Self-Assembly of Platelet Lysates Proteins into Microparticles by Unnatural Disulfide Bonds for Bottom-Up Tissue Engineering

abstract

There is a demand to design microparticles holding surface topography while presenting inherent bioactive cues for applications in the biomedical and biotechnological fields. Using the pool of proteins present in human-derived platelet lysates (PLs), the production of protein-based microparticles via a simple and cost-effective method is reported, exploring the prone redox behavior of cysteine (Cy-SH) amino acid residues. The forced formation of new intermolecular disulfide bonds results in the precipitation of the proteins as spherical, pompom-like microparticles with adjustable sizes (15-50 & mu;m in diameter) and surface topography consisting of grooves and ridges. These PL microparticles exhibit extraordinary cytocompatibility, allowing cell-guided microaggregates to form, while also working as injectable systems for cell support. Early studies also suggest that the surface topography provided by these PL microparticles can support osteogenic behavior. Consequently, these PL microparticles may find use to create live tissues via bottom-up procedures or injectable tissue-defect fillers, particularly for bone regeneration, with the prospect of working under xeno-free conditions. Proteins from human-derived platelet lysates (PLs) produce microparticles by forming unnatural disulfide bonds (-S-S-). In this study, protein-based microparticles are produced with defined surface topography and tunable size using a direct, simple, and low-cost methodology. These bioactive microstructures allow cell-guided microaggregates to form and have applications in bottom-up approaches.image

keywords

OSTEOGENIC DIFFERENTIATION; CELLS; SERUM

subject category

Chemistry; Science & Technology - Other Topics; Materials Science; Physics

authors

Gomes, MC; Pinho, AR; Custódio, C; Mano, JF

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

Full human-based multi-scale constructs with jammed regenerative pockets for bone engineering. (REBORN)

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)

Hidrogéis de Lisados de Plaquetas para Regeneração do Miocárdio (BEAT)

Unlocking the scientific excellence and innovation capacity of the University of Aveiro in supramolecular multicomponent biomaterials for enabling advanced biomaterials for healthcare (SUPRALIFE)

acknowledgements

This work was financially supported by the European Research Council grant agreement ERC-2021-ADG-883370 (project REBORN). This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020, financed by national funds through the FCT/MEC (PIDDAC). This work was also supported by the Programa Operacional Competitividade e Internacionalizacao (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the Beat project (PTDC/BTM-MAT/30869/2017, POCI-01-0145-FEDER-030869). This work was also funded by the European Union's Horizon Europe research and innovation programme under the grant agreement No. 101079482 ("SUPRALIFE").& nbsp;The Beat project is also acknowledged for the individual Junior Researcher contracts of MCG. The authors would like to acknowledge the financial support of the Portuguese Foundation for Science and Technology (FCT) for the individual contract 2020.01647.CEECIND of CC.