resumo
This study proposes a tunable ink engineering methodology to allow 3D printing processability of highly bioactive but otherwise low-viscous and unprintable blood-derived materials. The hypothesis relies on improving the viscoelasticity and shear thinning behavior of platelet lysates (PL) and albumins (BSA) solutions by covalent coupling, enabling simultaneous extrusion and photocrosslinking upon filament deposition. The available amine groups on proteins (PL and BSA) are exploited for coupling with carboxyl groups present in methacrylated proteins (hPLMA and BSAMA), by leveraging carbodiimide chemistry. This reaction enabled the creation of a pre-gel from these extremely low-viscous materials (approximate to 1 Pa), with precise tuning of the reaction, resulting in inks with a range of controlled viscosities and elasticities. Shape-fidelity analysis is performed on 3D-printed multilayered constructs, demonstrating the ability to reach clinically relevant sizes (>2 cm in size). After photocrosslinking, the scaffolds showcased a mechanically robust structure with sustained protein release over time. Bioactivity is evaluated using human adipose-derived stem cells, resulting in increased viability and metabolic activity over time. The herein described research methodology widens the possibilities for the use of low-viscosity materials in 3D printing but also enables the direct application of patient and blood-derived materials in precision medicine.
palavras-chave
CROSS-LINKING; HYDROGELS; MECHANISM
categoria
Chemistry; Science & Technology - Other Topics; Materials Science
autores
Sobreiro-Almeida, R; Santos, SC; Decarli, MC; Costa, M; Correia, TR; Babilotte, J; Custódio, CA; Moroni, L; Mano, JF
nossos autores
Catarina de Almeida Custódio
Investigador Auxiliar
João Mano
Professor Catedrático
Rita Sobreiro Almeida
Investigador Júnior
Tiago Ruivo Correia
Investigador JúniorProjectos
Human Platelet Lysates-based Scaffolds for Interfacial Multi-tissue Repair (INTERLYNK)
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)
agradecimentos
R.S.-A. and S.C.S. contributed equally to this work. The authors wish to acknowledge the European Union's Horizon 2020 research and innovation programme under the scope of InterLynk project (grant agreement No. 953169), as well as the research grant BI/UI89/10722/2023 (M.C.). The support from the Foundation for Science and Technology (FCT), Lisbon, Portugal on the individual contracts (DOI 10.54499/2022.04605.CEECIND/CP1720/CT0021, R.S-A and 10.54499/2020.01647.CEECIND/CP1589/CT0034, C.A.C) and on the Ph.D. grants (SFRH/BD/144520/2019, S.C.S. and 2023.00647.BD, M.C.) is also greatly acknowledged. This work was developed within the scope of 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/MCTES (PIDDAC).