Design of a Novel Composite H₂S‐Releasing Hydrogel for Cardiac Tissue Repair

Abstract

The design of 3D scaffolds is a crucial step in the field of regenerative medicine. Scaffolds should be degradable and bioresorbable as well as display good porosity, interconnecting pores, and topographic features; these properties favour tissue integration and vascularization. These requirements could be fulfilled by hybrid hydrogels using a combination of natural and synthetic components. Here, the mechanical and biological properties of a polyethylene glycol-fibrinogen hydrogel (PFHy) are improved in order to favour the proliferation and differentiation of human Sca-1(pos) cardiac progenitor cells (hCPCs). PFHys are modified by embedding air- or perfluorohexane-filled bovine serum albumin microbubbles (MBs) and characterized. Changes in cell morphology are observed in MBs-PFHys, suggesting that MBs could enhance the formation of bundles of cells and influence the direction of the spindle growth. The properties of MBs as carriers of active macromolecules are also exploited. For the first time, enzyme-coated MBs have been used as systems for the production of hydrogen sulfide (H2 S)-releasing scaffolds. Novel H2 S-releasing PFHys are produced, which are able to improve the growth of hCPCs. This novel 3D cell-scaffold system will allow the assessment of the effects of H2 S on the cardiac muscle regeneration with its potential applications in tissue repair.

Hydrogen Sulfide-Releasing Fibrous Membranes: Potential Patches for Stimulating Human Stem Cells Proliferation and Viability under Oxidative Stress

“…These results were also in agreement with our previous studies [24,34], where the hydrogel scaffolds and DADS based nanoemulsions were able to increase the cMSC proliferation and α-sma expression. Therefore, H 2 S-relasing fibrous scaffolds might stimulate the tissue repair by activating adult resident stem cells.…”

“…In general, the effects of H 2 S-donors on stem cells have not been widely investigated yet, and even more the effects of H 2 S slow-releasing biomats [24,25,26,47]. In this context, the influence of the H 2 S-releasing PFM on adult stem cells was here assessed.…”

“…H 2 S-releasing materials could exert a wide range of protective actions, vasodilation, angiogenesis, antioxidant, and anti-inflammatory effects, improving the regenerative capacity of tissue engineering grafts, especially in cardiovascular systems [20,21,22,23]. Recently, it was demonstrated that H 2 S-functionalized hydrogels and fibers are able to enhance the proliferation of human cardiac progenitor/stem cells [24], cardiomyocytes and immortalized fibroblast cell lines [25], and to improve the wound healing process [26]. …”

H2S-releasing nanoemulsions: a new formulation to inhibit tumor cells proliferation and improve tissue repair

“…1 μl of 10 mg/ml FITC in DMSO solution was added to 100 μl of NEs (with 3 mg/ml BSA) in 15 mM sodium bicarbonate, pH 8.0, buffer and the mixture incubated at room temperature for 2 h in dark condition. Using this protocol the coupling efficiency of the fluorochrome to BSA after 2 h of incubation was about 52%, with a final ratio of 2.9/1 fluorochorme/protein moles, calculated as previously described [154, 155]. Protein concentrations were measured with the BCA protein assay (Sigma-Aldrich, Milan, Italy).…”

“…The H 2 S production by NEs was assessed using methylene blue assay [20, 155, 156]. The total volume of the reaction solution was 150 μl and it was constituted of 3 mM sodium thiosulfate, 1 mM DTT and 50 mM Tris HCl, pH 7.4 buffer.…”