Engineering Biomimetic Nanofiber Microspheres with Tailored Size, Predesigned Structure, and Desired Composition via Gas Bubble–Mediated Coaxial Electrospray

Abstract

Minimally invasive therapies avoiding surgical complexities evoke great interest in developing injectable biomedical devices. Herein, a versatile approach is reported for engineering injectable and biomimetic nanofiber microspheres (NMs) with tunable sizes, predesigned structures, and desired compositions via gas bubble–mediated coaxial electrospraying. The sizes and structures of NMs are controlled by adjusting processing parameters including air flow rate, applied voltage, distance, and spinneret configuration in the coaxial setup. Importantly, unlike the self‐assembly method, this technique can be used to fabricate NMs from any material feasible for electrospinning or other nanofiber fabrication techniques. To demonstrate the versatility, open porous NMs are successfully fabricated that consist of various short nanofibers made of poly(ε‐caprolactone), poly(lactic‐co‐glycolic acid), gelatin, methacrylated gelatin, bioglass, and magneto‐responsive polymer composites. Open porous NMs support human neural progenitor cell growth in 3D with a larger number and more neurites than nonporous NMs. Additionally, highly open porous NMs show faster cell infiltration and host tissue integration than nonporous NMs after subcutaneous injection to rats. Such a novel class of NMs holds great potential for many biomedical applications such as tissue filling, cell and drug delivery, and minimally invasive tissue regeneration.

Freeze‐Casting with 3D‐Printed Templates Creates Anisotropic Microchannels and Patterned Macrochannels within Biomimetic Nanofiber Aerogels for Rapid Cellular Infiltration

“…[ 30 ] After freeze‐drying, aerogels were crosslinked by GA vapor to enhance their mechanical stability like our previously reported procedure. [ 39,40 ] Figure S1B(i–vi),C(i–vi) (Supporting Information) shows scanning electron microscopy (SEM) images of the horizontal and vertical sections of crosslinked PCL/gelatin (1:1) nanofiber aerogels without and with 3D‐printed sacrificial templates fabricated using isotropic freezing. Nanofiber aerogels produced without 3D‐printed sacrificial templates had random porous structures from both a horizontal and a vertical view (Figure S1B(ii,v), Supporting Information).…”

Advanced fabrication for electrospun three-dimensional nanofiber aerogels and scaffolds

“…To further leverage the potential of electrospinning-mediated electrospray technology to develop open porous microspheres, the same group [ 58 ] employed gas bubbles driven co-axial electrospraying of short nanofibers; the gas bubbles comprised the core whereas the short nanofibers comprised the shell of microspheres ( Fig. 15 ).…”

“… Advantages Fabricate NMs from any material feasible for electrospinning Disadvantages Complex preparation process; Crosslinking agent toxicity Applications Biomimetic and injectable carrier; Osteogenesis; Angiogenesis; Tissue filling; Cell and drug delivery Ref [ 56 , 57 ] Origami and cell sheet engineering Mechanism Cells were seeded on both two sides of the electrospun nanofiber film and use the co-cultured membrane to fabricate bio-tubular scaffolds or nanofiber boxes via origami. Advantages Cell infiltration; Intricate architectures Disadvantages Complex preparation process; High requirements for operators Applications 3D tissue construction; Vascular grafts regeneration Ref [ [58] , [59] , [60] ] Centrifugal electrospinning Mechanism Use an electrospun rotating spinneret and obtain nanofiber from a conductive iron circular collector surrounding the spinneret. Advantages Promote production rates; High orientation Disadvantages Require special equipment; Few types of the fiber structure Applications Mass production of electrospun fibers; Drug release Ref [ 61 ] …”

Preparation of Single, Heteromorphic Microspheres, and Their Progress for Medical Applications

“…This new type of microsphere has great potential in many biomedical applications, such as tissue filling, cell and drug delivery, and minimally invasive tissue regeneration. [ 53 ]…”