Regeneration of ischemic heart using hyaluronic acid‐based injectable hydrogel

Abstract

An injectable hydrogel was applied to regenerate a myocardial infarction and functional recovery of the heart. A myocardial infarction was induced in rat by circumflex artery ligation. A hyaluronic acid-based hydrogel was injected into the epicardium of the infarcted area. Then, cardiac functions and regeneration of the myocardium in sham-operated (SHAM), myocardial infarction (MI), and gel-injected group (GEL) (n = 6) were evaluated 4 weeks after the injection. Measurements of the thickness of the wall showed that the thickness in the GEL group increased by up to 200% compared with that in the MI group (p < 0.001). The infarcted area of the left ventricular in the GEL group decreased by 53% compared with the MI group (p < 0.001). The number of arterioles and capillaries in the border zone of the GEL group increased by 152% and 148%, whereas the apoptotic index decreased by 42% (p < 0.05). Measurement of the heart functions, such as ejection fraction, arterial elastance (Ea), dP/dt max, and dP/dt min, indicated that the injection of a hydrogel significantly facilitated the functional recovery compared with the MI group. Because of its simplicity, easy applicability, and a great regenerating potential, this injectable hydrogel promises as a treatment for myocardial infarction.

Injectable Acellular Hydrogels for Cardiac Repair

“…Hyaluronic acid (HA) is a polysaccharide that is abundant in the body and plays a role in several biological processes that include angiogenesis, cell migration, and scar reduction depending on its molecular weight, and the addition of functional groups allows for tunability in material properties [55][56][57][58][59][60]. In one example, acrylated HA was mixed with a thiol-terminated PEG crosslinker (PEG-SH 4 ) and crosslinked via Michael-type addition; the mixture was injected into a rat MI model 2 weeks post-MI [33]. Four weeks after treatment, heart function was evaluated; HA treatment led to significantly decreased infarct size, increased EF, and increased arteriole and capillary density.…”

“…However, these approaches are limited by the invasive procedure in which they are applied, and clinical adoption has not occurred. In order to circumvent the invasive surgical placement of restraining devices early post-MI, our group and others have begun to explore the use of injectable materials, and specifically hydrogels, to limit infarct expansion and normalize the regional stress distribution [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”

Hydrogels for Cardiac Tissue Repair and Regeneration

“…It was reported that the modifi ed HA hydrogel provided a signifi cantly higher ejection fraction, increased wall thickness and better vessel formation, suggesting that the HA hydrogels can offer promising solution for cardiac tissue repair after MI [38]. of treatment, it was observed that the myocardial structure begin to regenerate, prevent fi brous tissue formation and signifi cantly recover heart function in a rat MI model [38].…”

“…of treatment, it was observed that the myocardial structure begin to regenerate, prevent fi brous tissue formation and signifi cantly recover heart function in a rat MI model [38]. to the cell alone injection [44,45].…”

Biomaterial‐Enhanced Cell and Drug Delivery: Lessons Learned in the Cardiac Field and Future Perspectives

“…The benefit is hypothesised to be a function of mechanical properties (45)(46)(47)(48) and injection pattern (48) of the therapy in question, or, less commonly, is attributed to the bioactive potential of the injected material. (49)(50)(51)(52) In vivo, acute infarct rodent studies by Dobner (53) and the Christman group have been completed. (49,54) The studies investigated the effect of injecting a bio-inert non-degradable and degradable synthetic polymer polyethylene glycol (PEG) of low and high moduli (0.5+/-0.1 kPa and ≈ 10 kPa).…”