High-Throughput Manufacture of 3D Fiber Scaffolds for Regenerative Medicine

Abstract

Engineered scaffolds used to regenerate mammalian tissues should recapitulate the underlying fibrous architecture of native tissue to achieve comparable function. Current fibrous scaffold fabrication processes, such as electrospinning and three-dimensional (3D) printing, possess application-specific advantages, but they are limited either by achievable fiber sizes and pore resolution, processing efficiency, or architectural control in three dimensions. As such, a gap exists in efficiently producing clinically relevant, anatomically sized scaffolds comprising fibers in the 1-100 mm range that are highly organized. This study introduces a new highthroughput, additive fibrous scaffold fabrication process, designated in this study as 3D melt blowing (3DMB). The 3DMB system described in this study is modified from larger nonwovens manufacturing machinery to accommodate the lower volume, high-cost polymers used for tissue engineering and implantable biomedical devices and has a fiber collection component that uses adaptable robotics to create scaffolds with predetermined geometries. The fundamental process principles, system design, and key parameters are described, and two examples of the capabilities to create scaffolds for biomedical engineering applications are demonstrated.

Multiscale Anisotropic Tissue Biofabrication via Bulk Acoustic Patterning of Cells and Functional Additives in Hybrid Bioinks

“…The melt blowing setup and processing is described elsewhere. [ 11 ] The key melt blowing process parameters included die to collector distance (DCD = 150 mm), fiber deposition offset (FDO = 80 mm), and surface velocity of the collector (SVC = 150 m min −1 or 700 m min −1 ) to achieve different fiber diameters (Figure 2E). Post fabrication, the scaffolds were treated with NaOH to improve hydrophilicity.…”

“…Increase in the frequency of rocking leads to decrease in the size of the CM. E) Fabrication of PM via melt‐blowing [ 11 ] and subsequent cryosectioning. Increase in the surface speed of the collection mandrel leads to reduction in the diameter of melt blown PCL fibers, while increase in the cutter offset of the cryosectioner leads to increase in the length of the derived PM.…”

“…For tissue engineering strategies aiming to create biomimetic tissues, achieving the appropriate organization of cells is a precursor to achieving the desired organization of ECM and biomechanical functionality. Studies using fibrous polymer scaffolds, such as those made using electrospinning, [ 10 ] melt‐blowing [ 11 ] and extrusion printing [ 12 ] have typically relied on microarchitectural contact guidance to impart cell and ECM organization along the fiber orientation. Of late, bioprinting of cell‐laden bioinks has been established as a versatile technology for fabrication of complex tissues such as the heart, [ 13,14 ] liver [ 15,16 ] and skin, [ 17,18 ] featuring multiple types of cells, biomaterial matrices and additives.…”

Inherently Distinctive Potentialities and Uses of Nanocellulose Based on its Nanoarchitecture

“…Three-dimensional (3D) printing is an emerging methodology that allows the fabrication of soft biocompatible hydrogels into 3D tissue-like or organ-like structures in advanced tissue engineering (Zhao et al 2015), drug screening (Thomas and Willerth 2017), and regenerative medicine (Shirwaiker et al 2020). Direct printing using "bio-ink" comprising high-viscoelasticity multifunctional cells/biomaterial composites facilitates the production of printed constructs with mechanical strength.…”

Process hybridization schemes for multiscale engineered tissue biofabrication

“…Some electrospinning strategies to achieve higher production rates without compromising the resolution include the use of multiple needles (Theron, Yarin, Zussman, & Kroll, 2005) or needleless techniques (Yarin & Zussman, 2004), although the scaffolds can end up being too dense to facilitate cellular and nutrient infiltration. For applications in which nanoscale resolution is not a primary concern, melt blowing can be used as an alternative to electrospinning to achieve production rates that are at least an order of magnitude higher (Shirwaiker et al, 2020). Among AM techniques, mask projection stereolithography (SLA) techniques utilizing digital micromirror devices or light projectors are especially powerful to achieve high throughput at a moderate resolution (Cui et al, 2017).…”