3D-printed aerogels as theranostic implants monitored by fluorescence bioimaging

• Published in: Bioactive materials 2024-11, Vol.41, p.471-484
• Main Authors: Iglesias-Mejuto, Ana, Pinto, Rui, Faísca, Pedro, Catarino, José, Rocha, João, Durães, Luisa, Gaspar, Maria Manuela, Reis, Catarina Pinto, García-González, Carlos A.
• Format: Article
• Language: English
• Subjects: Acids; Aerogels; Alginates; Alginic acid; Animal models; Aqueous solutions; Biocompatibility; Biodegradation; Biomedical materials; Carbon dioxide; Cell culture; Contrast agents; Ethanol; Fluorescence; Hydroxyapatite; Implantation; In vivo fluorescence; In vivo methods and tests; Medical imaging; Nanoparticles; Nanostructured materials; Nanotechnology devices; Nitrates; Performance evaluation; Physicochemical properties; Quantum dots; Scaffolds; Scanning electron microscopy; Surgical implants; Theranostic implants; Three dimensional printing; Tissue engineering; Tomography; Transplants & implants; Upconversion nanoparticles
• ISSN: 2452-199X; 2097-1192; 2452-199X
• DOI: 10.1016/j.bioactmat.2024.07.033

Aerogel scaffolds are nanostructured materials with beneficial properties for tissue engineering applications. The tracing of the state of the aerogels after their implantation is challenging due to their variable biodegradation rate and the lack of suitable strategies capable of in vivo monitoring the scaffolds. Upconversion nanoparticles (UCNPs) have emerged as advanced tools for in vitro bioimaging because of their fluorescence properties. In this work, highly fluorescent UCNPs were loaded into aerogels to obtain theranostic implants for tissue engineering and bioimaging applications. 3D-printed alginate-hydroxyapatite aerogels labeled with UCNPs were manufactured by 3D-printing and supercritical CO2 drying to generate personalize-to-patient aerogels. The physicochemical performance of the resulting structures was evaluated by printing fidelity measurements, nitrogen adsorption-desorption analysis, and different microscopies (confocal, transmission and scanning electron microscopies). Stability of the aerogels in terms of physicochemical properties was also tested after 3 years of storage. Biocompatibility was evaluated in vitro by different cell and hemocompatibility assays, in ovo and in vivo by safety and bioimaging studies using different murine models. Cytokines profile, tissue index and histological evaluations of the main organs unveiled an in vivo downregulation of the inflammation after implantation of the scaffolds. UCNPs-decorated aerogels were first-time manufactured and long-term traceable by fluorescence-based bioimaging until 3 weeks post-implantation, thereby endorsing their suitability as tissue engineering and theranostic nanodevices (i.e. bifunctional implants). [Display omitted] •Theranostic implants were manufactured by a dual processing strategy combining 3D-printing and supercritical CO2 drying.•UCNPs-decorated aerogels were physicochemically stable and highly fluorescent after 3 years of storage.•In vitro cell studies and hemocompatibility assays demonstrated the suitability of the 3D-printed aerogels for tissue engineering.•In vivo tests showed the biocompatibility and the monitoring capability of the theranostic implants.