Bioengineered analog of stromal cell-derived factor 1? preserves the biaxial mechanical properties of native myocardium after infarction.
Journal of the mechanical behavior of biomedical materials
2019; 96: 165?71
Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, often leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1? analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Male Wistar rats (n?=?45) underwent sham surgery (n?=?15) or permanent left anterior descending coronary artery ligation. Rats sustaining MI were randomized for intramyocardial injections of either saline (100??L, n?=?15) or ESA (6??g/kg, n?=?15), delivered at four standardized borderzone sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Tensile testing of the anterolateral LV wall was performed using a displacement-controlled biaxial load frame, and modulus was determined after constitutive modeling. At 4 weeks post-MI, compared to saline controls, ESA-treated hearts had greater wall thickness (1.68?±?0.05?mm vs 1.42?±?0.08?mm, p?=?0.008), smaller end-diastolic LV internal dimension (6.88?±?0.29?mm vs 7.69?±?0.22?mm, p?=?0.044), and improved ejection fraction (62.8?±?3.0% vs 49.4?±?4.5%, p?=?0.014). Histologic analysis revealed significantly reduced infarct size for ESA-treated hearts compared to saline controls (29.4?±?2.9% vs 41.6?±?3.1%, p?=?0.021). Infarcted hearts treated with ESA exhibited decreased modulus compared to those treated with saline in both the circumferential (211.5?±?6.9?kPa vs 264.3?±?12.5?kPa, p?=?0.001) and longitudinal axes (194.5?±?6.5?kPa vs 258.1?±?14.4?kPa, p?0.001). In both principal directions, ESA-treated infarcted hearts possessed similar tissue compliance as sham non-infarcted hearts. Overall, intramyocardial ESA therapy improves post-MI ventricular remodeling and function, reduces infarct size, and preserves native LV biaxial mechanical properties.
View details for PubMedID 31035067
Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier.
Nature biomedical engineering
2019; 3 (8): 611?20
Post-operative adhesions form as a result of normal wound healing processes following any type of surgery. In cardiac surgery, pericardial adhesions are particularly problematic during reoperations, as surgeons must release the adhesions from the surface of the heart before the intended procedure can begin, thereby substantially lengthening operation times and introducing risks of haemorrhage and injury to the heart and lungs during sternal re-entry and cardiac dissection. Here we show that a dynamically crosslinked supramolecular polymer-nanoparticle hydrogel, with viscoelastic and flow properties that enable spraying onto tissue as well as robust tissue adherence and local retention in vivo for two weeks, reduces the formation of pericardial adhesions. In a rat model of severe pericardial adhesions, the hydrogel markedly reduced the severity of the adhesions, whereas commercial adhesion barriers (including Seprafilm and Interceed) did not. The hydrogels also reduced the severity of cardiac adhesions (relative to untreated animals) in a clinically relevant cardiopulmonary-bypass model in sheep. This viscoelastic supramolecular polymeric hydrogel represents a promising clinical solution for the prevention of post-operative pericardial adhesions.
View details for DOI 10.1038/s41551-019-0442-z
View details for PubMedID 31391596
Asynchronous fate decisions by single cells collectively ensure consistent lineage composition in the mouse blastocyst
Intercellular communication is essential to coordinate the behaviour of individual cells during organismal development. The preimplantation mammalian embryo is a paradigm of tissue self-organization and regulative development; however, the cellular basis of these regulative abilities has not been established. Here we use a quantitative image analysis pipeline to undertake a high-resolution, single-cell level analysis of lineage specification in the inner cell mass (ICM) of the mouse blastocyst. We show that a consistent ratio of epiblast and primitive endoderm lineages is achieved through incremental allocation of cells from a common progenitor pool, and that the lineage composition of the ICM is conserved regardless of its size. Furthermore, timed modulation of the FGF-MAPK pathway shows that individual progenitors commit to either fate asynchronously during blastocyst development. These data indicate that such incremental lineage allocation provides the basis for a tissue size control mechanism that ensures the generation of lineages of appropriate size.
View details for DOI 10.1038/ncomms13463
View details for Web of Science ID 000387993300001
View details for PubMedID 27857135
View details for PubMedCentralID PMC5120222