Tunable hybrid 3D printing cryogels - a personalized vehicle towards bone regeneration

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ICE Krakow

ICE Krakow

ul. Marii Konopnickiej 17 30-302 Kraków


Monteiro, Luís (Aveiro Institute of Materials, Department of Chemistry, University of Aveiro )


Despite key limitations such as host bone supply and quality, donor site morbidity, and immunogenicity, autologous and allograft bone are still considered the clinical standard of care for bone repair [1]. In addition, biomaterials for bone regeneration should be not only biocompatible and osteoconductive, but also osteoinductive [1, 2]. Developing a biomaterial that comprises all the key features all-in-one, such as: i) improve vascularization, ii) bioactivity towards tissue regeneration, iii) easy appliance and iv) avoid host rejection, remain a major research topic nowadays. The development of such material often lacks in particular aspects, like reduced nutrient diffusion or cell perfusion, lack of biological cues, no organized structure or resemble the target tissue and last the difficulty to develop the biomaterials which drawbacks the translational into the clinic. Here we propose the development of a 3D-printed nanocomposite cryogel, based on laminarin combined with bioactive mesoporous silica nanoparticles, with an anisotropic topology achieved by a simple freeze casting method. This lamellar topography resembles the bone structure and it’s supposed to favor vascularization [3]. The cryogel characteristic porosity structure allows a better nutrient diffusion, cell perfusion and offers the possibility to be injected. In addition, the cryogels excel in their mechanical features, once they present high stiffness and toughness, and no obvious recovery loss at 40% strain, these characteristics match those of targeted implantation tissue, which are stiff but not fragile. It is also demonstrated that the presented cryogel method is more advantageous than the commonly used technique of freeze-drying a hydrogel. Overall, the macroporous cryogels show a better recovery, with no deformation of pores, while the freeze-dried cryogels, after suffering load and unload compression cycles, exhibit a tendency to squeeze and lose their porosity. Lastly, the nanoparticles enclosed on the cryogel matrix allow us to enhance the bioactivity, suitable for bone regeneration. Resorting an SBF assay, the loading of bioactive silica nanoparticles into the cryogels enhanced greatly hydroxyapatite growing on top of the scaffolds. Our results demonstrated that these materials are highly reproducible, easy castable into multiples structures, injectable, bioactive, encompassing an oriented structure, and as far as the authors know, are the first 3D-printable anisotropic nanocomposite cryogels to be reported. We anticipate that this study prompts the development of a different array of anisotropic nanocomposite cryogels, covering more complex structures, helping the scientific community reach a step further to a clinical application respecting bone regeneration.

1. Armiento, A.R., et al., Advanced Functional Materials, 2020, 30, 1909874.
2. Lyons, J.G., et al., Front Bioeng Biotechnol, 2020, 8, 922.
3. Goyos-Ball, L., et al., Journal of the European Ceramic Society, 2017, 37, 5009.

The work was developed within the scope of the project CICECO – Aveiro Institute of Materials (UIDB/50011/2020&UIDP/50011/2020) and project COP2P (PTDC/QUI-QOR/30771/2017, POCI-01-0145-FEDER-030771), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. J.M.M.R thanks FCT for his individual contract (CEECIND/01363/2018). L.M and E.J.C. also thank FCT for their PhD grants (SFRH/BD/144880/2019 and 2020.06767.BD, respectively).


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