A paintable and adhesive hydrogel cardiac patch with sustained release of ANGPTL4 for infarcted heart repair

The infarcted heart undergoes irreversible pathological remodeling after reperfusion involving left ventricle dilation and excessive inflammatory reactions in the infarcted heart,frequently leading to fatal functional damage.Extensive attempts have been made to attenuate pathological remodeling in infarcted hearts using cardiac patches and anti-inflammatory drug delivery.In this study,we developed a paintable and adhesive hydrogel patch using dextran-aldehyde(dex-ald)and gelatin,incorporating the anti-inflammatory protein,ANGPTL4,into the hydrogel for sustained release directly to the infarcted heart to alleviate inflammation.We optimized the material composition,including polymer concentration and molecular weight,to achieve a paintable,adhesive hydrogel using 10%gelatin and 5%dex-ald,which displayed in-situ gel formation within 135 s,cardiac tissue-like modulus(40.5 kPa),suitable tissue adhesiveness(4.3 kPa),and excellent mechanical stability.ANGPTL4 was continuously released from the gelatin/dex-ald hydrogel without substantial burst release.The gelatin/dex-ald hydrogel could be conveniently painted onto the beating heart and degraded in vivo.Moreover,in vivo studies using animal models of acute myocardial infarction revealed that our hydrogel cardiac patch containing ANGPTL4 significantly improved heart tissue repair,evaluated by echocardiography and histological evaluation.The heart tissues treated with ANGPTL4-loaded hydrogel patches exhibited increased vascularization,reduced inflammatory macrophages,and structural maturation of cardiac cells.Our novel hydrogel system,which allows for facile paintability,appropriate tissue adhesiveness,and sustained release of anti-inflammatory drugs,will serve as an effective platform for the repair of various tissues,including heart,muscle,and cartilage.

Wet tissue adhesive polymeric powder hydrogels for skeletal muscle regeneration

Volumetric muscle loss(VML)frequently results from traumatic incidents and can lead to severe functional disabilities.Hydrogels have been widely employed for VML tissue regeneration,which are unfortunately ineffective because of the lack of intimate contact with injured tissue for structural and mechanical support.Adhesive hydrogels allow for strong tissue connections for wound closure.Nevertheless,conventional adhesive hydrogels exhibit poor tissue adhesion in moist,bleeding wounds due to the hydration layer at the tissue–hydrogel interfaces,resulting in insufficient performance.In this study,we developed a novel,biocompatible,wet tissue adhesive powder hydrogel consisting of dextran-aldehyde(dex-ald)and gelatin for the regeneration of VML.This powder absorbs the interfacial tissue fluid and buffer solution on the tissue,spontaneously forms a hydrogel,and strongly adheres to the tissue via various molecular interactions,including the Schiff base reaction.In particular,the powder composition with a 1:4 ratio of dex-ald to gelatin exhibited optimal characteristics with an appropriate gelation time(258 s),strong tissue adhesion(14.5 kPa),and stability.Dex-ald/gelatin powder hydrogels presented strong adhesion to various organs and excellent hemostasis compared to other wet hydrogels and fibrin glue.A mouse VML injury model revealed that the dex-ald/gelatin powder hydrogel significantly improved muscle regeneration,reduced fibrosis,enhanced vascularization,and decreased inflammation.Consequently,our wet-adhesive powder hydrogel can serve as an effective platform for repairing various tissues,including the heart,muscle,and nerve tissues.