Mesopore Controls the Responses of Blood Clot‐Immune Complex via Modulating Fibrin Network

Abstract

Formation of blood clots, particularly the fibrin network and fibrin network‐mediated early inflammatory responses, plays a critical role in determining the eventual tissue repair or regeneration following an injury. Owing to the potential role of fibrin network in mediating clot‐immune responses, it is of great importance to determine whether clot‐immune responses can be regulated via modulating the parameters of fibrin network. Since the diameter of D‐terminal of a fibrinogen molecule is 9 nm, four different pore sizes (2, 8, 14, and 20 nm) are rationally selected to design mesoporous silica to control the fibrinogen adsorption and modulate the subsequent fibrin formation process. The fiber becomes thinner and the contact area with macrophages decreases when the pore diameters of mesoporous silica are greater than 9 nm. Importantly, these thinner fibers grown in pores with diameters larger than 9 nm inhibit the M1‐polorazation of macrophages and reduce the productions of pro‐inflammatory cytokines and chemokines by macrophages. These thinner fibers reduce inflammation of macrophages through a potential signaling pathway of cell adhesion‐cytoskeleton assembly‐inflammatory responses. Thus, the successful regulation of the clot‐immune responses via tuning of the mesoporous pore sizes indicates the feasibility of developing advanced clot‐immune regulatory materials.

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“…Raw data of FASTQ format was generated, further being calculated into read counts and TPM data for downstream analysis. Bioinformatic analysis of transcriptome data was conducted using R studio 4.0 (The R Foundation, USA) and Cytoscape 3.8 (The Cytoscape Consortium, USA) software as previously described [ 35 ].…”

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“…Ta-MBGs used in the present study possess nanopores of about 4 nm [ 52 ] and probably were accessible to fibrinogen. Another study [ 58 ] explored the effect of mesopore size on the fibrinogen adsorption and hence the fibrin network formation. Considering fibrinogen’s dimensions: length of 47.5 nm (E domain) and diameter of 6 × 9 nm (D domain), they tested the effect of various mesopore sizes (2, 8, 14, and 20 nm) on the fibrinogen adsorption to analyze linear growth of fibrinogen’s D domain in clot formation [ 58 ].…”

“…Another study [ 58 ] explored the effect of mesopore size on the fibrinogen adsorption and hence the fibrin network formation. Considering fibrinogen’s dimensions: length of 47.5 nm (E domain) and diameter of 6 × 9 nm (D domain), they tested the effect of various mesopore sizes (2, 8, 14, and 20 nm) on the fibrinogen adsorption to analyze linear growth of fibrinogen’s D domain in clot formation [ 58 ]. Their study concluded that the pore sizes more than 9 nm (D domain dimension), i.e.…”

“…Their study concluded that the pore sizes more than 9 nm (D domain dimension), i.e. 14 and 20 nm, were able to adsorb fibrinogen while the smaller mesopores (2 and 8 nm) had little effect [ 58 ]. Mesoporous architecture with 2 and 8 nm pores was instrumental in water absorption and hence the enhancement of clot formation, but the enhancement due to fibrinogen adsorption was minimal [ 58 ].…”

“…14 and 20 nm, were able to adsorb fibrinogen while the smaller mesopores (2 and 8 nm) had little effect [ 58 ]. Mesoporous architecture with 2 and 8 nm pores was instrumental in water absorption and hence the enhancement of clot formation, but the enhancement due to fibrinogen adsorption was minimal [ 58 ]. We hypothesize that there is a connection between fibrin and glass particles in our study, the mechanism, however, was not investigated.…”