Gelatin Methacryloyl Bioadhesive Improves Survival and Reduces Scar Burden in a Mouse Model of Myocardial Infarction

Abstract

Background Delivery of hydrogels to the heart is a promising strategy for mitigating the detrimental impact of myocardial infarction ( MI ). Challenges associated with the in vivo delivery of currently available hydrogels have limited clinical translation of this technology. Gelatin methacryloyl (Gel MA ) bioadhesive hydrogel could address many of the limitations of available hydrogels. The goal of this proof‐of‐concept study was to evaluate the cardioprotective potential of Gel MA in a mouse model of MI . Methods and Results The physical properties of Gel MA bioadhesive hydrogel were optimized in vitro. Impact of Gel MA bioadhesive hydrogel on post‐ MI recovery was then assessed in vivo. In 20 mice, Gel MA bioadhesive hydrogel was applied to the epicardial surface of the heart at the time of experimental MI . An additional 20 mice underwent MI but received no Gel MA bioadhesive hydrogel. Survival rates were compared for Gel MA ‐treated and untreated mice. Left ventricular function was assessed 3 weeks after experimental MI with transthoracic echocardiography. Left ventricular scar burden was measured with postmortem morphometric analysis. Survival rates at 3 weeks post‐ MI were 89% for Gel MA ‐treated mice and 50% for untreated mice ( P =0.011). Left ventricular contractile function was better in Gel MA ‐treated than untreated mice (fractional shortening 37% versus 26%, P <0.001). Average scar burden in Gel MA ‐treated mice was lower than in untreated mice (6% versus 22%, P =0.017). Conclusions Epicardial Gel MA bioadhesive application at the time of experimental MI was performed safely and was associated with significantly improved post‐ MI survival compared with control animals. In addition, Gel MA treatment was associated with significantly better preservation of left ventricular function and reduced scar burden.

Engineering Tissues of the Central Nervous System: Interfacing Conductive Biomaterials with Neural Stem/Progenitor Cells

“…For example, bio‐ionic liquids (e.g., based on choline) have been used to functionalize biomaterials, such as gelatin and polyethylene glycol, to yield biocompatible, conductive scaffolds that can promote healing of cardiac tissue in animal models. [ 403,404 ] Given their natural origin, bio‐ionic liquids likely offer better biocompatibility than other conductive materials. Furthermore, while biomaterial composites with carbon‐based materials or CPs are opaque, those with bio‐ionic liquids typically remain transparent, which is an advantage for imaging of cells laden throughout 3D scaffolds.…”

“…As NS/PCs cannot efficiently differentiate when cultured in a non-degradable, 3D hydrogel, biodegradability is needed. [389] For this reason, hydrogel biomaterials are often made with protease-degradable sites or from naturally biodegradable materials. For example, chitosan-graphene nanoparticles were disbursed within collagen I hydrogels, creating an enzymatically degradable, highly cytocompatible scaffold for NS/PCs.…”

Microsphere-Embedded Hydrogel Sustained-Release System to Inhibit Postoperative Epidural Fibrosis

“…Previous studies have demonstrated that the GelMA bioadhesive hydrogel reduced scar formation. 23 In this work, there are two main effects: (i) the injectable RSV@PLGA-GelMA hydrogel acts as a physical barrier to cover defects, and it prevents the scar from invading into the epidural area and (ii) simultaneously, RSV will be released from the hydrogel matrix; thus, a better anti-epidural fibrosis will be achieved. In this study, we further identify the type of collagen through picric−Sirius Red staining.…”

“…21,22 To the best of our knowledge, very few literature has explored the detailed therapeutic efficacy in managing epidural fibrosis utilizing GelMA hydrogels, although it was proved to have a positive effect on reducing cardiac fibrosis after myocardial infarction in a mouse model. 23 On the other hand, the effectiveness and efficiency of the singular hydrogel matrix strategy actually are limited; injecting anti-proliferation drug may achieve a better effect theoretically.…”

Therapeutic Acellular Scaffolds for Limiting Left Ventricular Remodelling-Current Status and Future Directions

“…Other studies have reported hydrogel scaffolds prepared from various biocompatible polymeric materials that included N-isopropylacrylamide (NIPAAm), poly N-isopropylacrylamide (PNIPAAm), 2-hydroxyethyl methacrylate (HEMA), methacrylate polylactide (MAPLA), dextran (Dex), poly(ε-caprolactone) (PCL) and gelatine [ 79 , 80 , 81 ]. Poly (NIPAAm-co-HEMA-co-MAPLA) hydrogels [ 79 ] in an infarcted swine model, whereas Dex-PCL-HEMA/PNIPAAm (DPHP) hydrogels [ 80 ] and gelatine methacryloyl hydrogels [ 81 ] in infarcted rodents have also been shown to attenuate LV remodelling and improve cardiac function.…”