Hybrid micro-/nanoprotein platform provides endocrine-like and extracellular matrix-like cell delivery of growth factors

Abstract

Protein materials are versatile tools in diverse biomedical fields. Among them, artificial secretory granules (SGs), mimicking those from the endocrine system, act as mechanically stable reservoirs for the sustained release of proteins as oligomeric functional nanoparticles. Only validated in oncology, the physicochemical properties of SGs, along with their combined drug-releasing and scaffolding abilities, make them suitable as smart topographies in regenerative medicine for the prolonged delivery of growth factors (GFs). Thus, considering the need for novel, safe, and cost-effective materials to present GFs, in this study, we aimed to biofabricate a protein platform combining both endocrine-like and extracellular matrix fibronectin-derived (ECM-FN) systems. This approach is based on the sustained delivery of a nanostructured histidine-tagged version of human fibroblast growth factor 2. The GF is presented onto polymeric surfaces, interacting with FN to spontaneously generate nanonetworks that absorb and present the GF in the solid state, to modulate mesenchymal stromal cell (MSC) behavior. The results show that SGs-based topographies trigger high rates of MSCs proliferation while preventing differentiation. While this could be useful in cell therapy manufacture demanding large numbers of unspecialized MSCs, it fully validates the hybrid platform as a convenient setup for the design of biologically active hybrid surfaces and in tissue engineering for the controlled manipulation of mammalian cell growth.

The study was mainly funded by the Agencia Española de Investigacioń (AEI) through the project PID2020-116174RBI00 granted to A.V. The authors are indebted to AEI for granting additional projects on the construction of protein materials of clinical interest (PID2019-105416RB-I00/AEI/10.13039/ 501100011033 and PDC2022-133858-I00 to E.V., PID2022- 1368450 OB-10/AEI/10.13039/501100011033 to A.V. and E.V.), to AGAUR (SGR 2021 00092 to A.V.), and to ISCIII (PI20/00400 and PI23/00318 to UU) co-funded by European Regional Development Fund (ERDF, a way to make Europe). U.U. was supported by the Miguel Servet contract (CP19/ 00028) from ISCIII, co-funded by the European Social Fund (ESF investing in your future). A.V. received an ICREA ACADEMIA award. M.J.D. is also indebted to the EPSRC grant (EP/P001114/1). We would like to thank ISCIII for funding through CIBER-BBN (CB06/01/0014) and the Ministry of Science for funding the ICTS Platform Nanbiosis. H.L.-L. received a predoctoral fellowship from AGAUR (2019 FI_B 00352).

Peer Reviewed

3 - Salut i Benestar

9 - Indústria, Innovació i Infraestructura

Postprint (published version)