Self-Searching Writing of Human-Organ-Scale Three-Dimensional Topographic Scaffolds with Shape Memory by Silkworm-like Electrospun Autopilot Jet.

Bioengineered scaffolds satisfying both the physiological and anatomical considerations could potentially repair partially damaged tissues to whole organs. Although three-dimensional (3D) printing has become a popular approach in making 3D topographic scaffolds, electrospinning stands out from all other techniques for fabricating extracellular matrix mimicking fibrous scaffolds. However, its complex charge-influenced jet-field interactions and the associated random motion were hardly overcome for almost a century, thus preventing it from being a viable technique for 3D topographic scaffold construction. Herein, we constructed, for the first time, geometrically challenging 3D fibrous scaffolds using biodegradable poly(ε-caprolactone), mimicking human-organ-scale face, female breast, nipple, and vascular graft, with exceptional shape memory and free-standing features by a novel field self-searching process of autopilot polymer jet, essentially resembling the silkworm-like cocoon spinning. With a simple electrospinning setup and innovative writing strategies supported by simulation, we successfully overcame the intricate jet-field interactions while preserving high-fidelity template topographies, via excellent target recognition, with pattern features ranging from 100's µm to 10's cm. A 3D cell culture study ensured the anatomical compatibility of the so-made 3D scaffolds. Our approach brings the century-old electrospinning to the new list of viable 3D scaffold constructing techniques, which goes beyond applications in tissue engineering.

Novel Self-Directing Single-Polymer Jet Developing Layered-Like 3D Buckled Microfibrous Scaffolds for Tissue Engineering Applications.

Electrospinning is a promising technique for the fabrication of bioscaffolds in tissue engineering applications. Pertaining issues of multiple polymer jets and bending instabilities result in random paths which lend poor controllability over scaffolds morphology for affecting the porosity and mechanical stability. The present study alleviates these challenges by demonstrating a novel self-directing single jet taking a specifically patterned path to deposit fibers into circular and uniform scaffolds without tuning any externally controlled parameters. High-speed camera observation revealed that the charge retention and dissipation on the collected fibers caused rapid autojet switching between the two jetting modes, namely, a microcantilever-like armed jet motion and a whipping motion, which sequentially expand the area and thickness of the scaffolds, respectively, in a layered-like fashion. The physical properties showed that the self-switching dual-jet modes generated multilayered microfibrous scaffolds (MFSs) with dual morphologies and varied fiber packing density, thereby establishing the gradient porosity and mechanical strength (through buckled fibers) in the scaffolds. In vitro studies showed that as-spun scaffolds are cell-permeable hierarchical 3D microporous structures enabling lateral cell seeding into multiple layers. The cell proliferation on days 6 and 9 increased 21% and 38% correspondingly on MFSs than on nanofibrous scaffolds (NFSs) done by conventional multijets electrospinning. Remarkably, this novel and single-step process is highly reproducible and tunable for developing fibrous scaffolds for tissue engineering applications.

Bio-inspired in situ crosslinking and mineralization of electrospun collagen scaffolds for bone tissue engineering.

Bone disorders are the most common cause of severe long term pain and physical disability, and affect millions of people around the world. In the present study, we report bio-inspired preparation of bone-like composite structures by electrospinning of collagen containing catecholamines and Ca(2+). The presence of divalent cation induces simultaneous partial oxidative polymerization of catecholamines and crosslinking of collagen nanofibers, thus producing mats that are mechanically robust and confer photoluminescence properties. Subsequent mineralization of the mats by ammonium carbonate leads to complete oxidative polymerization of catecholamines and precipitation of amorphous CaCO3. The collagen composite scaffolds display outstanding mechanical properties with Young's modulus approaching the limits of cancellous bone. Biological studies demonstrate that human fetal osteoblasts seeded on to the composite scaffolds display enhanced cell adhesion, penetration, proliferation, differentiation and osteogenic expression of osteocalcin, osteopontin and bone matrix protein when compared to pristine collagen or tissue culture plates. Among the two catecholamines, mats containing norepinephrine displayed superior mechanical, photoluminescence and biological properties than mats loaded with dopamine. These smart multifunctional scaffolds could potentially be utilized to repair and regenerate bone defects and injuries.

Biomimetic approaches for cell implantation to the restoration of infarcted myocardium.

Compelling evidences accumulated over the years have proven stem cells as a promising source for regenerative medicine. However, the inadequacy with the design of delivery modalities has prolonged the research in realizing an ideal cell-based approach for the regeneration of infarcted myocardium. Currently, some modest improvements in cardiac function have been documented in clinical trials with stem cell treatments, although regenerating a fully functional myocardium remains a dream for cardiac surgeons. This review provides an overview on the significance of stem cell therapy, the current attempts to resolve the drawbacks with the cell implantation approach and the various stratagems adopted with electrospun hybrid nanofibers for implementation in myocardial regenerative therapy.

Controlled release of titanocene into the hybrid nanofibrous scaffolds to prevent the proliferation of breast cancer cells.

Electrospun hybrid nanofibrous scaffolds have gained much importance in the field of tissue engineering and drug delivery applications owing to its multifaceted properties. In this study, the properties of composite polycaprolactone (PCL)/silk fibroin (SF) nanofibrous scaffolds was investigated as a potential scaffold for cell growth and also a drug eluting mat to control the proliferation of MCF-7 cells. Titanocene dichloride was chosen as the model drug to study its antitumor efficacy on MCF-7 cell lines. Fascinating properties relating to crystallization of silk fibroin and binding of drug has also been discussed for the controlled release of drugs. The presence of amino acid residues in silk fibroin plays a big role in the cell-scaffold interaction, the nature of drug binding and also its release characteristics to control the cell proliferation. Studies on material properties for the hybrid nanofibrous scaffolds showed interrelated changes in fiber diameter and mechanical behavior for the drug loaded nanofibers. Significant decrease in fiber diameters from 352±52 nm to 281±44.5 nm and sharp increase in tensile stress from 4.5 MPa to 50.3 MPa was observed for 0.03% drug loaded scaffolds with respect to PCL fibers. Cell viability and cell morphology study was performed to analyze the effect of different concentrations of titanocene dichloride loaded on PCL/silk fibroin nanofibrous scaffolds. Maximum cell viability inhibition percentage of change 26.93% was obtained for 0.03% titanocene with respect to 0.01% on day 3. The obtained results proved that the drug loaded hybrid mat to control the proliferation of MCF-7 cells at different time points and serve as a model for cancer therapy.