Sodium Phytate‐Incorporated Gelatin‐Silicate Nanoplatelet Composites for Enhanced Cohesion and Hemostatic Function of Shear‐Thinning Biomaterials

Abstract

Shear‐thinning biomaterials (STBs) based on gelatin‐silicate nanoplatelets (SNs) are emerging as an alternative to conventional coiling and clipping techniques in the treatment of vascular anomalies. Improvements in the cohesion of STB hydrogels pave the way toward their translational application in minimally invasive therapies such as endovascular embolization repair. In the present study, sodium phytate (Phyt) additives are used to tune the electrostatic network of SNs‐gelatin STBs, thereby promoting their mechanical integrity and facilitating injectability through standard catheters. We show that an optimized amount of Phyt enhances storage modulus by approximately one order of magnitude and reduces injection force by ≈58% without compromising biocompatibility and hydrogel wet stability. The Phyt additives are found to decrease the immune responses induced by SNs. In vitro embolization experiments suggest a significantly lower rate of failure in Phyt‐incorporated STBs than in control groups. Furthermore, the addition of Phyt leads to accelerated blood coagulation (reduces clotting time by ≈45% compared to controls) due to the contributions of negatively charged phosphate groups, which aid in the prolonged durability of STB in coagulopathic patients. Therefore, the proposed approach is an effective method for the design of robust and injectable STBs for minimally invasive treatment of vascular malformations.

Polyphenolic Gelatin-Based Bioadhesives

“…For instance, shear-thinning biomaterials formed by incorporation of silicate nanoplatelets into gelation solutions promote cohesion and injectability while imparting hemostatic effects. 45 The effects of phenolic compounds in gelatin solutions are discussed below with regard to their integration chemistry.…”

“…Polyphenolic moieties can alter the behavior of gelation in solution, depending on their integration process. , Based on this effect, further biomaterial strategies can be undertaken to tune pregel viscosity. For instance, shear-thinning biomaterials formed by incorporation of silicate nanoplatelets into gelation solutions promote cohesion and injectability while imparting hemostatic effects . The effects of phenolic compounds in gelatin solutions are discussed below with regard to their integration chemistry.…”

Injectable Shear‐Thinning Hydrogels with Sclerosing and Matrix Metalloproteinase Modulatory Properties for the Treatment of Vascular Malformations

“…Injectable STBs based on Gel-SN (containing 1.5% w/v gelatin and 4.5% w/v SNs) hydrogels are versatile platforms for minimally invasive endovascular embolization due to their robust structure and hemostatic function. [13,14] As a combinatorial strategy, DOX was incorporated into the Gel-SN hydrogels (Gel-SN-DOX 𝛼 hydrogels where 𝛼 represents the DOX content in % w/v) to improve embolizing efficiency through aneurysm endothelial ablation and MMP activity inhibition. As shown in Figure 2A, the surface charge distribution of SNs is anisotropic with positive edges and negative surfaces.…”

“…Based on previous studies, the additional intermolecular electrostatic interactions introduced by DOX improve the hydrogel integrity and mechanical properties. [14] The impacts of DOX-triggered interactions on the mechanical characteristics of Gel-SN hydrogels were studied using rheological analyses. According to Figure 2C, the viscosity of all the hydrogels decreased by increasing the shear rate.…”

“…[8a] In our previous study, we developed an injectable shearthinning biomaterial (STB) based on silicate nanoplatelets (SNs) and gelatin (Gel-SN) nanocomposites for minimally invasive endovascular embolization, [13] wherein the hemostatic function of SNs and hydrogel cohesion was enhanced via sodium phytate (Phyt) additives. [14] The resulting hydrogels showed great potential as an injectable matrix for integration with microcatheters in EVAR. These effects are critical in hydrogel stability and successful embolization for blockage of vasculatures in vivo.…”