TABLE 1.
Different stimuli-responsive hydrogels employed for cardiac tissue engineering.
| Type of stimuli-responsive hydrogels | Stimuli-responsive hydrogel system | Study model | Purpose of use | Outcomes | References | |
|---|---|---|---|---|---|---|
| Physical stimuli-responsive hydrogels | Temperature-responsive hydrogels | Chitosan (CH)-gold nanoparticles GNP loaded with mesenchymal stem cells (MSCs) (CH-GNP/MSCs) | In vitro assessment | Cardiac tissue engineering | The integration of GNP could boost the properties of thermo-sensitive CH hydrogels for CTE | Baei et al. (2016) |
| Poly (N-isopropylacrylamide (PNIPAAm) containing poly-lactic-co-glycolic acid (PLGA)-encapsulated PVP/H2O2 core/shell microspheres | In vitro (cardiac fibroblast, cardiomyocyte, and endothelial cell) | Treatment of myocardial infarction | Improved survival of the cardiac cells under low oxygen states that imitates the myocardial infarction models | Fan et al. (2018) | ||
| Gellan gum/reduced graphene oxide hydrogel | In vitro (rat myoblasts (H9C2)) | Development of myocardial tissue engineering scaffold | Gellan gum/reduced graphene oxide hydrogel are promising scaffolds for CTE | Zargar et al. (2019) | ||
| Chitosan (CH)/dextran (DEX)/β–glycerophosphate (β-GP) loaded with umbilical cord mesenchymal stem cells (UCMSCs) | In vitro (3T3 cells and human umbilical vein endothelial cells (HUVECs)) | Cell delivery carrier for therapy of myocardial infarction | Chitosan (CH)/dextran (DEX)/β–glycerophosphate (β-GP) loaded UCMS is a potential vehicle to deliver cells for CTE | Ke et al. (2020) | ||
| β-glycerophosphate (β -GP) and different kinds of hydrolyzed collagen (HC)-chitosan (CH) hydrogel | In vitro (Fetal human ventricular cardiomyocytes cell line RL-14) | Regeneration of the cardiac tissue | The hydrogels found to be promising in increasing cell survival for engineering of infarcted heart tissue | Orozco-Marín et al. (2021) | ||
| Light/Photo-responsive hydrogels | Collagen-polydopamine hydrogel (Col-PDA) | In vitro assessment | Control of the cardiomyocyte and neuron activity | Collagen-polydopamine hydrogel (Col-PDA) are promising photo sensitive platforms for applications in tissue engineering | Gholami Derami et al. (2021) | |
| Cell-degradable poly (2-alkyl-2-oxazoline) (Pox) hydrogel | In vivo (rat myocardial infarction model) | Epicardial placement of mesenchymal stem cells for myocardial repair | The synthetic hydrogels are substantial platforms for epicardial delivery of the loaded cells employed for CTE | You et al. (2021) | ||
| Carbon nanotube (CNT)-incorporated photo-cross-linkable gelatin methacrylate (GelMA) hydrogels | In vitro assessment | Cardiac engineering and bio actuators | CNT-GelMA are unique multifunctional scaffolds for engineering of infarcted hearts | Shin et al. (2013) | ||
| Gelatin methacrylate-reduced graphene oxide (GelMA-rGO) nanocomposite hydrogels | In vitro (cardiomyocytes cell culture) | Cardiac Tissue Engineering | GelMA-rGO hydrogels are outstanding scaffolds for CTE applications in vitro | Shin et al. (2016) | ||
| Electro-responsive hydrogels | Poly-3-amino-4-methoxy benzoic acid (PAMB) crosslinked Gelatin (Gt) hydrogels | In vivo (rat MI model) | Propagation of the electrical impulse at the MI site to prevent cardiac arrhythmia and preserve ventricular function | Improved ventricular functions and decreased arrhythmia due to the MI in the PAMB-Gt hydrogels treated animals | Zhang et al. (2020a) | |
| Polyacrylic acid (PAA) mixed with Oxidized alginate (OAlg.)/Gelatin (Gt) hydrogel | In vivo (rat MI model) | MI repair | The PAA mixed with OAlg./Gel hydrogel could efficiently reduce cardiac remodeling and improved cardiac function restoration | Song et al. (2021a) | ||
| Magnetic-responsive hydrogels | Chitosan-carbon nanotubes (CH/CNTs) nano scaffold hydrogel | In vivo (neonatal rat heart cells) | Cardiac tissue engineering | the integration of carbon nanofibers into the CH platforms improved the characters of scaffolds employed for CTE | Martins et al. (2014) | |
| Collagen (Col)/magnetic iron oxide (Fe3O4) nanoparticles coated with Polyethylene glycol (PEG) | In vitro assessment | Cardiac tissue engineering | Improved conductive properties of collagen by the incorporation of nanoparticles with improved outcomes of CTE | Bonfrate et al. (2017) | ||
| Magnetic Alginate (Alg.) hydrogel scaffolds | In vitro assessment | Cardiac tissue engineering | Fabrication of proficient pre-vascularized constructs potential for transplantation applications | Sapir et al. (2012) | ||
| Polyethylene glycol (PEG) diacrylate magnetic nanoparticles hydrogels | In vitro assessment | Cardiac muscle cells engineering | Development of sophisticated platforms for drug delivery and actuation activities for CTE purposes | Vannozzi et al. (2018) | ||
| -Cryogels based on Gelatin methacrylate (GelMA) and elastin adapted with carbon nanotubes (CNTs) and magnetic nanoparticles (MNPs) | - In vitro assessment | -Cardiac tissue engineering | -Enhanced engineering of the infarcted heart tissue | Pardo et al. (2021) | ||
| Pressure-responsive hydrogels | Polymer polyaniline (PAni) hydrogel | In vitro (cardiomyocytes culture) | Supports cardiomyocyte organization into a spontaneously contracting system | The composites improved cardiac cell organization into a freely contracting structure with potential application in CTE | Chakraborty et al. (2018) | |
| -Cyclodextrin-Hyaluronic acid (CD-HA) and Adamantane -Hyaluronic (Ad-HA) hydrogels | -Ex vivo (porcine cardiac tissue) | -Cardiac tissue engineering | -Amelioretd CTE with improved restoration of the cardiac functions | Chen et al. (2017b) | ||
| Ultrasound/acoustic-responsive hydrogels | Silk sericin (MSS)-Fe2O3nanocomposite hydrogels loaded with secretome (Sec) biomolecules (Sec@MSS) | In vitro (cardiomyocytes culture) | Reduction of the Doxorubicin (DOX) induced cardiotoxicity in human stem cell-derived cardiac muscle cells | Sec@MSS are promising and potent platforms for application in CTE | Zhang et al. (2021a) | |
| Heparin-binding based, Gd(III)-tagged PEG hydrogels | In vivo (mouse myocardium) | To deliver and monitor cardiac progenitor/stem cell engraftment for implantation | Heparin-binding based, Gd(III)-tagged PEG hydrogel systems presented a tailored cell delivery and potential to assess the transplanted materials for CTE | Speidel et al. (2017) | ||
| Chemical stimuli-responsive hydrogels | PH-responsive hydrogels | Poly-N-isopropyl-acrylamide- Butyl acrylate- Propyl-acrylic acid (PNIPAAm-BA-PAA) composite hydrogels | In vivo (rat MI model) | Improvement of the angiogenesis in infarcted myocardium | Enhanced angiogenesis and sustained topical delivery of growth factors with restored cardiac functions | Garbern et al. (2011) |
| PNIPAAm with mono carbon nanotubes hydrogel entrapping stem cells | In vivo (rat MI model) | MI treatment | Improved cardiac tissue engineering | Peña et al. (2018) | ||
| Hydrogen bond crosslinked ureido-pyrimidinone group to PEG | In vivo (pig MI model) | MI treatment | Improved delivery of growth factors and ameliorated CTE | Bastings et al. (2014) | ||
| NIPAAm hydrogel cross linked with Di(ethylene glycol) divinyl ether (DEGDVE) [p (NIPAAm-co-DEGDVE)] | In vitro assessment | Cardiac Tissue Engineering | Enhanced drug release abilities of the hydrogel with potential promises in CTE | Werzer et al. (2019) | ||
| Ionic strength-responsive hydrogels | Iron-Dopamine-gelatin (GelDA)-Dopamine-polypyrrole (DA-PPy) (Fe-GelDA and DA-PPy) composite hydrogels | In vivo (rat MI model) | MI treatment | Pronounced enhancement of the cardiac function restoration with improved angiogenesis | Wu et al. (2020) | |
| Polypyrrole-Chitosan (PPY-CH) hydrogel | In vivo (rat MI model) | Prevention of heart failure | -Improved cardiac functions anddeclined arrhythmia following MI | He et al. (2020) | ||
| Self-healing ionic hydrogel (POG1) with biocompatiblepolyacrylic acid (PAA) | In vivo (rat MI model) | MI repair | Reduced cardiac remodeling and enhanced restoration of the heart functions after MI | Song et al. (2021b) | ||
| Biological stimuli-responsive hydrogels | Enzyme-responsive hydrogels | Matrix metalloproteinases (MMP-2) and elastase combined with Proline-Leucine-Glycine-Leucine-Alanine-Glycine (PLG|LAG) polypeptides to form biopolymer hydrogels | In vivo (rat MI model) | MI treatment | Ameliorated cardiac tissue engineering abilities after MI | Carlini et al. (2019) |
| Physical stimuli-responsive hydrogels | MMP-injectable hydrogels utilizingHyaluronic acid (HA) | In vitro assessment | MI treatment | Promising enzyme-responsive platforms for CTE | Li et al. (2022a) | |
| Recombinant protein glutathione-S-transferase (GST)-TIMP-bFGF by combining bFGF, MMP-2/9-degradable -Proline-Leucine-Glycine-Leucine-Alanine-Glycine (PLG|LAG) peptide, (TIMP), and GST entrapped in a GSH-modified collagen (Col) hydrogel (GST-TIMP-bFGF/collagen-GSH) hydrogels | In vivo (rat MI model) | Growth factor delivery | GST-TIMP-bFGF/collagen-GSH hydrogels could enhance the angiogenesis and reduce remodeling with improved delivery of growth factors | Fan et al. (2019a) | ||
| Antigen/antibody-responsive hydrogels | Sulfated glycosaminoglycan-like ECM-mimetic injectable collagen (Col) hydrogel loaded with Artificial apoptotic cells (AACs) and vascular endothelial growth factor (VEGF) | In vivo (rat MI model) | MI treatment | Increased neovascularization at the site of MI with marked enahncement of the heart functions after MI repair | Zhang et al. (2021c) | |
| Magnetic basic structure nanoparticles (Fe3O4-SiO2) hydrogel augmented with hydrazine hydrate and aldehyde-PEG to improve antibody conjugation (Fe3O4@SiO2-PEG) | In vivo (rabbit and rat models of MI) | MI treatment | Reduced infarct size and enhanced ventricular functions with ameliorated neovascularization | Liu et al. (2020) | ||