Tissue-Adhesive Hydrogel Spray System for Live Cell Immobilization on Biological Surfaces

Gelatin hydrogels are used as three-dimensional cell scaffolds and can be prepared using various methods. One widely accepted approach involves crosslinking gelatin amino groups with poly(ethylene glycol) (PEG) modified with N-hydroxysuccinimide ester (PEG-NHS). This method enables the encapsulation of live cells within the hydrogels and also facilitates the adhesion of the hydrogel to biological tissues by crosslinking their surface amino groups. Consequently, these hydrogels are valuable tools for immobilizing cells that secrete beneficial substances in vivo. However, the application of gelatin hydrogels is limited due to the requirement for several minutes to solidify under conditions of neutral pH and polymer concentrations suitable for live cells. This limitation makes it impractical for use with biological tissues, which have complex shapes or inclined surfaces, restricting its application to semi-closed spaces. In this study, we propose a tissue-adhesive hydrogel that can be sprayed and immobilized with live cells on biological tissue surfaces. This hydrogel system combines two components: (1) gelatin/PEG-NHS hydrogels and (2) instantaneously solidifying PEG hydrogels. The sprayed hydrogel solidified within 5 s after dispensing while maintaining the adhesive properties of the PEG-NHS component. The resulting hydrogels exhibited protein permeability, and the viability of encapsulated human mesenchymal stem/stromal cells (hMSCs) remained above 90% for at least 7 days. This developed hydrogel system represents a promising approach for immobilizing live cells on tissue surfaces with complex shapes

Tissue-Adhesive Hydrogel Spray System for Live Cell Immobilization on Biological Surfaces

Gelatin hydrogels are used as three-dimensional cell scaffolds and can be prepared using various methods. One widely accepted approach involves crosslinking gelatin amino groups with poly(ethylene glycol) (PEG) modified with N-hydroxysuccinimide ester (PEG-NHS). This method enables the encapsulation of live cells within the hydrogels and also facilitates the adhesion of the hydrogel to biological tissues by crosslinking their surface amino groups. Consequently, these hydrogels are valuable tools for immobilizing cells that secrete beneficial substances in vivo. However, the application of gelatin hydrogels is limited due to the requirement for several minutes to solidify under conditions of neutral pH and polymer concentrations suitable for live cells. This limitation makes it impractical for use with biological tissues, which have complex shapes or inclined surfaces, restricting its application to semi-closed spaces. In this study, we propose a tissue-adhesive hydrogel that can be sprayed and immobilized with live cells on biological tissue surfaces. This hydrogel system combines two components: (1) gelatin/PEG-NHS hydrogels and (2) instantaneously solidifying PEG hydrogels. The sprayed hydrogel solidified within 5 s after dispensing while maintaining the adhesive properties of the PEG-NHS component. The resulting hydrogels exhibited protein permeability, and the viability of encapsulated human mesenchymal stem/stromal cells (hMSCs) remained above 90% for at least 7 days. This developed hydrogel system represents a promising approach for immobilizing live cells on tissue surfaces with complex shapes

Tissue-Adhesive Hydrogel Spray System for Live Cell Immobilization on Biological Surfaces

Gelatin hydrogels are used as three-dimensional cell scaffolds and can be prepared using various methods. One widely accepted approach involves crosslinking gelatin amino groups with poly(ethylene glycol) (PEG) modified with N-hydroxysuccinimide ester (PEG-NHS). This method enables the encapsulation of live cells within the hydrogels and also facilitates the adhesion of the hydrogel to biological tissues by crosslinking their surface amino groups. Consequently, these hydrogels are valuable tools for immobilizing cells that secrete beneficial substances in vivo. However, the application of gelatin hydrogels is limited due to the requirement for several minutes to solidify under conditions of neutral pH and polymer concentrations suitable for live cells. This limitation makes it impractical for use with biological tissues, which have complex shapes or inclined surfaces, restricting its application to semi-closed spaces. In this study, we propose a tissue-adhesive hydrogel that can be sprayed and immobilized with live cells on biological tissue surfaces. This hydrogel system combines two components: (1) gelatin/PEG-NHS hydrogels and (2) instantaneously solidifying PEG hydrogels. The sprayed hydrogel solidified within 5 s after dispensing while maintaining the adhesive properties of the PEG-NHS component. The resulting hydrogels exhibited protein permeability, and the viability of encapsulated human mesenchymal stem/stromal cells (hMSCs) remained above 90% for at least 7 days. This developed hydrogel system represents a promising approach for immobilizing live cells on tissue surfaces with complex shapes

Apoptosis inhibitor of macrophage depletion decreased M1 macrophage accumulation and the incidence of cardiac rupture after myocardial infarction in mice

<div><p>Background</p><p>Cardiac rupture is an important cause of death in the acute phase after myocardial infarction (MI). Macrophages play a pivotal role in cardiac remodeling after MI. Apoptosis inhibitor of macrophage (AIM) is secreted specifically by macrophages and contributes to macrophage accumulation in inflamed tissue by maintaining survival and recruiting macrophages. In this study, we evaluated the role of AIM in macrophage accumulation in the infarcted myocardium and cardiac rupture after MI.</p><p>Methods and results</p><p>Wild-type (WT) and AIM^‒/‒ mice underwent permanent left coronary artery ligation and were followed-up for 7 days. Macrophage accumulation and phenotypes (M1 pro-inflammatory macrophage or M2 anti-inflammatory macrophage) were evaluated by immunohistological analysis and RT-PCR. Matrix metalloproteinase (MMP) activity levels were measured by gelatin zymography. The survival rate was significantly higher (81.1% vs. 48.2%, <i>P</i><0.05), and the cardiac rupture rate was significantly lower in AIM^{<b>‒/‒</b>} mice than in WT mice (10.8% vs. 31.5%, <i>P</i><0.05). The number of M1 macrophages and the expression levels of M1 markers (iNOS and IL-6) in the infarcted myocardium were significantly lower in AIM^{<b>‒/‒</b>} mice than in WT mice. In contrast, there was no difference in the number of M2 macrophages and the expression of M2 markers (Arg-1, CD206 and TGF-β1) between the two groups. The ratio of apoptotic macrophages in the total macrophages was significantly higher in AIM^{<b>‒/‒</b>} mice than in WT mice, although MCP-1 expression did not differ between the two groups. MMP-2 and 9 activity levels in the infarcted myocardium were significantly lower in AIM^{<b>‒/‒</b>} mice than in WT mice.</p><p>Conclusions</p><p>These findings suggest that AIM depletion decreases the levels of M1 macrophages, which are a potent source of MMP-2 and 9, in the infarcted myocardium in the acute phase after MI by promoting macrophage apoptosis, and leads to a decrease in the incidence of cardiac rupture and improvements in survival rates.</p></div

Survival rates for the WT and AIM^‒/‒ groups after MI.

<p>Kaplan-Meier survival curves for the WT and AIM^{<b>‒/‒</b>} groups after MI. *<i>P</i><0.05 compared with WT mice.</p

Echocardiographic data for the WT and AIM^‒/‒ groups before and 3, 7 days after MI.

<p>Echocardiographic data for the WT and AIM^‒/‒ groups before and 3, 7 days after MI.</p

MMP-2 and 9 activity levels in the infarcted myocardium of WT and AIM^‒/‒ mice at 7 days after MI.

<p>A representative image of gelatin zymography (<b>A</b>), and quantitative analyses of MMP-2 (<b>B</b>) and 9 (<b>C</b>) activity levels in the infarcted myocardium of WT and AIM^{<b>‒/‒</b>} mice at 7 days after MI. *<i>P</i><0.05 compared with sham-operated WT mice, ^#<i>P</i><0.05 compared with WT-MI mice, n = 6 per group.</p

Macrophage accumulation in the infarcted myocardium of WT and AIM^‒/‒ mice.

<p>Representative images of immunohistochemical staining for MAC-3 positive cells in the infarcted myocardium of WT and AIM^{<b>‒/‒</b>} mice at 3 days after MI <b>(A)</b>. The scale bars indicate 200 μm. The number of MAC-3 positive cells in the infarcted myocardium of WT and AIM^{<b>‒/‒</b>} mice at 3 days after MI <b>(B)</b>. *<i>P</i><0.05 compared with WT mice.</p

Hemodynamic data for the WT and AIM^‒/‒ groups at 3 days after MI.

<p>Hemodynamic data for the WT and AIM^‒/‒ groups at 3 days after MI.</p

Cardiac rupture in WT and AIM^‒/‒ mice after MI.

<p>The number of animals that died of cardiac rupture in the WT and AIM^{<b>‒/‒</b>} groups <b>(A)</b>, and the percentages of mice in each group that suffered cardiac rupture after MI <b>(B)</b>. *<i>P</i><0.05 compared with WT mice.</p