Evaluation of an Injectable Hydrogel Based on Hyaluronic Acid–Chitosan/β‐Glycerophosphate‐Loaded Mesenchymal Stem Cells in Enhancing the Therapeutic Efficacy of Myocardial Infarction

Abstract

Myocardial infarction (MI), which is due to cardiac dysfunction, results in morbidity and mortality. Moreover, the cellular activity of transplanted mesenchymal stem cells (MSCs) generally limits their therapeutic efficacy in the treatment of MI. Here, inject able hyaluronic acid-chitosan/𝜷-glycerophosphate (HA-CS/𝜷-GP) hydrogel-loaded MSCs are prepared, after which their effects on the treatment of MI are investigated. The synthesized HA-CS/𝜷-GP hydrogels exhibit swelling ratio, an in vitro degradation value, and a gelatin time of 82.19 ± 4.1, 88.18% ± 2.4%, and 9 s, respectively. Further, rheological studies revealed that the elastic modulus of the HA-CS/𝜷-GP hydrogels is ≥230 Pa, exhibiting large elastic to viscous modulus ratio, which indicates their mechanical strength. Furthermore, the in vitro 3T3 cell and MSC culture studies confirm the good biocompatibility of the HA-CS and HA-CS/𝜷-GP hydrogels. The implantation of the synthesized hydrogels in the mouse MI model considerably improves the therapeutic effect of the MSCs (enhanced cardiac function, reduced cardiomyocyte apoptosis, and increased vascularization) for the first time. The innovative synergistic strategy of combining injectable HA-CS and HA-CS/𝜷-GP hydro gels with MSCs may be suitable for the effective treatment of cardiac morbidity due to MIs.

Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models

“…Here, we implemented such a novel therapeutic formulation to enhance drug bioavailability at cancer lesions, based on a versatile chitosan-βGP thermogel platform which, being liquid before contact with the body, offers easier handling and positioning into the lesions. In particular, among thermo-sensitive gel systems, chitosan-βGP has been employed mostly in regenerative medicine 38 , 39 . Several research groups carried out the synthesis and characterization of chitosan-based nanocomposite injectable hydrogels 40 but very few reported the pharmacokinetic profile of anticancer drugs incorporated into nanoparticle contained in hydrogels 41 .…”

Chitosan-Based Scaffolds for the Treatment of Myocardial Infarction: A Systematic Review

“…Among the biocompatible compounds are natural polymers, such as alginate [ 88 ], gelatin [ 85 ] and chitosan [ 89 ], and biodegradable synthetic polymers, such as polycaprolactone [ 89 ], polypyrrole [ 90 ] and polyvinyl alcohol [ 91 ]. These polymers help renew dysfunctional tissue and provide structural support for the development of stem cells.…”

“…There are two types of scaffolds capable of promoting bioactivity in the implantation areas: microfilamentous and microporous scaffolds [ 84 ], with three composition types: natural, synthetic and hybrid [ 89 ], and two forms of application: patches and injections [ 103 ]. Ideally, each must be able to conduct electricity, allow for the differentiation of the stem cells into the cardiomyocytes and have Young’s modulus similar to the native myocardial tissue [ 104 , 105 ].…”

Insight into Heart-Tailored Architectures of Hydrogel to Restore Cardiac Functions after Myocardial Infarction

“…Adjusting conditions of chemical/enzymatic polymerization may lower this risk, but could lead to unclear drug release kinetics, undesirable mechanical properties and premature polymerization within the equipment . External triggers (UV light) are always required for polymerization of hydrogels which are incorporated with functionalized groups. , A rotational rheometer can be employed to measure the gelation characteristics of hydrogel solutions changing with their storage (elastic) modulus and loss (viscous) modulus …”

“…106,107 A rotational rheometer can be employed to measure the gelation characteristics of hydrogel solutions changing with their storage (elastic) modulus and loss (viscous) modulus. 108 As alginate hydrogels have been reported to degrade slowly in vivo, partially oxidized alginate (OA) presenting aldehyde functional groups on the polymer chains is responsible for gelation time and optimizing the partial oxidation of alginate hydrogels would enable its biodegradation in a more digestible and faster manner. 109 A new oxygen delivery system based on a thermosensitive, injectable and fast gelation hydrogel could constantly release O 2 for as long as 4 weeks.…”