Designing of a Multifunctional 3D-Printed Biomimetic Theragenerative Aerogel Scaffold via Mussel-Inspired Chemistry: Bioactive Glass Nanofiber-Incorporated Self-Assembled Silk Fibroin with Antibacterial, Antiosteosarcoma, and Osteoinductive Properties

abstract

Biomaterial-mediated bone tissue engineering (BTE) offers an alternative, interesting approach for the restoration of damaged bone tissues in postsurgery osteosarcoma treatment. This study focused on synthesizing innovative composite inks, integrating self-assembled silk fibroin (SF), tannic acids (TA), and electrospun bioactive glass nanofibers 70SiO(2)-25CaO-5P(2)O(5) (BGNF). By synergistically combining the unique characteristics of these three components through self-assembly and microextrusion-based three-dimensional (3D) printing, our goal was to produce durable and versatile aerogel-based 3D composite scaffolds. These scaffolds were designed to exhibit hierarchical porosity along with antibacterial, antiosteosarcoma, and bone regeneration properties. Taking inspiration from mussel foot protein attachment chemistry involving the coordination of dihydroxyphenylalanine (DOPA) amino acids with ferric ions (Fe3+), we synthesized a tris-complex catecholate-iron self-assembled composite gel. This gel formation occurred through the coordination of oxidized SF (SFO) with TA and polydopamine-modified BGNF (BGNF-PDA). The dynamic nature of the coordination ligand-metal bonds within the self-assembled SFO matrix provided excellent shear-thinning properties, allowing the SFO-TA-BGNF complex gel to be extruded through a nozzle, facilitating 3D printing into scaffolds with outstanding shape fidelity. Moreover, the developed composite aerogels exhibited multifaceted features, including NIR-triggered photothermal antibacterial and in vitro photothermal antiosteosarcoma properties. In vitro studies showcased their excellent biocompatibility and osteogenic features as seeded cells successfully differentiated into osteoblasts, promoting bone regeneration in 21 days. Through comprehensive characterizations and biological validations, our antibacterial scaffold demonstrated promise as an exceptional platform for concurrent bone regeneration and bone cancer therapy, setting the stage for their potential clinical application.

keywords

CARBON DOTS; CANCER; THERAPY

subject category

Science & Technology - Other Topics; Materials Science

authors

Abie, N; Ünlü, C; Pinho, AR; Gomes, MC; Remmler, T; Herb, M; Grumme, D; Tabesh, E; Shahbazi, MA; Mathur, S; Mano, JF; Maleki, H

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

acknowledgements

H.M. acknowledges the support of the German Research Foundation (DFG, Projektnummer 467116484) for financial assistance. N.A. and C.U. acknowledge Dr. Aman Bhardwaj for initial assistance in the electrospinning process and Dr. Michael Wilhelm for XPS measurement. N.A. would like to acknowledge Kingsley Chijioke for TGA/DSC measurements, Khan Le for SEM analysis support, and Ruth Bruker for her kind assistance in SEM-EDX analyses. Part of this work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020, and LA/P/0006/2020, financed by national funds through the FCT/MCTES (PIDDAC). A.R.P. acknowledges FCT for a Ph.D. grant (2021.05888.BD). This work was also supported by grants from the state of North-Rhine-Westphalia, Germany (AZ: 323-8.04.10.02-141905), German Center for Infection Research, DZIF (TTU 08.927 and TTU 08.928), and the Deutsche Forschungsgemeinschaft (DFG), SFB 670 to M.H. and D.G. procured by Prof. Dr. Martin Kronke. M.H. and D.G. thank Prof. Martin Kronke for funding their position.