion and migration capacity. The obtained alginate-HA aerogel scaffolds were highly porous, biocompatible, with high fidelity to the CAD-pattern and also allowed the attachment and proliferation of mesenchymal stem cells (MSCs). An enhancement of the fibroblast migration toward the damaged area was observed in the presence of the aerogel formulations tested, which is positive in terms of bone regeneration.

Solvent-Free Approaches for the Processing of Scaffolds in Regenerative Medicine.

The regenerative medicine field is seeking novel strategies for the production of synthetic scaffolds that are able to promote the in vivo regeneration of a fully functional tissue. The choices of the scaffold formulation and the manufacturing method are crucial to determine the rate of success of the graft for the intended tissue regeneration process. On one hand, the incorporation of bioactive compounds such as growth factors and drugs in the scaffolds can efficiently guide and promote the spreading, differentiation, growth, and proliferation of cells as well as alleviate post-surgical complications such as foreign body responses and infections. On the other hand, the manufacturing method will determine the feasible morphological properties of the scaffolds and, in certain cases, it can compromise their biocompatibility. In the case of medicated scaffolds, the manufacturing method has also a key effect in the incorporation yield and retained activity of the loaded bioactive agents. In this work, solvent-free methods for scaffolds production, i.e., technological approaches leading to the processing of the porous material with no use of solvents, are presented as advantageous solutions for the processing of medicated scaffolds in terms of efficiency and versatility. The principles of these solvent-free technologies (melt molding, 3D printing by fused deposition modeling, sintering of solid microspheres, gas foaming, and compressed CO2 and supercritical CO2-assisted foaming), a critical discussion of advantages and limitations, as well as selected examples for regenerative medicine purposes are herein presented.