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 are 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.

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. Post-processing 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 analysis revealed crystallinity from 30–50%, modulus from 0.5MPa to 4MPa, and ultimate strength 1 to 5 MPa depending on the processing method. Fabrication and post-processing combined provided fibers with extensibility from 100 to 400% ultimate strain. Fibers strained to 100% exhibited 4th 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 micro-structural 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.

Fiber units are conserved design motifs that bestow intrinsic stiffness to biological tissues. Collagen fibrils are the fundamental unit of fibrous tissues with controlled assembly and multiscale structure‐function properties. Characteristic non‐linear tissue response is afforded through energy dissipation at the stiff‐soft interfaces of fibril collagen and extrafibrillar matrix components. The goal of this research is to develop a 3D silk hydrogel microfiber platform with bioinspired toughening mechanisms. Batch fabrication and post‐processing renders fibers that can be handled and with tunable features, as well as loading of components to improve material responses. Matrix loading of a glycoprotein, bovine serum albumin (BSA), adds a primary defense mechanism to material failure in the form of sacrificial bonds. This enables nano‐ to micro‐scale rearrangement with strain and improved fiber toughness compared to silk‐only fibers. Further biomimicry is added via matrix loading of a biosilica precursor peptide, R5, enabling biomineralization in the form of silicification. Inorganic mineral deposition of Silk‐BSA‐R5 hydrogel microfibers provides a fibrous scaffold for applications that require fibril‐mineral interfaces for load transduction. This microfiber platform introduces a methodology for meticulous fibrous scaffold design with biomimetic fibril hierarchy, toughening mechanisms, and loading capabilities for systematic tissue engineering applications.

No abstract

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.