Advanced Material Catheter (AMCath), a minimally invasive endocardial catheter for the delivery of fast-gelling covalently cross-linked hyaluronic acid hydrogels

Abstract

Injectable hydrogels that aim to mechanically stabilise the weakened left ventricle (LV) wall to restore cardiac function or to deliver stem cells in cardiac regenerative therapy have shown promising data. However, the clinical translation of hydrogel-based therapies has been limited due to difficulties injecting them through catheters. We have engineered a novel catheter (AMCath) that overcomes translational hurdles associated with delivering fast-gelling covalently cross-linked hyaluronic acid hydrogels to the myocardium. We developed an experimental technique to measure the force required to inject such hydrogels and determined the mechanical/ viscoelastic properties of the resulting hydrogels. The preliminary in vivo feasibility of delivering fast-gelling hydrogels through AMCath was demonstrated by accessing the porcine LV and showing that the hydrogel was retained in the myocardium postinjection (three 200μL injections delivered, 192, 204 and 183μL measured). However, the mechanical properties of the hydrogels were reduced by passage through AMCath (≤20.62% reduction). We have also shown AMCath can be used to deliver c-ADSC loaded hydrogels without compromising the viability (80% viability) of the c-ADSCs in vitro. Therefore, we show that hydrogel/catheter compatibility issues can be overcome as we have demonstrated the minimally invasive delivery of a fast gelling covalently cross-linked hydrogel to the beating myocardium.

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

“…Recent advancements in catheter technology for local delivery of hydrogels to the heart could be exploited in order to overcome this hurdle. [ 267 ] Furthermore, localized and repeated delivery of factors to the heart could be achieved by implantable and replenishable reservoirs. [ 268 ]…”

Hydrogels in adipose tissue engineering—Potential application in post‐mastectomy breast regeneration

“…Fibronectin‐derived RGD is an oligopeptide that stimulates integrin‐mediated cell adhesion (Wang et al, ). An HA derivative, reported by Dolan et al, bearing both hydroxyphenol moiety and RGD, can undergo HRP‐mediated cross‐linking, which forms robust hydrogels suitable for cell attachment (Ma et al, ). The thermoresponsive behaviour of HA composites, with inclusion of synthetic biomaterials, has been explored and has shown potential for adipose tissue regeneration.…”

“…A feasibility study in humans was then undertaken, which showed effective implantation and photo‐cross‐linking in abdominal soft tissue; however, an inflammatory reaction was observed surrounding the implant (Hillel et al, ). Dual syringe systems are utilised in enzyme‐mediated cross‐linking techniques, and the reaction occurs in situ (Dolan et al, ; Lee, Bae, & Kurisawa, ). Finally, thermoresponsive polymers are those that form hydrogels at body temperature (37°C) but are still found in a liquid state at room temperature (25°C; Klouda & Mikos, ; Payne, Dolan, O'Sullivan, Cryan, & Kelly, ).…”

An injectable alginate/extra cellular matrix (ECM) hydrogel towards acellular treatment of heart failure

“…Rheological assessment of each hydrogel took place by monitoring the storage (G') and loss (G") modulus using an AR1000ex Rheometer (TA Instruments, USA) as previously described 48,49 . Testing was performed at 20 °C using a shear stress sweep between 10 and 80 Pa, and a 40 mm diameter 4° cone.…”

“…A Zwick mechanical testing machine (Z050, Zwick/Roell, Germany) was used to determine the force required to inject the hydrogels through the needle and the catheter, as previously described 48,49…”