MS-proteomics provides insight into the host responses towards alginate microspheres
Research article published in Materials today. Bio (2022)
Abstract
Protein adsorption to biomaterial surfaces is considered a determining factor for the host response. Here we detail the protein adsorption profiles of alginate hydrogel microspheres relevant for cell therapy using mass spectrometry (MS)-based proteomics. The investigated microspheres include sulfated alginate (SA), high G alginate (HiG), and poly-l-lysine coated alginate (AP), which previously have been shown to exhibit different inflammatory and fibrotic responses. The biological significance was assessed in lepirudin-anticoagulated human whole blood (hWB) by functional analysis of the acute-phase responses (complement and coagulation). Proteomic profiling revealed distinct signatures for the microspheres, wherein Ingenuity Pathway Analysis identified complement and coagulation as the top enriched canonical pathways. The levels of complement and coagulation activators and inhibitors were distinctly different, which was reflected in the functional hWB analyses: SA was highly enriched with inhibitory factors of complement and coagulation (e.g. C1 inhibitor, factor H, antithrombin-III, heparin cofactor 2), other heparin-binding proteins and factors promoting fibrinolysis (factor XII, plasma kallikrein), conforming to an anti-inflammatory and anti-fibrotic profile. HiG enriched moderate levels of complement inhibitors, conforming to a low-inflammatory and pro-fibrotic profile. AP showed the most prominent enrichment of complement activators (e.g. C3, properdin, C-reactive protein) and low levels of inhibitors, conforming to a pro-inflammatory and highly pro-fibrotic profile. In conclusion, the extensive enrichment of inhibitory acute-phase proteins on SA could be a determining factor for its reduced host response. The interactions between the plasma proteins and hydrogel surfaces shown herein point to proteomics as an important supplement to existing in vitro and in vivo methods for designing biocompatible alginate-based hydrogels.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
Protein adsorption to biomaterial surfaces is considered a determining factor for the host response.
Warum dies für die Hirudotherapie relevant ist
This study used mass spectrometry-based proteomics to characterize protein adsorption profiles of alginate hydrogel microspheres (sulfated alginate, high-G alginate, poly-L-lysine-coated alginate) and assessed functional acute-phase responses in lepirudin-anticoagulated human whole blood. Distinct complement and coagulation protein enrichment signatures corresponded to each microsphere's inflammatory and fibrotic profile, with sulfated alginate enriching inhibitory factors. The lepirudin/hirudin relevance is limited to its role as a research anticoagulant enabling functional complement/coagulation assays. Caveat: no leeches or hirudotherapy are involved; lepirudin served only as an anticoagulant tool, and the study concerns biomaterial host responses, not leech-derived therapeutics.
Zitation
MS-proteomics provides insight into the host responses towards alginate microspheres
Coron AE et al. · Materials today. Bio, 2022
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