Electrically Conductive Collagen-PEDOT:PSS Hydrogel Prevents Post-Infarct Cardiac Arrhythmia and Supports hiPSC-Cardiomyocyte Function.

Myocardial infarction (MI) causes cell death, disrupts electrical activity, triggers arrhythmia, and results in heart failure, whereby 50-60% of MI-associated deaths manifest as sudden cardiac deaths (SCD). The most effective therapy for SCD prevention is implantable cardioverter defibrillators (ICDs). However, ICDs contribute to adverse remodeling and disease progression and do not prevent arrhythmia. This work develops an injectable collagen-PEDOT:PSS (poly(3,4-ethylenedioxythiophene) polystyrene sulfonate) hydrogel that protects infarcted hearts against ventricular tachycardia (VT) and can be combined with human induced pluripotent stem cell (hiPSC)-cardiomyocytes to promote partial cardiac remuscularization. PEDOT:PSS improves collagen gel formation, micromorphology, and conductivity. hiPSC-cardiomyocytes in collagen-PEDOT:PSS hydrogels exhibit near-adult sarcomeric length, improved contractility, enhanced calcium handling, and conduction velocity. RNA-sequencing data indicate enhanced maturation and improved cell-matrix interactions. Injecting collagen-PEDOT:PSS hydrogels in infarcted mouse hearts decreases VT to the levels of healthy hearts. Collectively, collagen-PEDOT:PSS hydrogels offer a versatile platform for treating cardiac injuries.

3D-Printed Multifunctional Hydrogels with Phytotherapeutic Properties: Development of Essential Oil-Incorporated ALG-XAN Hydrogels for Wound Healing Applications.

This study aimed to develop three-dimensional (3D)-printed hydrogels containing phytotherapeutic agents as multifunctional wound dressings. In this regard, 3D-printed sodium alginate (ALG)-xanthan gum (XAN) hydrogels incorporated with different clove essential oil (CLV) concentrations were produced by the extrusion-based 3D-printing technology. Rheology measurements, filament fusion, and filament collapse analyses indicated that XAN's blending overcame the challenges associated with ALG's printability and shape fidelity. Attenuated total reflection-Fourier-transform infrared (ATR-FTIR) spectra and total phenolic content assay confirmed the presence of CLV in the 3D-printed hydrogels. Additionally, the releasing profile showed that CLV exhibited long-term release for up to 28 days. Furthermore, the incorporation of CLV increased 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging while reducing the S. aureus and E. coli relative bacterial viability; thereby, the CLV incorporation enhanced the 3D-printed ALG-XAN hydrogel antioxidant and antibacterial activity. In addition, anti-inflammatory activity was assessed using Raw 264.7 macrophage-like cells, and the results demonstrated that CLV reduced nitric oxide (NO) concentration in medium, indicating a potential anti-inflammatory effect. Moreover, in vitro cytotoxicity results showed that the incorporation of CLV has no toxic effect on NHDF cells, whereas the proliferation of NHDF cells exhibited a dose-dependent response. In conclusion, the present study shows not only the development of a new ALG-XAN biomaterial ink but also the potential benefit of natural phytotherapeutics incorporated into 3D-printed hydrogels as a multifunctional wound dressing.

Collagen Hydrogel Containing Polyethylenimine-Gold Nanoparticles for Drug Release and Enhanced Beating Properties of Engineered Cardiac Tissues.

Cardiac tissue engineering is a promising strategy to prevent heart failure. However, several issues remain unsolved, including efficient electrical coupling and incorporating factors to enhance tissue maturation and vascularization. Herein, a biohybrid hydrogel that enhances beating properties of engineered cardiac tissues and allows drug release concurrently is developed. Gold nanoparticles (AuNPs) with different sizes (18-241 nm) and surface charges (33.9-55.4 mV) are synthesized by reducing gold (III) chloride trihydrate using branched polyethyleneimine (bPEI). These nanoparticles increase gel stiffness from ≈91 to ≈146 kPa, enhance electrical conductivity of collagen hydrogels from ≈40 to 49-68 mS cm-1 , and allow slow and steady release of loaded drugs. Engineered cardiac tissues based on bPEI-AuNP-collagen hydrogels and either primary or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes show enhanced beating properties. hiPSC-derived cardiomyocytes exhibit more aligned and wider sarcomeres in bPEI-AuNP-collagen hydrogels compared to collagen hydrogels. Furthermore, the presence of bPEI-AuNPs result in advanced electrical coupling evidenced by synchronous and homogenous calcium flux throughout the tissue. RNA-seq analyses are in agreement with these observations. Collectively, this data demonstrate the potential of bPEI-AuNP-collagen hydrogels to improve tissue engineering approaches to prevent heart failure and possibly treat diseases of other electrically sensitive tissues.