3D-printed injectable nanocomposite cryogel scaffolds for bone tissue regeneration

abstract

Cryogels are known for their high water content and interconnected macroporosity, two relevant features in tissue engineering approaches. The cryogel structure can support tissue growth as it allows nutrient and oxygen diffusion, removal of waste products, as well as an enhancement of cell infiltration and proliferation. Bioactive glass nanoparticles are biocompatible and clinically approved bioactive materials widely used as implants in the human body to repair or replace diseased or damaged bones. They are known to facilitate bone binding while stimulating bone growth. Indeed, the combination of cryogels with bioactive nanoparticles has already demonstrated promising results for bone regeneration. Although the developed biomaterials succeed in bone regeneration, they lack suitability for minimal invasive procedures or patient-specificity. Here, we demonstrate a freeform 3D printed nanocomposite cryogel, resorting to an ink composed of functionalized gelatin and bioactive glass nanoparticles with methacrylate groups. Complex structures with multiple layers were 3D printed in a xanthan gum supporting bath. The developed 3D printed nanocomposite cryogels demonstrate the ability to recover their shape without any permanent damage, withstanding up to 65 % compression upon injection. Additionally, they stimulate the differentiation of human adipose-derived stem cells into the osteoblast lineage, therefore promoting bone tissue growth. We further demonstrated their suitability for minimal invasive therapeutics by filling a reproduction of a maxillofacial defect. The developed 3D-printed nanocomposite cryogels offer robust shape-recovery properties, easy injectability, tailored geometry into patient-specific injuries, and high osteogenic bioactivity, showcasing its versatility for bone regeneration purposes.

keywords

BIOACTIVE GLASS; DIFFERENTIATION; NETWORKS

subject category

Science & Technology - Other Topics; Materials Science

authors

Castanheira, EJ; Maia, JR; Monteiro, LPG; Sobreiro-Almeida, R; Wittig, NK; Birkedal, H; Rodrigues, JMM; Mano, JF

Groups

G2 - Photonic, Electronic and Magnetic Materials
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)

Collaboratory for Emerging Technologies, CoLab (EMERGING TECHNOLOGIES)

Metodologias eficientes para a conjugação de polissacarídeos naturais com péptidos para obtenção de membranas multifuncionais para regeneração periodontal. (COP2P)

Human Platelet Lysates-based Scaffolds for Interfacial Multi-tissue Repair (INTERLYNK)

acknowledgements

Work developed under the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (DOI 10.54499/UIDB/50011/2020) , UIDP/50011/2020 (DOI 10.54499/UIDP/50011/2020) & LA/P/0006/2020 (DOI 10.54499/LA/P/0006/2020) , financed by national funds through the FCT/MEC (PIDDAC) . This work was also funded by the Programa Operacional Competitividade e Internacionalizacao (POCI) and Programa Operacional Regional do Centro - Centro 2020, in the component FEDER, through FCT/MCTES in the scope of the project COP2P (PTDC/QUIQOR/30771/2017 - POCI-01-0145-FEDER-30771) and also funded by European Union's Horizon 2020 research and innovation programme under the scope of Inter Lynk project with grant agreement No 953169. E.J.C, J.R.M., L.P.G.M., R.S.A., and J.M.M.R. gratefully acknowledge FCT for the individual PhD grants (SFRH/BD/144880/2019 - E.J.C.; PRT/BD/154735/2023 - J.R.M.; 10.54499/2020.06767.BD - L.P.G.M.) and individual researcher contracts (DOI: 10.54499/2022.04605.CEE-CIND/CP1720/CT0021 - R.S.A.; DOI: 10.54499/CEECIND/01363/2018/CP1559/CT0022 - J.M.M.R.) , respectively. Use of the Novo Nordisk Foundation research infrastructure AXIA (grant NNF19OC0055801) is gratefully acknowledged. The authors would also like to acknowledge M.Sc. Anastasiia Sadetskaia from Aarhus University for the acquisition of the TEM micrographs.