Biomimetic matrices for myocardial stabilization and stem cell transplantation

Abstract

Although natural biological matrices have demonstrated modest improvement in the survival of cells transplanted into the infarcted myocardium, these materials have not been amenable to systematic optimization and therefore have limited potential to treat post infarct cardiac injuries. Here we have developed tunable bioactive semi-interpenetrating polymer network (sIPN) hydrogels with matrix metalloproteinase (MMP) labile crosslinkers to be used as an assistive microenvironment for transplantation of bone marrow derived mesenchymal stem cells (BMSCs) into the infarcted myocardium. Injectable sIPN hydrogels were designed with a range of mechanical and biological properties that yielded material-dependent BMSC proliferation in vitro. Five groups were evaluated to treat myocardial infarction (MI) in adult mice: saline injection; green fluorescent protein (GFP)(+)-BMSCs delivered in saline; a sIPN matrix; a sIPN + GFP(+)-BMSCs; and Matrigel™ + GFP(+)-BMSCs. Injection of cells alone created a transient improvement in LV function that declined over time, and the synthetic hydrogel without cells resulted in the highest LV function at 6 weeks. Donor GFP-positive cells were detected after matrix-enhanced transplantation, but not without matrix support. Biomimetic sIPN hydrogel matrices succeeded both in mechanically supporting the injured myocardium and modestly enhancing donor cell survival. These matrices provide a foundation for systematic development of "pro-survival" microenvironments, and improvement in the long-term results of cardiac stem cell transplantation therapies.

Scleral Reinforcement Through Host Tissue Integration with Biomimetic Enzymatically Degradable Semi-Interpenetrating Polymer Network

“…This interpretation is also consistent with the relatively slow degradation rate for the degradable peptide crosslinker used in our study, quantified in a separate in vitro study. 55 Unlike native, untreated fibrous sclera, the collagen fibers within the edsIPN did not appear to have any organized fiber orientation. Although the cellular infiltration of the implants resulted in an apparent thickening of the outer fibrous layer of the sclera, this increase in thickness was not detected by high-frequency ultrasonography, suggesting either that this scleral integration layer had altered impedance compared with the natural sclera or that the combined attenuating effect of all the preceding intervening ocular surfaces rendered our device insufficiently sensitive to detect the boundaries of this most posterior layer.…”

Heart regeneration after myocardial infarction using synthetic biomaterials

“…Six weeks after implantation, hydrogels were at the site of injection and GFP-BMSC could be detected. However, BMSC-hydrogel treatment did not show any improvement in ejection fraction (EF) and fractional shortening (FS) compared to non loaded hydrogels and free BMSC injection [52]. Concurrently, Li X.Y.…”

Stem Cell-Based Cardiac Tissue Engineering

“…However, the mechanism responsible for functional improvements as a result of injection of biomaterials alone is yet to be elucidated. One possible explanation is that the injection of biomaterials results in mechanical stabilization of the ventricle irrespective of effects on cellular function or survival [22]. To facilitate further comparison between different studies, it appears necessary to standardize the experimental conditions and MI models.…”