An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats

Abstract

Background A new post–myocardial infarction (MI) therapy is injection of high-water content polymeric biomaterial gels (hydrogels) into damaged myocardium to modulate cardiac negative remodeling and preserve heart function. Methods We investigated the therapeutic potential of a novel gelatinized alginate hydrogel with a unique microstructure of uniform capillary-like channels (termed Capgel). Shortly (48 hours) after induced anterior MI, Sprague Dawley rats received intramyocardial injection of Capgel directly into the antero-septal wall at the infarct border zone (n=12) or no injection (n=10, controls). Echocardiograms were performed at 48h (week 0) and 4 weeks (week 4) to evaluate left ventricular function. Results Echocardiograms showed 27% improvement of left ventricular systolic function over time with gel injection: fractional shortening increased from 26±3% at week 0 to 33±2% at week 4 (p=0.001). Capgel was present at the injection site after 4 weeks, but was minimal at 8 weeks. The remaining gel was heavily populated by CD68+ macrophages with CD206+ clusters and blood vessels. An in vitro experiment was performed to assess Angiotensin-(1-7) released from Capgel. Angiotensin-(1-7) was released from the Capgel in a sustained manner for 90 days. Conclusions Use of Capgel, a degradable, bioactive hydrogel composed of gelatinized capillary-alginate gel, appears safe for intramyocardial injection, is associated with improved left ventricular function after MI in rats, and may provide a long-term supply of Angiotensin-(1-7).

Capillary alginate gel (Capgel™) for the treatment of full-thickness dermal wounds in a hypoxic mouse model

“…After one month, Capgel TM was observed as being well-received by the host tissue, having been infiltrated by host cells, blood vessels and containing a collagen matrix. [18] The patent capillaries in Capgel TM provide a reservoir for soluble factors and wound exudate as well as surface area for host cell adhesion, migration and differentiation. The volumizing ability of Capgel TM aids in limiting wound contracture, thus providing a larger granulation bed more consistent with the original volume of the affected site.…”

Ventricular wall biomaterial injection therapy after myocardial infarction: Advances in material design, mechanistic insight and early clinical experiences

“…In addition, the injected hydrogel was vascularized and populated by CD68 + macrophages. These macrophages largely showed an M2-like phenotype as marked by CD206 expression, suggesting a constructive remodeling response [86]. Similar local tissue responses have been observed in disease models treated with decellularized matrix materials [26, 28, 87].…”

“…Rocca et al have fabricated a gelatinized alginate hydrogel with uniform capillary-like channels and directly injected this hydrogel into the antero-septal wall at the infarct border zone [86]. Cardiac function was improved compared to saline injection control in a rat injection trial.…”

Injectable Hydrogel-Based Nanocomposites for Cardiovascular Diseases

“…Therefore, there are many scholars who have developed other natural hydrogels and studied their role in promoting cardiovascular disease repair to replace ECM. Currently developed hydrogels biomaterials include chitosan natural hydrogels (Li J. et al, 2013), hyaluronic acid hydrogels (Yoon et al, 2009), sodium alginate hydrogels (Rocca et al, 2016), and so on. As an immunological linear neutral polysaccharide, hyaluronic acid has multiple acid and hydroxyl groups in the molecule, which can be modified into different forms of hydrogels, including soft or hard hydrogels, as well as nanoparticles and electrospinning.…”

“…In addition, the easily degradable, non-toxic sodium alginate hydrogel can be modified without modification and induced specific properties for a wide range of applications (Hadley and Silva, 2019). Once the degradable alginate hydrogel was designed to own a microstructure to sustain the release of angiopoietin, it can promote cardiac repair (Rocca et al, 2016) and that is why it widely used in cardiac engineering (Ruvinov and Cohen, 2016). According to the rapid development of alginate hydrogel, a multicenter prospective randomized controlled trial called AUGMENT-HF followed up for 1 year was conducted and found that patients with advanced heart failure (HF) using calcium alginate-injected hydrogel presented better cardiac function and clinical outcome rather than who accepting clinical standard medicine therapy (SMT) (Mann et al, 2016).…”