On the Biomechanics of Cardiac S-Looping in the Chick: Insights From Modeling and Perturbation Studies.

Cardiac looping is an important embryonic developmental stage where the primitive heart tube (HT) twists into a configuration that more closely resembles the mature heart. Improper looping leads to congenital defects. Using the chick embryo as the experimental model, we study cardiac s-looping wherein the primitive ventricle, which lay superior to the atrium, now assumes its definitive position inferior to it. This process results in a heart loop that is no longer planar with the inflow and outflow tracts now lying in adjacent planes. We investigate the biomechanics of s-looping and use modeling to understand the nonlinear and time-variant morphogenetic shape changes. We developed physical and finite element models and validated the models using perturbation studies. The results from experiments and models show how force actuators such as bending of the embryonic dorsal wall (cervical flexure), rotation around the body axis (embryo torsion), and HT growth interact to produce the heart loop. Using model-based and experimental data, we present an improved hypothesis for early cardiac s-looping.

Fabrication of elastomeric silk fibers.

Methods to generate fibers from hydrogels, with control over mechanical properties, fiber diameter, and crystallinity, while retaining cytocompatibility and degradability, would expand options for biomaterials. Here, we exploited features of silk fibroin protein for the formation of tunable silk hydrogel fibers. The biological, chemical, and morphological features inherent to silk were combined with elastomeric properties gained through enzymatic crosslinking of the protein. Postprocessing via methanol and autoclaving provided tunable control of fiber features. Mechanical, optical, and chemical analyses demonstrated control of fiber properties by exploiting the physical cross-links, and generating double network hydrogels consisting of chemical and physical cross-links. Structure and chemical analyses revealed crystallinity from 30 to 50%, modulus from 0.5 to 4 MPa, and ultimate strength 1-5 MPa depending on the processing method. Fabrication and postprocessing combined provided fibers with extensibility from 100 to 400% ultimate strain. Fibers strained to 100% exhibited fourth order birefringence, revealing macroscopic orientation driven by chain mobility. The physical cross-links were influenced in part by the drying rate of fabricated materials, where bound water, packing density, and microstructural homogeneity influenced cross-linking efficiency. The ability to generate robust and versatile hydrogel microfibers is desirable for bottom-up assembly of biological tissues and for broader biomaterial applications.

On the role of intrinsic and extrinsic forces in early cardiac S-looping.

BACKGROUND: Looping is a crucial phase during heart development when the initially straight heart tube is transformed into a shape that more closely resembles the mature heart. Although the genetic and biochemical pathways of cardiac looping have been well studied, the biophysical mechanisms that actually effect the looping process remain poorly understood. Using a combined experimental (chick embryo) and computational (finite element modeling) approach, we study the forces driving early s-looping when the primitive ventricle moves to its definitive position inferior to the common atrium. RESULTS: New results from our study indicate that the primitive heart has no intrinsic ability to form an s-loop and that extrinsic forces are necessary to effect early s-looping. They support previous studies that established an important role for cervical flexure in causing early cardiac s-looping. Our results also show that forces applied by the splanchnopleure cannot be ignored during early s-looping and shed light on the role of cardiac jelly. Using available experimental data and computer modeling, we successfully developed and tested a hypothesis for the force mechanisms driving s-loop formation. CONCLUSIONS: Forces external to the primitive heart tube are necessary in the later stages of cardiac looping. Experimental and model results support our proposed hypothesis for forces driving early s-looping.

Silk Protein Bioresorbable, Drug-Eluting Ear Tubes: Proof-of-Concept.

Otitis media with effusion (OEM) is a common pediatric pathology treated with topical fluoroquinolones (ear drops) and tympanoplasty tube, also referred to as ear tube, implantation for middle ear drainage. Commercially available ear tubes are fabricated using poly (lactic-co-glycolic acid) synthetic materials that are associated with long-complications due to premature extrusion. Resorbable materials have emerged as desirable alternatives to reduce extrusion-related complications, but often limited by fast resorption rates. Therefore, resorbable tubes with long-term functional integrity are required for future clinical translation. In this communication, a proof-of-concept study is reported on a bioresorbable and drug-eluting silk ear tube device. Preliminary in vitro assessments reveal time-dependent drug elution and antimicrobial properties, while maintaining long-term functional integrity in vivo. This report provides evidence of a silk ear tube with potential for future clinical translation and OEM treatment.